Effective Connectivity of Cortical Sensorimotor Networks During Finger Movement Tasks: A Simultaneous fNIRS,fMRI, EEG Study

Recently, interest has been growing to understand the underlying dynamic directional relationship between simultaneously activated regions of the brain during motor task performance. Such directionality analysis (or effective connectivity analysis), based on non-invasive electrophysiological (electroencephalography—EEG) and hemodynamic (functional near infrared spectroscopy—fNIRS; and functional magnetic resonance imaging—fMRI) neuroimaging modalities can provide an estimate of the motor task-related information flow from one brain region to another. Since EEG, fNIRS and fMRI modalities achieve different spatial and temporal resolutions of motor-task related activation in the brain, the aim of this study was to determine the effective connectivity of cortico-cortical sensorimotor networks during finger movement tasks measured by each neuroimaging modality. Nine healthy subjects performed right hand finger movement tasks of different complexity (simple finger tapping-FT, simple finger sequence-SFS, and complex finger sequence-CFS). We focused our observations on three cortical regions of interest (ROIs), namely the contralateral sensorimotor cortex (SMC), the contralateral premotor cortex (PMC) and the contralateral dorsolateral prefrontal cortex (DLPFC). We estimated the effective connectivity between these ROIs using conditional Granger causality (GC) analysis determined from the time series signals measured by fMRI (blood oxygenation level-dependent-BOLD), fNIRS (oxygenated-O₂Hb and deoxygenated-HHb hemoglobin), and EEG (scalp and source level analysis) neuroimaging modalities. The effective connectivity analysis showed significant bi-directional information flow between the SMC, PMC, and DLPFC as determined by the EEG (scalp and source), fMRI (BOLD) and fNIRS (O₂Hb and HHb) modalities for all three motor tasks. However the source level EEG GC values were significantly greater than the other modalities. In addition, only the source level EEG showed a significantly greater forward than backward information flow between the ROIs. This simultaneous fMRI, fNIRS and EEG study has shown through independent GC analysis of the respective time series that a bi-directional effective connectivity occurs within a cortico-cortical sensorimotor network (SMC, PMC and DLPFC) during finger movement tasks.     

Isolating the sources of widespread physiological fluctuations in functional near-infrared spectroscopy signals

Physiological fluctuations at low frequency (<0.1 Hz) are prominent in functional near-infrared spectroscopy (fNIRS) measurements in both resting state and functional task studies. In this study, we used the high spatial resolution and full brain coverage of functional magnetic resonance imaging (fMRI) to understand the origins and commonalities of these fluctuations. Specifically, we applied a newly developed method, regressor interpolation at progressive time delays, to analyze concurrently recorded fNIRS and fMRI data acquired both in a resting state study and in a finger tapping study. The method calculates the voxelwise correlations between blood oxygen level dependent (BOLD) fMRI and fNIRS signals with different time shifts and localizes the areas in the brain that highly correlate with the fNIRS signal recorded at the surface of the head. The results show the wide spatial distribution of this physiological fluctuation in BOLD data, both in task and resting states. The brain areas that are highly correlated with global physiological fluctuations observed by fNIRS have a pattern that resembles the venous system of the brain, indicating the blood fluctuation from veins on the brain surface might strongly contribute to the overall fNIRS signal.     

用于疼痛感知与评估的功能性近红外光谱成像研究进展

疼痛是一种涉及感觉、运动和认知的复杂体验。传统的疼痛评估方法有主观偏倚性较强的特点,但激发了人们对客观疼痛评估成像技术的兴趣。研究表明,在体时大脑痛觉可被定量评估,其中的功能性近红外光谱(fNIRS)技术,因其具有时间分辨率高、成本低、便携等特点,及其可在复杂临床环境中可实时观测疼痛的优势,已被疼痛研究所关注。为了进一步揭示疼痛在临床环境中的潜在皮质作用机制,以构建优化的实验范式设计为基础,综述了与疼痛相关的脑部区域、fNIRS探针定位和数据处理算法的研究进展,特别是现有fNIRS技术在疼痛研究中的主要发现;探讨fNIRS成像与人工智能算法相结合用于疼痛研究和客观评估的相关进展,并对未来发展方向和尚待优化的问题提出建议。     

Neural activation in cognitive motor processes: comparing motor imagery and observation of gymnastic movements

The simulation concept suggested by Jeannerod (Neuroimage 14:S103-S109, 2001) defines the S-states of action observation and mental simulation of action as action-related mental states lacking overt execution. Within this framework, similarities and neural overlap between S-states and overt execution are interpreted as providing the common basis for the motor representations implemented within the motor system. The present brain imaging study compared activation overlap and differential activation during mental simulation (motor imagery) with that while observing gymnastic movements. The fMRI conjunction analysis revealed overlapping activation for both S-states in primary motor cortex, premotor cortex, and the supplementary motor area as well as in the intraparietal sulcus, cerebellar hemispheres, and parts of the basal ganglia. A direct contrast between the motor imagery and observation conditions revealed stronger activation for imagery in the posterior insula and the anterior cingulate gyrus. The hippocampus, the superior parietal lobe, and the cerebellar areas were differentially activated in the observation condition. In general, these data corroborate the concept of action-related S-states because of the high overlap in core motor as well as in motor-related areas. We argue that differential activity between S-states relates to task-specific and modal information processing.     

Influence of muscle activity on brain oxygenation during verbal fluency assessed with functional near-infrared spectroscopy

A large part of the literature of functional near-infrared spectroscopy (fNIRS) deals with overt verbal fluency. It has been claimed that fNIRS has a low susceptibility to movement related artefacts as, for example, associated with overt speech. However, so far, no study has investigated this assumption in an experimental design. Therefore, we examined a group of 16 healthy subjects during performance of two verbal fluency tasks (experiment 1: phonological fluency; experiment 2: semantical fluency, paced answers, pronouncing vs. writing). We measured changes of oxygenated (O₂Hb) and deoxygenated haemoglobin (HHb) over fronto-temporal (brain) areas via fNIRS, while temporalis muscle activity was simultaneously assessed by means of electromyography (EMG). Statistical analyses indicated comparable word production, higher increases of O₂Hb and higher decreases of HHb over fronto-temporal areas during word fluency in contrast to the control task weekday reciting. This fNIRS pattern indicates fluency related activation and was found for pronouncing and for writing in both experiments. Regarding the EMG data, fluency related activity was only found for pronouncing, not for writing. Thus, muscle activity cannot account for fluency related fNIRS activity during writing. Additionally, correlation analyses showed no systematic associations of fNIRS and EMG signals. In conclusion, we found arguments that fNIRS actually allows for the measurement of brain activity over fronto-temporal areas during verbal fluency. Nonetheless, further studies should evaluate more direct associations between fNIRS and EMG signals by specific experimental manipulations and data analysing approaches that allow dealing fNIRS and EMG raw data simultaneously.     

Motor Cortex Activity During Functional Motor Skills: An fNIRS Study

Assessments of brain activity during motor task performance have been limited to fine motor movements due to technological constraints presented by traditional neuroimaging techniques, such as functional magnetic resonance imaging. Functional near-infrared spectroscopy (fNIRS) offers a promising method by which to overcome these constraints and investigate motor performance of functional motor tasks. The current study used fNIRS to quantify hemodynamic responses within the primary motor cortex in twelve healthy adults as they performed unimanual right, unimanual left, and bimanual reaching, and stepping in place. Results revealed that during both unimanual reaching tasks, the contralateral hemisphere showed significant activation in channels located approximately 3 cm medial to the C3 (for right-hand reach) and C4 (for left-hand reach) landmarks. Bimanual reaching and stepping showed activation in similar channels, which were located bilaterally across the primary motor cortex. The medial channels, surrounding Cz, showed significantly higher activations during stepping when compared to bimanual reaching. Our results extend the viability of fNIRS to study motor function and build a foundation for future investigation of motor development in infants during nascent functional behaviors and monitor how they may change with age or practice.     

Acute moderate exercise enhances compensatory brain activation in older adults

A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation.     

The effects of APOE on brain activity do not simply reflect the risk of Alzheimer's disease

Possession of the APOE-ε4 allele is the best established genetic risk factor for sporadic Alzheimer's disease (AD), while the ε2 allele may confer protection against the disease. Previous functional magnetic resonance imaging (fMRI) studies have shown an effect of APOE genotype on brain function, typically by comparing only ε4 carriers with noncarriers. Here we included a wide range of genotype groups to determine how closely the effects of APOE on brain function are related to differences in relative risk for AD. We used functional magnetic resonance imaging (fMRI) to compare the pattern of activation during an episodic encoding task and during a counting Stroop task in 76 adults, aged 32 to 55, with different APOE genotypes (23 ε2/ε3, 20 ε3/ε3, 26 ε3/ε4, and 7 ε4/ε4). Strikingly, participants with an increased risk (ε4 carriers) and with a decreased risk (ε2 carriers) for AD both showed increased activation, relative to ε3 homozygotes, during both tasks. The increased activation was due to decreased deactivation or paradoxical activation of nontask-related regions of the brain, which suggests an intrinsic effect of APOE on the differentiation of functional cortical networks. These results question the often assumed link between APOE, the blood oxygenation level dependent (BOLD) response, and AD risk.     

Activation in ventro-lateral prefrontal cortex during the act of tasting: An fNIRS study

The act of tasting is the product of inseparable integrative behavior consisting of multi-sensory processing and orolingual motor coordination. Often tasting-induced brain activity is looked at in a reductionist manner as a set of isolated components. However, brain activity as a whole during tasting may not simply be the sum of isolated brain responses; therefore, attempting to look at the cortical activation in a more holistic manner is important. Using functional near-infrared spectroscopy (fNIRS), we assessed cortical responses during tasting, contrasting observed neuronal activation of the lateral prefrontal cortex (LPFC), of 19 healthy participants before and during tasting of 8 ml of sweet-based solutions. To examine the activated brain structure, we estimated the anatomical regions of the measured location in standard brain space. We also included simple tongue tapping movement (TT) and word fluency (WF) tasks as comparative functional markers. Significant activity was found in channels (CHs) estimated to be in the bilateral oral motor areas during the TT task, and those in the LPFC, primarily in the left hemisphere, during the WF task. During the tasting task, significant activation was observed in CHs estimated to lie in the ventral part of pre- and post-central gyri as well as in the ventro-LPFC (VLPFC). The activated regions partly overlapped with those detected during TT or WF tasks, but extended more anteriorly and ventrally. Our study suggests that, in addition to tongue motor areas, the VLPFC is involved in the act of tasting.     

Removal of the skin blood flow artifact in functional near-infrared spectroscopic imaging data through independent component analysis

We investigate whether the functional near-infrared spectroscopic (fNIRS) signal includes a signal from the changing skin blood flow. During a locomotor task on a treadmill, changes in the hemodynamic response in the front-parietal area of healthy human subjects are simultaneously recorded using an fNIRS imaging system and a laser Doppler tissue blood flow meter. Independent component analysis (ICA) for fNIRS signals is performed. The skin blood flow changes during locomotor tasks on a treadmill. The activated spatial distribution of one of the components separated by ICA reveals an overall increase in fNIRS channels. To evaluate the uniformity of the activated spatial distribution, we define a new statistical value-the coefficient of spatial uniformity (CSU). The CSU value is a highly discriminating value (e.g., 2.82) compared with values of other components (e.g., 1.41, 1.10, 0.96, 0.61, and 0.58). In addition, the independent component signal corresponding to the activated spatial distribution is similar to changes in skin blood flow measured with the laser Doppler tissue blood flow meter. The coefficient of correlation indicates strong correlation. Localized activation areas around the premotor and medial somatosensory cortices are shown more clearly by eliminating the extracted component.     

Analysis of “task-positive” and “task-negative” functional networks during the performance of the Symbol Digit Modalities Test in patients at presentation with clinically isolated syndrome suggestive of multiple sclerosis

An abnormal pattern of brain activations has been shown in patients with multiple sclerosis during the performance of several cognitive tasks. The aim of this study is to investigate abnormalities of the patterns of activation/deactivation in the functional networks related to “task-positive” and “task-negative” events during the execution of the Symbol Digit Modalities Test (SDMT) in patients with clinically isolated syndromes (CIS) and preserved cognitive abilities. Eighteen CIS patients within 3 months from their first clinical attack and 15 healthy controls (HC) underwent neuropsychological assessment and performed an adapted functional magnetic resonance imaging (fMRI) version of the SDMT. “Task-positive” responses to task execution and “task-negative” activity of the default mode network were compared between groups. A regression analysis was performed to investigate the correlation between fMRI results and T2 lesion load (T2 LL) and brain atrophy. Neuropsychological performance did not differ between groups. Compared to HC, CIS patients exhibited an enhanced deactivation of the “task-negative” network at the level of the posterior cingulate cortex, whereas no differences between groups were found when the patterns of “task-positive” events were compared. A regression analysis detected a correlation (p < 0.001,r ranging from 0.62 to 0.73) between T2 LL and “task-positive” activations of areas that are part of the attention network, comprising the anterior cingulate gyrus, left prefrontal gyrus and inferior parietal lobe. No correlation was found between patterns of functional modifications and brain atrophy. CIS patients experience an enhanced pattern of brain deactivations during cognitive performances, which might contribute to their normal neuropsychological status.     

Circadian variability is negligible in primary visual cortices as measured by fNIRS.

Neural activation leads to an increase of regional cerebral blood flow. Most of the functional imaging studies implicitly assume that variability of the hemodynamic response throughout a single day is negligible. To test this assumption we measured brain activation by functional near-infrared spectroscopy (fNIRS) in the visual cortex of ten subjects six times throughout the day, from 0800-1800 h, during an event-related checkerboard paradigm. Concentration of oxygenated hemoglobin increased, whereas concentration of deoxygenated hemoglobin decreased at each time point examined, without significant influences of daytime. Variability of the hemodynamic response was higher across subjects than for single subjects across day. In conclusion, our study is the first one supporting the common practice of ignoring circadian variability in functional imaging studies.     

Optical Mapping of Brain Activation and Connectivity in Occipitotemporal Cortex During Chinese Character Recognition

In this study, functional near-infrared spectroscopy (fNIRS) was used to examine the brain activation and connectivity in occipitotemporal cortex during Chinese character recognition (CCR). Eighteen healthy participants were recruited to perform a well-designed task with three categories of stimuli (real characters, pseudo characters, and checkerboards). By inspecting the brain activation difference and its relationship with behavioral data, the left laterality during CCR was clearly identified in the Brodmann area (BA) 18 and 19. In addition, our novel findings also demonstrated that the bilateral superior temporal gyrus (STG), bilateral BA 19, and left fusiform gyrus were also involved in high-level lexical information processing such as semantic and phonological ones. Meanwhile, by examining functional brain networks, we discovered that the right BA 19 exhibited enhanced brain connectivity. In particular, the connectivity in the right fusiform gyrus, right BA 19, and left STG showed significant correlation with the performance of CCR. Consequently, the combination of fNIRS technique with functional network analysis paves a new avenue for improved understanding of the cognitive mechanism underlying CCR.     

Age-related changes in prefrontal activity during walking in dual-task situations: A fNIRS study

Background

Previous studies suggest that the human gait is under control of higher-order cognitive processes, located in the frontal lobes, such that an age-related degradation of cognitive capabilities has a negative impact on gait.

Methods

Using functional Near-Infrared-Spectroscopy (fNIRS) we investigate the frontocortical hemodynamic correlates of dual-task walking in two conditions. 15 young and 10 older individuals walked on a treadmill while completing concurrent tasks that had either visual (checking) or verbal-memory (alphabet recall) demands. We compared subjects' motor performance, as well as their prefrontal activity in single- and dual-task walking.

Results

Our behavioral data partly confirm previous accounts on higher dual-task costs in stepping parameters (i.e., decreased step duration) in old age, particularly with a visual task and negative dual-task cost (i.e., improved performance) during the verbal task in young adults. Functional imaging data revealed little change of prefrontal activation from single- to dual-task walking in young individuals. In the elderly, however, prefrontal activation substantially decreased during dual-task walking with a complex visual task.

Conclusion

We interpret these findings as evidence for a shift of processing resources from the prefrontal cortex to other brain regions when seniors face the challenge of walking and concurrently executing a visually demanding task.     

Comparable fMRI activity with differential behavioural performance on mental rotation and overt verbal fluency tasks in healthy men and women

To explicate the neural correlates of sex differences in visuospatial and verbal fluency tasks, we examined behavioural performance and blood-oxygenation-level-dependent (BOLD) regional brain activity, using functional magnetic resonance imaging, during a three-dimensional (3D) mental rotation task and a compressed sequence overt verbal fluency task in a group of healthy men (n=9) and women (n=10; tested during the low-oestrogen phase of the menstrual cycle). Men outperformed women on the mental rotation task, and women outperformed men on the verbal fluency task. For the mental rotation task, men and women activated areas in the right superior parietal lobe and the bilateral middle occipital gyrus in association with the rotation condition. In addition, men activated the left middle temporal gyrus and the right angular gyrus. For verbal fluency, men activated areas in the bilateral superior frontal gyrus, right cingulate gyrus, left precentral gyrus, left medial frontal gyrus, left inferior frontal gyrus, thalamus, left parahippocampal gyrus and bilateral lingual gyrus, and women activated areas in the bilateral inferior frontal gyrus and left caudate. Despite observing task related activation in the hypothesised areas in men and women, no areas significantly differentiated the two sexes. Our results demonstrate comparable brain activation in men and women in association with mental rotation and verbal fluency function with differential performance, and provide support for sex differences in brain–behaviour relationships.     

Figural memory performance and functional magnetic resonance imaging activity across the adult lifespan

We examined performance and functional magnetic resonance imaging activity in participants (n = 235) aged 17–81 years on a nonverbal recognition memory task, figural memory. Reaction time, error rate, and response bias measures indicated that the youngest and oldest participants were faster, made fewer errors, and showed a more conservative response bias than participants in the median age ranges. Encoding and Recognition phases activated a distributed bilateral network encompassing prefrontal, subcortical, lateral, and medial temporal and occipital regions. Activation during Encoding phase did not correlate with age. During Recognition, task-related activation for correctly identified targets (Hit-Targets) correlated linearly positively with age; nontask related activity correlated negative quadratically with age. During correctly identified distractors (Hit-Distractors) activity in task-related regions correlated positive linearly with age, nontask activity showed positive and negative quadratic relationships with age. Missed-Targets activity did not correlate with age. We concluded that figural memory performance and functional magnetic resonance imaging activity during Recognition but not Encoding was affected both by continued maturation of the brain in the early 20s and compensatory recruitment of additional brain regions during recognition memory in old age.     

Social Inclusion Enhances Biological Motion Processing: A Functional Near-Infrared Spectroscopy Study

Humans are especially tuned to the movements of other people. Neural correlates of this social attunement have been proposed to lie in and around the right posterior superior temporal sulcus (STS) region, which robustly responds to biological motion in contrast to a variety of non-biological motions. This response persists even when no form information is provided, as in point-light displays (PLDs). The aim of the current study was to assess the ability of functional near-infrared spectroscopy (fNIRS) to reliably measure brain responses to PLDs of biological motion, and determine the sensitivity of these responses to interpersonal contextual factors. To establish reliability, we measured brain activation to biological motion with fNIRS and functional magnetic resonance imaging (fMRI) during two separate sessions in an identical group of 12 participants. To establish sensitivity, brain responses to biological motion measured with fNIRS were subjected to an additional social manipulation where participants were either socially included or excluded before viewing PLDs of biological motion. Results revealed comparable brain responses to biological motion using fMRI and fNIRS in the right supramarginal gyrus. Further, social inclusion increased brain responses to biological motion in right supramarginal gyrus and posterior STS. Thus, fNIRS can reliably measure brain responses to biological motion and can detect social experience-dependent modulations of these brain responses.     

Automatic schizophrenic discrimination on fNIRS by using complex brain network analysis and SVM

Background

Schizophrenia is a kind of serious mental illness. Due to the lack of an objective physiological data supporting and a unified data analysis method, doctors can only rely on the subjective experience of the data to distinguish normal people and patients, which easily lead to misdiagnosis. In recent years, functional Near-Infrared Spectroscopy (fNIRS) has been widely used in clinical diagnosis, it can get the hemoglobin concentration through the variation of optical intensity.

Methods

Firstly, the prefrontal brain networks were constructed based on oxy-Hb signals from 52-channel fNIRS data of schizophrenia and healthy controls. Then, Complex Brain Network Analysis (CBNA) was used to extract features from the prefrontal brain networks. Finally, a classier based on Support Vector Machine (SVM) is designed and trained to discriminate schizophrenia from healthy controls. We recruited a sample which contains 34 healthy controls and 42 schizophrenia patients to do the one-back memory task. The hemoglobin response was measured in the prefrontal cortex during the task using a 52-channel fNIRS system.

Results

The experimental results indicate that the proposed method can achieve a satisfactory classification with the accuracy of 85.5%, 92.8% for schizophrenia samples and 76.5% for healthy controls. Also, our results suggested that fNIRS has the potential capacity to be an effective objective biomarker for the diagnosis of schizophrenia.

Conclusions

Our results suggested that, using the appropriate classification method, fNIRS has the potential capacity to be an effective objective biomarker for the diagnosis of schizophrenia.

     

The claustrum/insula region integrates conceptually related sounds and pictures

The brain is able to create coherent percepts from multisensory input. This phenomenon, known as multisensory integration (MSI), is a ubiquitous feature of everyday life and has been found to be essential for a reliable interaction with the environment. Recent functional neuroimaging studies suggest that several different networks are engaged in various forms of MSI depending on the nature of information being integrated. However, little is known about the neural basis of a fundamental form of MSI in natural conditions; integration of common auditory and visual objects which are conceptually related, such as when we look at a cat and hear a meowing sound. Here we used event-related fMRI to compare the brain response to conceptually related and unrelated pairs of audio-visual stimuli denoting common objects. Our protocol was designed to preclude contamination of the results by cognitive processes additional to those needed for MSI. The results indicate that higher-order temporal and occipital areas respond to coincident sounds and pictures regardless of their semantic relationship; whereas, the right claustrum/insula region is differentially activated in association with multisensory integration of conceptually related common objects. This observation has important implications for understanding how multimodal information about common objects is represented in the brain.     

Human cerebellum plays an important role in memory-timed finger movement: an fMRI study

The purpose of this study was to determine, by using functional magnetic resonance imaging, the areas of the brain activated during a memory-timed finger movement task and compare these with those activated during a visually cued movement task. Because it is likely that subjects engage in subvocalization associated with chronometric counting to achieve accurate timing during memory-timed movements, the authors sought to determine the areas of the brain activated during a silent articulation task in which the subjects were instructed to reproduce the same timing as for the memory-timed movement task without any lip movements or vocalization. The memory-timed finger movement task induced activation of the anterior lobe of the cerebellum (lobules IV and V) bilaterally, the contralateral primary motor area, the supplementary motor area (SMA), the premotor area (PMA), the prefrontal cortex, and the posterior parietal cortex bilaterally, compared with the resting condition. The same areas in the SMA and left prefrontal cortex were activated during the silent articulation task compared with the resting condition. The anterior lobe of the cerebellum on both sides was also activated during the silent articulation task compared with the resting condition, but these activations did not reach statistical significance (P < 0.05 corrected). In addition, the anterior cerebellum on both sides showed significant activation during the memory-timed movement task when compared with the visually cued finger movement task. The visually cued finger movement task specifically activated the ipsilateral PMA and the intraparietal cortex bilaterally. The results indicate that the anterior lobe of the cerebellum of both sides, the SMA, and the left prefrontal cortex were probably involved in the generation of accurate timing, functioning as a clock within the CNS, and that the dorsal visual pathway may be involved in the generation of visually cued movements.