REVIEW published: 21 January 2020 doi: 10.3389/fnagi.2019.00367 Functional Near-Infrared Spectroscopy to Study Cerebral Hemodynamics in Older Adults During Cognitive and Motor Tasks: A Review Cristina Udina 1,2,3* , Stella Avtzi 4 , Turgut Durduran 4,5 , Roee Holtzer 6,7 , Andrea L. Rosso 8 , Carmina Castellano-Tejedor 1,2,3 , Laura-Monica Perez 1,2 , Luis Soto-Bagaria 1,2 and Marco Inzitari 1,2,3 1 Parc Sanitari Pere Virgili, Barcelona, Spain, 2 RE-FiT Barcelona Research Group, Vall d’Hebrón Institute of Research, Barcelona, Spain, 3 Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain, 4 Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, Barcelona, Spain, 5 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain, 6 Ferkauf Graduate School of Psychology, Yeshiva University, New York, NY, United States, 7 Department of Neurology, Albert Einstein College of Medicine, New York, NY, United States, 8 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States The integrity of the frontal areas of the brain, specifically the prefrontal cortex, are critical to preserve cognition and mobility in late life. Prefrontal cortex regions are involved in executive functions and gait control and have been related to the performance of dual-tasks. Dual-task performance assessment may help identify older adults at Edited by: Hans J. Grabe, risk of negative health outcomes. As an alternative to neuroimaging techniques that University of Greifswald, Germany do not allow assessment during actual motion, functional Near-Infrared Spectroscopy Reviewed by: (fNIRS) is a non-invasive technique that can assess neural activation through the Dafin F. Muresanu, Iuliu Haţieganu University of Medicine measurement of cortical oxygenated and deoxygenated hemoglobin levels, while the and Pharmacy, Romania person is performing a motor task in a natural environment as well as during cognitive Sarah Anne Fraser, tasks. The aim of this review was to describe the use of fNIRS to study frontal lobe University of Ottawa, Canada hemodynamics during cognitive, motor and dual-tasks in older adults. From the 46 *Correspondence: Cristina Udina included publications, 20 studies used only cognitive tasks, three studies used motor cudina@perevirgili.cat tasks and 23 used dual-tasks. Our findings suggest that fNIRS detects changes in frontal activation in older adults (cognitively healthy and mild cognitive impairment), Received: 20 June 2019 Accepted: 16 December 2019 especially while performing cognitive and dual-tasks. In both the comparison between Published: 21 January 2020 older and younger adults, and in people with different neurological conditions, compared Citation: to healthier controls, the prefrontal cortex seems to experience a higher activation, which Udina C, Avtzi S, Durduran T, Holtzer R, Rosso AL, could be interpreted in the context of proposed neural inefficiency and limited capacity Castellano-Tejedor C, Perez L-M, models. Further research is needed to establish standardized fNIRS protocols, study Soto-Bagaria L and Inzitari M (2020) the cerebral hemodynamic in different neurological and systemic conditions that might Functional Near-Infrared Spectroscopy to Study Cerebral influence cortical activation and explore its role in predicting incident health outcomes Hemodynamics in Older Adults During such as dementia. Cognitive and Motor Tasks: A Review. Front. Aging Neurosci. 11:367. Keywords: functional Near-Infrared Spectroscopy, gait, dual task, motor task, cognition, older adults, prefrontal doi: 10.3389/fnagi.2019.00367 cortex, cerebral hemodynamics Frontiers in Aging Neuroscience | www.frontiersin.org 1 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults INTRODUCTION brain function with a relatively high spatial resolution, are non- invasive and the most used technique to date to assess neural The worldwide aging of the population makes tackling aging- activity during specific task activation (Rosen and Savoy, 2012). associated disability an urgent priority. Cognitive impairment Several fMRI studies have demonstrated the relevance of PFC and mobility disability are key contributors to dementia and for executive functions (Wager et al., 2004; Venkatraman et al., loss of independence in the activities of daily living and have 2010; Yaple et al., 2019) and DT (Szameitat et al., 2002; Dux et al., a synergistic effect (Verghese et al., 2014). The integrity of the 2006; Jurado and Rosselli, 2007). Limitations of both MRI and frontal areas of the brain, specifically the PFC, are critical to fMRI include their relatively high cost, unsuitability for many preserve cognition and mobility in late life (Beauchet et al., older adults due to metal implants in the body, claustrophobia or 2016). PFC regions carry out executive functions, i.e., higher inability to lie still for long periods. Further, due to the nature of order cognitive functions essential to plan and execute complex the scanner, the tasks are carried out in unnatural environments goal-directed actions, which are also key for motor control which may alter their relevance to the real-world and do not allow in older adults (Inzitari et al., 2007). The loss of integrity in functional analysis of brain activity during locomotion. Imagined frontal or prefrontal regions, either due to neurodegeneration, gait has been used as a way to study the neural correlates of cerebrovascular disease or due to their interactions, contributes locomotion with fMRI (Zwergal et al., 2012; Blumen et al., to the development of dementia (Burgmans et al., 2009; Kisler 2014); however, it is not entirely clear how well this mimics et al., 2017) and mobility impairments (De Laat et al., 2011). brain activation during actual walking. Other options, although The PFC has also been implicated in performance of DT (Sala they do not allow online assessment of gait either, include PET et al., 1995; Dux et al., 2006; Filmer et al., 2013), that are studies after walk trials with administration of fludeoxyglucose- motor tasks performed simultaneously with a secondary, usually 18 tracer (la Fougère et al., 2010). We refer the reader to Holtzer a cognitive task. DT increases the cognitive demand of walking et al. (2014) for a comprehensive review on neuroimaging of and potentially results in a decrease in task performance in one locomotion in aging. or both tasks relative to when the tasks are performed separately Emerging alternatives to fMRI, based on near-infrared as ST. DT performance assessment may help identify older adults diffuse optical techniques, allow measurements in more realistic at higher risk of incident cognitive decline (Ceïde et al., 2018; environments and during motion (Boas et al., 2014; Scholkmann Rosso et al., 2019), disability, frailty and mortality (Verghese et al., 2014). Accumulating evidence supports the use of these et al., 2012). One of the goals of the study of cognitive aging techniques for the study of frontal hemodynamic and metabolic is to elucidate neural mechanisms that underlie the ability of changes (Agbangla et al., 2017; Gramigna et al., 2017). These the aging brain to cope with decline in cognitive functions and diffuse optical techniques such as fNIRS (Durduran et al., efficiency. Several hypothesis have been described and there is still 2010; Ferrari and Quaresima, 2012) allow the study of tissue no consensus regarding definitions of several concepts (Cabeza composition by emitting near-infrared light (∼650–950 nm) et al., 2018). Two of the previously described hyphotheses are: the into biological tissue and collecting the photons that undergo “neural inefficiency hypothesis” (Rypma and D’Esposito, 2000; multiple scattering and absorption (i.e., diffuse) and emerge Holtzer et al., 2009) or “compensation by upregulation” (Cabeza few centimeters away from the injection point (Delpy and et al., 2018), according to which older adults show increased Cope, 1997; Durduran et al., 2010). At these wavelengths the activity of the same networks recruited by younger counterparts main absorbers in tissues, i.e., O2 Hb and HHb, differentially in order to meet behavioral demands, and the “capacity limitation absorb light in a wavelength dependent manner. Therefore, most hypothesis” (Cabeza, 2004; Holtzer et al., 2009) which postulates common fNIRS methods can relate changes in the detected that older adults, while recruiting the same brain networks as light intensity at different wavelengths to changes in oxygenated young adults, would show a reduced activation compared to their and deoxygenated hemoglobin concentrations by utilizing the younger counterparts (Holtzer et al., 2009; Stern, 2009). modified Beer-Lambert law (Scholkmann et al., 2014). This is Classic clinical and epidemiological studies have based their a signal similar to the blood oxygen level dependent (BOLD) assessment of PFC on a static, structural basis, mainly through signal from fMRI but can be obtained by portable (even wearable) magnetic resonance imaging (MRI) techniques, which have instrumentation and flexible fiber-optic probes. The majority shown a contribution of both cortical frontal and PFC volumes of the systems are using source and detector probes placed (Rosano et al., 2008; Weinstein et al., 2012) and subcortical on the scalp of the head. The most common source-detector alterations to executive dysfunction/dementia (Jokinen et al., separations are of few centimeters. Able to detect signal coming 2009) and mobility limitations (Baezner et al., 2008). In addition, from superficial cortical layers (Ferrari and Quaresima, 2012), functional neuroimaging techniques, such as functional MRI fNIRS measurement is based on the neurovascular coupling (fMRI), allow the study of PFC by assessing the hemodynamic (oxygen consumption to meet energy demands in activated changes due to neurovascular coupling that are triggered by its cerebral areas cause an increase in blood flow resulting in an neural activation (Buchbinder, 2016). fMRI studies assess whole increase of O2 Hb and decrease of HHb) and both the analysis and acquisition methods are still being developed with O2 Hb Abbreviations: AD, Alzheimer’s disease; DT, dual-task; fNIRS, Functional changes appearing more reliable as a marker of brain activation Near-Infrared Spectroscopy; HHb, deoxygenated hemoglobin; MCI, mild since it has shown high reproducibility and stability over time cognitive impairment; NGA, Neurological Gait Abnormalities; O2 Hb, oxygenated hemoglobin; PD, Parkinson’s disease; PFC, prefrontal cortex; ST, single task; VF, (Plichta et al., 2006) and has the highest correlation to fMRI verbal fluency. BOLD measures (Strangman et al., 2002). fNIRS studies usually Frontiers in Aging Neuroscience | www.frontiersin.org 2 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults consist of a combination of resting periods, to assess baseline change in cerebral hemodynamics after an intervention, those brain activity, and different kinds of tasks. Brain activation is then not written in English and those that do not describe the age calculated by comparing hemoglobin measurements at baseline of the participants in the manuscript were excluded. In order and during the task, although there is a high heterogeneity in to focus on most recent literature, we limited the publication data processing and analysis methods. Regarding its advantages, date to the previous 5 years. The last search was performed on fNIRS is a lower cost modality than fMRI, usable at point- August 29th, 2018. of-care, and allows measurements during mobility tasks. These The article selection was performed in three phases (review advantatges allow the potential use of the technique to assess of titles, abstracts, and full-texts). Two independent reviewers cerebral blood flow and oxygenation with application in different (CU and MI) reviewed the titles and abstracts resulting from pathologies (e.g., stroke, psychiatric disorders,. . . ) resulting thus the search, in order to assess potential inclusion. From the in continuous growth on relevant literature (Noda et al., 2017; selected articles, we performed a full manuscript review to assess Giacalone et al., 2019). However, the main limitations of most if the article met the eligibility criteria. Discrepancies were solved fNIRS devices include: (i) the limited penetration depth, allowing through consensus. only the interrogation of superficial layers of the cortex in the adult brain, (ii) the assessment of a limited portion of the cortical surface with often a low spatial resolution with the probes RESULTS that are attached to the scalp, not allowing complete whole- brain imaging, (iii) issues with extracerebral contamination from General Description superficial tissues (i.e., cutaneous or skull perfusion) and (iv) As depicted in the flow-chart (Figure 1), after removing motion artifacts. duplicates, our search resulted in 134 items. After excluding Recent studies have expanded the use of fNIRS in the records by title and abstract screening (n = 46), 89 full-text assessment of PFC of older adults during cognitive or motor articles were assessed for eligibility. Studies not meeting the above tests (Verghese et al., 2017). These studies show changes in PFC described eligibility criteria such as sample/subgroup mean age hemodynamics during the execution of cognitive or motor tasks, (n = 19), the aim/topic focus of our review (n = 6) (i.e., use and also report differences according to the person’s age and of NIRS to monitor cancer treatment), methodological aspects cognitive function. However, these findings are still preliminary of the design of studies (n = 6) (i.e., different location of the and it is not yet clear if there is a specific pattern according to probes or NIRS measures performed to assess the effect of an age or cognitive status, nor about how these differences should be intervention) and review articles (n = 11), were excluded. We interpreted. Recently published reviews have assessed the results finally included 46 articles in our review. of studies on fNIRS during cognitive tasks (Herold et al., 2018) or Of the 46 included articles, 13 included a mix of younger dual tasks (Gramigna et al., 2017; Herold et al., 2017; Leone et al., and older participants (Heilbronner and Münte, 2013; 2017; Vitorio et al., 2017; Stuart et al., 2018; Kahya et al., 2019) Ohsugi et al., 2013; Beurskens et al., 2014; Müller et al., 2014; and some of them have chosen to focus on specific clinical profiles Oboshi et al., 2014; Hernandez et al., 2016; Bierre et al., 2017; (Gramigna et al., 2017; Vitorio et al., 2017) or on methodological Mirelman et al., 2017; Rosso et al., 2017; Hawkins et al., 2018) aspects such as fNIRS signal processing (Herold et al., 2017, 2018; whereas 29 included only older adults (Doi et al., 2013; Heinzel Vitorio et al., 2017). To the best of our knowledge, our review et al., 2013, 2015; Niu et al., 2013; Clark et al., 2014; Vermeij is the first to focus specifically on older adults regardless of their et al., 2014; Dupuy et al., 2015; Holtzer et al., 2015, 2016, 2017a,b, clinical profile and to assess, from a clinical point of view, studies 2018a,b; Laguë-Beauvais et al., 2015; Al-Yahya et al., 2016; using only cognitive or motor tasks, as well as DTs. Maidan et al., 2016, 2017; Mahoney et al., 2016; Nieuwhof et al., The aim of this review is to describe, through an updated 2016; Osofundiya et al., 2016; Takeuchi et al., 2016; Uemura et al., literature search, the use of optical techniques, specifically fNIRS, 2016; Yeung et al., 2016a,b; Chen et al., 2017; Huppert et al., to study brain hemodynamics, with a focus on frontal regions, 2017; Verghese et al., 2017; Yap et al., 2017; Halliday et al., 2018; in relation to cognitive and physical function in normal and Katzorke et al., 2018; Lucas et al., 2018; Mori et al., 2018; Thumm pathological older adult populations. et al., 2018). Moreover, 26 studies included only cognitively normal participants (Heilbronner and Münte, 2013; Heinzel et al., 2013, 2015; Ohsugi et al., 2013; Beurskens et al., 2014; Clark METHODS et al., 2014; Müller et al., 2014; Oboshi et al., 2014; Vermeij et al., 2014; Holtzer et al., 2015, 2016, 2017a,b, 2018a,b; Osofundiya This is a narrative review. We performed, however, a search et al., 2016; Bierre et al., 2017; Chen et al., 2017; Huppert et al., using pre-set criteria, to make sure that we considered all the 2017; Mirelman et al., 2017; Rosso et al., 2017; Verghese et al., relevant articles on the topic. We included manuscripts that 2017; Halliday et al., 2018; Lucas et al., 2018), seven compared have aimed to study frontal and prefrontal lobe hemodynamics participants with different cognitive status [without cognitive (excluding those focusing on other brain regions) using fNIRS impairment, with MCI or with mild AD] (Doi et al., 2013; Niu to measure oxygenated and deoxygenated hemoglobin levels et al., 2013; Al-Yahya et al., 2016; Uemura et al., 2016; Yeung during cognitive, motor and DTs in older adults. Articles were et al., 2016a,b; Yap et al., 2017; Katzorke et al., 2018), three studies included if the mean age of the sample or a separately analyzed focused on older adults with previous history of stroke (Al-Yahya subgroup was 60 years or older. Review articles, studies assessing et al., 2016; Hawkins et al., 2018; Mori et al., 2018), five assessed Frontiers in Aging Neuroscience | www.frontiersin.org 3 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults FIGURE 1 | Flow chart diagram of the review process. patients with parkinsonian syndromes (Mahoney et al., 2016; (Osofundiya et al., 2016; Huppert et al., 2017). Ten studies did Maidan et al., 2016, 2017; Nieuwhof et al., 2016; Thumm et al., not describe the participant setting (Niu et al., 2013; Oboshi et al., 2018) and two with Multiple Sclerosis (Hernandez et al., 2016; 2014; Al-Yahya et al., 2016; Uemura et al., 2016; Maidan et al., Chaparro et al., 2017). 2017; Mirelman et al., 2017; Rosso et al., 2017; Katzorke et al., Looking at the older adults subgroups that were included in 2018; Mori et al., 2018; Thumm et al., 2018). the studies, there was a wide range of mean ages, from 61 ± 4 The majority, 29 studies, used O2 Hb to assess brain activation (Hernandez et al., 2016) to 88.1 ± 6 (Huppert et al., 2017). The while nine studies (Heilbronner and Münte, 2013; Beurskens largest sample size was 1052 participants (Heinzel et al., 2015) et al., 2014; Müller et al., 2014; Al-Yahya et al., 2016; Hyodo et al., while a sample of 12 older adults was the smallest (Nieuwhof 2016; Nieuwhof et al., 2016; Rosso et al., 2017; Halliday et al., et al., 2016). Most source populations were community-dwelling 2018; Katzorke et al., 2018) used both O2 Hb and HHb and one but two studies included older adults living in nursing home used only Total Hb (Huppert et al., 2017). Two studies calculated Frontiers in Aging Neuroscience | www.frontiersin.org 4 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults the Total Oxygenation Index (O2 Hb/Total Hb x 100) in order to while performing VF tasks: one showed an increased activation assess brain hemodynamics (Clark et al., 2014; Bierre et al., 2017). and another found a decreased activation on bilateral inferior In the following paragraphs, we will use the term activation to frontal junction in healthy older adults while middle frontal refer to changes in these hemoglobin indices. gyri and supramarginal gyri showed an increased activation Twenty-three studies measuring single cognitive or motor (interpreted as compensatory mechanisms) (Heinzel et al., 2013). tasks performed intra-group comparisons of the cerebral Cognitively healthy older adults showed an increased prefrontal activation during different tasks and the rest periods (see articles activation while performing a working memory task with visual listed in Tables 1, 2A), whereas the other 23 studies compared recognition (Oboshi et al., 2014) as well as with increasing cerebral hemodynamics between single and DT (see articles working memory load during a N-back task (Vermeij et al., listed in Table 2B). Twenty-four studies performed comparisons 2014). Studies using other executive function tests, found an of cerebral activation patterns between different groups (either increase in frontal lobe activation during executive function young vs. old, MCI vs. cognitively normal, healthy vs. stroke tasks (Heilbronner and Münte, 2013; Albinet et al., 2014; Müller etc.) (Heilbronner and Münte, 2013; Niu et al., 2013; Ohsugi et al., 2014; Bierre et al., 2017; Huppert et al., 2017). One study, et al., 2013; Beurskens et al., 2014; Müller et al., 2014; Oboshi instead of reporting only the mean values of O2 Hb, addressed et al., 2014; Laguë-Beauvais et al., 2015; Al-Yahya et al., 2016; the association between O2 Hb variability and behavioral results Hernandez et al., 2016; Maidan et al., 2016, 2017; Mahoney et al., during an executive function task (Halliday et al., 2017). They 2016; Osofundiya et al., 2016; Takeuchi et al., 2016; Uemura et al., reported that within-person O2 Hb variability was associated 2016; Yeung et al., 2016a,b; Bierre et al., 2017; Mirelman et al., with better accuracy and faster performance but between-person 2017; Rosso et al., 2017; Yap et al., 2017; Hawkins et al., 2018; variability was associated with slower performance. Katzorke et al., 2018; Mori et al., 2018). Some studies, beyond assessing frontal hemodynamics, Comparison of Healthy Old Versus Young Adults investigated the influence of other clinical characteristics in the Healthy older adults showed higher frontal activation than reported frontal activation findings (Albinet et al., 2014; Dupuy younger persons while performing a visuomotor task with et al., 2015; Hyodo et al., 2016; Osofundiya et al., 2016; Holtzer increasing executive function demand (Bierre et al., 2017). et al., 2016, 2017a,b, 2018a; Verghese et al., 2017; Halliday et al., Moreover, a different activation pattern during executive function 2018; Lucas et al., 2018) (see Table 3). tests between age groups was observed. According to Heilbronner and Münte (2013), in older adults, activation shifted rostrally Studies Assessing the Effect of Cognitive on the left hemisphere and dorsally on the right hemisphere Tasks during the inhibition task, while Müller et al. (2014) reported We found 20 articles assessing cerebral activation during an additional activation in left medial and lateral PFC during cognitive tasks (Table 1). The most frequent cognitive task the TMT-B (while more ventral activation was evidenced in was VF (Heinzel et al., 2013, 2015; Yeung et al., 2016a; Yap younger counterparts). The effect of prioritization of a stimulus et al., 2017; Katzorke et al., 2018). Generally, VF tests ask the was assessed in one study (Laguë-Beauvais et al., 2015) where the participants to produce the maximum number of words starting participants were asked to prioritize one of two stimuli displayed with a specific letter (phonemic) or belonging to a pre-specified (priority block) or to give the same priority to both stimuli semantic category (semantic). Three studies used N-back tests (equal block). A change in the activation pattern between the (Niu et al., 2013; Vermeij et al., 2014; Yeung et al., 2016b), priority and equal conditions was found only in the older adults which assess working memory function. N-back tasks are usually group, with a less lateralized pattern (bilateral dorsolateral PFC designed as conditions with increasing working-memory load: 0- activation) when not prioritizing either stimuli. back (subject has to detect if the presented stimulus is the one described as target), 1-back (the subject has to remember if the Comparison by Cognitive Status presented stimulus was presented on the previous position) and Regarding the studies assessing older adults with different 2-back conditions (the participant must be able to remember if cognitive status, three studies using VF tasks reported an the stimulus is the same presented 2 positions before). From the increased activation during the task in MCI (Yeung et al., 2016a; twelve remaining studies, eleven used different tests of executive Yap et al., 2017) and mild AD (Yap et al., 2017) while Katzorke functions (i.e., Stroop, symbol digit coding and shifting attention et al. (2018) found a decreased activation during VF in MCI test, Go/No go inhibition task, Trail Making Test part B, etc.) patients. Yap et al. (2017) compared the activation pattern in (Heilbronner and Münte, 2013; Albinet et al., 2014; Müller et al., cognitively healthy older adults, MCI and mild AD and found the 2014; Oboshi et al., 2014; Dupuy et al., 2015; Laguë-Beauvais highest O2 Hb increase in MCI older adults followed by healthy et al., 2015; Hyodo et al., 2016; Bierre et al., 2017; Huppert and AD participants, although the difference was not statistically et al., 2017; Halliday et al., 2017, 2018) and one used an episodic significant. Increasing working memory load led to lower frontal memory task (Uemura et al., 2016). lobe activation during a N-back task in MCI, compared to healthy controls (Niu et al., 2013; Yeung et al., 2016b). Only one Cognitively Healthy Older Adults study measured PFC activation during encoding and retrieval of Regarding the studies that assessed frontal hemodynamics episodic memory, and it found a decreased activation on bilateral in cognitively healthy older adults, two studies by dorsolateral cortex during memory retrieval in amnestic MCI Heinzel et al. (2015) showed different activation patterns (Uemura et al., 2016). Frontiers in Aging Neuroscience | www.frontiersin.org 5 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults Studies Assessing the Effect of Motor were also heterogeneous. According to Mahoney et al. (2016), Tasks older adults with parkinsonian syndromes showed higher PFC All the studies that used isolated motor tasks in order to activation while performing a postural control task (compared assess PFC hemodynamics (n = 3) enrolled older adults with to participants with mild parkinsonian signs or without these). parkinsonian syndromes but were heterogeneous regarding Participants with PD walking on a straight walkway showed the motor tasks paradigm (Table 2A). The reported results an increased PFC activation, compared to the baseline, and a TABLE 1 | Summary of the studies assessing fNIRS measures during cognitive tasks in older adults. First author Sample size (N) Paradigm description Main fNIRS results (Journal, Clinical year), Country characteristics of the sample (mean age + SD) NIRS optodes localization Verbal fluency Heinzel N = 325 Healthy Tasks: With increasing age: (Neurobiol (64.6 ± 7.3). Prefrontal, – Phonetic verbal fluency. ⇓: Lower activation on bilateral inferior frontal Aging, 2013), temporal and parietal. – Semantic verbal fluency. junction during verbal fluency. Germany – Control task: reciting week days. Increased bilateral activation at middle frontal gyri (Heinzel et al., Three trials: 30 s each. and supramarginal gyri. 2013) Rest: 30 sec after each trial. Heinzel N = 1052 Healthy Tasks: ⇑: Increased activation during both verbal fluencies (PLoS One (65.2 ± 6.8). Prefrontal, – Phonetic verbal fluency. (compared to control task). 2015), parietal and – Semantic verbal fluency. Stronger response in phonological than semantic Germany fronto-temporal. – Control task: reciting week days. (increased activation in right prefrontal and bilateral (Heinzel et al., Three trials: 30 s each. inferior parietal regions extending toward 2015) Rest: 30 sec after each trial. postcentral gyri and decreased in bilateral fronto-temporal areas). Yeung N = 52 MCI Tasks: ⇑: Increased O2 Hb bilaterally during verbal fluency (Front Aging (69.1 ± 6.2); Healthy – Semantic verbal fluency. Two task blocks, in both groups. No significant group differences. Neurosci., (68.8 ± 6.1). Prefrontal. 60 s each. Control group showed left lateralization of frontal 2016), China Rest: repeat “1, 2, 3, 4” out loud. Before and lobe activation (whereas MCI group did not). (Yeung et al., after VF task. 2016a) Yap N = 61 Healthy Task: ⇑: Highest O2 Hb increase during task was (Front Aging (72.6 ± 8.5); MCI – Semantic verbal fluency (60 s). observed in MCI followed by healthy and mild AD. Neurosci., (73.1 ± 8.2); Mild AD Rest: 20 s before and after task. 2017), Malaysia (74.7 ± 10). Prefrontal (Yap et al., and part of temporal. 2017) Katzorke N = 110 Healthy Tasks: ⇓: Decreased PFC activation during semantic (Psychiatry Res (74.2 ± 1.6); MCI – Letter verbal fluency. verbal fluency in MCI compared to healthy controls Neuroimaging, (74.0 ± 1.6). – Semantic verbal fluency. (but not during phonological verbal fluency). 2018), Fronto-temporal. – Control (weekdays). Germany Three trials per task: 30 sec each. (Katzorke et al., Rest: 30 s after each task. 2018) N-back tasks Niu N = 24 MCI Task: ⇓: MCI participants showed lower O2 Hb (CNS Neurosci (64.8 ± 7.2); healthy – Digit N-back task (0-back and 1-back concentrations in the left dorsolateral PFC, right Ther., 2013), (63.5 ± 5.3). Frontal, conditions). Three blocks in each supplementary motor area and left superior China (Niu parietal and temporal. condition: 20 trials for each block followed temporal regions compared to control group. et al., 2013) by 1000 ms interstimulus period. Rest: No rest time specified. Vermeij N = 18 Healthy older Task: ⇑: Increased working-memory load associated (Front Aging adults (70.8 ± 5.0). – Spatial N-back (0-back, 1-back and increased prefrontal activation and decreased Neurosci., Prefrontal. 2-back conditions). performance. 2014), 60 trials (500 ms each) with 3000 ms interval Netherlands between trials. (Vermeij et al., Rest: Initial 1 min-baseline (staring at screen). 2014) (Continued) Frontiers in Aging Neuroscience | www.frontiersin.org 6 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults TABLE 1 | Continued First author Sample size (N) Paradigm description Main fNIRS results (Journal, Clinical year), Country characteristics of the sample (mean age + SD) NIRS optodes localization Yeung N = 52 MCI Task: ⇓: MCI group did not show frontal activation. (Dement Geriatr (69.1 ± 6.3); cognitively – Digit N-back task (0-back and 2-back Tended to reduce activation with high working Cogn Disord., normal (68.8 ± 6.1). conditions). 20 trials (1000 ms each) memory load. 2016), China Frontal. followed by 1000 ms interval between ⇑: Control group: frontal activation in high working (Yeung et al., trials. memory load (2-back condition). 2016b) Rest: 30 s between blocks. Other tests for executive functions Heilbronner N = 35. Healthy older Task: ⇑: Older adults showed activation in frontal areas. (Neuroimage, adults (68 ± 1.4); – Cognitive Go/No Go inhibition task: Go Compared to young participants, activation shifted 2013), younger adults group stimulus: press button; No Go stimulus: rostrally (left hemisphere) and dorsally (right Germany (23.1 ± 0.4). inhibit pressing button. hemisphere) in older adults. (Heilbronner Frontotemporal. 1083 stimuli in 5 trials. and Münte, Rest: Rest in a self-paced manner. 2013) * Albinet N = 40 Healthy old Task: ⇑: Increasing activation in relation to task difficulty. (Front Aging adults: high-fit – Random Number Generation: participants High-fit group showed greater increase in O2 Hb. Neurosci., (67.32 ± 4.48); low-fit asked to say random number when heard 2014), France (68.88 ± 3.87) a tone. Fast pace (tone/1 s) and slow pace (Albinet et al., Prefrontal (tone/1.5 s). 2014) Two trials of 100 responses at each pace. – Control: count in order from one to nine. Müller N = 40 Older adults Task: ⇑: Older adults showed bilateral ventrolateral and (Neuropsychologia, (70.9 ± 3.5); younger – Adapted version of Trail Making Test (TMT) dorsolateral prefrontal and premotor cortex 2014), adults (25.7 ± 3.0). A and B. activation during TMT-B (more channels active in Germany PFC, motor and – Control task: retrace 90 interconnected the right hemisphere). (Müller et al., premotor regions. circles. Additional activation in medial and lateral PFC in 2014) Each test presented three times (30 s each). elderly (younger participants show more ventral Rest: 30 s after each test. PFC, especially in the left hemisphere). Oboshi N = 120 Healthy older Task: ⇑: Older adults: O2 Hb increase during working (PLoS One, adults (71.0 ± 6.4); – Visual working memory task. memory task. Young adults: Higher O2 Hb increase 2014), Japan younger adults Six blocks (28.8 s each). during pre-task (compared to elderly). (Oboshi et al., (21.7 ± 3.3). Prefrontal. Rest: 30 s. Both groups: lower activation during pre-task is 2014) associated with higher O2 Hb change during working memory task. * Dupuy N = 58 Healthy older Task: ⇑: High-fit women showed increased activation in (Front Hum adults (62.9 ± 5.4); – Modified Stroop-task with two conditions: right inferior frontal gyrus (independent of age Neurosci., young adults naming (identify the color of the ink); group). 2015), Canada (24.6 ± 3.6). Prefrontal. executive or incongruent (color of the ink (Dupuy et al., not matching the color-word displayed). 2015) Four trial-blocks (60 s each). Rest: 60 s between blocks. * Hyodo N = 60 Healthy older Task: Higher fitness levels and left-lateralized PFC (Neuroimage, adults (70.3 ± 3.2). – Modified Stroop-task: participants asked activation related to shorter Stroop interference 2015), Japan Prefrontal. to decide if word is printed in the color time. (Hyodo et al., written below the word (neutral and Higher fitness associated with more left-lateralized 2016) incongruent conditions). activation. 60 trials (30 neutral and 30 incongruent trials). Rest: 9–13 s interstimulus interval. (Continued) Frontiers in Aging Neuroscience | www.frontiersin.org 7 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults TABLE 1 | Continued First author Sample size (N) Paradigm description Main fNIRS results (Journal, Clinical year), Country characteristics of the sample (mean age + SD) NIRS optodes localization Laguë- N = 35 Healthy older Task: Priority condition: Beauvais adults (63.47 ± 3.67); – Color task: identify color of an “X” on – Older adults: activation in the left dorsolateral (Brain and young adults screen (by typing on keyboard). prefrontal cortex and bilateral ventrolateral cortex Cognition, (23.94 ± 2.32). – Letter task: identify “K” or “L” on screen (by during DT. 2015), Canada Prefrontal. typing on keyboard). – Young adults: dual mixed trials showed greater (Laguë- • Conditions: changes in more frontal areas, especially right Beauvais et al., sided. – Single pure: only an “X” or letter is 2015) Equal condition: displayed to perform one of the tasks. – Dual mixed: both an “X” and a letter are – Older adults: dual mixed trials engaged bilateral displayed and have to be answered. These dorsolateral prefrontal cortex, compared to are performed under the instruction to single trials. prioritize the letter over the color task – Young adults: no differences between activation (Priority Block) or to give the same priority during dual mixed and single trials. Single trials to both tasks (Equal Block). showed change in activation in right posterior Rest: staring at fixation cross on screen dorsolateral prefrontal cortex for HHb. (1000 ms). The activation change between priority and equal conditions was found only in older adults. Bierre N = 72 Healthy older Task: ⇑: Older adults showed increased O2 Hb in relation (J Gerontol A adults (66 ± 3.8); – Visuomotor tasks (increasing executive to increasing task difficulty. Biol Sci Med young adults demand): Older adults showed higher O2 Hb compared to Sci., 2017), (21.9 ± 2.7). Frontal. 1) Basic visuomotor performance. younger adults New Zealand 2) Adding inhibition. (Bierre et al., 3) Adding need to switch between tasks. 2017) Rest: 2 min (sitting). Halliday N = 25 Healthy older Task: Greater mean O2 Hb during congruent (easier) task (Neurophoton., adults (75.88 ± 3.28) – Computerized cognitive task: Multi-Source associated with faster performance and during 2017), Canada Prefrontal. Interference Task (congruent and incongruent (more difficult) task, with slower (Halliday et al., incongruent condition). performance. 2017) Fifteen trials in a 30 s block. Greater O2 Hb variability at within-person level Rest: 60 s baseline before task. 20 s between associated with better accuracy and faster blocks. performance. Greater O2 Hb variability at between-person level associated with slower performance. Huppert N = 19 Older adults Tasks: ⇑: Left Broadmann’s area (BA) 10 (right superior (PLoS One, (88.1 ± 6.0). Frontal. – Stroop Test. frontal) activation during Symbol Digit Coding and 2017), USA – Symbol Digit Coding. Shifting Attention Test. (Huppert et al., – Shifting Attention Test. Right BA-10, right BA-45 and left BA-10 activated 2017) Rest: 30 s (quiet sitting baseline). during Stroop test. * Halliday N = 27 Older adults Task: ⇑: Fallers: activation during congruent and (J Clin Exp (76.1 ± 3.3). Prefrontal. – Computerized cognitive task: Multi-Source incongruent task; recruited additional tissue to Neuropsychol., Interference Task (congruent and perform at similar level. 2018), Canada incongruent condition). Non-fallers: no active channels during congruent (Halliday et al., Fifteen trials in a 30 s block (total of 4 blocks task; little activation during incongruent task (medial 2018) for each condition). right prefrontal cortex). Rest: No rest time specified. Memory test Uemura N = 130 Amnestic MCI Task: ⇓: Reduced activation in bilateral dorsolateral (Int J Geriatr (71.8 ± 43); healthy – Encoding and retrieval of 10 words cortex during memory retrieval in amnestic MCI. Psychiatry, older adults (20–30 s respectively). No significant group effects during encoding. 2016), Japan (71.7 ± 3.9). Prefrontal. Repeat vowels: Pre-task (10 s), rest after task (Uemura et al., (20–30 s) and post-task (10 s). 2016) AD, Alzheimer’s Disease; DT, dual-task; fNIRS, Functional Near-Infrared Spectroscopy; HHb, deoxygenated hemoglobin; MCI, Mild Cognitive Impairment; O2 Hb, oxygenated hemoglobin; PFC, Prefrontal Cortex; ST, single task; SD, Standard Deviation; VF, Verbal Fluency. *Articles assessing modulation of health characteristics on brain activation (Table 3). Frontiers in Aging Neuroscience | www.frontiersin.org 8 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults TABLE 2 | Summary of the studies assessing fNIRS measures during motor and/or dual-tasks in older adults. First author Sample size (N) Paradigm description Main fNIRS results (Journal, Clinical year), Country characteristics of the sample (mean age + SD) NIRS optodes localization (2A) Motor tasks Mahoney N = 269 Parkinsonian Task: ⇑: Parkinsonian syndromes: increased prefrontal (Brain Res., syndrome (81.2 ± 5.9); – Postural control while standing and silently activation to maintain postural control (compared to 2016), USA Mild parkinsonian signs counting for 10 sec. the other two groups). (Mahoney et al., (77.5 ± 6.7); healthy 2016) adults (74.4 ± 6.1). Prefrontal. Maidan N = 49 PD without Task: ⇑: Increased activation during walking and (Brain Topogr., cognitive impairment or – Walk with turns: 30-m walk and 180◦ turn. decrease during turns (compared to baseline). 2017), Israel freezing of gait – Five trials: 20 s of quiet standing between ⇑: Older adults with lower gait speed (<1 m/sec): (Maidan et al., (72.8 ± 1). Frontal. walk and turn. higher activation during turns (compared to older 2017) Rest: 20 s before and after each walk (quiet adults with normal gait speed). standing). Thumm N = 20 PD (69.8 ± 6.4). Task: ⇓: Lower activation during treadmill walking (Gait Posture, Prefrontal. – 30-m over-ground vs. treadmill walking. (compared to over-ground walking). 2018), Israel – Five trials (30 s each). (Thumm et al., Rest: 20 s quiet standing. 2018) (2B) Dual-tasks Doi N = 16 Older adults Tasks: ⇑: Increased prefrontal activation during DT walking (Aging Clin Exp with MCI (75.4 ± 7.2). – ST: 10-m walk. compared to ST walking. Res., 2013), Prefrontal. – DT: 10-m walk + phonetic verbal fluency. Japan (Doi – Three trials in each condition (20 s each). et al., 2013) Rest: 10 s pre-task and 30 s post-task (standing). Ohsugi N = 35 Healthy older Tasks: ⇑: Higher O2 Hb values during DT compared to (BMC adults (77.9 ± 5.3) vs. – ST: seated stepping while forward stepping as ST. ST count showed higher activation Neurosc., young (26 ± 3.6). counting from 0. compared to stepping. 2013), Japan Prefrontal. – ST: serial 7-subtraction from 100. ⇑: Older adults: higher O2 Hb levels during DT (Ohsugi et al., – DT: stepping + subtraction. compared to younger adults. 2013) – Each task repeated three times (30 s each). Rest: 30 s (self-paced counting). Beurskens N = 25 Healthy older Tasks: ⇓: Older adults: lower activation during (Int J adults (71.0 ± 3.8) vs. – ST: treadmill walk. walk + check compared to ST walk. No significant Physchophysiol., younger adults – ST: checking boxes on paper. difference between walk + alphabet vs. walk. 2014), (24.5 ± 3.3). Prefrontal. – ST: reciting alternate alphabet. Young: no significant difference in activation during Germany – DT: walk + check. ST vs. DT. (Beurskens – DT: walk + alphabet. ⇑: Higher activation in younger adults compared to et al., 2014) Each task: 30 s and repeated twice. older adults during visually demanding dual-task Rest: seated (duration is not specified). (walk + check). Clark N = 16 Older adults Tasks: ⇑: Increased activation during DT walk + verbal (Front Aging with mild mobility – ST: 90-meter walk (5 × 18 m). fluency, walk + vest, walk + obstacles. Although Neurosci., difficulties (77.2 ± 5.6). – Walk + phonetic verbal fluency. not significative, there was a trend toward increase 2015) (Clark Prefrontal. – Walk + dimmed light. during DT walk carrying tray and walk with dimmed et al., 2014) – Walk + carrying tray. light. – Walk + 6 obstacles negotiation. – Walk + weighted vest. Rest: 1 min quite standing between tasks. (Continued) Frontiers in Aging Neuroscience | www.frontiersin.org 9 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults TABLE 2 | Continued First author Sample size (N) Paradigm description Main fNIRS results (Journal, Clinical year), Country characteristics of the sample (mean age + SD) NIRS optodes localization Holtzer N = 348 Healthy older Tasks: ⇑: Bilateral increases in O2 Hb during DT compared (Neuroimage, adults (76.8 ± 6.8). – ST: Walk 3 loops on 14-feet walkway. to normal walk. In ST walk, after an initial increase, 2015), USA Prefrontal. – ST: 30 s reciting alternate alphabet. O2 Hb levels decrease in the course of the walk. (Holtzer et al., – DT: Walk + alphabet. While during the DT walk, O2 Hb remains elevated 2015) Rest: 10 s standing still and counting silently during the task. before tasks. Al-Yahya N = 19 Chronic stroke Tasks: ⇑: Higher O2 Hb during DT compared to ST in (Neurorehabil (66.2 ± 8.3); healthy – ST: feet tapping. stroke participants compared to healthy controls. Neural Repair, controls (56.2 ± 9.5). – ST: backward count. 2016), UK Prefrontal. – DT: feet tap + count. (Al-Yahya et al., Five trials (30 s for each task). 2016) Rest: 25–45 s in a pseudo-random order after each task. Hernández N = 16 Multiple Tasks: ⇑: Higher O2 Hb levels in MS compared to healthy (J Neurol Sci., Sclerosis (57 ± 5); – ST: Walk 3 loops on walkway. controls in walking tasks. 2016), USA healthy controls – ST: 30 s reciting alternate alphabet. Larger increase in O2 Hb from ST walk to DT in MS (Hernandez (61 ± 4). Prefrontal. – DT: Walk + alphabet. compared to healthy controls. et al., 2016) Rest: 10 s standing still and counting silently before tasks. * Holtzer N = 236 Healthy older Tasks: ⇑: Normal gait: Higher O2 Hb levels in DT compared (Brain Topogr, adults (75.5 ± 6.5). – ST: Walk 3 loops on 14-feet electronic to ST walk. 2016), USA Prefrontal. walkway. ⇓: Central NGA: attenuated changes in PFC O2 Hb (Holtzer et al., – ST: Reciting alternate alphabet (30 s). levels from ST to DT compared to peripheral NGA 2016) – DT: Walk + alphabet. and normal gait group. Rest: 10 s standing still and counting silently ⇑: Peripheral NGA showed greatest increase in before tasks. O2 Hb during DT. Maidan N = 106 PD Tasks: ⇑: Increased frontal activation during DT walking (Neurorehabil (71.6 ± 0.9); healthy – ST: Walk on 30-m walkway (30 s). compared with ST walking in healthy group. Neural Repair, older adults – DT: Walk + serial subtractions. ⇓: In PD, HbO2 levels did not increase during DT. 2016) (Maidan (70.4 ± 0.9). Prefrontal. – DT: Walk + obstacles. ⇑: In PD, HbO2 increased during walk + obstacle et al., 2016) 5 trials each task. compared with ST walking. Rest: 1 min before whole paradigm starts and ⇑: Higher increase in activation during ST walking in 20 s standing before and after tasks. PD compared to healthy controls. No significant difference between groups during DT walks. Nieuwhof N = 12 Parkinson’s Tasks: ⇑ All tasks increased O2 Hb during task compared (Pilot Feasibility Disease (70.1 ± 5.4). – DT: Walk + counting forward. to rest. Stud., 2016), Prefrontal. – DT: Walk + serial 3 or 7-substraction. Netherlands – DT: Walk + reciting digit spans. (Nieuwhof Five blocks (with 3 tasks each); 40 s each et al., 2016) task. Rest: 20 s still-standing before/after task and 1–2 min random rest (while listening to instructions). At least 1 min stand before block. * Osofundiya N = 20 Cognitively Tasks: ⇑: Higher PFC activation during DT and precision (Clin Biomech., healthy older adults: – ST: walk (30 s). walk compared to ST walk. 2016), USA obese (80.5 ± 6.8) vs. – DT: walk + reciting alphabet (30 s). ⇑: Obesity associated greater activation in all tasks (Osofundiya non-obese – DT: walk and step on targets on walkway but specially during precision walking. et al., 2016) (80.6 ± 7.5). Prefrontal (precision walk). Two blocks: 4 trials (30 s each) per block. Rest: quiet sitting (30 s) before start; 10 s quiet standing between trials; 2 min seating between blocks. (Continued) Frontiers in Aging Neuroscience | www.frontiersin.org 10 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults TABLE 2 | Continued First author Sample size (N) Paradigm description Main fNIRS results (Journal, Clinical year), Country characteristics of the sample (mean age + SD) NIRS optodes localization Takeuchi N = 31 Healthy older Task: No difference between young vs. old in PFC (BMC adults (71.7 ± 3.3); – ST: walk for 30 s around a 2.5 m-radius activation during DT. Less PFC lateralization in older Neurosci., young adults circle adults to suppress DT cost in gait performance. 2016), Japan (25.9 ± 4.4) Prefrontal. – ST: smartphone-based touch game (Takeuchi et al., (sitting). Participants instructed to touch in 2016) ascending order a set of numbers on screen. – DT: walk + touch. Rest: not described. Chaparro N = 22 Healthy older Task: ⇑: Higher activation during DT compared to normal (J Neuroeng adults (63.1 ± 4.4); – ST: alternate alphabet reciting (standing) walk. Rehabil., 2017), multiple sclerosis – ST: Normal walk ⇑: MS older adults: larger increase in O2 Hb during USA (Chaparro (56.2 ± 5.1) Prefrontal. – DT: walk while reciting alternate alphabet all tasks in all conditions compared to healthy older et al., 2017) Walk: 30 s warm-up walk; 30 s test; 15 s adults (especially during DT without partial body deceleration weight support). Rest: 10 s before each task (quiet standing). Protocol performed with and without partial body weight support Chen N = 90 Healthy older Tasks: ⇑: Higher activation during DT compared to ST in (Gait Posture, adults (78 ± 15.5). – ST: Walk 3 loops on 14ft electronic both normal walk and walk with obstacles. 2017), USA Prefrontal. walkway. ⇑: Participants with slower gait showed higher (Chen et al., – DT: Walk + alternate alphabet reciting. increase in O2 Hb during walk with obstacles 2017) – ST: Walk with obstacle negotiation. compared to unobstructed walk (relative to – DT: Walk with obstacle + alternate participants with normal gait). alphabet reciting. Rest: 10 s standing still and counting silently before tasks. * Holtzer N = 318 Healthy older Tasks: ⇓: Higher levels of perceived task-related stress (Eur J adults (76.6 ± 6.7). – ST: Walk (3 loops on 14-feet electronic associated attenuation of brain activation from ST Neurosci., Prefrontal. walkway). to DT. 2017), USA – ST: Reciting alternate alphabet (30 s). (Holtzer et al., – DT: Walk + alphabet. 2017a) Rest: 10 s standing still and counting silently before tasks. * Holtzer N = 314 Healthy older Tasks: ⇑: Increased O2 Hb levels during DT walking (J Gerontol A adults (76.8 ± 6.7). – ST: Walk 3 loops on 14-feet electronic compared with ST walking. Biol Sci Med Prefrontal. walkway. ⇓: Higher levels of subjective fatigue attenuated the Sci., 2017), – ST: Reciting alternate alphabet (30 s). increase in O2 Hb from ST to DT walking. USA (Holtzer – DT: Walk + alphabet. et al., 2017b) Rest: 10 s standing still and counting silently before tasks. Mirelman N = 43. Healthy older Tasks: ⇑: Older participants increased O2 Hb during DT (Brain Cogn., adults (69.7 ± 5.8); – ST: Walk on 30-m walkway. compared to ST walk and during ST walk 2017), Israel younger adults – DT: Walk + serial subtraction. compared to rest periods. (Mirelman et al., (30.9 ± 3.7). Prefrontal. – DT: Walk + obstacles. ⇑: Young adults: Activation during DT compared to 2017) Three loops on walkway for 30 s for each ST walk. No increase in O2 Hb during ST walking task. (compared to rest). Rest: 20 s quiet standing before/after tasks. ⇑: Older adults showed higher O2 Hb levels in all tasks compared to younger participant. (Continued) Frontiers in Aging Neuroscience | www.frontiersin.org 11 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults TABLE 2 | Continued First author Sample size (N) Paradigm description Main fNIRS results (Journal, Clinical year), Country characteristics of the sample (mean age + SD) NIRS optodes localization Rosso N = 16 Healthy older Tasks: ⇑: Older adults had greater activation of prefrontal (Gait Posture, adults (74 ± 5); – ST: Attention task (seated). and temporal regions compared to younger adults. 2017), USA younger adults – ST: Postural control (standing). (Rosso et al., (24 ± 3). Left prefrontal, – DT: Postural control + attention task. 2017) temporal, and motor. Three trials of each task (121 s each). Rest: 30 s sitting or standing before and after each task. * Verghese N = 166 Healthy older Tasks: ⇑: DT walk showed higher PFC activation than ST (Neurology, adults (74.9 ± 6.1). – ST: Walk 3 loops on 14-feet walkway. walk. 2017), USA Prefrontal. – ST: Reciting alternate alphabet (30 s). Higher PFC activation levels on fNIRS during DT (Verghese – DT: Walk + alphabet. predicted incident falls. et al., 2017) Rest: 10 s standing still and counting silently before tasks. Mori N = 28 Post-stroke Tasks: ⇓: Stroke participants: Lower PFC activation during (Gait Posture, (>6 months) with – ST: Serial subtractions of 3 (standing). DT compared to healthy participants. 2018), Japan hemiparesis – DT: Walk around a circle with 2.5 m (Mori et al., (61.1 ± 9.3); healthy radius + serial subtractions of 3. 2018) controls (66.3 ± 13.3). 3 trials. Prefrontal. Rest: 60 s (repeat sequence of numbers 1–10). Hawkins N = 48 Post-stroke Tasks: ⇑: Elderly vs. young: Higher O2 Hb increase during (Hum Mov Sci., (>4 years) with – ST: Walk on an 18-m oval-shaped course. normal walk and obstacle negotiation in the early 2018), USA hemiparesis – DT: Walk + obstacle negotiation. time period. In the late time period, higher PFC (Hawkins et al., (58.0 ± 9.3); older – DT: Walk + phonetic verbal fluency. activation during normal walk (but not with 2018) adults with mild gait Rest: quiet standing (duration not specified). obstacles). deficits (77.2 ± 5.6); ⇑: Stroke participants: Higher O2 Hb increase young healthy adults during normal walk and obstacle negotiation (22.4 ± 3.2). Prefrontal. compared to young participants. Greater activation during obstacle negotiation compared to elderly in the late time period. O2 Hb increase was highest in the post-stroke group, followed by older and young adults. * Holtzer N = 315 Healthy old Tasks: ⇑: Participants without diabetes: increased O2 Hb (Brain Cogn., (76.8 ± 6.7). Prefrontal. – ST: Walk 3 loops on 14-feet walkway. levels during DT compared to ST walk. 2018), USA – ST: Reciting alternate alphabet (30 s). ⇓: Diabetes: attenuated increase in O2 Hb levels (Holtzer et al., – DT: Walk + alphabet. from ST walk to DT (compared to non-diabetics). 2018a) Rest: 10 s standing still and counting silently before tasks. * Lucas N = 55 Healthy older Tasks: ⇑: Higher PFC activation during DT compared to (J Gerontol A adults (74.7 ± 4.9). – ST: Walk 3 loops on 20-feet walkway. ST. Biol Sci Med Prefrontal. – DT: Walk + reciting alternate alphabet. ⇑: Poorer white matter integrity associates greater Sci., 2018), Rest: 10 s standing still and counting silently increase in O2 Hb levels during DT. USA (Lucas before tasks. et al., 2018) AD, Alzheimer’s disease; DT, dual-task; fNIRS, Functional Near-Infrared Spectroscopy; MCI, Mild Cognitive Impairment; NGA, Neurological Gait Abnormalities; O2 Hb, oxygenated hemoglobin; PD, Parkinson’s disease; PFC, Prefrontal Cortex; ST, single task; SD, Standard Deviation; VF, Verbal Fluency. *Articles assessing modulation of health characteristics on brain activation (Table 3). decrease when performing 180◦ turns (Maidan et al., 2017). Studies Assessing the Effect of Dual However, when comparing older adults with different gait speed, Tasking participants with gait speed lower than 1m/sec showed higher Twenty-three articles assessed PFC hemodynamics while activation during turns, compared to those with normal gait performing DT (Table 2B). Studies included in this review speed. Thumm et al. reported lower O2 Hb levels while walking used walking (Doi et al., 2013; Beurskens et al., 2014; Clark on a treadmill vs. over-ground walking in PD participants et al., 2014; Holtzer et al., 2015, 2016, 2017a,b, 2018a,b; (Thumm et al., 2018). Maidan et al., 2016; Nieuwhof et al., 2016; Takeuchi et al., Frontiers in Aging Neuroscience | www.frontiersin.org 12 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults TABLE 3 | Studies assessing effect modification by different health characteristics (Ohsugi et al., 2013; Mirelman et al., 2017; Rosso et al., on PFC activation. 2017; Hawkins et al., 2018). Only one study reported lower First author (Journal, year) (reference) Clinical variables activation in older adults, compared to younger older adults, during a walk and visual check DT (Beurskens et al., 2014) Halliday et al. (J Clin Exp Neuropsychol., 2017) (Halliday Fallers versus et al., 2018) non-fallers and Takeuchi et al. (2016) did not find significant differences Holtzer et al. (Brain Topogr, 2016) (Holtzer et al., 2016) Neurological Gait between age groups. Abnormalities Osofundiya (Clin Biomech., 2016) (Osofundiya et al., Obesity Other Clinical Conditions 2016) The effect of dual tasking in older adults with MCI was assessed Holtzer et al. (Eur J Neurosci, 2017) (Holtzer et al., Levels of perceived in one of the included studies, which found an increased 2017a) task-related stress activation during DT compared to ST walking (Doi et al., 2013). Holtzer et al. (J Gerontol A Biol Sci Med Sci., 2017) Fatigue Frontal hemodynamics has also been studied in stroke patients, (Holtzer et al., 2017b) although these studies included participants with heterogeneous Verghese et al. (Neurology, 2017) (Verghese et al., 2017) Longitudinal association with falls clinical characteristics (mainly the time after the stroke event) Holtzer et al. (Brain Cogn., 2018) (Holtzer et al., 2018a) Diabetes and DT paradigms (i.e., Task protocols). Compared to healthy Lucas et al. (J Gerontol A Biol Sci Med Sci., 2018) Relation with white controls, patients with stroke history showed higher activation (Lucas et al., 2018) matter integrity during counting while feet tapping (Al-Yahya et al., 2016) but Hyodo et al. (Neuroimage, 2015) (Hyodo et al., 2016) Fitness levels a lower activation during counting while walking in another Albinet (Front Aging Neurosci., 2014) (Albinet et al., study (Mori et al., 2018). Walking while negotiating obstacles 2014) caused a higher activation in stroke patients compared to Dupuy (Front Hum Neurosci., 2015) (Dupuy et al., 2015) younger adults (Hawkins et al., 2018). PD patients show an increase in frontal activation during DT that involve walking 2016; Chaparro et al., 2017; Chen et al., 2017; Mirelman et al., and counting or reciting digit spans compared to the resting 2017; Verghese et al., 2017; Hawkins et al., 2018; Lucas et al., baseline periods (Nieuwhof et al., 2016). Middle-aged Multiple 2018; Mori et al., 2018), feet tapping (Al-Yahya et al., 2016), Sclerosis older adults show increased PFC activation during stepping (Ohsugi et al., 2013) and postural control (Rosso ST and DT walking and larger increases in O2 Hb levels from et al., 2017) as the motor task and VF (Doi et al., 2013; Clark ST to DT when compared to healthy older adults (Hernandez et al., 2014; Hawkins et al., 2018), calculation (Ohsugi et al., et al., 2016; Chaparro et al., 2017). Multiple Sclerosis participants 2013; Al-Yahya et al., 2016; Maidan et al., 2016; Nieuwhof show an especially larger increase in activation (compared to et al., 2016; Mirelman et al., 2017; Mori et al., 2018), alphabet healthy counterparts) when not provided with partial body (Beurskens et al., 2014; Holtzer et al., 2015, 2016, 2017a,b, weight support (Chaparro et al., 2017). 2018; Chaparro et al., 2017; Chen et al., 2017; Verghese et al., 2017; Lucas et al., 2018), digit span (Nieuwhof et al., 2016), Association Between Activation and visual (Beurskens et al., 2014) or attention (Takeuchi et al., Clinical Variables 2016; Rosso et al., 2017) tasks as the added cognitive tasks. Other studies assessed how different variables modulate the Other studies used challenging factors while walking such as PFC activation during cognitive, motor tasks and DT (Table 3). obstacle negotiation or carrying a tray as the secondary task to Publications from the “Central Control of Mobility in Aging” assess DT performance (Clark et al., 2014; Maidan et al., 2016; (CCMA) study, including community-dwelling older adults Osofundiya et al., 2016; Chen et al., 2017; Mirelman et al., 2017; without dementia, found that activation of PFC during DT, Hawkins et al., 2018). compared to ST, was lower in participants with central NGA compared to peripheral NGA or with normal gait. In fact, the Cognitively Healthy Older Adults highest O2 Hb increase during DT was showed by participants The vast majority of studies reported an increase in with peripheral NGA (Holtzer et al., 2016). Also in participants PFC activation in cognitively healthy older adults while from the CCMA study, higher levels of self-perceived stress performing several types of DT compared to a ST (Ohsugi and fatigue were associated with attenuation of brain activation et al., 2013; Clark et al., 2014; Holtzer et al., 2015, patterns (lower increase in O2 Hb levels from ST to DT walking) 2017a,b; Maidan et al., 2016; Osofundiya et al., 2016; (Holtzer et al., 2017a,b). Participants with diabetes from the Chen et al., 2017; Mirelman et al., 2017; Verghese et al., same study showed lower PFC activation during DT, compared 2017; Lucas et al., 2018). Only one article reported lower to non-diabetics (Holtzer et al., 2018a), while obese cognitively O2 Hb levels during walking while performing a visual healthy older adults from a different study showed higher check task compared to ST walk in the older adults group activation, especially during a precision walking task, compared (Beurskens et al., 2014). to non-obese counterparts (Osofundiya et al., 2016). When combining fNIRS with cerebral microstructural white matter Comparison of Cognitively Healthy Older Versus integrity assessment, using MRI with Diffusion Tensor Imaging Younger Adults (DTI), altered white matter integrity was associated to higher Older older adults showed higher PFC activation during O2 Hb levels during DT walk compared to normal walk in DT in most studies, compared to younger participants the CCMA study (Lucas et al., 2018). Using data from the Frontiers in Aging Neuroscience | www.frontiersin.org 13 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults same study, Verghese et al. (2017) revealed higher risk of activation in MCI older adults with increasing working memory incident falls in older adults with higher levels of PFC activation load (Niu et al., 2013; Yeung et al., 2016b). Importantly, during DT. It is important to note that this is the only article neural inefficiency and capacity limitation theories are not included in our review that assessed the relationship between mutually exclusive and likely both play a role in determining PFC hemodynamic and outcomes in a longitudinal manner. activation levels. Furthermore, in a separate sample, fallers compared to non- Regarding the studies focusing on older adults with other fallers (history of falls in the previous 2 years) had higher specific diseases, the findings support an activation of PFC activation while performing executive function tasks (Halliday during gait as ST (Maidan et al., 2017) and DT (Nieuwhof et al., 2018). The effect of fitness level on frontal activation during et al., 2016) in adults with PD (compared to rest periods). The executive functions tasks among cognitively healthy participants only study that assessed PFC during postural control found a was addressed in three studies. Although they assessed the higher activation in participants with parkinsonian syndromes level of fitness with different instruments, it seems that higher relative to healthier controls (Mahoney et al., 2016). This levels of fitness might produce larger increases in prefrontal could be interpreted in the context of the neural inefficiency activation (Albinet et al., 2014). Two of these studies used two theory, where adults with impaired postural mechanisms as seen different versions of modified Stroop tasks and while one found in PD (Baltadjieva et al., 2006; Benítez-Rivero et al., 2013), a more left-lateralized activation in the high-fit participants need a higher PFC activation to maintain postural control. (Hyodo et al., 2016), the other study found an increased Similar results, of higher activation than healthy controls, activation in right inferior frontal gyrus in the high-fit group were obtained in Multiple Sclerosis participants (Hernandez (Dupuy et al., 2015). et al., 2016; Chaparro et al., 2017) whereas stroke patients reported more heterogeneous results. This might be due to different clinical characteristics of the samples and of the DISCUSSION DT paradigms (Al-Yahya et al., 2016; Hawkins et al., 2018; Mori et al., 2018). Summary and Interpretation of Findings Studies that investigated the effect of several clinical Our review identified 46 articles that reported the assessment variables on the PFC activation during DT found a higher of frontal and PFC hemodynamics in older adults using fNIRS activation in participants with peripheral NGA, lower during cognitive, motor and DTs. stress and fatigue levels, obesity, non-diabetics and altered This has revealed a quite homogeneous pattern of activation of white matter integrity in MRI. The only study that assessed the PFC in cognitively healthy older adults during cognitive and prediction of longitudinal outcomes of frontal hemodynamics, DTs compared to rest and to single-task conditions, respectively. found a higher risk of falls associated with higher PFC This supports the use of fNIRS investigations to detect changes in activation. However, most of these findings come from a frontal hemodynamics in older adults. single sample. According to the results from three studies, Cognitively healthy older adults, compared to younger ones, higher levels of fitness might produce larger increases in show a higher activation during executive function tasks and prefrontal activation during executive functions tasks in DTs (Ohsugi et al., 2013; Bierre et al., 2017; Mirelman et al., healthy older adults (Albinet et al., 2014; Dupuy et al., 2015; 2017; Rosso et al., 2017; Hawkins et al., 2018). However, one Hyodo et al., 2016). study reported lower activation during walking while performing Overall, our findings suggest that fNIRS studies are able a visual check task compared to ST walk in the older adults group to detect changes in frontal and PFC activation in older and compared to the younger group (Beurskens et al., 2014). adults (both cognitively healthy and MCI), especially while The results in older adults with various degrees of cognitive performing cognitive and DTs that are believed to engage impairment are more heterogeneous. Overall, MCI older adults the frontal areas of the brain. In particular, in both the show increased PFC activation during VF tasks (Yeung et al., comparison between older and younger adults, and in 2016a; Yap et al., 2017) and during DT compared to ST (Doi people with different neurological conditions, compared et al., 2013). However, gradually increasing working memory load to healthier controls, the PFC seems to experience a causes a lower activation compared to healthy controls (Niu et al., higher activation, which could be interpreted in the 2013; Yeung et al., 2016b). context of proposed neural inefficiency and limited These findings are in line with previously proposed capacity models. hypotheses, such as the “neural inefficiency theory” (Rypma and D’Esposito, 2000; Holtzer et al., 2009), according to which older Methodological Aspects and Limitations adults show increased activity of the same networks recruited Main limitations of the fNIRS technique arise either due to by younger counterparts in order to meet behavioral demands. physical or technological constraints of the setups, due to analysis On the other hand, the lower activation in the healthy old methods, or due to the nature of the study itself. It is well subgroup relative to younger adults could be interpreted as an known that the recorded signal contains information not only inability to meet the increased cognitive demands during the from brain activation due to a specific stimulus or task but more complex DT (Beurskens et al., 2014) and is supported is also affected by extra-cerebral (skull and scalp perfusion) by the “capacity limitation hypothesis” (Cabeza, 2004; Holtzer as well as systemic parameters (heart and respiratory rate, et al., 2009). This theory might also explain the decrease in blood pressure, Mayer waves). Nowadays, the fNIRS community Frontiers in Aging Neuroscience | www.frontiersin.org 14 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults has made not only technological improvements but also has alone (not as dual task), the studies are limited to older developed an abundance of methods to attempt to overcome the adults with Parkinson syndromes. The samples are also very abovementioned limitations (Tachtsidis and Scholkmann, 2016). heterogeneous regarding the mean age ranges and other clinical Current instrumentation provides the ability of using multiple characteristics. In most of the included studies, inclusion source detector pairs that cover a wide range of tissue penetration criteria take into account age and cognitive function, but depth, giving the possibility to record short channel preparation individuals of the samples or within the comparison groups and regress out signal coming from superficial tissue layers when might be heterogeneous regarding aspects which might using continuous wave light sources (Yücel et al., 2015). On affect the cerebral neurovascular coupling and metabolism, the other hand, emerging methods that employ pulsed light such as cardiovascular risk load, atherosclerosis, small sources [time-resolved NIRS (TRS)], allow for the possibility to vessels disease etc. discriminate between intra- and extra cerebral signals (Torricelli Our work is not exempt from limitations. In particular, the et al., 2014). These methods were prohibitively complex but non-systematic search strategy might lead to possible missing have recently begun to become practical (Pifferi et al., 2016). In relevant published literature on the topic. However, we consider this context, to cover a large imaging area, multiple channels our pre-defined search strategy sufficiently comprehensive to can be used in combination with MRI, thus overcoming the include the most if not all relevant ones. lack of anatomical information and allow for localization of the origin of NIRS signal (Okamoto et al., 2004). Another technical Clinical Implications and Future limitation, could originate from the differential path length factor Directions (DPF), used in modified Beer-Lambert law (Cope and Delpy, Our findings support the potential role of fNIRS in research 1988), that could lead in cross-talk between oxygenated and and clinical practice to study cognition and mobility in aging. deoxygenated hemoglobin measurements and false calculations As mentioned, fNIRS is a non-invasive technique, which can (Hoshi, 2007). Regarding the analysis methods of the acquired assess brain regions involved in executive functions, which fNIRS signal, to date, there is no standard method established are key to goal-oriented behaviors and preserved cognitive (Pfeifer et al., 2018). Some of the most common strategies and motor functions. In particular, fNIRS allows to obtain include the use of low-pass filters to remove heart rate or relevant information regarding neural activation while the person instrumental noise and high pass filters to extract low frequency is performing a real motor task in a natural environment, systemic noise. Signal analysis methods are also heterogeneous in a relatively inexpensive way. However, further research is in the current literature (Kirilina et al., 2012; Zhang et al., needed to confirm those findings and to establish standardized 2016). Furthermore, in functional studies and especially in motor protocols (for tasks protocols and fNIRS data acquisition and DT, motion artifacts play an important role, therefore, and processing). Further research should also focus more on motion correction processes are widely used, covering a wide cerebral hemodynamic in different neurological diseases and range of proposed methods (Wavelet filtering, Kalman filtering, on the influence of systemic conditions (e.g., vascular risk spline interpolation, etc.) (Cooper et al., 2012; Brigadoi et al., factors such as diabetes and hypertension) on brain activation 2014). In general, for more accurate results when designing an patterns as assessed with fNIRS. Furthermore, fNIRS-derived fNIRS experimental protocol or analysis method, it is crucial brain activation patterns can be utilized as predictors of incident to take into account, potential particularities that each studied health outcomes including but not limited to dementia. population might have. A recent study demonstrated that within session training The heterogeneity in task protocols, methodology and small resulted in improved DT walking that was coupled with reduced sample sizes in most of the included articles may limit the activation in the PFC among healthy older adults suggesting interpretation of the findings, although the studies with larger improved neural efficiency due to practice (Holtzer et al., 2018b). samples show promising results in similar directions. The great Moreover, the presence of fear of falling delayed practice-related majority of the reviewed articles measured activation only over improvements in PFC efficiency during DT walking (Holtzer frontal areas, avoiding the assessment of possible compensatory et al., 2019). These findings suggest that fNIRS can be used to activations in distant areas of the brain (Stern, 2005; Holtzer quantify neuroplasticity, monitor improvement in PFC efficiency et al., 2009). This may be mainly due to the simplicity of due to practice and detect the effect of clinically relevant variables the application over hairless areas and can be overcome with such as fear of falling on brain function and efficiency during better probe designs. active walking. Hence, it is appropriate to consider the inclusion Furthermore, differences in cerebral activation patterns of fNIRS at least as a secondary outcome measure in clinical trials detected by fNIRS could be actually related to structural designed to assess the effect of treatment on brain neuroplasticity alterations, as recently reported in an MRI-fNIRS study (Wagshul and efficiency as well as for the development and monitoring of et al., 2019) where higher activation in healthy older adults during rehabilitation/training programs. DT was related to reduced cortical volumes, especially in bilateral superior and rostral-middle frontal cortex. More evidence is needed supporting this concept. CONCLUSION Other gaps and limitations might limit the generalizability of the results produced by the studies published to date. In conclusion, our review supports the use of fNIRS as a Regarding studies reporting the results of the motor task neuroimaging technique to study changes in the hemodynamic Frontiers in Aging Neuroscience | www.frontiersin.org 15 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults response in the frontal cortex during cognitively demanding tasks extracted the relevant data from the included publications and during active walking under single and DT conditions in to write the manuscript. SA, TD, RH, AR, CC-T, L-MP, older adults. From a pathophysiological perspective this approach and LS-B contributed in the redaction and revision of might help characterize the evolution of functional impairments the manuscript. in different neurological diseases in older adults as well as in healthy aging. FUNDING AUTHOR CONTRIBUTIONS This work was partially supported through the MEDPHOTAGE project (DTS16/00099) which was supported by the “Instituto CU and MI designed the concept of this manuscript, de Salud Carlos III” (ISCIII) and “Fondo Europeo de Desarrollo reviewed abstracts and full-text publications to assess Regional (FEDER)” through the “Desarrollo Tecnológico en eligibility, and wrote the first draft of the manuscript. CU Salud” (DTS) program (Spain). REFERENCES Buchbinder, B. R. (2016). Functional Magnetic Resonance Imaging. In Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms, 1st Edn. Agbangla, N. F., Audiffren, M., and Albinet, C. T. (2017). Use of near-infrared Amsterdam: Elsevier. spectroscopy in the investigation of brain activation during cognitive aging: a Burgmans, S., van Boxtel, M. P. J., Smeets, F., Vuurman, E. F. P. M., Gronenschild, systematic review of an emerging area of research. Ageing Res. Rev. 38, 52–66. E. H. B. M., Verhey, F. R. J., et al. (2009). Prefrontal cortex atrophy predicts doi: 10.1016/j.arr.2017.07.003 dementia over a six-year period. Neurobiol. Aging 30, 1413–1419. doi: 10.1016/ Albinet, C. T., Mandrick, K., Bernard, P. L., Perrey, S., and Blain, H. (2014). j.neurobiolaging.2007.11.028 Improved cerebral oxygenation response and executive performance as a Cabeza, R. (2004). Task-independent and task-specific age effects on brain activity function of cardiorespiratory fitness in older women: a FNIRS study. Front. during working memory, visual attention and episodic retrieval. Cereb. Cortex Aging Neurosci. 6:272. doi: 10.3389/fnagi.2014.00272 14, 364–375. doi: 10.1093/cercor/bhg133 Al-Yahya, E., Johansen-Berg, H., Kischka, U., Zarei, M., Cockburn, J., and Cabeza, R., Albert, M., Belleville, S., Craik, F. I. M., Duarte, A., Grady, C. L., et al. Dawes, H. (2016). Prefrontal cortex activation while walking under dual-task (2018). Maintenance, reserve and compensation: the cognitive neuroscience conditions in stroke. Neurorehabil. Neural Repair 30, 591–599. doi: 10.1177/ of healthy ageing. Nat. Rev. Neurosci. 19, 701–710. doi: 10.1038/s41583-018- 1545968315613864 0068-2 Baezner, H., Blahak, C., Poggesi, A., Pantoni, L., Inzitari, D., Chabriat, H., Ceïde, M. E., Ayers, E. I., Lipton, R., and Verghese, J. (2018). Walking while et al. (2008). Association of gait and balance disorders with age-related white talking and risk of incident dementia. Am. J. Geriatr. Psychiatry 26, 580–588. matter changes: the LADIS study. Neurology 70, 935–942. doi: 10.1212/01.wnl. doi: 10.1016/j.jagp.2017.12.009 0000305959.46197.e6 Chaparro, G., Balto, J. M., Sandroff, B. M., Holtzer, R., Izzetoglu, M., Motl, Baltadjieva, R., Giladi, N., Gruendlinger, L., Peretz, C., and Hausdorff, J. M. (2006). R. W., et al. (2017). Frontal brain activation changes due to dual-tasking under Marked alterations in the gait timing and rhythmicity of patients with de novo partial body weight support conditions in older adults with multiple sclerosis. Parkinson’s disease. Eur. J. Neurosci. 24, 1815–1820. doi: 10.1111/j.1460-9568. J. Neuroeng. Rehabil. 14, 1–10. doi: 10.1186/s12984-017-0280-8 2006.05033.x Chen, M., Pillemer, S., England, S., Izzetoglu, M., Mahoney, J. R., and Holtzer, Beauchet, O., Allali, G., Annweiler, C., and Verghese, J. (2016). Association of R. (2017). Neural correlates of obstacle negotiation in older adults: an FNIRS motoric cognitive risk syndrome with brain volumes: results from the GAIT study. Gait Posture 58, 130–135. doi: 10.1016/j.gaitpost.2017.07.043 study. J. Gerontol. A Biol. Sci. Med. Sci. 71, 1081–1088. doi: 10.1093/gerona/ Clark, D. J., Rose, D. K., Ring, S. A., and Porges, E. C. (2014). Utilization of glw012 central nervous system resources for preparation and performance of complex Benítez-Rivero, S., Marín-Oyaga, V. A., García-Solís, D., Huertas-Fernández, I., walking tasks in older adults. Front. Aging Neurosci. 6:217. doi: 10.3389/fnagi. García-Gómez, F. J., Jesús, S., et al. (2013). Clinical features and 123 I-FP-CIT 2014.00217 SPECT imaging in vascular parkinsonism and Parkinson’s disease. J. Neurol. Cooper, R. J., Selb, J., Gagnon, L., Phillip, D., Schytz, H. W., Iversen, H. K., et al. Neurosurg. Psychiatry 84, 122–129. doi: 10.1136/jnnp-2012-302618 (2012). A systematic comparison of motion artifact correction techniques for Beurskens, R., Helmich, I., Rein, R., and Bock, O. (2014). Age-related changes in functional near-infrared spectroscopy. Front. Neurosci. 6:147. doi: 10.3389/ prefrontal activity during walking in dual-task situations: a FNIRS study. Int. J. fnins.2012.00147 Psychophysiol. 92, 122–128. doi: 10.1016/j.ijpsycho.2014.03.005 Cope, M., and Delpy, D. T. (1988). System for long-term measurement of Bierre, K. L., Lucas, S. J. E., Guiney, H., Cotter, J. D., and Machado, L. cerebral blood and tissue oxygenation on newborn infants by near infra- (2017). Cognitive difficulty intensifies age-related changes in anterior frontal red transillumination. Med. Biol. Eng. Comput. 26, 289–294. doi: 10.1007/ hemodynamics: novel evidence from near-infrared spectroscopy. J. Gerontol. BF02447083 A Biol. Sci. Med. Sci. 72, 181–188. doi: 10.1093/gerona/glw061 De Laat, K. F., Tuladhar, A. M., Van Norden, A. G. W., Norris, D. G., Zwiers, M. P., Blumen, H. M., Holtzer, R., Brown, L. L., Gazes, Y., and Verghese, J. (2014). and De Leeuw, F. E. (2011). Loss of white matter integrity is associated with gait Behavioral and neural correlates of imagined walking and walking-while- disorders in cerebral small vessel disease. Brain 134, 73–83. doi: 10.1093/brain/ talking in the elderly. Hum. Brain Mapp. 35, 4090–4104. doi: 10.1002/hbm. awq343 22461 Delpy, D. T., and Cope, M. (1997). Quantification in tissue near–infrared Boas, D. A., Elwell, C. E., Ferrari, M., and Taga, G. (2014). Twenty spectroscopy. Philos. Trans. R. Soc. Lond. B Biol. Sci. 352, 649–659. doi: 10.1098/ years of functional near-infrared spectroscopy: introduction for the rstb.1997.0046 special issue. Neuroimage 85, 1–5. doi: 10.1016/j.neuroimage.2013. Doi, T., Makizako, H., Shimada, H., Park, H., Tsutsumimoto, K., Uemura, K., 11.033 et al. (2013). Brain activation during dual-task walking and executive function Brigadoi, S., Ceccherini, L., Cutini, S., Scarpa, F., Scatturin, P., Selb, J., et al. (2014). among older adults with mild cognitive impairment: a FNIRS study. Aging Clin. Motion artifacts in functional near-infrared spectroscopy: a comparison of Exp. Res. 25, 539–544. doi: 10.1007/s40520-013-0119-5 motion correction techniques applied to real cognitive data. Neuroimage 85, Dupuy, O., Gauthier, C. J., Fraser, S. A., Desjardins-Crèpeau, L., Desjardins, M., 181–191. doi: 10.1016/j.neuroimage.2013.04.082 Mekary, S., et al. (2015). Higher levels of cardiovascular fitness are associated Frontiers in Aging Neuroscience | www.frontiersin.org 16 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults with better executive function and prefrontal oxygenation in younger and older and prefrontal cortex efficiency in older adults. J. Gerontol. A 74, 1076–1083. women. Front. Hum. Neurosci. 9:66. doi: 10.3389/fnhum.2015.00066 doi: 10.1093/gerona/gly181 Durduran, T., Choe, R., Baker, W. B., and Yodh, A. G. (2010). Diffuse optics for Holtzer, R., Kraut, R., Izzetoglu, M., and Ye, K. (2019). The effect of fear of falling tissue monitoring and tomography. Rep. Prog. Phys. 73:076701. doi: 10.1088/ on prefrontal cortex activation and efficiency during walking in older adults. 0034-4885/73/7/076701 Geroscience 41, 89–100. doi: 10.1007/s11357-019-00056-4 Dux, P. E., Ivanoff, J., Asplund, C. L., and Marois, R. (2006). Isolation of a central Holtzer, R., Mahoney, J. R., Izzetoglu, M., Wang, C., England, S., and Verghese, bottleneck of information processing with time-resolved FMRI. Neuron 52, J. (2015). Online fronto-cortical control of simple and attention-demanding 1109–1120. doi: 10.1016/j.neuron.2006.11.009 locomotion in humans. Neuroimage 112, 152–159. doi: 10.1016/j.neuroimage. Ferrari, M., and Quaresima, V. (2012). A brief review on the history of 2015.03.002 human functional near-infrared spectroscopy (fnirs) development and fields Holtzer, R., Rakitin, B. C., Steffener, J., Flynn, J., Kumar, A., and Stern, Y. (2009). of application. Neuroimage 63, 921–935. doi: 10.1016/j.neuroimage.2012. Age effects on load-dependent brain activations in working memory for novel 03.049 material. Brain Res. 1249, 148–161. doi: 10.1016/j.brainres.2008.10.009 Filmer, H. L., Mattingley, J. B., and Dux, P. E. (2013). Improved multitasking Holtzer, R., Schoen, C., Demetriou, E., Mahoney, J. R., Izzetoglu, M., Wang, C., following prefrontal TDCS. Cortex 49, 2845–2852. doi: 10.1016/j.cortex.2013. et al. (2017a). Stress and gender effects on prefrontal cortex oxygenation levels 08.015 assessed during single and dual-task walking conditions. Eur. J. Neurosci. 45, Giacalone, G., Zanoletti, M., Re, R., Germinario, B., Contini, D., Spinelli, L., et al. 660–670. doi: 10.1111/ejn.13518 (2019). Time-Domain Near-Infrared Spectroscopy In Acute Ischemic Stroke Holtzer, R., Verghese, J., Allali, G., Izzetoglu, M., Wang, C., and Mahoney, J. R. Patients. Neurophotonics 6:015003. doi: 10.1117/1.NPh.6.1.015003 (2016). Neurological gait abnormalities moderate the functional brain signature Gramigna, V., Pellegrino, G., Cerasa, A., Cutini, S., Vasta, R., Olivadese, G., of the posture first hypothesis. Brain Topogr. 29, 334–343. doi: 10.1007/s10548- et al. (2017). Near-infrared spectroscopy in gait disorders: is it time to begin? 015-0465-z Neurorehabil. Neural Repair 31, 402–412. doi: 10.1177/1545968317693304 Holtzer, R., Yuan, J., Verghese, J., Mahoney, J. R., Izzetoglu, M., and Wang, C. Halliday, D. W. R., Hundza, S. R., Garcia-Barrera, M. A., Klimstra, M., (2017b). Interactions of subjective and objective measures of fatigue defined in Commandeur, D., Lukyn, T. W., et al. (2018). Comparing executive function, the context of brain control of locomotion. J. Gerontol. A Biol. Sci. Med. Sci. 72, evoked hemodynamic response, and gait as predictors of variations in mobility 417–423. doi: 10.1093/gerona/glw167 for older adults. J. Clin. Exp. Neuropsychol. 40, 151–160. doi: 10.1080/13803395. Hoshi, Y. (2007). Functional near-infrared spectroscopy: current status and future 2017.1325453 prospects. J. Biomed. Optics 12:062106. doi: 10.1117/1.2804911 Halliday, D. W. R., Mulligan, B. P., Garrett, D. D., Schmidt, S., Hundza, S. R., Huppert, T. J., Karim, H., Lin, C., Alqahtani, B. A., Greenspan, S. L., and Sparto, Garcia-Barrera, M. A., et al. (2017). Mean and variability in functional P. J. (2017). Functional imaging of cognition in an old-old population: a case brain activations differentially predict executive function in older adults: an for portable functional near-infrared spectroscopy. PLoS One 12:e0184918. doi: investigation employing functional near-infrared spectroscopy. Neurophotonics 10.1371/journal.pone.0184918 5:011013. doi: 10.1117/1.nph.5.1.011013 Hyodo, K., Dan, I., Kyutoku, Y., Suwabe, K., Byun, K., Ochi, G., et al. (2016). Hawkins, K. A., Fox, E. J., Daly, J. J., Rose, D. K., Christou, E. A., and McGuirk, The association between aerobic fitness and cognitive function in older men T. E. (2018). Prefrontal over-activation during walking in people with mobility mediated by frontal lateralization. Neuroimage 125, 291–300. doi: 10.1016/j. deficits: interpretation and functional implications. Hum. Mov. Sci. 59, 46–55. neuroimage.2015.09.062 doi: 10.1016/j.humov.2018.03.010 Inzitari, M., Baldereschi, M., Di Carlo, A., Di Bari, M., Marchionni, N., Scafato, Heilbronner, U., and Münte, T. F. (2013). Rapid event-related near-infrared E., et al. (2007). Impaired attention predicts motor performance decline in spectroscopy detects age-related qualitative changes in the neural correlates of older community-dwellers with normal baseline mobility: results from the response inhibition. Neuroimage 65, 408–415. doi: 10.1016/j.neuroimage.2012. italian longitudinal study on aging (ILSA). J. Gerontol. A Biol. Sci. Med. Sci. 09.066 62, 837–843. doi: 10.1093/gerona/62.8.837 Heinzel, S., Metzger, F. G., Ehlis, A. C., Korell, R., Alboji, A., Haeussinger, F. B., Jokinen, H., Kalska, H., Ylikoski, R., Madureira, S., Verdelho, A., Van Der Flier, et al. (2013). Aging-related cortical reorganization of verbal fluency processing: W. M., et al. (2009). Longitudinal cognitive decline in subcortical ischemic a functional near-infrared spectroscopy study. Neurobiol. Aging 34, 439–450. vascular disease -the ladis study. Cerebrovasc. Dis. 27, 384–391. doi: 10.1159/ doi: 10.1016/j.neurobiolaging.2012.05.021 000207442 Heinzel, S., Metzger, F. G., Ehlis, A. C., Korell, R., Alboji, A., Haeussinger, F. B., Jurado, M. B., and Rosselli, M. (2007). The elusive nature of executive functions: et al. (2015). Age and vascular burden determinants of cortical hemodynamics a review of our current understanding. Neuropsychol. Rev. 17, 213–233. doi: underlying verbal fluency. PLoS One 10:e0138863. doi: 10.1371/journal.pone. 10.1007/s11065-007-9040-z 0138863 Kahya, M., Moon, S., Ranchet, M., Vukas, R. R., Lyons, K. E., Pahwa, R., et al. Hernandez, M. E., Holtzer, R., Chaparro, G., Jean, K., Balto, J. M., Sandroff, B. M., (2019). Brain activity during dual task gait and balance in aging and age-related et al. (2016). Brain activation changes during locomotion in middle-aged to neurodegenerative conditions: a systematic review. Exp. Gerontol. 128:110756. older adults with multiple sclerosis. J. Neurol. Sci. 370, 277–283. doi: 10.1016/j. doi: 10.1016/j.exger.2019.110756 jns.2016.10.002 Katzorke, A., Zeller, J. B. M., Müller, L. D., Lauer, M., Polak, T., Deckert, J., et al. Herold, F., Wiegel, P., Scholkmann, F., and Müller, N. (2018). Applications (2018). Decreased hemodynamic response in inferior frontotemporal regions of functional near-infrared spectroscopy (FNIRS) neuroimaging in exercise– in elderly with mild cognitive impairment. Psychiatry Res. Neuroimaging 274, cognition science: a systematic, methodology-focused review. J. Clin. Med. 11–18. doi: 10.1016/j.pscychresns.2018.02.003 7:466. doi: 10.3390/jcm7120466 Kirilina, E., Jelzow, A., Heine, A., Niessing, M., Wabnitz, H., Brühl, R., et al. (2012). Herold, F., Wiegel, P., Scholkmann, F., Thiers, A., Hamacher, D., and Schega, The physiological origin of task-evoked systemic artefacts in functional near L. (2017). Functional near-infrared spectroscopy in movement science: infrared spectroscopy. Neuroimage 61, 70–81. doi: 10.1016/j.neuroimage.2012. a systematic review on cortical activity in postural and walking tasks. 02.074 Neurophotonics 4:041403. doi: 10.1117/1.nph.4.4.041403 Kisler, K., Nelson, A. R., Montagne, A., and Zlokovic, B. V. (2017). Cerebral blood Holtzer, R., Epstein, N., Mahoney, J. R., Izzetoglu, M., and Blumen, H. M. (2014). flow regulation and neurovascular dysfunction in alzheimer disease. Nat. Rev. Neuroimaging of mobility in aging: a targeted review. J. Gerontol. A Biol. Sci. Neurosci. 18, 419–434. doi: 10.1038/nrn.2017.48 Med. Sci. 69, 1375–1388. doi: 10.1093/gerona/glu052 la Fougère, C., Zwergal, A., Rominger, A., Förster, S., Fesl, G., Dieterich, M., et al. Holtzer, R., George, C. J., Izzetoglu, M., and Wang, C. (2018a). The effect of diabetes (2010). Real versus imagined locomotion: a [18F]-FDG PET-FMRI comparison. on prefrontal cortex activation patterns during active walking in older adults. Neuroimage 50, 1589–1598. doi: 10.1016/j.neuroimage.2009.12.060 Brain Cogn. 125, 14–22. doi: 10.1016/j.bandc.2018.03.002 Laguë-Beauvais, M., Fraser, S. A., Desjardins-Crépeau, L., Castonguay, N., Holtzer, R., Izzetoglu, M., Chen, M., and Wang, C. (2018b). Distinct FNIRS- Desjardins, M., Lesage, F., et al. (2015). Shedding light on the effect of priority Derived HbO2 trajectories during the course and over repeated walking trials instructions during dual-task performance in younger and older adults: a under single- and dual-task conditions: implications for within session learning FNIRS study. Brain Cogn. 98, 1–14. doi: 10.1016/j.bandc.2015.05.001 Frontiers in Aging Neuroscience | www.frontiersin.org 17 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults Leone, C., Feys, P., Moumdjian, L., D’Amico, E., Zappia, M., and Patti, F. Rosano, C., Aizenstein, H., Brach, J., Longenberger, A., Studenski, S., and Newman, (2017). Cognitive-motor dual-task interference: a systematic review of neural A. B. (2008). Gait measures indicate underlying focal gray matter atrophy in correlates. Neurosci. Biobehav. Rev. 75, 348–360. doi: 10.1016/j.neubiorev.2017. the brain of older adults. J. Gerontol. A Biol. Sci. Med. Sci. 63, 1380–1388. 01.010 doi: 10.1093/gerona/63.12.1380 Lucas, M., Wagshul, M. E., Izzetoglu, M., and Holtzer, R. (2018). Moderating effect Rosen, B. R., and Savoy, R. L. (2012). FMRI at 20: has it changed the world? of white matter integrity on brain activation during dual-task walking in older Neuroimage 62, 1316–1324. doi: 10.1016/j.neuroimage.2012.03.004 adults. J. Gerontol. A 74, 435–441. doi: 10.1093/gerona/gly131 Rosso, A. L., Cenciarini, M., Sparto, P. J., Loughlin, P. J., Furman, J. M., and Mahoney, J. R., Holtzer, R., Izzetoglu, M., Zemon, V., Verghese, J., and Allali, G. Huppert, T. J. (2017). Neuroimaging of an attention demanding dual-task (2016). The role of prefrontal cortex during postural control in parkinsonian during dynamic postural control. Gait Posture 57, 193–198. doi: 10.1016/j. syndromes a functional near-infrared spectroscopy study. Brain Res. 1633, gaitpost.2017.06.013 126–138. doi: 10.1016/j.brainres.2015.10.053 Rosso, A. L., Metti, A. L., Faulkner, K., Redfern, M., Yaffe, K., Launer, L., Maidan, I., Bernad-Elazari, H., Giladi, N., Hausdorff, J. M., and Mirelman, A. et al. (2019). Complex walking tasks and risk for cognitive decline in high (2017). When is higher level cognitive control needed for locomotor tasks functioning older adults. J. Alzheimers Dis. 71, S65–S73. doi: 10.3233/JAD- among patients with Parkinson’s disease? Brain Topogr. 30, 531–538. doi: 10. 181140 1007/s10548-017-0564-0 Rypma, B., and D’Esposito, M. (2000). Isolating the neural mechanisms of age- Maidan, I., Nieuwhof, F., Bernad-Elazari, H., Reelick, M. F., Bloem, B. R., Giladi, related changes in human working memory. Nat. Neurosci. 3, 509–515. doi: N., et al. (2016). The role of the frontal lobe in complex walking among 10.1038/74889 patients with Parkinson’s disease and healthy older adults: an FNIRS study”. Sala, S., Baddeley, A., Papagno, C., and Spinnler, H. (1995). Dual-task paradigm: Neurorehabil. Neural Repair 30, 963–971. doi: 10.1177/1545968316650426 a means to examine the central executive. Ann. N. Y. Acad. Sci. 769, 161–172. Mirelman, A., Maidan, I., Bernad-Elazari, H., Shustack, S., Giladi, N., and doi: 10.1111/j.1749-6632.1995.tb38137.x Hausdorff, J. M. (2017). Effects of aging on prefrontal brain activation during Scholkmann, F., Kleiser, S., Jaako Metz, A., Zimmermann, R., Mata Pavia, J., challenging walking conditions. Brain Cogn. 115, 41–46. doi: 10.1016/j.bandc. Wolf, U., et al. (2014). A review on continuous wave functional near-infrared 2017.04.002 spectroscopy and imaging instrumentation and methodology. Neuroimage 85, Mori, T., Takeuchi, N., and Izumi, S. (2018). Prefrontal cortex activation during 6–27. doi: 10.1016/j.neuroimage.2013.05.004 a dual task in patients with stroke. Gait Posture 59, 193–198. doi: 10.1016/j. Stern, Y. (2005). Brain networks associated with cognitive reserve in healthy young gaitpost.2017.09.032 and old adults. Cereb. Cortex 15, 394–402. doi: 10.1093/cercor/bhh142 Müller, L. D., Guhn, A., Zeller, J. B. M., Biehl, S. C., Dresler, T., Hahn, T., et al. Stern, Y. (2009). Cognitive reserve. Neuropsychologia 47, 2015–2028. doi: 10.1016/ (2014). Neural correlates of a standardized version of the trail making test j.neuropsychologia.2009.03.004 in young and elderly adults: a functional near-infrared spectroscopy study. Strangman, G., Culver, J. P., Thompson, J. H., and Boas, D. A. (2002). A Neuropsychologia 56, 271–279. doi: 10.1016/j.neuropsychologia.2014.01.019 quantitative comparison of simultaneous bold FMRI and NIRS recordings Nieuwhof, F., Reelick, M. F., Maidan, I., Mirelman, A., Hausdorff, J. M., and Olde during functional brain activation. Neuroimage 17, 719–731. doi: 10.1006/nimg. Rikkert, M. G. M. (2016). Measuring prefrontal cortical activity during dual task 2002.1227 walking in patients with Parkinson’s disease: feasibility of using a new portable Stuart, S., Vitorio, R., Morris, R., Martini, D. N., Fino, P. C., and Mancini, M. FNIRS device. Pilot Feasibility Stud. 2, 1–11. doi: 10.1186/s40814-016-0099-2 (2018). Cortical activity during walking and balance tasks in older adults and Niu, H., Li, X., Chen, Y., Ma, C., Zhang, J., and Zhang, Z. (2013). Reduced frontal in people with Parkinson’s disease: a structured review. Maturitas 113, 53–72. activation during a working memory task in mild cognitive impairment: a non- doi: 10.1016/j.maturitas.2018.04.011 invasive near-infrared spectroscopy study. CNS Neurosci. Ther. 19, 125–131. Szameitat, A. J., Schubert, T., Müller, K., Von Yves, and Cramon, D. (2002). doi: 10.1111/cns.12046 Localization of executive functions in dual-task performance with FMRI. Noda, T., Nakagome, K., Setoyama, S., and Matsushima, E. (2017). Working J. Cogn. Neurosci. 14, 1184–1199. doi: 10.1162/089892902760807195 memory and prefrontal/temporal hemodynamic responses during post- Tachtsidis, I., and Scholkmann, F. (2016). False positives and false negatives in task period in patients with schizophrenia: a multi-channel near-infrared functional near-infrared spectroscopy: issues, challenges, and the way forward. spectroscopy study. J. Psychiatr. Res. 95, 288–298. doi: 10.1016/j.jpsychires.2017. Neurophotonics 3:031405. doi: 10.1117/1.NPh.3.3.031405 09.001 Takeuchi, N., Mori, T., Suzukamo, Y., Tanaka, N., and Izumi, S. (2016). Parallel Oboshi, Y., Kikuchi, M., Shimizu, Y., Yoshimura, Y., Hiraishi, H., Okada, H., et al. processing of cognitive and physical demands in left and right prefrontal (2014). Pre-task prefrontal activation during cognitive processes in aging: a cortices during smartphone use while walking. BMC Neurosci. 17:9. doi: 10. near-infrared spectroscopy study. PLoS One 9:e098779. doi: 10.1371/journal. 1186/s12868-016-0244-0 pone.0098779 Thumm, P. C., Maidan, I., Brozgol, M., Shustak, S., Gazit, E., Shema Shiratzki, Ohsugi, H., Ohgi, S., Shigemori, K., and Schneider, E. B. (2013). Differences in dual- S., et al. (2018). Treadmill walking reduces pre-frontal activation in patients task performance and prefrontal cortex activation between younger and older with Parkinson’s disease. Gait Posture 62, 384–387. doi: 10.1016/j.gaitpost.2018. adults. BMC Neurosci. 14:10. doi: 10.1186/1471-2202-14-10 03.041 Okamoto, M., Dan, H., Shimizu, K., Takeo, K., Amita, T., Oda, I., et al. (2004). Torricelli, A., Contini, D., Pifferi, A., Caffini, M., Re, R., Zucchelli, L., et al. (2014). Multimodal assessment of cortical activation during apple peeling by NIRS and Time domain functional nirs imaging for human brain mapping. Neuroimage FMRI. Neuroimage 21, 1275–1288. doi: 10.1016/j.neuroimage.2003.12.003 85, 28–50. doi: 10.1016/j.neuroimage.2013.05.106 Osofundiya, O., Benden, M. E., Dowdy, D., and Mehta, R. K. (2016). Obesity- Uemura, K., Shimada, H., Doi, T., Hakizako, H., Tsutsumimoto, K., Park, H., et al. specific neural cost of maintaining gait performance under complex conditions (2016). Reduced prefrontal oxygenation in mild cognitive impairment during in community-dwelling older adults. Clin. Biomech. 35, 42–48. doi: 10.1016/j. memory retrieval. Int. J. Geriatr. Psychiatry 31, 583–591. doi: 10.1002/gps.4363 clinbiomech.2016.03.011 Venkatraman, V. K., Aizenstein, H., Guralnik, J., Newman, A. B., Glynn, N. W., Pfeifer, M. D., Scholkmann, F., and Labruyère, R. (2018). Signal processing in Taylor, C., et al. (2010). Executive control function, brain activation and white functional near-infrared spectroscopy (fnirs): methodological differences lead matter hyperintensities in older adults. Neuroimage 49, 3436–3442. doi: 10. to different statistical results. Front. Hum. Neurosci. 11:641. doi: 10.3389/ 1016/j.neuroimage.2009.11.019 fnhum.2017.00641 Verghese, J., Annweiler, C., Ayers, E., Barzilai, N., Beauchet, O., Bennett, D. A., Pifferi, A., Contini, D., Dalla Mora, A., Farina, A., Spinelli, L., and Torricelli, A. et al. (2014). Motoric cognitive risk syndrome: multicountry prevalence (2016). New frontiers in time-domain diffuse optics, a review. J. Biomed. Optics and dementia risk. Neurology 83, 718–726. doi: 10.1212/WNL.000000000000 21:091310. doi: 10.1117/1.JBO.21.9.091310 0717 Plichta, M. M., Herrmann, M. J., Baehne, C. G., Ehlis, A. C., Richter, M. M., Verghese, J., Holtzer, R., Lipton, R. B., and Wang, C. (2012). Mobility stress test Pauli, P., et al. (2006). Event-related functional near-infrared spectroscopy approach to predicting frailty, disability, and mortality in high-functioning (FNIRS): are the measurements reliable? Neuroimage 31, 116–124. doi: 10.1016/ older adults. J. Am. Geriatr. Soc. 60, 1901–1905. doi: 10.1111/j.1532-5415.2012. j.neuroimage.2005.12.008 04145.x Frontiers in Aging Neuroscience | www.frontiersin.org 18 January 2020 | Volume 11 | Article 367 Udina et al. Frontal Lobe Activation in Older Adults Verghese, J., Wang, C., Ayers, E., Izzetoglu, M., and Holtzer, R. (2017). Brain Yeung, M. K., Sze, S. L., Woo, J., Kwok, T., Shum, D. H. K., Yu, R., et al. (2016a). activation in high-functioning older adults and falls: prospective cohort study. Altered frontal lateralization underlies the category fluency deficits in older Neurology 88, 191–197. doi: 10.1212/WNL.0000000000003421 adults with mild cognitive impairment: a near-infrared spectroscopy study. Vermeij, A., van Beek, A. H. E. A., Reijs, B. L. R., Claassen, J. A. H. R., and Kessels, Front. Aging Neurosci. 8:59. doi: 10.3389/fnagi.2016.00059 R. P. C. (2014). An exploratory study of the effects of spatial working-memory Yeung, M. K., Sze, S. L., Woo, J., Kwok, T., Shum, D. H., Yu, R., et al. (2016b). load on prefrontal activation in low- and high-performing elderly. Front. Aging Reduced frontal activations at high working memory load in mild cognitive Neurosci. 6:303. doi: 10.3389/fnagi.2014.00303 impairment: near-infrared spectroscopy. Dement. Geriatr. Cogn. Disord. 42, Vitorio, R., Stuart, S., Rochester, L., Alcock, L., and Pantall, A. (2017). FNIRS 278–296. doi: 10.1159/000450993 response during walking — artefact or cortical activity? A systematic Yücel, M. A., Selb, J., Aasted, C. M., Petkov, M. P., Becerra, L., Borsook, D., et al. review. Neurosci. Biobehav. Rev. 83, 160–172. doi: 10.1016/j.neubiorev.2017. (2015). Short separation regression improves statistical significance and better 10.002 localizes the hemodynamic response obtained by near-infrared spectroscopy Wager, T. D., Jonides, J., and Reading, S. (2004). Neuroimaging studies of for tasks with differing autonomic responses. Neurophotonics 2:035005. doi: shifting attention: a meta-analysis. Neuroimage 22, 1679–1693. doi: 10.1016/j. 10.1117/1.NPh.2.3.035005 neuroimage.2004.03.052 Zhang, X., Noah, J. A., and Hirsch, J. (2016). Separation of the global and local Wagshul, M. E., Lucas, M., Ye, K., Izzetoglu, M., and Holtzer, R. (2019). components in functional near-infrared spectroscopy signals using principal Multi-modal neuroimaging of dual-task walking: structural MRI and FNIRS component spatial filtering. Neurophotonics 3:015004. doi: 10.1117/1.NPh.3.1. analysis reveals prefrontal grey matter volume moderation of brain activation 015004 in older adults. Neuroimage 189, 745–754. doi: 10.1016/j.neuroimage.2019. Zwergal, A., Linn, J., Xiong, G., Brandt, T., Strupp, M., and Jahn, K. (2012). Aging of 01.045 human supraspinal locomotor and postural control in FMRI. Neurobiol. Aging Weinstein, A. M., Voss, M. W., Prakash, Chaddock, L., Szabo, A., White, S. M., 33, 1073–1084. doi: 10.1016/j.neurobiolaging.2010.09.022 et al. (2012). The association between aerobic fitness and executive function is mediated by prefrontal cortex volume. Brain Behav. Immun. 26, 811–819. Conflict of Interest: The authors declare that the research was conducted in the doi: 10.1016/j.bbi.2011.11.008 absence of any commercial or financial relationships that could be construed as a Yap, K. H., Ung, W., Ebenezer, E. G. M., Nordin, N., Chin, P., Sugathan, S., et al. potential conflict of interest. (2017). Visualizing hyperactivation in neurodegeneration based on prefrontal oxygenation: a comparative study of mild Alzheimer’s disease, mild cognitive Copyright © 2020 Udina, Avtzi, Durduran, Holtzer, Rosso, Castellano-Tejedor, Perez, impairment, and healthy controls. Front. Aging Neurosci. 9:287. doi: 10.3389/ Soto-Bagaria and Inzitari. This is an open-access article distributed under the terms fnagi.2017.00287 of the Creative Commons Attribution License (CC BY). The use, distribution or Yaple, Z. A., Stevens, W. D., and Arsalidou, M. (2019). Meta-analyses of the n-back reproduction in other forums is permitted, provided the original author(s) and the working memory task: FMRI evidence of age-related changes in prefrontal copyright owner(s) are credited and that the original publication in this journal cortex involvement across the adult lifespan. Neuroimage 196, 16–31. doi: 10. is cited, in accordance with accepted academic practice. No use, distribution or 1016/j.neuroimage.2019.03.074 reproduction is permitted which does not comply with these terms. Frontiers in Aging Neuroscience | www.frontiersin.org 19 January 2020 | Volume 11 | Article 367