Multivariate sharp-wave ripples in schizophrenia during awake state.

AIMS: Schizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp-wave ripples (SPW-Rs) have been reported in SZ. As SPW-Rs play a critical role in memory, their irregularities can cause psychotic symptoms and cognitive dysfunction in patients with SZ. In this study, we investigated the SPW-Rs in human SZ. METHODS: We measured whole-brain activity using magnetoencephalography (MEG) in patients with SZ (n = 20) and sex- and age-matched healthy participants (n = 20) during open-eye rest. We identified SPW-Rs and analyzed their occurrence and time-frequency traits. Furthermore, we developed a novel multivariate analysis method, termed "ripple-gedMEG" to extract the global features of SPW-Rs. We also examined the association between SPW-Rs and brain state transitions. The outcomes of these analyses were modeled to predict the positive and negative syndrome scale (PANSS) scores of SZ. RESULTS: We found that SPW-Rs in the SZ (1) occurred more frequently, (2) the delay of the coupling phase (3) appeared in different brain areas, (4) consisted of a less organized spatiotemporal pattern, and (5) were less involved in brain state transitions. Finally, some of the neural features associated with the SPW-Rs were found to be PANSS-positive, a pathological indicator of SZ. These results suggest that widespread but disorganized SPW-Rs underlies the symptoms of SZ. CONCLUSION: We identified irregularities in SPW-Rs in SZ and confirmed that their alternations were strongly associated with SZ neuropathology. These results suggest a new direction for human SZ research.

The Characteristics of Power Spectral Density in Bipolar Disorder at the Resting State.

Bipolar disorder (BD) is a common psychiatric disorder, but its pathophysiology is not fully elucidated. The current study focused on its electrophysiological characteristics, especially power spectral density (PSD). Resting state with eyes opened magnetoencephalography data were collected from 21 patients with BD and 22 healthy controls. The whole brain's PSD was calculated from source reconstructed waveforms at each frequency band (delta: 1-3 Hz, theta: 4-7 Hz, alpha: 8-12 Hz, low beta: 13-19 Hz, high beta: 20-29 Hz, and gamma: 30-80 Hz). We compared PSD values on the marked vertices at each frequency band between healthy and patient groups using a Mann-Whitney rank test to examine the relationship between significantly different PSD and clinical measures. The PSD in patients with BD was significantly decreased in lower frequency bands, mainly in the default mode network (DMN) areas (bilateral medial prefrontal cortex, bilateral precuneus, left inferior parietal lobe, and right temporal cortex in the alpha band) and salience network areas (SAL; left anterior insula [AI] at the delta band, anterior cingulate cortex at the theta band, and right AI at the alpha band). No significant differences in PSD were observed at low beta and high beta. PSD was not correlated with age or other clinical scales. Altered PSDs of the DMN and SAL were observed in the delta, theta, and alpha bands. These alterations contribute to the vulnerability of BD through the disturbance of self-referential mental activity and switching between the default mode and frontoparietal networks.

Disrupted local beta band networks in schizophrenia revealed through graph analysis: A magnetoencephalography study.

AIMS: Schizophrenia (SZ) is characterized by psychotic symptoms and cognitive impairment, and is hypothesized to be a 'dysconnection' syndrome due to abnormal neural network formation. Although numerous studies have helped elucidate the pathophysiology of SZ, many aspects of the mechanism underlying psychotic symptoms remain unknown. This study used graph theory analysis to evaluate the characteristics of the resting-state network (RSN) in terms of microscale and macroscale indices, and to identify candidates as potential biomarkers of SZ. Specifically, we discriminated topological characteristics in the frequency domain and investigated them in the context of psychotic symptoms in patients with SZ. METHODS: We performed graph theory analysis of electrophysiological RSN data using magnetoencephalography to compare topological characteristics represented by microscale (degree centrality and clustering coefficient) and macroscale (global efficiency, local efficiency, and small-worldness) indices in 29 patients with SZ and 38 healthy controls. In addition, we investigated the aberrant topological characteristics of the RSN in patients with SZ and their relationship with SZ symptoms. RESULTS: SZ was associated with a decreased clustering coefficient, local efficiency, and small-worldness, especially in the high beta band. In addition, macroscale changes in the low beta band are closely associated with negative symptoms. CONCLUSIONS: The local networks of patients with SZ may disintegrate at both the microscale and macroscale levels, mainly in the beta band. Adopting an electrophysiological perspective of SZ as a failure to form local networks in the beta band will provide deeper insights into the pathophysiology of SZ as a 'dysconnection' syndrome.

Prospects for Future Methodological Development and Application of Magnetoencephalography Devices in Psychiatry.

Magnetoencephalography (MEG) is a functional neuroimaging tool that can record activity from the entire cortex on the order of milliseconds. MEG has been used to investigate numerous psychiatric disorders, such as schizophrenia, bipolar disorder, major depression, dementia, and autism spectrum disorder. Although several review papers on the subject have been published, perspectives and opinions regarding the use of MEG in psychiatric research have primarily been discussed from a psychiatric research point of view. Owing to a newly developed MEG sensor, the use of MEG devices will soon enter a critical period, and now is a good time to discuss the future of MEG use in psychiatric research. In this paper, we will discuss MEG devices from a methodological point of view. We will first introduce the utilization of MEG in psychiatric research and the development of its technology. Then, we will describe the principle theory of MEG and common algorithms, which are useful for applying MEG tools to psychiatric research. Next, we will consider three topics-child psychiatry, resting-state networks, and cortico-subcortical networks-and address the future use of MEG in psychiatry from a broader perspective. Finally, we will introduce the newly developed device, the optically-pumped magnetometer, and discuss its future use in MEG systems in psychiatric research from a methodological point of view. We believe that state-of-the-art electrophysiological tools, such as this new MEG system, will further contribute to our understanding of the core pathology in various psychiatric disorders and translational research.

Similar activation patterns in the prefrontal cortex for Chinese and Japanese verbal fluency tests with syllable cues as revealed by near-infrared spectroscopy.

The verbal fluency test (VFT) is utilized in neuropsychology to evaluate the cognitive function of the prefrontal cortex (PFC) in the human brain. We present a novel Chinese VFT similar to the established Japanese VFT; both tests prompt a syllable to the subject. However, it was uncertain whether the Chinese VFT can activate the PFC and whether PFC activation patterns are similar between the two tests. Here we administered the Chinese VFT to 30 native Chinese speakers and the Japanese VFT to 30 native Japanese speakers. We used near-infrared spectroscopy (NIRS) to observe PFC activation. Then we compared the similarities between the Chinese VFT and the Japanese VFT. The subjects generated an average of 12.8 ± 4.7 words during the Chinese VFT. NIRS indicates that the concentration of oxygenated hemoglobin during the test was significantly higher than those before and after the test. It exhibited similar PFC activation patterns with the Japanese VFT. The novel Chinese VFT can activate the PFC in the human brain effectively in Chinese speakers. Our work thus provides the first validated phonetically cued Chinese VFT, unique from other not strictly phonemic Chinese VFTs, and facilitates the diagnosis of various PFC-related cognitive impairments.

Alterations of Heartbeat Evoked Magnetic Fields Induced by Sounds of Disgust.

The majority of the models of emotional processing attribute subjective emotional feelings to physiological changes in the internal milieu, which are sensed by the interoceptive system. These physiological reactions evoked by emotional phenomena occur via the autonomic nervous system, and give rise to alterations in body-mind interactions that are characterized by heartbeat evoked magnetic fields (HEFs) involving brain regions associated with emotional perception. The current study used magnetoencephalography (MEG) to examine regional cortical activity and connectivity changes in HEFs provoked by the emotion of disgust. MEG results from 39 healthy subjects (22 female) revealed that passively listening to sounds of disgust elicited right insular cortical activity and enhancement of cortical connectivity between the right anterior ventral insular cortex and left ventromedial prefrontal cortex, demonstrated by phase lag indexes in the beta frequency range. Furthermore, inter-trial coherence significantly increased at 19 Hz and 23 Hz, and decreased at 14 Hz, which highlights the involvement of low beta oscillations in emotional processing. As these results were based on spontaneously triggered bioelectrical signals, more indigenous and induced signals were extracted with a block designed experiment. The insular cortices play an important role in emotional regulation and perception as the main cortical target for signals with interoceptive information, providing direct substrates of emotional feelings. The current results provide a novel insight into frequency properties of emotional processing, and suggest that emotional arousal evoked by listening to sounds of disgust partially impact the autonomic nervous system, altering HEFs via connectivity changes in the right anterior ventral insular cortex and left ventromedial prefrontal cortex.

Frequency-Specific Resting Connectome in Bipolar Disorder: An MEG Study.

BACKGROUND: Bipolar disorder (BD) is a serious psychiatric disorder that is associated with a high suicide rate, and for which no clinical biomarker has yet been identified. To address this issue, we investigated the use of magnetoencephalography (MEG) as a new prospective tool. MEG has been used to evaluate frequency-specific connectivity between brain regions; however, no previous study has investigated the frequency-specific resting-state connectome in patients with BD. This resting-state MEG study explored the oscillatory representations of clinical symptoms of BD via graph analysis. METHODS: In this prospective case-control study, 17 patients with BD and 22 healthy controls (HCs) underwent resting-state MEG and evaluations for depressive and manic symptoms. After estimating the source current distribution, orthogonalized envelope correlations between multiple brain regions were evaluated for each frequency band. We separated regions-of-interest into seven left and right network modules, including the frontoparietal network (FPN), limbic network (LM), salience network (SAL), and default mode network (DMN), to compare the intra- and inter-community edges between the two groups. RESULTS: In the BD group, we found significantly increased inter-community edges of the right LM-right DMN at the gamma band, and decreased inter-community edges of the right SAL-right FPN at the delta band and the left SAL-right SAL at the theta band. Intra-community edges in the left LM at the high beta band were significantly higher in the BD group than in the HC group. The number of connections in the left LM at the high beta band showed positive correlations with the subjective and objective depressive symptoms in the BD group. CONCLUSION: We introduced graph theory into resting-state MEG studies to investigate the functional connectivity in patients with BD. To the best of our knowledge, this is a novel approach that may be beneficial in the diagnosis of BD. This study describes the spontaneous oscillatory brain networks that compensate for the time-domain issues associated with functional magnetic resonance imaging. These findings suggest that the connectivity of the LM at the beta band may be a good objective biological biomarker of the depressive symptoms associated with BD.

Timing of phase-amplitude coupling is essential for neuronal and functional maturation of audiovisual integration in adolescents.

OBJECTIVE: The ability to integrate audiovisual information matures late in adolescents, but its neuronal mechanism is still unknown. Recent studies showed that phase-amplitude coupling (PAC) of neuronal oscillations, which is defined as the modulation of high-frequency amplitude by low-frequency phase, is associated with audiovisual integration in adults. Thus, we investigated how PAC develops in adolescents and whether it is related to the functional maturation of audiovisual integration. In particular, we focused on the timing of PAC (or the coupling phase), which is defined as the low-frequency phase with maximum high-frequency amplitude. METHODS: Using magnetoencephalography (MEG) on 15 adults and 14 adolescents while they performed an audiovisual speech integration task, we examined PAC in association cortexes with a trial-by-trial analysis. RESULTS: Whereas delta-beta coupling was consistently observed in both adults and adolescents, we found that the timing of delta-beta PAC was delayed by 20-40 milliseconds in adolescents compared with adults. In addition, a logistic regression analysis revealed that the task performance improves as the timing of delta-beta PAC in the right temporal pole (TP) got closer to the trough position (180 degrees). CONCLUSION: These results suggest that the timing of PAC is essential for binding audiovisual information and underlies the developmental process in adolescents.

Brain functional alterations observed 4-weekly in major depressive disorder following antidepressant treatment.

BACKGROUND: Major depressive disorder (MDD) is a heterogeneous condition. Identifying the brain responses to antidepressant treatment is of particular interest as these may represent potential neural networks related to treatment response, forming one aspect of the biological markers of MDD. Near-infrared spectroscopy (NIRS) is suitable for repeated measurements with short intervals because of its noninvasiveness, and can provide detailed time courses of functional alterations in prefrontal regions. METHODS: We conducted a 12-week longitudinal study to explore prefrontal hemodynamic changes at 4-week intervals following sertraline treatment in 11 medication-naïve participants with MDD using 52-channel NIRS. RESULTS: While all participants achieved remission after treatment, intra-class correlation coefficient of oxygenated hemoglobin [oxy-Hb] values throughout the 12-week observation was moderate at the spatially and temporally contiguous cluster located in the left inferior frontal and temporal gyri. There was a significant negative correlation between mean [oxy-Hb] values in the significant cluster at 4 weeks and changes in Hamilton Rating Scale for Depression total score from 4 to 8 weeks (r = -0.73, P = 0.011) and from 4 to 12 weeks (r = -0.63, P = 0.039). LIMITATIONS: Without healthy controls for comparison, we were unable to fully evaluate whether improvement of [oxy-Hb] activations after treatment in MDD reached normal levels or not. CONCLUSION: Our NIRS findings of detailed prefrontal hemodynamic alterations over short interval observations such as 4 weeks may have revealed potential trait marker for MDD and biological maker for predicting clinical response to sertraline treatment in MDD.

[FreeSurfer as a Platform for Associating Brain Structure with Function].

FreeSurfer is open source software used to process and analyze magnetic resonance imaging of the human brain. It is a convenient tool that helps elucidate various structural characteristics the brain. In this review, we introduce the various structural indices of the brain, analyzed using FreeSurfer and magnetoencephalography, which can evaluate neural activity with high temporal and spatial resolution. We consider that the FreeSurfer has great potential as a platform for multimodal neuroimaging studies.

Neural mechanisms of mental schema: a triplet of delta, low beta/spindle and ripple oscillations.

Schemas are higher-level knowledge structures that integrate and organise lower-level representations. As internal templates, schemas are formed according to how events are perceived, interpreted and remembered. Although these higher-level units are assumed to play a fundamental role in our daily life from an early age, the neuronal basis and mechanisms of schema formation and use remain largely unknown. It is important to elucidate how the brain constructs and maintains these higher-level units. In order to examine the possible neural underpinnings of schema, we recapitulate previous work and discuss their findings related to schemas as the brain template. We specifically focused on low beta/spindle oscillations, which are assumed to be the key components of schemas, and propose that the brain template is implemented with a triplet of neural oscillations, that is delta, low beta/spindle and ripple oscillations.

Aberrant Spatial and Temporal Prefrontal Activation Patterns in Medication-Naïve Adults with ADHD.

Previous near-infrared spectroscopy (NIRS) studies using a verbal fluency task (VFT) have consistently reported that adults with attention-deficit hyperactivity disorder (ADHD) showed significantly smaller oxygenated-hemoglobin [oxy-Hb] activations in the prefrontal cortex (PFC) compared to those in healthy controls (HC). Despite this consistent evidence of brain dysfunction in ADHD, ADHD is currently diagnosed based only on subjective clinical and scoring measures, which are often unreliable. Hence, it is necessary to establish objective neuroimaging biomarkers for ADHD. While most NIRS studies have utilized averaged [oxy-Hb] values during the whole task period for group comparisons, we used a cluster-based non-parametric randomization test to compare the [oxy-Hb] time-course changes with a 0.1-s time resolution between drug-naïve adults with ADHD and HC, which may provide us with more details regarding abnormal prefrontal activation patterns in ADHD. A total of 101 participants, consisting of 63 drug-naïve adult individuals with ADHD and 38 HC, were included in this study. We identified that adults with ADHD showed significantly smaller [oxy-Hb] activations than those in HC at spatially and temporally connected clusters located in the bilateral PFC (more prominent on the left) and temporal brain region (more prominent on the left). We further found that aberrant [oxy-Hb] activation differs according to the time period during the task or according to brain location. Our findings indicate more detailed aberrant prefrontal and temporal activation patterns of ADHD compared with those in previous studies, possibly representing a biological marker for ADHD.

Familial Influences on Mismatch Negativity and Its Association with Plasma Glutamate Level: A Magnetoencephalographic Study in Twins.

Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission. Thirty-three pairs of monozygotic (MZ) and 10 pairs of dizygotic (DZ) twins underwent MMNm recording. The MMNm in response to tone duration changes, tone frequency changes, and phonemic changes was recorded using 204-channel magnetoencephalography. Of these, 26 MZ and 7 DZ twin pairs underwent blood sampling for determination of plasma amino acid levels. MMNm peak strength showed relatively high correlations in both MZ and DZ twin pairs. The differences in MMNm latencies tended to correlate with the differences in plasma amino acid levels within MZ pairs, while no significant correlation was observed after the Bonferroni correction. We observed a familial trait in MMNm strength. The differences in MMN latency in MZ twins might be influenced by changes in glutamate levels and glutamate-glutamine cycling; however, the results need to be replicated.

Neural oscillations in the temporal pole for a temporally congruent audio-visual speech detection task.

Though recent studies have elucidated the earliest mechanisms of processing in multisensory integration, our understanding of how multisensory integration of more sustained and complicated stimuli is implemented in higher-level association cortices is lacking. In this study, we used magnetoencephalography (MEG) to determine how neural oscillations alter local and global connectivity during multisensory integration processing. We acquired MEG data from 15 healthy volunteers performing an audio-visual speech matching task. We selected regions of interest (ROIs) using whole brain time-frequency analyses (power spectrum density and wavelet transform), then applied phase amplitude coupling (PAC) and imaginary coherence measurements to them. We identified prominent delta band power in the temporal pole (TP), and a remarkable PAC between delta band phase and beta band amplitude. Furthermore, imaginary coherence analysis demonstrated that the temporal pole and well-known multisensory areas (e.g., posterior parietal cortex and post-central areas) are coordinated through delta-phase coherence. Thus, our results suggest that modulation of connectivity within the local network, and of that between the local and global network, is important for audio-visual speech integration. In short, these neural oscillatory mechanisms within and between higher-level association cortices provide new insights into the brain mechanism underlying audio-visual integration.

The inhibition/excitation ratio related to task-induced oscillatory modulations during a working memory task: A multtimodal-imaging study using MEG and MRS.

Detailed studies on the association between neural oscillations and the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate have been performed in vitro. In addition, recent functional magnetic resonance imaging studies have characterized these neurotransmitters in task-induced deactivation processes during a working memory (WM) task. However, few studies have investigated the relationship between these neurotransmitters and task-induced oscillatory changes in the human brain. Here, using combined magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS), we investigated the modulation of GABA and glutamate + glutamine (Glx) concentrations related to task-induced oscillations in neural activity during a WM task. We first acquired resting-state MRS and MEG data from 20 healthy male volunteers using the n-back task. Time-frequency analysis was employed to determine the power induced during the encoding and retention phases in perigenual anterior cingulate cortex (pg-ACC), mid-ACC, and occipital cortex (OC). Statistical analysis showed that increased WM load was associated with task-induced oscillatory modulations (TIOMs) of the theta-gamma band relative to the zero-back condition (TIOM0B) in each volume of interest during the encoding phase of the n-back task. The task-induced oscillatory modulations in the two-back condition relative to the zero-back condition (TIOM2B-0B) were negatively correlated with the percent rate change of the correct hit rate for 2B-0B, but positively correlated with GABA/Glx. The positive correlation between TIOM2B-0B and GABA/Glx during the WM task indicates the importance of the inhibition/excitation ratio. In particular, a low inhibition/excitation ratio is essential for the efficient inhibition of irrelevant neural activity, thus producing precise task performance.

Magnetoencephalography study of the effect of attention modulation on somatosensory processing in patients with major depressive disorder.

AIMS: Although affective and/or attention modulation of somatosensory processing has been well studied, the biological bases of somatic symptoms in patients with major depressive disorder (MDD) have rarely been examined. To elucidate changes in somatosensory processing underlying somatic symptoms in patients with MDD, we conducted a magnetoencephalography study of patients with MDD and healthy controls. METHODS: After median nerve stimulation, somatosensory evoked fields (SEF) were recorded in 10 patients with MDD and 10 sex-, age-, and height-matched healthy volunteers under somatosensory attending, visually attending, and non-attending conditions. The latencies and magnitudes of N20m and P60m SEF were examined. RESULTS: In the MDD group, P60m latency was significantly prolonged, irrespective of attention modulation, whereas N20m latency and root mean squares N20m and P60m amplitudes remained unchanged. Prolonged P60m latency negatively correlated with the somatosensory threshold, which was relatively high in the MDD group. Prolonged P60m latency also negatively correlated with a state of anxiety during the examination, but not with depressive symptoms or psychotropic medication. CONCLUSIONS: These results suggested that patients with MDD experience dysfunction in somatosensory information processing, approximately 60 ms after stimuli, irrespective of attentional conditions.

Relationship of γ-aminobutyric acid and glutamate+glutamine concentrations in the perigenual anterior cingulate cortex with performance of Cambridge Gambling Task.

The anterior cingulate cortex (ACC), consisting of the perigenual ACC (pgACC) and mid-ACC (i.e., affective and cognitive areas, respectively), plays a significant role in the performance of gambling tasks, which are used to measure decision-making behavior under conditions of risk. Although recent neuroimaging studies have suggested that the γ-aminobutyric acid (GABA) concentration in the pgACC is associated with decision-making behavior, knowledge regarding the relationship of GABA concentrations in subdivisions of the ACC with gambling task performance is still limited. The aim of our magnetic resonance spectroscopy study is to investigate in 20 healthy males the relationship of concentrations of GABA and glutamate+glutamine (Glx) in the pgACC, mid-ACC, and occipital cortex (OC) with multiple indexes of decision-making behavior under conditions of risk, using the Cambridge Gambling Task (CGT). The GABA/creatine (Cr) ratio in the pgACC negatively correlated with delay aversion score, which corresponds to the impulsivity index. The Glx/Cr ratio in the pgACC negatively correlated with risk adjustment score, which is reported to reflect the ability to change the amount of the bet depending on the probability of winning or losing. The scores of CGT did not significantly correlate with the GABA/Cr or Glx/Cr ratio in the mid-ACC or OC. Results of this study suggest that in the pgACC, but not in the mid-ACC or OC, GABA and Glx concentrations play a distinct role in regulating impulsiveness and risk probability during decision-making behavior under conditions of risk, respectively.

Near-infrared spectroscopic study of frontopolar activation during face-to-face conversation in major depressive disorder and bipolar disorder.

Major depressive disorder (MDD) and bipolar disorder (BD) patients show speech characteristics that vary greatly according to mood state. In a previous study, we found impaired temporal and right inferior frontal gyrus (IFG) activation in schizophrenia during face-to-face conversation; no study had, however, previously investigated mood disorders during face-to-face conversation. Here, we investigated frontal and temporal lobe activation during conversation in patients with MDD and BD. Frontal and temporal lobe activation was measured using near-infrared spectroscopy (NIRS) in 29 patients with MDD, 31 patients with BD, and 31 normal controls (NC). We compared continuous activation and rapid change of activation with talk/listen phase changes during the conversation and analyzed the correlation between these indices and clinical variables. Both the MDD and BD groups showed decreased continuous activation in the left dorsolateral prefrontal (DLPFC) and left frontopolar cortices (FPCs); they also showed decreased rapid change in bilateral FPC activation. In the MDD group, the rapid change of activation was positively correlated with Global Assessment of Functioning (GAF) scores. In the BD group, continuous activation was negatively correlated with age of onset. These results indicate that frontal activation during conversation decreases in both MDD and BD. However, both continuous activation and rapid change may reflect the pathophysiological character of MDD and BD; in particular, the reduced amount of rapid change in the right FPC may be related to impaired adaptive ability in MDD.

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.

Reduced dorsolateral prefrontal cortical hemodynamic response in adult obsessive-compulsive disorder as measured by near-infrared spectroscopy during the verbal fluency task.

BACKGROUND: Near-infrared spectroscopy has helped our understanding of the neurobiological mechanisms of psychiatric disorders and has advantages including noninvasiveness, lower cost, and ease of use compared with other imaging techniques, like functional magnetic resonance imaging. The verbal fluency task is the most common and well established task used to assess cognitive activation during near-infrared spectroscopy. Recent functional neuroimaging studies have shown that the orbitofrontal cortex and other brain regions, including the dorsolateral prefrontal cortex, may play important roles in the pathophysiology of obsessive-compulsive disorder (OCD). This study aimed to evaluate hemodynamic responses in the dorsolateral prefrontal cortex in patients with OCD using near-infrared spectroscopy during the verbal fluency task and to compare these with dorsolateral prefrontal cortex responses in healthy controls. METHODS: Twenty patients with OCD and 20 controls matched for age, gender, handedness, and estimated intelligence quotient participated in this study. The verbal fluency task was used to elicit near-infrared spectroscopic activation and consisted of a 30-second pre-task, followed by three repetitions of a 20-second verbal fluency task (total 60 seconds), followed by a 70-second post-task period. The near-infrared spectroscopy experiment was conducted on the same day as surveys of obsessive-compulsive symptoms, depression, and anxiety. Z-scores for changes in the concentration of oxygenated hemoglobin were compared between the OCD patients and controls in 14 channels set over the left and right dorsolateral prefrontal cortex and frontopolar areas. RESULTS: During the verbal fluency task, significant task-related activation was detected in both the OCD group and the controls. Changes in oxygenated hemoglobin concentration in the right dorsolateral prefrontal cortex were significantly smaller in the OCD group than in the controls, but were not statistically significant after correction for multiple comparisons. CONCLUSION: Patients with OCD have reduced prefrontal, especially right dorsolateral prefrontal, cortical hemodynamic responses as measured by near-infrared spectroscopy during the verbal fluency task. These results support the hypothesis that the dorsolateral prefrontal cortex plays a role in the pathophysiology of OCD.