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Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks, which have been widely applied in the field of central neurological diseases, such as stroke, Parkinson’s disease, and mental disorders. Although significant advances have been made in neuromodulation technologies, the identification of optimal neurostimulation parameters including the cortical target, duration, and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits. Moreover, the neural mechanism underlying neuromodulation for improved behavioral performance remains poorly understood. Recently, advancements in neuroimaging have provided insight into neuromodulation techniques. Functional near-infrared spectroscopy, as a novel non-invasive optical brain imaging method, can detect brain activity by measuring cerebral hemodynamics with the advantages of portability, high motion tolerance, and anti-electromagnetic interference. Coupling functional near-infrared spectroscopy with neuromodulation technologies offers an opportunity to monitor the cortical response, provide real-time feedback, and establish a closed-loop strategy integrating evaluation, feedback, and intervention for neurostimulation, which provides a theoretical basis for development of individualized precise neurorehabilitation. We aimed to summarize the advantages of functional near-infrared spectroscopy and provide an overview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation, transcranial electrical stimulation, neurofeedback, and brain-computer interfaces. Furthermore, the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized. In conclusion, functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central neural reorganization to achieve better functional recovery from central nervous system diseases.

BackgroundRobot-assisted therapy (RAT) has received considerable attention in stroke motor rehabilitation. Characteristics of brain functional response associated with RAT would provide a theoretical basis for choosing the appropriate protocol for a patient. However, the cortical response induced by RAT remains to be fully elucidated due to the lack of dynamic brain functional assessment tools.ObjectiveTo guide the implementation of clinical therapy, this study focused on the brain functional responses induced by RAT in patients with different degrees of motor impairment.MethodsA total of 32 stroke patients were classified into a low score group (severe impairment, n = 16) and a high score group (moderate impairment, n = 16) according to the motor function of the upper limb and then underwent RAT training in assistive mode with simultaneous cerebral haemodynamic measurement by functional near-infrared spectroscopy (fNIRS). Functional connectivity (FC) and the hemisphere autonomy index (HAI) were calculated based on the wavelet phase coherence among fNIRS signals covering bilateral prefrontal, motor and occipital areas.ResultsSpecific cortical network response related to RAT was observed in patients with unilateral moderate-to-severe motor deficits in the subacute stage. Compared with patients with moderate dysfunction, patients with severe impairment showed a wide range of significant FC responses in the bilateral hemispheres induced by RAT with the assistive mode, especially task-related involvement of ipsilesional supplementary motor areas.ConclusionUnder assisted mode, RAT-related extensive cortical response in patients with severe dysfunction might contribute to brain functional organization during motor performance, which is considered the basic neural substrate of motor-related processes. In contrast, the limited cortical response related to RAT in patients with moderate dysfunction may indicate that the training intensity needs to be adjusted in time according to the brain functional state. fNIRS-based assessment of brain functional response assumes great importance for the customization of an appropriate protocol training in the clinical practice.

IntroductionThe m-NMES had been demonstrated to redistribute brain resources and induce plastic changes in the stroke patients. However, the physiological mechanism and clinical efficacy of m-NMES combination with existing clinical rehabilitation programs remains unclear in patients with aphasia after stroke. This study aimed to investigate the effects of simultaneous use of m-NMES and language training (m-NMES-LT) with on cerebral oscillations and brain connection, as well as the effect on clinical efficacy.Materials and methodsTotal 21 right–handed adult patients with aphasia were randomly assigned to language training (LT) group and m-NMES-LT group, and tissue concentration of oxyhemoglobin and deoxyhemoglobin oscillations were measured by functional near-infrared spectroscopy in resting and treatment state during three consecutive weeks. Five characteristic frequency signals (I, 0.6–2 Hz; II, 0.145–0.6 Hz; III, 0.052–0.145 Hz; IV, 0.021–0.052 Hz; and V, 0.0095–0.021 Hz) were identified using the wavelet method. The wavelet amplitude (WA) and wavelet phase coherence (WPCO) were calculated to describe the frequency-specific cortical activities.ResultsThe m-NMES-LT induced significantly higher WA values in contralesional PFC in intervals I, II, and V, and ipsilesional MC in intervals I-V than the resting state. The WPCO values between ipsilesional PFC-MC in interval III-IV, and between bilateral MC in interval III-IV were significantly higher than resting state. In addition, there was a significant positive correlation between WPCO and Western Aphasia Battery in m-NMES-LT group.ConclusionThe language training combined with neuromuscular electrical stimulation on median nerve could improve and achieve higher clinical efficacy for aphasia. This is attributed to the m-NMES-LT could enhance cortical activation and brain functional connectivity in patients with aphasia, which was derived from myogenic, neurogenic, and endothelial cell metabolic activities.

BackgroundThis study aimed to assess brain oxygenation status and cerebral autoregulation function in subjects with cognitive dysfunction.MethodsThe Montreal Cognitive Assessment (MoCA) was applied to divide the subjects into three groups: cognitive impairment (Group CI, 72.50 ± 10.93 y), mild cognitive impairment (Group MCI, 72.02 ± 9.90 y), and normal cognition (Group NC, 70.72 ± 7.66 y). Near-infrared spectroscopy technology and a non-invasive blood pressure device were used to simultaneously measure changes in cerebral tissue oxygenation signals in the bilateral prefrontal lobes (LPFC/RPFC) and arterial blood pressure (ABP) signals from subjects in the resting state (15 min). The coupling between ABP and cerebral oxyhemoglobin concentrations (Δ [O2Hb]) was calculated in very-low-frequency (VLF, 0.02–0.07 Hz) and low-frequency (LF, 0.07–0.2 Hz) bands based on the dynamical Bayesian inference approach. Pearson correlation analyses were used to study the relationships between MoCA scores, tissue oxygenation index, and strength of coupling function.ResultsIn the interval VLF, Group CI (p = 0.001) and Group MCI (p = 0.013) exhibited significantly higher coupling strength from ABP to Δ [O2Hb] in the LPFC than Group NC. In the interval LF, coupling strength from ABP to Δ [O2Hb] in the LPFC was significantly higher in Group CI than in Group NC (p = 0.001). Pearson correlation results showed that MoCA scores had a significant positive correlation with the tissue oxygenation index and a significant negative correlation with the coupling strength from ABP to Δ [O2Hb].ConclusionThe significantly increased coupling strength may be evidence of impaired cerebral autoregulation function in subjects with cognitive dysfunction. The Pearson correlation results suggest that indicators of brain oxygenation status and cerebral autoregulation function can reflect cognitive function. This study provides insights into the mechanisms underlying the pathophysiology of cognitive impairment and provides objective indicators for screening cognitive impairment in the elderly population.

ObjectiveVirtual reality (VR) grasping exercise training helps patients participate actively in their recovery and is a critical approach to the rehabilitation of hand dysfunction. This study aimed to explore the effects of active participation and VR grasping on brain function combined with the kinematic information obtained during VR exercises.MethodsThe cerebral oxygenation signals of the prefrontal cortex (LPFC/RPFC), the motor cortex (LMC/RMC), and the occipital cortex (LOC/ROC) were measured by functional near-infrared spectroscopy (fNIRS) in 18 young people during the resting state, grasping movements, and VR grasping movements. The EPPlus plug-in was used to collect the hand motion data during simulated interactive grasping. The wavelet amplitude (WA) of each cerebral cortex and the wavelet phase coherence (WPCO) of each pair of channels were calculated by wavelet analysis. The total difference in acceleration difference of the hand in the VR grasping movements was calculated to acquire kinematic characteristics (KCs). The cortical activation and brain functional connectivity (FC) of each brain region were compared and analyzed, and a significant correlation was found between VR grasping movements and brain region activation.ResultsCompared with the resting state, the WA values of LPFC, RPFC, LMC, RMC, and ROC increased during the grasping movements and the VR grasping movements, these changes were significant in LPFC (p = 0.0093) and LMC (p = 0.0007). The WA values of LMC (p = 0.0057) in the VR grasping movements were significantly higher than those in the grasping movements. The WPCO of the cerebral cortex increased during grasping exercise compared with the resting state. Nevertheless, the number of significant functional connections during VR grasping decreased significantly, and only the WPCO strength between the LPFC and LMC was enhanced. The increased WA of the LPFC, RPFC, LMC, and RMC during VR grasping movements compared with the resting state showed a significant negative correlation with KCs (p < 0.001).ConclusionThe VR grasping movements can improve the activation and FC intensity of the ipsilateral brain region, inhibit the FC of the contralateral brain region, and reduce the quantity of brain resources allocated to the task. Thus, ordered grasping exercises can enhance active participation in rehabilitation and help to improve brain function.

Stroke is one of the primary causes of motor disorders, which can seriously affect the patient’s quality of life. However, the assessment of the upper limb affected by stroke is commonly based on scales, and the characteristics of brain reorganization induced by limb movement are not clear. Thus, this study aimed to investigate stroke-related cortical reorganization based on functional near infrared spectroscopy (fNIRS) during upper limb multi-joint linkage movement with reference to the Fugl–Meyer Assessment of the upper extremities (FMA-UE). In total, 15 stroke patients and 15 healthy subjects participated in this study. The functional connectivity (FC) between channels and the regions of interest (ROI) was calculated by Pearson’s correlation coefficient. The results showed that compared with the control group, the FC between the prefrontal cortex and the motor cortex was significantly increased in the resting state and the affected upper limb’s multi-joint linkage movements, while the FC between the motor cortex was significantly decreased during the unaffected upper limb’s multi-joint linkage movements. Moreover, the significantly increased ROI FC in the resting state showed a significantly positive correlation with FMA-UE in stroke patients (p < 0.05). This study highlights a new biomarker for evaluating the function of movement in stroke patients and provides guidance for rehabilitation training.

The present study aimed to investigate the effect of an auricular acupuncture intervention on the relationship between changes in oxyhemoglobin concentration (Δ [O2Hb]) and arterial blood pressure (ABP). The cerebral oxygenation signals in the bilateral prefrontal cortex (PFC), sensorimotor cortex (SMC), and temporal lobe cortex (TLC) of 15 patients with hypertension were measured by a 24-channel functional near-infrared spectroscopy (fNIRS) device before (State_R) and after (State_AT) the auricular acupuncture intervention. Coupling strength was used to quantitatively evaluate the strength of the couplings between ABP and Δ [O2Hb] in low-frequency oscillations (LF, 0.07–0.2 ​Hz) and very-low-frequency oscillations (VLF, 0.02–0.07 ​Hz). Results showed that the changes in wavelet amplitudes in the LF and VLF intervals did not exhibit significant differences after auricular acupuncture. The coupling strength from ABP to Δ [O2Hb] was significantly lower in the LF range after auricular acupuncture in the bilateral PFC, SMC, and TLC (p ​

Functional near-infrared spectroscopy (fNIRS) has gained great interest as a noninvasive modality to study the changes in cerebral hemodynamics related to brain activity. The unique and beneficial characteristics of fNIRS allow ecologically effective investigations of all ages and conditions in more realistic and clinical environments. In this review, we provide a comprehensive description of fNIRS basics, analytical method developments and applications in stroke rehabilitation. We first review various new methods for the time-series processing and functional analysis of fNIRS data. Then, we review the fNIRS-based application in clinical research for stroke rehabilitation and highlight the exciting developments based on fNIRS. Finally, we discuss the possible technical limitations of the implementation of fNIRS and provide suggestions from different aspects for practical application.

Older adults with mild cognitive impairment (MCI) have a high risk of developing Alzheimer’s disease. Gait performance is a potential clinical marker for the progression of MCI into dementia. However, the relationship between gait and brain functional connectivity (FC) in older adults with MCI remains unclear. Forty-five subjects [MCI group, n = 23; healthy control (HC) group, n = 22] were recruited. Each subject performed a walking task (Task 01), counting backward–walking task (Task 02), naming animals–walking task (Task 03), and calculating–walking task (Task 04). The gait parameters and cerebral oxygenation signals from the left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), right motor cortex (RMC), left occipital leaf cortex (LOL), and right occipital leaf cortex (ROL) were obtained simultaneously. Wavelet phase coherence was calculated in two frequency intervals: low frequency (interval I, 0.052–0.145 Hz) and very low frequency (interval II, 0.021–0.052 Hz). Results showed that the FC of RPFC–RMC is significantly lower in interval I in Task 03 compared with that in Task 02 in the MCI group (p = 0.001). Also, the right relative symmetry index (IDpsR) is significantly lower in Task 03 compared with that in Task 02 (p = 0.000). The IDpsR is positively correlated with the FC of RPFC–RMC in interval I in the MCI group (R = 0.205, p = 0.041). The gait symmetry such as left relative symmetry index (IDpsL) and IDpsR is significantly lower in the dual-task (DT) situation compared with the single task in the two groups (p < 0.05). The results suggested that the IDpsR might reflect abnormal change in FC of RPFC–RMC in interval I in the MCI population during Task 03. The gait symmetry is affected by DTs in both groups. The findings of this study may have a pivotal role in the early monitoring and intervention of brain dysfunction among older adults with MCI.

This study aims to explore the effect of intermittent sequential pneumatic compression (ISPC) intervention on the coupling relationship between arterial blood pressure (ABP) and changes in oxyhaemoglobin (Δ [O2Hb]). The coupling strength between the two physiological systems was estimated using a coupling function based on dynamic Bayesian inference. The participants were 22 cerebral infarction patients and 20 age- and sex-matched healthy controls. Compared with resting state, the coupling strength from ABP to Δ [O2Hb] oscillations was significantly lower in the bilateral prefrontal cortex (PFC), sensorimotor cortex (SMC), and temporal lobe cortex (TLC) during the ISPC intervention in cerebral infarction patients in interval II. Additionally, the coupling strength was significantly lower in the bilateral SMC in both groups in interval III. These findings indicate that ISPC intervention may facilitate cerebral circulation in the bilateral PFC, SMC, and TLC in cerebral infarction patients. ISPC may promote motor function recovery through its positive influences on motor-related networks. Furthermore, the coupling between Δ [O2Hb] and ABP allows non-invasive assessments of autoregulatory function to quantitatively assess the effect of rehabilitation tasks and to guide therapy in clinical situations.

To reveal the physiological mechanism of the cognitive decline in subjects with hypertension, the functional connectivity (FC) was assessed by using the wavelet phase coherence (WPCO), and effective connectivity (EC) was assessed by using the coupling strength (CS) of near-infrared spectroscopy (NIRS) signals. NIRS signals were continuously recorded from the prefrontal cortex, sensorimotor cortex, and occipital lobes of 13 hypertensive patients (hypertension group, 70 ± 6.5 years old) and 16 elderly healthy subjects (control group, 71 ± 5.5 years old) in resting and standing periods. WPCO and CS were calculated in four frequency intervals: I, 0.6–2; II, 0.145–0.6; III, 0.052–0.145; and IV, 0.021–0.052 Hz. CS quantifies coupling amplitude. In comparison with the control group, the hypertension group showed significantly decreased (p < 0.05) WPCO and CS in intervals III and IV and in the resting and standing states. WPCO and CS were significantly decreased in the resting state compared with those in the standing state in the hypertension group (p < 0.05). Decreased WPCO and CS indicated a reduced network interaction, suggesting disturbed neurovascular coupling in subjects with hypertension. Compared with the control group, the hypertension group showed significantly lower Mini-Mental State Examination (MMSE) (p = 0.028) and Montreal Cognitive Assessment (MoCA) scores (p = 0.011). In the hypertension group, correlation analysis showed that WPCO and CS were significantly positively correlated with MMSE and MoCA scores, respectively. These findings may provide evidence of impaired cognitive function in hypertension and can enhance the understanding on neurovascular coupling.

This study aims to assess the posture-related changes in frequency-specific effective connectivity (EC) in elderly subjects by coupling function measured using functional near-infrared spectroscopy (fNIRS). The fNIRS signals were continuously recorded from the bilateral prefrontal cortex (PFC), motor cortex (MC), and occipital lobe (OL) in 17 healthy elderly and 19 healthy young subjects during sitting and standing states. EC was calculated based on Dynamic Bayesian inference in one low frequency interval I: 0.052–0.145 Hz and one very low frequency interval II: 0.021–0.052 Hz. Results show that in response to posture change, the coupling strength significantly increased in interval I of the young group from right PFC to MC (p < 0.05). Meanwhile, the coupling strength of the elderly group was significantly increased in interval II from the left PFC to right PFC (p = 0.008) and to left MC (p = 0.031) in the standing state as compared with that in the sitting state. Compared with that of the young group, the coupling strength of the elderly group was significantly decreased (p < 0.05) between the right PFC and left PFC in interval I and from PFC and OL to MC in interval II during the sitting state. The decreased EC in interval I was also positively correlated with cognitive scores in the elderly group. In addition, the coupling strength from MC to PFC in interval II during standing state was significantly increased in elderly subjects as compared with that in the young group. These results revealed the age-related changes in reorganization of interregional interactions for different postures. These findings may provide evidence of impaired cognitive function in the elderly and can deepen the understanding on age-related changes in neurovascular coupling.

Cerebral autoregulation (CA) is the complex homeostatic regulatory relationship between blood pressure (BP) and cerebral blood flow (CBF). This study aimed to analyze the frequency-specific coupling function between cerebral oxyhemoglobin concentrations (delta [HbO2]) and mean arterial pressure (MAP) signals based on a model of coupled phase oscillators and dynamical Bayesian inference. Delta [HbO2] was measured by 24-channel near-infrared spectroscopy (NIRS) and arterial BP signals were obtained by simultaneous resting-state measurements in patients with stroke, that is, 9 with left hemiparesis (L-H group), 8 with right hemiparesis (R-H group), and 17 age-matched healthy individuals as control (healthy group). The coupling functions from MAP to delta [HbO2] oscillators were identified and analyzed in four frequency intervals (I, 0.6-2 Hz; II, 0.145-0.6 Hz; III, 0.052-0.145 Hz; and IV, 0.021-0.052 Hz). In L-H group, the CS from MAP to delta [HbO2] in interval III in channel 8 was significantly higher than that in healthy group (p = 0.003). Compared with the healthy controls, the coupling in MAP→delta [HbO2] showed higher amplitude in interval I and IV in patients with stroke. The increased CS and coupling amplitude may be an evidence of impairment in CA, thereby confirming the presence of impaired CA in patients with stroke. In interval III, the CS in L-H group from MAP to delta [HbO2] in channel 16 (p = 0.001) was significantly lower than that in healthy controls, which might indicate the compensatory mechanism in CA of the unaffected side in patients with stroke. No significant difference in region-wise CS between affected and unaffected sides was observed in stroke groups, indicating an evidence of globally impaired CA. These findings provide a method for the assessment of CA and will contribute to the development of therapeutic interventions in stroke patients.

Driving a vehicle is a complex activity that requires high-level brain functions. This study aimed to assess the change in effective connectivity (EC) between the prefrontal cortex (PFC), motor-related areas (MA) and vision-related areas (VA) in the brain network among the resting, simple-driving and car-following states. Twelve young male right-handed adults were recruited to participate in an actual driving experiment. The brain delta [HbO2] signals were continuously recorded using functional near infrared spectroscopy (fNIRS) instruments. The conditional Granger causality (GC) analysis, which is a data-driven method that can explore the causal interactions among different brain areas, was performed to evaluate the EC. The results demonstrated that the hemodynamic activity level of the brain increased with an increase in the cognitive workload. The connection strength among PFC, MA and VA increased from the resting state to the simple-driving state, whereas the connection strength relatively decreased during the car-following task. The PFC in EC appeared as the causal target, while the MA and VA appeared as the causal sources. However, l-MA turned into causal targets with the subtask of car-following. These findings indicate that the hemodynamic activity level of the cerebral cortex increases linearly with increasing cognitive workload. The EC of the brain network can be strengthened by a cognitive workload, but also can be weakened by a superfluous cognitive workload such as driving with subtasks.

The present study aimed to evaluate the functional connectivity (FC) in relevant cortex areas during simulated driving with distraction based on functional near-infrared spectroscopy (fNIRS) method. Twelve subjects were recruited to perform three types of driving tasks, namely, straight driving, straight driving with secondary auditory task, and straight driving with secondary visual vigilance task, on a driving simulator. The wavelet amplitude (WA) and wavelet phase coherence (WPCO) of the fNIRS signals were calculated in six frequency intervals: I, 0.6-2 Hz; II, 0.145-0.6 Hz; III, 0.052-0.145 Hz; IV, 0.021-0.052 Hz; and V, 0.0095-0.021 Hz, VI, 0.005-0.0095Hz. Results showed that secondary tasks during driving led to worse driving performance, brain activity changes, and dynamic configuration of the connectivity. The significantly lower WA value in the right motor cortex in interval IV, and higher WPCO values in intervals II, V, and VI were found with additional auditory task. Significant standard deviation of speed and lower WA values in the left prefrontal cortex and right prefrontal cortex in interval VI, and lower WPCO values in intervals I, IV, V, and VI were found under the additional visual vigilance task. The results suggest that the changed FC levels in intervals IV, V, and VI were more likely to reflect the driver's distraction condition. The present study provides new insights into the relationship between distracted driving behavior and brain activity. The method may be used for the evaluation of drivers' attention level.