Background: The management of people affected by age-related neurological disorders requires the adoption of targeted and cost-effective interventions to cope with chronicity. Therapy adaptation and rehabilitation represent major targets requiring long-term follow-up of neurodegeneration or, conversely, the promotion of neuroplasticity mechanisms. However, affordable and reliable neurophysiological correlates of cerebral activity to be used throughout treatment stages are often lacking. The aim of this systematic review is to highlight actual applications of functional Near-Infrared Spectroscopy (fNIRS) as a versatile optical neuroimaging technology for investigating cortical hemodynamic activity in the most common chronic neurological conditions. Methods: We reviewed studies investigating fNIRS applications in Parkinson’s Disease (PD), Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) as those focusing on motor and cognitive impairment in ageing and Multiple Sclerosis (MS) as the most common chronic neurological disease in young adults. The literature search was conducted on NCBI PubMed and Web of Science databases by PRISMA guidelines. Results: We identified a total of 63 peer-reviewed articles. The AD spectrum is the most investigated pathology with 40 articles ranging from the traditional monitoring of tissue oxygenation to the analysis of functional resting-state conditions or cognitive functions by means of memory and verbal fluency tasks. Conversely, applications in PD (12 articles) and MS (11 articles) are mainly focused on the characterization of motor functions and their association with dual-task conditions. The most investigated cortical area is the prefrontal cortex, since reported to play an important role in age-related compensatory mechanism and neurofunctional changes associated to these chronic neurological conditions. Interestingly, only 9 articles applied a longitudinal approach. Conclusion: The results indicate that fNIRS is mainly employed for the cross-sectional characterization of the clinical phenotypes of these pathologies, whereas data on its utility for longitudinal monitoring as surrogate biomarkers of disease progression and rehabilitation effects are promising but still lacking.

Functional Near-Infrared Spectroscopy (fNIRS) captures activations and inhibitions of cortical areas and implements a viable approach to neuromonitoring in clinical research. Compared to more advanced methods, continuous wave fNIRS (CW-fNIRS) is currently used in clinics for its simplicity in mapping the whole sub-cranial cortex. Conversely, it often lacks hardware reduction of confounding factors, stressing the importance of a correct signal processing. The proposed pipeline includes movement artifact reduction (MAR), bandpass filtering (BPF), and principal component analysis (PCA). Eight MAR algorithms were compared among 23 young adult volunteers under motor-grasping task. Single-subject examples are shown followed by the percentage in energy reduction (ERD%) statistics by single steps and cumulative values. The block average of the hemodynamic response function was compared with generalized linear model fitting. Maps of significant activation/inhibition were illustrated. The mean ERD% of pre-processed signals concerning the initial raw signal energy reached 4%. A tested multichannel MAR variant showed overcorrection on 4-fold more expansive windows. All of the MAR algorithms found similar activations in the contralateral motor area. In conclusion, single channel MAR algorithms are suggested followed by BPF and PCA. The importance of whole cortex mapping for fNIRS integration in clinical applications was also confirmed by our results.

Functional near-infrared spectroscopy (fNIRS) is increasingly employed as an ecological neuroimaging technique in assessing age-related chronic neurological disorders, such as Parkinson’s disease (PD), mainly providing a cross-sectional characterization of clinical phenotypes in ecological settings. Current fNIRS studies in PD have investigated the effects of motor and non-motor impairment on cortical activity during gait and postural stability tasks, but no study has employed fNIRS as an ecological neuroimaging tool to assess PD at different stages. Therefore, in this work, we sought to investigate the cortical activity of PD patients during a motor grasping task and its relationship with both the staging of the pathology and its clinical variables. This study considered 39 PD patients (age 69.0 ± 7.64, 38 right-handed), subdivided into two groups at different stages by the Hoehn and Yahr (HY) scale: early PD (ePD; N = 13, HY = [1; 1.5]) and moderate PD (mPD; N = 26, HY = [2; 2.5; 3]). We employed a whole-head fNIRS system with 102 measurement channels to monitor brain activity. Group-level activation maps and region of interest (ROI) analysis were computed for ePD, mPD, and ePD vs. mPD contrasts. A ROI-based correlation analysis was also performed with respect to contrasted subject-level fNIRS data, focusing on age, a Cognitive Reserve Index questionnaire (CRIQ), disease duration, the Unified Parkinson’s Disease Rating Scale (UPDRS), and performances in the Stroop Color and Word (SCW) test. We observed group differences in age, disease duration, and the UPDRS, while no significant differences were found for CRIQ or SCW scores. Group-level activation maps revealed that the ePD group presented higher activation in motor and occipital areas than the mPD group, while the inverse trend was found in frontal areas. Significant correlations with CRIQ, disease duration, the UPDRS, and the SCW were mostly found in non-motor areas. The results are in line with current fNIRS and functional and anatomical MRI scientific literature suggesting that non-motor areas—primarily the prefrontal cortex area—provide a compensation mechanism for PD motor impairment. fNIRS may serve as a viable support for the longitudinal assessment of therapeutic and rehabilitation procedures, and define new prodromal, low-cost, and ecological biomarkers of disease progression.

Functional near-infrared spectroscopy (fNIRS) is an important non-invasive technique used to monitor cortical activity. However, a varying sensitivity of surface channels vs. cortical structures may suggest integrating the fNIRS with the subject-specific anatomy (SSA) obtained from routine MRI. Actual processing tools permit the computation of the SSA forward problem (i.e., cortex to channel sensitivity) and next, a regularized solution of the inverse problem to map the fNIRS signals onto the cortex. The focus of this study is on the analysis of the forward problem to quantify the effect of inter-subject variability. Thirteen young adults (six males, seven females, age 29.3 ± 4.3) underwent both an MRI scan and a motor grasping task with a continuous wave fNIRS system of 102 measurement channels with optodes placed according to a 10/5 system. The fNIRS sensitivity profile was estimated using Monte Carlo simulations on each SSA and on three major atlases (i.e., Colin27, ICBM152 and FSAverage) for comparison. In each SSA, the average sensitivity curves were obtained by aligning the 102 channels and segmenting them by depth quartiles. The first quartile (depth < 11.8 (0.7) mm, median (IQR)) covered 0.391 (0.087)% of the total sensitivity profile, while the second one (depth < 13.6 (0.7) mm) covered 0.292 (0.009)%, hence indicating that about 70% of the signal was from the gyri. The sensitivity bell-shape was broad in the source–detector direction (20.953 (5.379) mm FWHM, first depth quartile) and steeper in the transversal one (6.082 (2.086) mm). The sensitivity of channels vs. different cortical areas based on SSA were analyzed finding high dispersions among subjects and large differences with atlas-based evaluations. Moreover, the inverse cortical mapping for the grasping task showed differences between SSA and atlas based solutions. In conclusion, integration with MRI SSA can significantly improve fNIRS interpretation.

Fatigue and balance disorders are common in people with multiple sclerosis (PwMS), but the neural mechanisms linking them during postural control remain unclear. This cross-sectional study aims to examine associations between fatigue, balance impairment, and task-evoked cortical hemodynamics/connectivity. Sixteen PwMS (relapsing-remitting MS; EDSS < 3.5) and 19 healthy controls (HC) were enrolled. Based on the Modified Fatigue Impact Scale (MFIS), PwMS were classified as fatigued (f_PwMS, MFIS ≥ 38; n = 10) or non-fatigued (nf_PwMS, n = 6). Participants performed five 30 s trials of static stance on foam with eyes closed. fNIRS recorded frontal, temporal, and occipital cortical activity, while stabilometry measured center-of-pressure sway. In PwMS, MFIS showed a trend toward association with sway (r = 0.49; p = 0.06). Sway was higher in f_PwMS than nf_PwMS and HC but not significantly different (ANOVA p = 0.341). Compared with HC, PwMS showed increased bilateral prefrontal and reduced occipital HR. Stratified analyses showed greater HR in f_PwMS versus HC and nf_PwMS in bilateral BA10 and in temporo-parietal regions, with a right-hemisphere predominance. Global coherence did not differ across groups, but exploratory BA10 analysis showed higher prefrontal coherence in f_PwMS than nf_PwMS (p = 0.02). Fatigued PwMS exhibit amplified, right prefrontal and temporo-parietal activation and focal prefrontal hyper-connectivity, consistent with compensatory top–down control to maintain balance.