Reduced frontal functional asymmetry in schizophrenia during a cued continuous performance test assessed with near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) allows noninvasive, in vivo measurement of changes in the concentrations of oxygenated hemoglobin (O2Hb) and deoxygenated hemoglobin (HHb) in brain tissue based on their distinctive optical properties. A previous NIRS investigation on healthy subjects (Fallgatter and Strik 1997) found indications of right frontal activation during a Continuous Performance Test (CPT) that are consistent with results from positron emission tomography (PET) and event-related potentials studies. The indications consisted of right frontal blood oxygenation changes, consistent with a hemodynamic response, along with a significant left frontal increase in HHb. The current study investigated whether this characteristic lateralized frontal NIRS activation pattern was present in a group of nine schizophrenia patients during the execution of a CPT. In contrast to the previous study, no overall or hemispheric activation effects were found in the schizophrenia subjects. Direct comparison of the results of the two studies confirmed group differences, with a lack of lateralized activation in schizophrenia patients. Furthermore, a trend of higher left/right HHb ratios at rest and during activation was found in patients with schizophrenia. The finding is interpreted as a sign of reduced specific lateralized frontal reactivity, possibly based on a left hemisphere functional deficit.     

Between-brain coherence during joint n-back task performance: A two-person functional near-infrared spectroscopy study

The present study aimed to step into two-person neuroscience by investigating the hemodynamic correlates of between-brain connectivity during joint task performance. To test this approach, wireless functional near-infrared spectroscopy (fNIRS) was used to record brain signals during performance of a dual n-back task simultaneously in paired players as compared to single players. Evaluating functional connectivity between the paired players' brains using wavelet transform coherence (WTC) analysis revealed (1) a significant increase in between-brain coherence during joint task performance as compared to baseline condition. These patterns were observed in two frequency bands, i.e. in the heart rate (HR) frequency and in low-frequency oscillations (LFOs). (2) Averaged hemodynamic responses revealed larger responses in total hemoglobin concentration changes [tHb] for the paired players as compared to the single players; in addition, within the paired players groups joint task performance revealed larger changes in [tHb] as compared to a rest period and to a baseline condition. (3) No increase in behavioral performance was found in the paired players as compared to the single players. Our findings designate fNIRS as suitable tool for monitoring interpersonal performances between two subjects. The results show that two-person performance leads to relevant and significant effects, which are detectable using between-brain connectivity analysis. Using this approach can provide additional insight into interpersonal activation patterns not detectable using typical one-person experiments. Our study demonstrates the potential of simultaneously assessing cerebral hemodynamic responses for various two-person experimental paradigms and research areas where interpersonal performances are involved.     

Depression mediates the association between insula‐frontal functional connectivity and social interaction anxiety

High rates of comorbidity between depression and anxiety are frequently observed. However, few studies have investigated the relationship between depression and social interaction anxiety using a dimensional approach. The current study aimed to explore the associations between depression and social interaction anxiety with a multivariate approach in a comparably large dataset (n = 194, 95 males). All participants completed a structural and a resting‐state functional magnetic resonance imaging (fMRI) scan and self‐report measures of depression via Beck''s Depression Inventory II and social interaction anxiety by social interaction anxiety scale. Voxel‐based morphometry (VBM) results first identified grey matter volumes of insula were positively correlated with depression dimension scores. Next, whole brain seed‐to‐voxel analyses were conducted using a VBM‐identified insula as a seed region to examine associations between depression/social anxiety and functional connectivity. The results suggested that a significant positive effect of depression/social anxiety was found on the connectivity between insula and dorsal lateral prefrontal cortex (dlPFC). Moreover, variations in depression meditated the association between insula‐dlPFC connectivity and social interaction anxiety. Overall, the results indicate that individual differences in depression relate more to insula‐dlPFC coupling compared to social interaction anxiety.     

Perception of arousal in social anxiety: effects of false feedback during a social interaction

Cognitive models suggest that during social interactions, socially anxious individuals direct their attention to internal cues of arousal and use this information to erroneously infer how they appear to others. High (N=36) and low (N=36) socially anxious adults had a conversation with a stooge, and were led to believe by false feedback that they were experiencing either an increase or decrease in arousal, or evaluating the comfort level of the feedback equipment. Compared to the other groups, participants who believed their arousal had increased, reported greater anxiety, poorer perceived performance, more physical cues of anxiety, and greater underestimation of their performance and overestimation of the visibility of their anxiety. The effects were not specific to participants with high social anxiety. Observers rated the behaviour of participants who believed that their arousal had decreased most favourably. The results have implications for the treatment of social phobia.     

Understanding inverse oxygenation responses during motor imagery: a functional near-infrared spectroscopy study

Motor imagery (MI) is described as the mental rehearsal of voluntary movements. We used wireless functional near-infrared spectroscopy (fNIRS) recorded over secondary motor areas during performance of MI and motor execution (ME) in 11 healthy subjects, who either executed or imagined two drawing tasks differing in shape and frequency, i.e. simple (circle, 0.2 Hz) and complex (curved shape, 0.333 Hz). At the group level, results showed that fNIRS is capable of discriminating between the task mode, i.e. MI vs. ME, and the task complexity, i.e. simple vs. complex. At the single-subject level, we observed inverse oxygenation responses, i.e. a decrease in Δ[O(2) Hb] and/or increase in Δ[HHb]. These inverse responses only occurred during MI tasks and were highly correlated, in the first place, with task mode, and secondly with task complexity. Inverse Δ[O(2) Hb] responses are likely to reflect individual differences in performance-related signals and may contribute to the commonly observed inter-subject variability in fNIRS measurements. As MI is now widely used as a mental task in neurorehabilitative applications, the resulting oxygenation pattern may be of use for future developments. For this programme to be successful it is crucial to determine the sources of inter-subject variability. Our study presents a first effort in this direction, indicating that MI-related inverse Δ[O(2) Hb] responses are correlated, first, with task mode and, secondly, with task complexity.     

Inter-brain neural mechanism underlying turn-based interaction under acute stress in women: a hyperscanning study using functional near-infrared spectroscopy

With the ever-changing social environment, stress has exerted a substantial influence on social interaction. The present study examined the underlying cognitive and neural mechanism on how acute stress affected the real-time cooperative and competitive interaction with four hypothesized path models. We used the hyperscanning technique based on functional near-infrared spectroscopy (fNIRS) device to examine brain-to-brain coherence within the dyads engaging Pattern Game under acute stress manipulated through Trier Social Stress Test for Groups. Behavioral results showed stressed dyads exhibited better cooperative performance and higher self-other overlap level during the cooperative session than dyads in the control group. The fNIRS results identified higher interpersonal brain synchronization in the right temporal-parietal junction (r-TPJ) stronger Granger causality from partner-to-builder during the cooperative session in the stress group when compared with the control group. Our results corroborated better performance in the cooperative context and further identified that brain-to-brain coherence in r-TPJ and self-other overlap serially mediated the effect of acute stress on cooperative performance.     

Infant brain responses to social sounds: A longitudinal functional near-infrared spectroscopy study

Infants are responsive to and show a preference for human vocalizations from very early in development. While previous studies have provided a strong foundation of understanding regarding areas of the infant brain that respond preferentially to social vs. non-social sounds, how the infant brain responds to sounds of varying social significance over time, and how this relates to behavior, is less well understood. The current study uniquely examined longitudinal brain responses to social sounds of differing social-communicative value in infants at 3 and 6 months of age using functional near-infrared spectroscopy (fNIRS). At 3 months, infants showed similar patterns of widespread activation in bilateral temporal cortices to communicative and non-communicative human non-speech vocalizations, while by 6 months infants showed more similar, and focal, responses to social sounds that carried increased social value (infant-directed speech and human non-speech communicative sounds). In addition, we found that brain activity at 3 months of age related to later brain activity and receptive language abilities as measured at 6 months. These findings suggest areas of consistency and change in auditory social perception between 3 and 6 months of age.     

Decrease in prefrontal hemoglobin oxygenation during reaching tasks with delayed visual feedback: a near-infrared spectroscopy study

Visual feedback of hand movement is crucial to accurate reaching. Although previous studies have extensively examined spatial alteration of visual feedback (e.g., prism adaptation), temporal delay of visual feedback has been less explored. In the present study, we investigated the effect of delayed visual feedback of the moving hand in a reaching task. The prefrontal cortical activity was measured by near-infrared spectroscopy (NIRS). Twelve subjects performed reaching tasks under two conditions where visual feedback of their own hand was delayed by 200 ms (delay condition) or 0 ms (normal condition). Introducing the visual feedback delay significantly disrupted the reaching performance, although the subjects gradually adapted to the delay during the experiment. There was a clear tendency to overreach the target in the delay condition, even after the reaching movement had been practiced sufficiently in the normal condition. We observed marked oxy- and total-Hb decreases in the dorsal prefrontal area in the delay conditions. The decrease began shortly after task onset and diminished during the rest period, indicating that the decrease was task-induced. Furthermore, the oxy- and total-Hb decreases were significantly correlated with task performance--the degree of decrease was larger as the subject made more errors. We suggest that the decreases in oxy- and total-Hb at the dorsal prefrontal area are related with the visuomotor recalibration process.     

Developmental changes in frontal lobe function during a verbal fluency task: A multi-channel near-infrared spectroscopy study

Objective: Near-infrared spectroscopy (NIRS) is commonly used to investigate continuous changes of brain activation and has excellent time resolution. Verbal fluency task (VFT) is widely used as a neuropsychological test of frontal lobe function. The aim of this study was to investigate normal developmental change in frontal lobe function during VFT performance using multi-channel NIRS, specifically focusing on oxygenation hemoglobin (oxyHb) changes. Methods: The subjects were 9 adults and 37 childrens who were all healthy right-handed volunteers. Children were divided into four age groups (group A, 6–8 years; group B, 9–11 years; group C, 12–14 years; group D, 15–18 years). The [oxyHb] changes were measured with 22 channels of NIRS during VFT. We defined the frontopolar region as the region of interest for analysis, and calculated the Z-score to compare the data between groups. Results: The task performance changed with age. There were significant differences between group A and other groups. The Z-score of [oxyHb] also significantly increased with age, when comparing adults to groups A and B. The task performances decreased with time in all groups. In contrast, [oxyHb] only continued to increase in the adult group. Conclusion: The verbal retrieval functions begin to mature in early adolescence and continue to grow up to adulthood.     

Statistical segmentation of tone sequences activates the left inferior frontal cortex: a near-infrared spectroscopy study

Word segmentation, that is, discovering the boundaries between words that are embedded in a continuous speech stream, is an important faculty for language learners; humans solve this task partly by calculating transitional probabilities between sounds. Behavioral and ERP studies suggest that detection of sequential probabilities (statistical learning) plays an important role in the process of word segmentation. To identify the brain regions that are engaged during statistical segmentation of tone sequences, we measured changes in blood oxygenation using multichannel near-infrared spectroscopy (NIRS) while participants were exposed to continuous, nonlinguistic auditory sequences, the elements of which were organized into fixed "tone-words," but sequenced in random order. We habituated the participants to the tone-words by presenting the stimuli in a training phase prior to the presentation of the continuous tone sequences. After training, the statistical sequences, which included six tone-words, and the random sequences, which included 11 tones in random order, were presented alternately during NIRS recording. A large increase in the oxygenated hemoglobin concentration was observed in the left inferior frontal cortex (IFC) during the statistical sequence condition, but not during the random sequence condition. This suggests that the left IFC plays an important role in statistical segmentation of tone sequences, during which participants deploy the knowledge obtained in the training phase on the subsequent continuous sequence.     

Objective and perceived arousal during performance of tasks with elements of social threat: the influence of anxiety sensitivity

Background and objectives

Physiological arousal serves to maintain social anxiety disorder by skewing self-perception. Anxiety sensitivity is associated with the disorder and exaggerated perceptions of arousal, but has not been tested as explaining exaggerated perceived arousal in social contexts. The aim of this investigation was to address this issue.

Methods

A total of 42 individuals participated in three tasks associated with potential social threat (i.e., a speech, typing task, hyperventilation) and completed measures of trait social anxiety and anxiety sensitivity. State anxiety, perceived arousal, and objective arousal were assessed during each task.

Results

Trait social anxiety and anxiety sensitivity were correlated with state anxiety and perceived arousal, but not objective arousal, during the tasks. Anxiety sensitivity mediated the relationships between trait social anxiety and perceived arousal and between trait social anxiety and state anxiety for the typing and hyperventilation tasks.

Limitations

Although the sample likely included a number of individuals with social anxiety disorder, the sample was mostly comprised of individuals without a diagnosis. The current results can be extended to clinical presentations to some extent, but future research is needed to further explore the demonstrated relationships in samples of individuals with social anxiety disorder.

Conclusions

Anxiety sensitivity may play a crucial role in perceptions of arousal and state anxiety in the context of potential social threats, warranting attention from researchers and clinicians focussing on social anxiety disorder.     

Sex-related functional asymmetry of the amygdala: preliminary evidence using a case-matched lesion approach

We have reported previously that there appears to be an intriguing sex-related functional asymmetry of the prefrontal cortices, especially the ventromedial sector, in regard to social conduct, emotional processing, and decision-making, whereby the right-sided sector is important in men but not women and the left-sided sector is important in women but not men. The amygdala is another structure that has been widely implicated in emotion processing and social decision-making, and the question arises as to whether the amygdala, in a manner akin to what has been observed for the prefrontal cortex, might have sex-related functional asymmetry in regard to social and emotional functions. A preliminary test of this question was carried out in the current study, where we used a case-matched lesion approach and contrasted a pair of men cases and a pair of women cases, where in each pair one patient had left amygdala damage and the other had right amygdala damage. We investigated the domains of social conduct, emotional processing and personality, and decision-making. The results provide support for the notion that there is sex-related functional asymmetry of the amygdala in regard to these functions – in the male pair, the patient with right-sided amygdala damage was impaired in these functions, and the patient with left-sided amygdala damage was not, whereas in the female pair, the opposite pattern obtained, with the left-sided woman being impaired and the right-sided woman being unimpaired. These data provide preliminary support for the notion that sex-related functional asymmetry of the amygdala may entail functions such as social conduct, emotional processing, and decision-making, a finding that in turn could reflect (as either a cause or effect) differences in the manner in which men and women apprehend, process, and execute emotion-related information.     

Prefrontal brain activation during stop-signal response inhibition: an event-related functional near-infrared spectroscopy study

Previous lesion and neuroimaging studies have shown that the frontal lobes play an important role in response inhibition. In the present study event-related functional near-infrared spectroscopy (NIRS) was applied to investigate cerebral blood oxygenation in the right and left prefrontal cortex (PFC) in 15 male participants during the performance of a stop-change paradigm. Data analysis showed stronger brain activation in the left and right PFC during successful and failed stopping of initiated responses in comparison to a condition without stopping. Changes in cerebral blood oxygenation were more pronounced in the right than in the left PFC. No substantial activation changes were found during successful or failed changing of initiated responses (response inhibition and subsequent response re-engagement). The findings indicate that NIRS is suitable for the functional identification of prefrontal activation during the inhibition of initiated responses and provide further support for the contribution of the PFC to response inhibition.     

Noninvasive continuous monitoring of cerebral oxygenation periictally using near-infrared spectroscopy: a preliminary report

PURPOSE: To report on the use of near-infrared spectroscopy (NIRS) to examine the changes in cerebral oxygenation in the periictal period in patients with seizures. METHODS: Cerebral hemoglobin oxygen availability was monitored continuously and noninvasively with NIRS in three patients (one in the pediatric intensive care unit (ICU) and two in epilepsy-monitoring units) in conjunction with continuous EEG monitoring. Ictal events were recorded and compared with the pre-, intra-, and postictal periods for cerebral oxygen availability, as defined by oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and the redox state of cytochrome oxidase (cytox). RESULTS: Several important preliminary observations were made by using this technology. First, a preictal increase in cerebral oxygenation began between 1 and 2 h and >10 h before the ictal event. Second, despite adequate perfusion, based on an observed increased HbO2, reduction in cytox indicates a perfusion-metabolism mismatch during seizure activity. Third, continued seizure activity and even isolated ictal events were associated with decreased cerebral oxygen availability. Fourth, differences in cerebral oxygen availability were noted between different types of seizures (e.g., electrographic seizures were accompanied by rapid reductions in HbO2 and cerebral blood volume without reduction of cytox, whereas electroclinical seizures were characterized by marked increases in HbO2 with or without reduction of cytox). CONCLUSIONS: In this preliminary report on the use of NIRS for patients with seizures, we believe that NIRS allows continuous and noninvasive monitoring of changes in cerebral oxygenation periictally, thereby permitting investigations into the pathophysiology of seizures and the exploration of the potential of cerebral oximetry as a tool for seizure localization.     

Examination by near-infrared spectroscopy for evaluation of piano performance as a frontal lobe activation task

The purpose of this study was to reveal the activation of the frontal lobe in piano performance by the use of near-infrared spectroscopy. Participants wereseven healthy volunteer music college students. The results of the examination showed a tendency towards an increase in total hemoglobin volume over a wider area in the frontal part of the brain during an appropriate piano task compared with an easy piano task or the Keio version of the Wisconsin Card Sorting Test. The results suggest that piano performance is recognized as a frontal lobe-activating task and that performance of an appropriate piano task can be expected to elicit wider activation of the frontal lobe than an easy one.     

Cortical hemodynamic mechanisms of reversal learning using high-resolution functional near-infrared spectroscopy: A pilot study

ObjectivesReversal learning is widely used to analyze cognitive flexibility and characterize behavioral abnormalities associated with impulsivity and disinhibition. Recent studies using fMRI have focused on regions involved in reversal learning with negative and positive reinforcers. Although the frontal cortex has been consistently implicated in reversal learning, few studies have focused on whether reward and punishment may have different effects on lateral frontal structures in these tasks.MethodsDuring this pilot study on eight healthy subjects, we used functional near infra-red spectroscopy (fNIRS) to characterize brain activity dynamics and differentiate the involvement of frontal structures in learning driven by reward and punishment.ResultsWe observed functional hemispheric asymmetries between punishment and reward processing by fNIRS following reversal of a learned rule. Moreover, the left dorsolateral prefrontal cortex (l-DLPFC) and inferior frontal gyrus (IFG) were activated under the reward condition only, whereas the orbito-frontal cortex (OFC) was significantly activated under the punishment condition, with a tendency towards activation for the right cortical hemisphere (r-DLPFC and r-IFG). Our results are compatible with the suggestion that the DLPFC is involved in the detection of contingency change. We propose a new representation for reward and punishment, with left lateralization for the reward process.ConclusionsThe results of this pilot study provide insights into the indirect neural mechanisms of reversal learning and behavioral flexibility and confirm the use of fNIRS imaging in reversal-learning tasks as a translational strategy, particularly in subjects who cannot undergo fMRI recordings.     

Medial prefrontal cortex activity during the extinction of conditioned fear: an investigation using functional near-infrared spectroscopy

The majority of fear conditioning studies in humans have focused on fear acquisition rather than fear extinction. For this reason only a few functional imaging studies on fear extinction are available. A large number of animal studies indicate the medial prefrontal cortex (mPFC) as neuronal substrate of extinction. We therefore determined mPFC contribution during extinction learning after a discriminative fear conditioning in 34 healthy human subjects by using functional near-infrared spectroscopy. During the extinction training, a previously conditioned neutral face (conditioned stimulus, CS+) no longer predicted an aversive scream (unconditioned stimulus, UCS). Considering differential valence and arousal ratings as well as skin conductance responses during the acquisition phase, we found a CS+ related increase in oxygenated haemoglobin concentration changes within the mPFC over the time course of extinction. Late CS+ trials further revealed higher activation than CS- trials in a cluster of probe set channels covering the mPFC. These results are in line with previous findings on extinction and further emphasize the mPFC as significant for associative learning processes. During extinction, the diminished fear association between a former CS+ and a UCS is inversely correlated with mPFC activity--a process presumably dysfunctional in anxiety disorders.     

Functional near-infrared spectroscopy during the verbal fluency task of English-Speaking adults with mood disorders: A preliminary study

Functional near-infrared spectroscopy (fNIRS) provides a direct and objective assessment of cerebral cortex function. It may be used to determine neurophysiological differences between psychiatric disorders with overlapping symptoms, such as major depressive disorder (MDD) and bipolar disorder (BD). Therefore, this preliminary study aimed to compare fNIRS signals during the verbal fluency task (VFT) of English-speaking healthy controls (HC), patients with MDD and patients with BD. Fifteen HCs, 15 patients with MDD and 15 patients with BD were recruited. Groups were matched for age, gender, ethnicity and education. Relative oxy-haemoglobin and deoxy-haemoglobin changes in the frontotemporal cortex was monitored with a 52-channel fNIRS system. Integral values of the frontal and temporal regions were derived as a measure cortical haemodynamic response magnitude. Both patient groups had lower frontal and temporal region integral values than HCs, and patients with MDD had lower frontal region integral value than patients with BD. Moreover, patients could be differentiated from HCs using the frontal and temporal integral values, and patient groups could be differentiated using the frontal region integral values. VFT performance, clinical history and symptom severity were not associated with integral values. These results suggest that prefrontal cortex haemodynamic dysfunction occurs in mood disorders, and it is more extensive in MDD than BD. The fNIRS-VFT paradigm may be a potential tool for differentiating MDD from BD in clinical settings, and these findings need to be verified in a larger sample of English-speaking patients with mood disorders.     

Temporal lobe and inferior frontal gyrus dysfunction in patients with schizophrenia during face-to-face conversation: A near-infrared spectroscopy study

Schizophrenia (SC) is marked by poor social-role performance and social-skill deficits that are well reflected in daily conversation. Although the mechanism underlying these impairments has been investigated by functional neuroimaging, technical limitations have prevented the investigation of brain activation during conversation in typical clinical situations. To fill this research gap, this study investigated and compared frontal and temporal lobe activation in patients with SC during face-to-face conversation. Frontal and temporal lobe activation in 29 patients and 31 normal controls (NC) (n = 60) were measured during 180-s conversation periods by using near-infrared spectroscopy (NIRS). The grand average values of oxyhemoglobin concentration ([oxy-Hb]) changes during task performance were analyzed to determine their correlation with clinical variables and Positive and Negative Syndrome Scale (PANSS) subscores. Compared to NCs, patients with SC exhibited decreased performance in the conversation task and decreased activation in both the temporal lobes and the right inferior frontal gyrus (IFG) during task performance, as indicated by the grand average of [oxy-Hb] changes. The decreased activation in the left temporal lobe was negatively correlated with the PANSS disorganization and negative symptoms subscores and that in the right IFG was negatively correlated with illness duration, PANSS disorganization, and negative symptom subscores. These findings indicate that brain dysfunction in SC during conversation is related to functional deficits in both the temporal lobes and the right IFG and manifests primarily in the form of disorganized thinking and negative symptomatology.