Aberrant modular segregation of brain networks in female patients with bulimia nervosa.

OBJECTIVE: Bulimia nervosa (BN) is an eating disorder associated with the dysfunction of intrinsic brain networks. However, whether the network disruptions in BN patients manifest as dysconnectivity or imbalances of network modular segregation remains unclear. METHOD: We collected data from 41 women with BN and 41 matched healthy control (HC) women. We performed graph theory analysis based on resting-state functional magnetic resonance imaging (RS-fMRI) data; then, we computed the participation coefficient (PC) among brain modules to characterize the modular segregation for the BN and HC groups. The number of intra- and inter-modular connections was calculated to explain the PC changes. Additionally, we examined the potential associations of the measures mentioned above with clinical variables within the BN group. RESULTS: Compared with the HC group, the BN group showed significantly decreased PC in the fronto-parietal network (FPN), cingulo-opercular network (CON), and cerebellum (Cere). Additionally, the number of intra-modular connections of the default mode network (DMN) and the number of the inter-modular connections between the DMN and CON, FPN and Cere, and CON and Cere in the BN group were lower than those in the HC group. The nodal level analysis showed that the BN group had a decreased PC of the anterior prefrontal cortex (aPFC), dorsal frontal cortex (dFC), inferior parietal lobule (IPL), thalamus, and angular gyrus. Further, these metrics were significantly correlated with clinical variables in the BN group. DISCUSSION: These findings may provide novel insights to capture atypical topologies associated with pathophysiology mechanisms and clinical symptoms underlying BN.

Neural mechanism and heritability of complex motor sequence and audiovisual integration: A healthy twin study.

Complex motor sequencing and sensory integration are two key items in scales assessing neurological soft signs. However, the underlying neural mechanism and heritability of these two functions is not known. Using a healthy twin design, we adopted two functional brain imaging tasks focusing on fist-edge-palm (FEP) complex motor sequence and audiovisual integration (AVI). Fifty-six monozygotic twins and 56 dizygotic twins were recruited in this study. The pre- and postcentral, temporal and parietal gyri, the supplementary motor area, and the cerebellum were activated during the FEP motor sequence, whereas the precentral, temporal, and fusiform gyri, the thalamus, and the caudate were activated during AVI. Activation in the supplementary motor area during FEP motor sequence and activation in the precentral gyrus and the thalamic nuclei during AVI exhibited significant heritability estimates, ranging from 0.5 to 0.62. These results suggest that activation in cortical motor areas, the thalamus and the cerebellum associated with complex motor sequencing and audiovisual integration function may be heritable.

Altered intrinsic functional brain architecture in female patients with bulimia nervosa.

BACKGROUND: Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. METHODS: We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. RESULTS: We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. LIMITATIONS: We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. CONCLUSION: Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa.

Distinguishing bipolar and major depressive disorders by brain structural morphometry: a pilot study.

BACKGROUND: The clinical presentation of common symptoms during depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) poses challenges for accurate diagnosis. Disorder-specific neuroanatomical features may aid the development of reliable discrimination between these two clinical conditions. METHODS: For our sample of 16 BD patients, 19 MDD patients and 29 healthy volunteers, we adopted vertex-wise cortical based brain imaging techniques to examine cortical thickness and surface area, two components of cortical volume with distinct genetic determinants. Based on specific characteristics of neuroanatomical features, we then used support vector machine (SVM) algorithm to discriminate between patients with BD and MDD. RESULTS: Compared to MDD patients, BD patients showed significantly larger cortical surface area in the left bankssts, precuneus, precentral, inferior parietal, superior parietal and the right middle temporal gyri. In addition, larger volumes of subcortical regions were found in BD patients. In SVM discriminative analyses, the overall accuracy was 74.3 %, with a sensitivity of 62.5 % and a specificity of 84.2 % (p = 0.028). Compared to controls, larger surface area in the temporo-parietal regions were observed in BD patients, and thinner cortices in fronto-temporal regions were observed in MDD patients, especially in the medial orbito-frontal area. CONCLUSIONS: These findings have demonstrated distinct spatially distributed variations in cortical thickness and surface area in patients with BD and MDD, suggesting potentially varying etiological and neuropathological processes in these two conditions. The employment of multimodal classification on disorder-specific biological features has shed light to the development of potential classification tools that could aid diagnostic decisions.

Eight-week antidepressant treatment changes intrinsic functional brain topology in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: A recent study revealed disrupted topological organization of whole-brain networks in patients with major depressive disorder (MDD); however, these results were mostly driven by recurrent MDD patients, rather than first-episode drug-naïve (FEDN) patients. Furthermore, few longitudinal studies have explored the effects of antidepressant therapy on the topological organization of whole-brain networks. METHODS: We collected clinical and neuroimaging data from 159 FEDN MDD patients and 152 normal controls (NCs). A total of 115 MDD patients completed an eight-week antidepressant treatment procedure. Topological features of brain networks were calculated using graph theory-based methods and compared between FEDN MDD patients and NCs, as well as before and after treatment. RESULTS: Decreased global efficiency, local efficiency, small-worldness, and modularity were found in pretreatment FEDN MDD patients compared with NCs. Nodal degrees, betweenness, and efficiency decreased in several networks compared with NCs. After antidepressant treatment, the global efficiency increased, while the local efficiency, the clustering coefficient of the network, the path length, and the normalized characteristic path length decreased. Moreover, the reduction rate of the normalized characteristic path length was positively correlated with the reduction rate of retardation factor scores. LIMITATIONS: The interaction effects of groups and time on the topological features were not explored because of absence of the eighth-week data of NC group. CONCLUSIONS: The topological architecture of functional brain networks is disrupted in FEDN MDD patients. After antidepressant therapy, the global efficiency shifted toward recovery, but the local efficiency deteriorated, suggesting a correlation between recovery of retardation symptoms and global efficiency.

Neural correlates of the effect of implementation intention on prospective memory.

Prospective memory (PM) refers to the ability to remember to do something in the future. Implementation intention refers to a self-regulatory strategy in the form of "If …, then …" planning that can improve PM performance. However, the neural basis of the effect of implementation intention on PM remains unclear, as do the phases of PM that are affected by implementation intention. This study aimed to address these issues. Healthy participants were randomly assigned to the implementation intention (n = 18) and typical instruction (n = 20) conditions. All of them underwent functional magnetic resonance imaging (fMRI) scanning when performing a PM task, which differentiated encoding, maintenance, and execution phases. Results demonstrated that participants in the implementation intention group showed different brain activations compared to participants in the typical instruction group. During the encoding phase, the implementation intention group showed increased activations in the inferior frontal gyrus (BA 10) and supramarginal gyrus (BA 40) compared to the typical instruction group; during the maintenance phase, the typical instruction group showed stronger activations in the inferior frontal gyrus (BA 46) than the implementation intention group; during the execution phase, the typical instruction group showed increased activations in the precentral gyrus (BA 6) and middle frontal gyrus (BA 8) than the implementation intention group. These results demonstrated the neural correlates of implementation intention on PM in different phases, and support the conclusion of our previous review based on fMRI evidence that implementation intention's improvement of PM performance is not fully automatic.

Improving motivation through real-time fMRI-based self-regulation of the nucleus accumbens.

OBJECTIVE: Impaired nucleus accumbens (NAcc) activation is associated with amotivation and anhedonia, which are resistant to treatment with antipsychotics and antidepressants in schizophrenia. In this study, healthy participants were trained to self-regulate the activation of their NAcc, a brain region that plays an important role in motivation, using real-time functional magnetic resonance imaging (fMRI) neurofeedback. METHOD: The experimental group (N = 19) received feedback from the NAcc, whereas the control group (N = 5) received "sham" feedback from the posterior parahippocampal gyrus, a control brain region not normally related to motivation. All participants were trained to use mental strategies to regulate their NAcc activations in a 3T MRI scanner. RESULTS: For the learning effect of NAcc regulation, we found that the majority of participants (74%) in the experimental group successfully learned to self-regulate the NAcc. They also showed improved behavioral performance in motivation and decreased functional connectivity between the NAcc and the ventral medial prefrontal cortex and an increase in small-world properties in the reward circuit after training, indicating improved information integration in reward processing. However, improvement in motivation and modification of function connectivity were not observed in the sham control group and the participants who failed to self-regulate the NAcc in the experimental group. Self-regulation was influenced by the baseline motivation. CONCLUSIONS: These findings suggest that the NAcc could be self-regulated using real-time fMRI neurofeedback and can result in improved motivation in cognitive tasks. (PsycINFO Database Record

Neural correlates of audiovisual sensory integration.

OBJECTIVE: The present study aimed to investigate the neural basis of information matching during sensory integration using a spatial-temporal matching task in healthy individuals. METHOD: A total of 37 healthy participants were recruited to match spatial dots with an auditory tone sequence in a 3T GE Discovery MR750 scanner. In addition, they were examined with the sensory integration subscale of the Cambridge Neurological Inventory. RESULTS: We found that the bilateral occipital-parietal conjunction cortex and the precentral frontal gyrus were activated during the matching condition rather than in the nonmatching condition. Activation of the occipital-parietal conjunction cortex was associated with integration of information across visual and auditory modalities, whereas activation of the precentral frontal gyrus was associated with decision making of movements. In addition, activation of the left superior frontal gyrus was associated with scores on the sensory integration subscale of the Cambridge Neurological Inventory. CONCLUSIONS: These findings suggest that the bilateral occipital-parietal conjunction cortex is responsible for matching information input from multiple modalities during audiovisual sensory integration. (PsycINFO Database Record

Distinct processing of social and monetary rewards in late adolescents with trait anhedonia.

OBJECTIVE: Anticipatory and consummatory dissociation of hedonic experience may manifest as trait anhedonia in healthy and clinical populations. It is still unclear whether the underlying neural mechanisms of the monetary-based and affect-based incentive delay paradigms are distinct from each other. The present study aimed to examine the similarities and differences between the Affect Incentive Delay (AID) and the Monetary Incentive Delay (MID) imaging paradigms in relation to brain activations. METHOD: We administered the AID and the MID imaging tasks to 28 adolescent participants. A cue signaling the type of forthcoming feedback (reward or punishment) was displayed to the participants, followed by a target-hit task with corresponding reward or punishment. RESULTS: The striatal and limbic regions were activated during the anticipatory phase of MID, while there was no brain activation during the anticipatory phase of AID. In the consummatory phase, the MID task activated the medial frontal cortex, while the AID task activated the frontal and dorsal limbic regions. We further found that the anhedonic group exhibited significant hypoactivation than the nonanhedonic group at the left pulvinar, the left claustrum and the left insula to positive cues in the anticipatory phase of the AID task. CONCLUSIONS: The results suggest that the AID and the MID tasks have unique activation patterns. Our findings also suggest that the AID task may be more sensitive in detecting anhedonia in people with trait anhedonia.

The neural transfer effect of working memory training to enhance hedonic processing in individuals with social anhedonia.

Anhedonia, the diminished ability to experience pleasure, is a challenging negative symptom in patients with schizophrenia and can be observed in at-risk individuals with schizotypy. Deficits in hedonic processing have been postulated to be related to decreased motivation to engage in potentially rewarding events. It remains unclear whether non-pharmacological interventions, such as cognitive training, could improve anhedonia. The present study aimed to examine the neural mechanism for alleviating hedonic deficits with working memory (WM) training in individuals with social anhedonia. Fifteen individuals with social anhedonia were recruited and received 20 sessions of training on a dual n-back task, five sessions a week. Functional imaging paradigms of the Monetary Incentive Delay (MID) and the Affective Incentive Delay (AID) tasks were administered both before and after the training to evaluate the neural transfer effects on hedonic processing ability. Enhanced brain activations related to anticipation were observed at the anterior cingulate cortex, the left dorsal striatum and the left precuneus with the AID task, and at the dorsolateral prefrontal cortex and the supramarginal gyrus with the MID task. The present findings support that WM training may improve monetary-based and affective-based hedonic processing in individuals with social anhedonia.

Differences between attention-deficit disorder with and without hyperactivity: a 1H-magnetic resonance spectroscopy study.

Using proton magnetic resonance spectroscopy ((1)H-MRS) to investigate possible neurometabolic differences between the predominantly inattentive subtype (ADHD-I), the combined subtype (ADHD-C) and normal controls. Proton spectra were acquired bilaterally on the lenticular nucleus in 20 schoolboys having ADHD and 10 matched controls. The boys with ADHD were divided into ADHD-C subtype (n=10) and ADHD-I subtype (n=10) according to DSM-IV criteria. The peaks of N-acetylaspartate (NAA), Choline moieties (Cho), myo-inositol (mI), creatine (Cr) and alpha-Glx were measured and their ratios to Cr were calculated. One-way ANOVA and post-hoc Bonferroni tests were used to detect the difference of the peak-area ratios of NAA, Cho, mI, and alpha-Glx to Cr among the three groups. There was a significant overall group difference in the NAA/Cr ratio both in the right and left lenticular nucleus (right: P=0.002; left: P=0.003). Only the ADHD-C subtype group showed a significant difference with controls (right: P=0.001; left: P=0.003) the right lenticular nucleus, the NAA/Cr ratio in the ADHD-C group was significantly lower than that in the ADHD-I group (P=0.012). In the left lenticular nucleus, the NAA/Cr ratio in the ADHD-C group showed a significant trend compared to the ADHD-I group (P=0.06). This study demonstrated the existence of measurable difference between children with ADHD-C and ADHD-I using (1)H-MRS.

Functional MRI in attention-deficit hyperactivity disorder: evidence for hypofrontality.

Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.

Anticipatory pleasure predicts effective connectivity in the mesolimbic system.

Convergent evidence suggests the important role of the mesolimbic pathway in anticipating monetary rewards. However, the underlying mechanism of how the sub-regions interact with each other is still not clearly understood. Using dynamic causal modeling, we constructed a reward-related network for anticipating monetary reward using the Monetary Incentive Delay Task. Twenty-six healthy adolescents (Female/Male = 11/15; age = 18.69 ± 1.35 years; education = 12 ± 1.58 years) participated in the present study. The best-fit network involved the right substantia nigra/ventral tegmental area (SN/VTA), the right nucleus accumbens (NAcc) and the right thalamus, which were all activated during anticipation of monetary gain and loss. The SN/VTA directly activates the NAcc and the thalamus. More importantly, monetary gain modulated the connectivity from the SN/VTA to the NAcc and this was significantly correlated with subjective anticipatory pleasure (r = 0.649, p < 0.001). Our findings suggest that activity in the mesolimbic pathway during the anticipation of monetary reward could to some extent be predicted by subjective anticipatory pleasure.

Interhemispheric Connectivity in Drug-Naive Benign Childhood Epilepsy With Centrotemporal Spikes: Combining Function and Diffusion MRI.

Decreased intelligence quotients (IQ) have been consistently reported in drug-naive benign childhood epilepsy with centrotemporal spikes (BECTS). We aimed to identify the neurophysiological basis of IQ deficits by studying interhemispheric and anatomical functional connectivity in BECTS patients. Resting-state functional and structural magnetic resonance images were acquired in 32 children with BECTS and 25 healthy controls. The IQ was estimated using Wechsler Intelligence Scale for Children China-Revised. The functional connectivity between bilateral homotopic voxels was calculated and compared between groups. Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for analysis by diffusion-tensor imaging tractography. The fractional anisotropy, fiber length, and fiber number were compared between groups. Abnormal homotopic connectivities were correlated with IQ in BECTS patients. Compared with control subjects, patients showed decreased IQ, and decreased voxel-mirrored homotopic connectivity (VMHC) in the bilateral frontal lobule and cerebellum. The performance and full scale IQ significantly increased with the VMHC strength of the middle frontal gyrus (MFG) in controls but not in BECTS patients. A significant negative correlation was observed between VMHC in the premotor cortex and disease duration. Microstructural features within white matter tracts connecting functionally abnormal regions did not reveal any differences between groups. This study provides preliminary evidence for the disrupted functional cooperation between hemispheres in children with BECTS. The findings suggest that the hyposynchrony between the bilateral MFG may be involved in the decreased IQ of BECTS patients.

Local Activity and Causal Connectivity in Children with Benign Epilepsy with Centrotemporal Spikes.

The aim of the current study was to localize the epileptic focus and characterize its causal relation with other brain regions, to understand the cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 37 children with BECTS and 25 children matched for age, sex and educational achievement. We identified the potential epileptogenic zone (EZ) by comparing the amplitude of low frequency fluctuation (ALFF) of spontaneous blood oxygenation level dependent fMRI signals between the groups. Granger causality analysis was applied to explore the causal effect between EZ and the whole brain. Compared with controls, children with BECTS had significantly increased ALFF in the right postcentral gyrus and bilateral calcarine, and decreased ALFF in the left anterior cingulate cortex, bilateral putaman/caudate, and left cerebellum. ALFF values in the putaman/caudate were positively correlated with verbal IQ scores in patients. The ALFF values in cerebellum and performance IQ scores were negatively correlated in patients. These results suggest that ALFF disturbances in the putaman/caudate and cerebellum play an important role in BECTS cognitive dysfunction. Compared with controls, the patients showed increased driving effect from the EZ to the right medial frontal cortex and posterior cingulate cortex and decreased causal effects from the EZ to left inferior frontal gyrus. The causal effect of the left inferior frontal gyrus negatively correlated with disease duration, which suggests a relation between the epileptiform activity and language impairment. All together, these findings provide additional insight into the neurophysiological mechanisms of epilepitogenisis and cognitive dysfunction associated with BECTS.

Modulation of cold pain in human brain by electric acupoint stimulation: evidence from fMRI.

The purpose of this study is to investigate the modulation of pain responses in the human brain by electric acupoint stimulation (EAS). Eight healthy subjects were enrolled; each received real or mock EAS treatment in separate sessions. Cool (18 degrees C) and cold (2 degrees C) stimuli were delivered, during which functional magnetic resonance imaging scans were performed, before and after treatment. Real EAS specifically increased the pain-specific activation in bilateral secondary somatosensory area, medial prefrontal cortex, and Brodmann area (BA) 32, while it decreased the activation in contralateral primary somatosensory area, BA7, and BA24. We suggest that EAS may induce an analgesic effect via modulation of both the sensory and the emotional aspect of pain processing.

Relations between brain network activation and analgesic effect induced by low vs. high frequency electrical acupoint stimulation in different subjects: a functional magnetic resonance imaging study.

Two- or 100-Hz electrical acupoint stimulation (EAS) can induce analgesia via distinct central mechanisms. It has long been known that the extent of EAS analgesia showed tremendous difference among subjects. Functional MRI (fMRI) studies were performed to allocate the possible mechanisms underlying the frequency specificity as well as individual variability of EAS analgesia. In either frequencies, the averaged fMRI activation levels of bilateral secondary somatosensory area and insula, contralateral anterior cingulate cortex and thalamus were positively correlated with the EAS-induced analgesic effect across the subjects. In 2-Hz EAS group, positive correlations were observed in contralateral primary motor area, supplementary motor area, and ipsilateral superior temporal gyrus, while negative correlations were found in bilateral hippocampus. In 100-Hz EAS group, positive correlations were observed in contralateral inferior parietal lobule, ipsilateral anterior cingulate cortex, nucleus accumbens, and pons, while negative correlation was detected in contralateral amygdala. These results suggest that functional activities of certain brain areas might be correlated with the effect of EAS-induced analgesia, in a frequency-dependent dynamic. EAS-induced analgesia with low and high frequencies seems to be mediated by different, though overlapped, brain networks. The differential activations/de-activations in brain networks across subjects may provide a neurobiological explanation for the mechanisms of the induction and the individual variability of analgesic effect induced by EAS, or that of manual acupuncture as well.

Evidence from brain imaging with fMRI supporting functional specificity of acupoints in humans.

We tested whether the stimulation of acupoints in the same spinal segments could induce different central responses with functional magnetic resonance imaging (fMRI) study. Stimulation of acupoints ST36/SP6 (Zusanli/Sanyinjiao) or GB34/BL57 (Yanglingquan/Chengshan) both activated primary and secondary somatosensory area, insula, ventral thalamus, parietal Brodmann Area 40, temporal lobe, putamen, and cerebellum, while de-activated amygdala. Nevertheless, ST36/SP6 stimulation specifically activated orbital frontal cortex and de-activated hippocampus. Alternatively, stimulation of GB34/BL57 activated dorsal thalamus and inhibited those of primary motor area and premotor cortex. Thus, stimulation of acupoints in the same spinal segments induced distinct though overlapped cerebral response patterns, which indicated the existence of acupoint specificity.

Neural correlates of prospective memory in individuals with schizotypal personality features.

OBJECTIVE: Prospective memory (PM) refers to the ability to remember to perform actions in the future. Schizophrenia spectrum disorders show impairments in PM but neural correlates of these impairments remain unclear. The present study aimed to examine brain activation during PM to identify impairments in individuals with schizotypal personality features. METHOD: Nineteen participants with schizotypal features and 22 healthy controls participated in a functional MRI experiment while performing a PM task. RESULTS: Results showed that the prefrontal cortex (including Brodmann Area [BA] 10), middle temporal gyrus, and precuneus were activated when performing the PM task compared with baseline. The schizotypal and control groups did not differ in behavioral PM performance. However, participants with schizotypal features showed decreased activations in the inferior and medial frontal lobes (BA 45, and 8). CONCLUSIONS: These results confirmed that the PM network involves prefrontal cortex, including BA 10. The lower activation in prefrontal cortex of individuals with schizotypal features when performing a PM task indicates brain activation abnormality. Notably, this abnormality may occur in the absence of any behavioral manifestation. Our findings support the hypothesis of frontal lobe involvement in PM deficits observed in individuals with schizotypal features.

Interhemispheric functional connectivity and its relationships with clinical characteristics in major depressive disorder: a resting state fMRI study.

BACKGROUND: Abnormalities in large-scale, structural and functional brain connectivity have been increasingly reported in patients with major depressive disorder (MDD). However, MDD-related alterations in functional interaction between the cerebral hemispheres are still not well understood. Resting state fMRI, which reveals spontaneous neural fluctuations in blood oxygen level dependent signals, provides a means to detect interhemispheric functional coherence. We examined the resting state functional connectivity (RSFC) between the two hemispheres and its relationships with clinical characteristics in MDD patients using a recently proposed measurement named "voxel-mirrored homotopic connectivity (VMHC)". METHODOLOGY/PRINCIPAL FINDINGS: We compared the interhemispheric RSFC, computed using the VMHC approach, of seventeen first-episode drug-naive patients with MDD and seventeen healthy controls. Compared to the controls, MDD patients showed significant VMHC decreases in the medial orbitofrontal gyrus, parahippocampal gyrus, fusiform gyrus, and occipital regions including the middle occipital gyrus and cuneus. In MDD patients, a negative correlation was found between VMHC of the fusiform gyrus and illness duration. Moreover, there were several regions whose VMHC showed significant negative correlations with the severity of cognitive disturbance, including the prefrontal regions, such as middle and inferior frontal gyri, and two regions in the cereballar crus. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the functional coordination between homotopic brain regions is impaired in MDD patients, thereby providing new evidence supporting the interhemispheric connectivity deficits of MDD. The significant correlations between the VMHC and clinical characteristics in MDD patients suggest potential clinical implication of VMHC measures for MDD. Interhemispheric RSFC may serve as a useful screening method for evaluating MDD where neural connectivity is implicated in the pathophysiology.