Monocular and binocular mechanisms detect modulations of dot density and dot contrast.

Strong reciprocity has been demonstrated between (1) spatial modulations of dot density and modulations of dot luminance, and (2) modulations of dot density and modulations of dot contrast, in textures. The latter are much easier to detect when presented in phase with one another than when presented 180° out of phase, although out-of-phase modulations can also be detected given sufficient amplitude. This result supports the existence of two detection mechanisms: one that is excited by both density modulations and contrast modulations (quiescent when those modulations are presented 180° out of phase) and another that is relatively insensitive to either density modulations or contrast modulations (thus remaining stimulated regardless of phase angle). We investigate whether the mechanism responsible for detecting out-of-phase modulations depends on high-level computations (downstream from the confluence of monocular signals) or whether both mechanisms are situated at the monocular level of visual processing. Specifically, density-modulated and/or contrast-modulated stimuli were presented monocularly (i.e., to the same eye) or dichoptically (i.e., to opposite eyes). Out-of-phase modulations of density were much easier to detect when presented dichoptically. A dichoptic advantage was also found for out-of-phase density and contrast modulations. These dichoptic advantages imply conscious access to a mechanism at the monocular level of processing. When density modulations were presented dichoptically, 180° out of phase, detection thresholds were highest. Consequently, a mechanism with binocular input must also contribute to the detection of these modulations. We describe a minimal, image-based model for these results that contains one monocular computation and one binocular computation.

Dissecting Psychiatric Heterogeneity and Comorbidity with Core Region-Based Machine Learning.

Machine learning approaches are increasingly being applied to neuroimaging data from patients with psychiatric disorders to extract brain-based features for diagnosis and prognosis. The goal of this review is to discuss recent practices for evaluating machine learning applications to obsessive-compulsive and related disorders and to advance a novel strategy of building machine learning models based on a set of core brain regions for better performance, interpretability, and generalizability. Specifically, we argue that a core set of co-altered brain regions (namely 'core regions') comprising areas central to the underlying psychopathology enables the efficient construction of a predictive model to identify distinct symptom dimensions/clusters in individual patients. Hypothesis-driven and data-driven approaches are further introduced showing how core regions are identified from the entire brain. We demonstrate a broadly applicable roadmap for leveraging this core set-based strategy to accelerate the pursuit of neuroimaging-based markers for diagnosis and prognosis in a variety of psychiatric disorders.

Subthalamic stimulation modulates motor network in Parkinson's disease: recover, relieve and remodel.

Aberrant dynamic switches between internal brain states are believed to underlie motor dysfunction in Parkinson's disease. Deep brain stimulation of the subthalamic nucleus is a well-established treatment for the motor symptoms of Parkinson's disease, yet it remains poorly understood how subthalamic stimulation modulates the whole-brain intrinsic motor network state dynamics. To investigate this, we acquired resting-state functional magnetic resonance imaging time-series data from 27 medication-free patients with Parkinson's disease (mean age: 64.8 years, standard deviation: 7.6) who had deep brain stimulation electrodes implanted in the subthalamic nucleus, in both on and off stimulation states. Sixteen matched healthy individuals were included as a control group. We adopted a powerful data-driven modelling approach, known as a hidden Markov model, to disclose the emergence of recurring activation patterns of interacting motor regions (whole-brain intrinsic motor network states) via the blood oxygen level-dependent signal detected in the resting-state functional magnetic resonance imaging time-series data from all participants. The estimated hidden Markov model disclosed the dynamics of distinct whole-brain motor network states, including frequency of occurrence, state duration, fractional coverage and their transition probabilities. Notably, the data-driven decoding of whole-brain intrinsic motor network states revealed that subthalamic stimulation reshaped functional network expression and stabilized state transitions. Moreover, subthalamic stimulation improved motor symptoms by modulating key trajectories of state transition within whole-brain intrinsic motor network states. This modulation mechanism of subthalamic stimulation was manifested in three significant effects: recovery, relieving and remodelling effects. Significantly, recovery effects correlated with improvements in tremor and posture symptoms induced by subthalamic stimulation (P < 0.05). Furthermore, subthalamic stimulation was found to restore a relatively low level of fluctuation of functional connectivity in all motor regions to a level closer to that of healthy participants. Also, changes in the fluctuation of functional connectivity between motor regions were associated with improvements in tremor and gait symptoms (P < 0.05). These findings fill a gap in our knowledge of the role of subthalamic stimulation at the level of neural activity, revealing the regulatory effects of subthalamic stimulation on whole-brain inherent motor network states in Parkinson's disease. Our results provide mechanistic insight and explanation for how subthalamic stimulation modulates motor symptoms in Parkinson's disease.

Subthalamic and pallidal stimulation in Parkinson's disease induce distinct brain topological reconstruction.

The subthalamic nucleus (STN) and globus pallidus internus (GPi) are the two most common and effective target brain areas for deep brain stimulation (DBS) treatment of advanced Parkinson's disease. Although DBS has been shown to restore functional neural circuits of this disorder, the changes in topological organization associated with active DBS of each target remain unknown. To investigate this, we acquired resting-state functional magnetic resonance imaging (fMRI) data from 34 medication-free patients with Parkinson's disease that had DBS electrodes implanted in either the subthalamic nucleus or internal globus pallidus (n = 17 each), in both ON and OFF DBS states. Sixteen age-matched healthy individuals were used as a control group. We evaluated the regional information processing capacity and transmission efficiency of brain networks with and without stimulation, and recorded how stimulation restructured the brain network topology of patients with Parkinson's disease. For both targets, the variation of local efficiency in motor brain regions was significantly correlated (p < 0.05) with improvement rate of the Uniform Parkinson's Disease Rating Scale-III scores, with comparable improvements in motor function for the two targets. However, non-motor brain regions showed changes in topological organization during active stimulation that were target-specific. Namely, targeting the STN decreased the information transmission of association, limbic and paralimbic regions, including the inferior frontal gyrus angle, insula, temporal pole, superior occipital gyri, and posterior cingulate, as evidenced by the simultaneous decrease of clustering coefficient and local efficiency. GPi-DBS had a similar effect on the caudate and lenticular nuclei, but enhanced information transmission in the cingulate gyrus. These effects were not present in the DBS-OFF state for GPi-DBS, but persisted for STN-DBS. Our results demonstrate that DBS to the STN and GPi induce distinct brain network topology reconstruction patterns, providing innovative theoretical evidence for deciphering the mechanism through which DBS affects disparate targets in the human brain.

Anterior limb of the internal capsule tractography: relationship with capsulotomy outcomes in obsessive-compulsive disorder.

OBJECTIVES: Surgical procedures targeting the anterior limb of the internal capsule (aLIC) can be effective in patients with selected treatment-refractory obsessive-compulsive disorder (OCD). The aLIC consists of white-matter tracts connecting cortical and subcortical structures and show a topographical organisation. Here we assess how aLIC streamlines are affected in OCD compared with healthy controls (HCs) and which streamlines are related with post-capsulotomy improvement. METHODS: Diffusion-weighted MRI was used to compare white-matter microstructure via the aLIC between patients with OCD (n=100, 40 women, mean of age 31.8 years) and HCs (n=88, 39 women, mean of age 29.6 years). For each individual, the fractional anisotropy (FA) and streamline counts were calculated for each white-matter fibre bundle connecting a functionally defined prefrontal and subcortical region. Correlations between tractography measures and pre-capsulotomy and post-capsulotomy clinical outcomes (in obsessive-compulsive, anxiety and depression scores 6 months after surgery) were assessed in 41 patients with OCD. RESULTS: Hierarchical clustering dendrograms show an aLIC organisation clustering lateral and dissociating ventral and dorsal prefrontal-thalamic streamlines, findings highly relevant to surgical targeting. Compared with HCs, patients with OCD had lower aLIC FA across multiple prefrontal cortical-subcortical regions (p<0.0073, false discovery rate-adjusted). Greater streamline counts of the dorsolateral prefrontal-thalamic tracts in patients with OCD predicted greater post-capsulotomy obsessive-compulsive improvement (p=0.016). In contrast, greater counts of the dorsal cingulate-thalamic streamlines predicted surgical outcomes mediated by depressive and anxiety improvements. CONCLUSIONS: These findings shed light on the critical role of the aLIC in OCD and may potentially contribute towards precision targeting to optimise outcomes in OCD.

Normative Analysis of Individual Brain Differences Based on a Population MRI-Based Atlas of Cynomolgus Macaques.

The developmental trajectory of the primate brain varies substantially with aging across subjects. However, this ubiquitous variability between individuals in brain structure is difficult to quantify and has thus essentially been ignored. Based on a large-scale structural magnetic resonance imaging dataset acquired from 162 cynomolgus macaques, we create a species-specific 3D template atlas of the macaque brain, and deploy normative modeling to characterize individual variations of cortical thickness (CT) and regional gray matter volume (GMV). We observed an overall decrease in total GMV and mean CT, and an increase in white matter volume from juvenile to early adult. Specifically, CT and regional GMV were greater in prefrontal and temporal cortices relative to early unimodal areas. Age-dependent trajectories of thickness and volume for each cortical region revealed an increase in the medial temporal lobe, and decreases in all other regions. A low percentage of highly individualized deviations of CT and GMV were identified (0.0021%, 0.0043%, respectively, P < 0.05, false discovery rate [FDR]-corrected). Our approach provides a natural framework to parse individual neuroanatomical differences for use as a reference standard in macaque brain research, potentially enabling inferences regarding the degree to which behavioral or symptomatic variables map onto brain structure in future disease studies.

Heightened perception of illusory motion is associated with symptom severity in schizophrenia patients.

Abnormal perceptual processing in schizophrenia may contribute to the development of positive symptoms such as hallucinations. Experimental findings suggest that such abnormalities result from impaired processing of local signals into complex cortical representations. Because complex processing is needed to generate the perception of illusory motion from local signals, deteriorated perception of illusory motion would be expected in schizophrenia. However, findings are mixed, and the relationship between complex motion processing and symptoms is unclear. Illusions with multiple flow components (e.g. rotation/expansion) are known to strongly engage specialized complex processing mechanisms that may be abnormal in schizophrenia, but have not yet been investigated. We used a recently constructed paradigm based on the Pinna-Brelstaff illusion to manipulate complex-flow illusory perception in a quantitative manner and probe associations with dimensional symptoms. In 102 patients and 90 controls, perceived speed and perceptual variability for the PBF were measured across a range of parameters. Meanwhile, eye movement was recorded and gaze parameters were analysed to examine effects on illusory perception. Our results showed that patients experienced faster illusory rotation than controls, while they made fewer eye fixations. This heightened illusory perception was significantly correlated with positive and general, but not negative, symptom scores. Our results indicate that unusual processing of complex-flow motion in patients may be specifically related to dimensional symptoms, which could provide a promising strategy for parsing heterogeneity in the schizophrenia syndrome. This further highlights the role of motion perception abnormalities in the pathophysiology of schizophrenia, thus encouraging future investigation into visual remediation therapeutics.

An Evaluation of the Psychometric Properties of the Sheehan Disability Scale in a Chinese Psychotherapy-Seeking Sample.

Although the Sheehan Disability Scale (SDS) is one of the most extensively used and tested disability measurements, there has only been one psychometric evaluation of its properties in a Chinese-speaking population. Here, we provide a comprehensive psychometric assessment of the scale in 465 Mandarin-speakers who were accessing information online regarding psychotherapy. Principal component analysis and subsequent confirmatory factor analysis indicated that the SDS is one-dimensional (normed fit index = 0.976, non-normed fit index = 0.97, comparative fit index = 0.98, goodness-of-fit index = 0.967, standardized root mean-square residual = 0.023, root mean-square error of approximation = 0.149). The SDS exhibited excellent internal consistency (α = .89) and moderate test-retest reliability when readministered approximately 8 days later (intraclass correlation coefficient = 0.55). Convergent validity was demonstrated by strong relationships with other measures of functional impairment (FI), while divergent validity was evidenced by fair correlation with a treatment ambivalence measure. Known-groups validity analyses showed that high FI was associated with significantly higher clinical scores of anxiety, depression, and obsessive-compulsive symptoms. Regression analysis indicated that the Depression Anxiety Stress Scale-21 score accounted for 37.6% of variance in FI. Overall, these findings support the reliability and validity of the SDS when used in Chinese treatment-seeking individuals, as well its usefulness as an online screening tool of FI.

Neuroplastic changes in resting-state functional connectivity after rTMS intervention for methamphetamine craving.

Amphetamine-type stimulants are the second most commonly abused illicit drug worldwide, with no effective medical treatments currently available. Previous studies have demonstrated that high frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) reduced cue-induced craving in patients with methamphetamine dependence. However, the neuroplastic mechanism underlying rTMS intervention in methamphetamine users remains to be elucidated. Sixty participants (40 males) with severe methamphetamine use disorder according to DSM-5 were randomized to receive either intermittent theta burst protocols (iTBS) (short bursts of 50 Hz rTMS repeated at a rate in the theta range (5 Hz), 2-sec on, 8-sec off for 5 min; 900 pulses) or sham rTMS over the DLPFC over four weeks (20 daily sessions). Resting state functional connectivity magnetic resonance imaging was acquired before and after rTMS intervention. Participants received drug related cue exposure and rated their craving before and after stimulation. Seed-based functional connectivity analysis was performed to probe rTMS-induced neuroplastic reorganization of brain functional networks. Results showed that twenty daily rTMS sessions decreased craving, increased functional connectivity between left DLPFC and inferior parietal lobule, and decreased functional connectivity between insula and inferior parietal lobule, medial temporal lobe and precuneus. Moreover, the increase of functional connectivity between DLPFC and inferior parietal lobule correlated with craving reduction. This study suggests that neuroplastic changes of frontoparietal functional connectivity contributes to craving reduction, shedding light on the therapeutic effect of rTMS on methamphetamine use disorder. This article is part of the special issue on Stress, Addiction and Plasticity.

MECP2 Duplication Causes Aberrant GABA Pathways, Circuits and Behaviors in Transgenic Monkeys: Neural Mappings to Patients with Autism.

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene-circuit-behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced ß-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene-circuit-behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2 However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.

Effect of PEGylated Magnetic PLGA-PEI Nanoparticles on Primary Hippocampal Neurons: Reduced Nanoneurotoxicity and Enhanced Transfection Efficiency with Magnetofection.

Despite broad application of nanotechnology in neuroscience, the nanoneurotoxicity of magnetic nanoparticles in primary hippocampal neurons remains poorly characterized. In particular, understanding how magnetic nanoparticles perturb neuronal calcium homeostasis is critical when considering magnetic nanoparticles as a nonviral vector for effective gene therapy in neuronal diseases. Here, we address the pressing need to systematically investigate the neurotoxicity of magnetic nanoparticles with different surface charges in primary hippocampal neurons. We found that unlike negative and neutral nanoparticles, positively charged magnetic nanoparticles (magnetic poly(lactic-co-glycolic acid) (PLGA)-polyethylenimine (PEI) nanoparticles, MNP-PLGA-PEI NPs) rapidly elevated cytoplasmic calcium levels in primary hippocampal neurons, mainly via extracellular calcium influx regulated by voltage-gated calcium channels. We went on to show that this perturbation of intracellular calcium homeostasis elicited serious cytotoxicity in primary hippocampal neurons. However, our next experiment demonstrated that PEGylation on the surface of MNP-PLGA-PEI NPs shielded the surface charge, thereby preventing the perturbation of intracellular calcium homeostasis. That is, PEGylated MNP-PLGA-PEI NPs reduced nanoneurotoxicity. Importantly, biocompatible PEGylated MNP-PLGA-PEI NPs under an external magnetic field enhanced transfection efficiency (>7%) of plasmid DNA encoding GFP in primary hippocampal neurons compared to NPs without external magnetic field mediation. Moreover, under an external magnetic field, this system achieved gene transfection in the hippocampus of the C57 mouse. Overall, this study is the first to successfully employ biocompatible PEGylated MNP-PLGA-PEI NPs for transfection using a magnetofection strategy in primary hippocampal neurons, thereby providing a nanoplatform as a new perspective for treating neuronal diseases or modulating neuron activities.

A graph representation of functional diversity of brain regions.

INTRODUCTION: Modern network science techniques are popularly used to characterize the functional organization of the brain. A major challenge in network neuroscience is to understand how functional characteristics and topological architecture are related in the brain. Previous task-based functional neuroimaging studies have uncovered a core set of brain regions (e.g., frontal and parietal) supporting diverse cognitive tasks. However, the graph representation of functional diversity of brain regions remains to be understood. METHODS: Here, we present a novel graph measure, the neighbor dispersion index, to test the hypothesis that the functional diversity of a brain region is embodied by the topological dissimilarity of its immediate neighbors in the large-scale functional brain network. RESULTS: We consistently identified in two independent and publicly accessible resting-state functional magnetic resonance imaging datasets that brain regions in the frontoparietal and salience networks showed higher neighbor dispersion index, whereas those in the visual, auditory, and sensorimotor networks showed lower neighbor dispersion index. Moreover, we observed that human fluid intelligence was associated with the neighbor dispersion index of dorsolateral prefrontal cortex, while no such association for the other metrics commonly used for characterizing network hubs was noticed even with an uncorrected p < .05. CONCLUSIONS: This newly developed graph theoretical method offers fresh insight into the topological organization of functional brain networks and also sheds light on individual differences in human intelligence.

Isoflurane-Induced Burst Suppression Increases Intrinsic Functional Connectivity of the Monkey Brain.

Animal functional magnetic resonance imaging (fMRI) has provided key insights into the physiological mechanisms underlying healthy and diseased brain states. In non-human primates, resting-state fMRI studies are commonly conducted under isoflurane anesthesia, where anesthetic concentration is used to roughly infer anesthesia depth. However, within the recommended isoflurane concentration range (1.00-1.50%), the brain state can switch from moderate anesthesia characterized by stable slow wave (SW) electroencephalogram (EEG) signals to deep anesthesia characterized by burst suppression (BS), which is electrophysiologically distinct from the resting state. To confirm the occurrence rate of BS activity in common setting of animal fMRI study, we conducted simultaneous resting-state EEG and fMRI experiments on 16 monkeys anesthetized using 0.80-1.30% isoflurane, and detected BS activity in two of them. Datasets either featured with BS or SW activity from these two monkeys were analyzed to investigate the intrinsic functional connectivity (FC) patterns during BS. In datasets with BS activity, we observed robust coupling between the BS pattern (the binary alternation between burst and suppression activity in EEG signal) and filtered BOLD signals in most brain areas, which was associated with a non-specific enhancement in whole brain connectivity. After eliminating the BS coupling effect by regressing out the BS pattern, we detected an overall increase in FC with a few decreased connectivity compared to datasets with SW activity. These affected connections were preferentially distributed within orbitofrontal cortex, between orbitofrontal and prefrontal/cingulate/occipital cortex, and between temporal and parietal cortex. Persistence of the default mode network and recovery of thalamocortical connections were also detected under deep anesthesia with BS activity. Taken together, the observed spatially specific alterations in BS activity induced by isoflurane not only highlight the necessity of EEG monitoring and careful data preprocessing in fMRI studies on anesthetized animals, but also advance our understanding of the underlying multi-phased mechanisms of anesthesia.

Brain Map of Intrinsic Functional Flexibility in Anesthetized Monkeys and Awake Humans.

Emerging neuroimaging studies emphasize the dynamic organization of spontaneous brain activity in both human and non-human primates, even under anesthesia. In a recent study, we were able to characterize the heterogeneous architecture of intrinsic functional flexibility in the awake, resting human brain using time-resolved analysis and a probabilistic model. However, it is unknown whether this organizational principle is preserved in the anesthetized monkey brain, and how anesthesia affects dynamic and static measurements of spontaneous brain activity. To investigate these issues, we collected resting-state functional magnetic resonance imaging (fMRI) datasets from 178 awake humans and 11 anesthetized monkeys (all healthy). Our recently established method, a complexity measurement (i.e., Shannon entropy) of dynamic functional connectivity patterns of each brain region, was used to map the intrinsic functional flexibility across the cerebral cortex. To further explore the potential effects of anesthesia, we performed time series analysis and correlation analysis between dynamic and static measurements within awake human and anesthetized monkey brains, respectively. We observed a heterogeneous profile of intrinsic functional flexibility in the anesthetized monkey brain, which showed some similarities to that of awake humans (r = 0.30, p = 0.007). However, we found that brain activity in anesthetized monkeys generally shifted toward random fluctuations. Moreover, there is a negative correlation between nodal entropy for the distribution of dynamic functional connectivity patterns and static functional connectivity strength in anesthetized monkeys, but not in awake humans. Our findings indicate that the heterogeneous architecture of intrinsic functional flexibility across cortex probably reflects an evolutionarily conserved aspect of functional brain organization, which persists across levels of cognitive processing (states of consciousness). The coupling between nodal entropy for the distribution of dynamic functional connectivity patterns and static functional connectivity strength may serve as a potential signature of anesthesia. This study not only offers fresh insight into the evolution of brain functional architecture, but also advances our understanding of the dynamics of spontaneous brain activity.

Modular Functional-Metabolic Coupling Alterations of Frontoparietal Network in Schizophrenia Patients.

Background: Brain functional dysconnectivity, as well as altered network organization, have been demonstrated to occur in schizophrenia. Brain networks are increasingly understood to exhibit modular community structures, which provides advantages in robustness and functional adaptivity. The frontoparietal network (FPN) serves as an important functional module, and metabolic and functional alterations in the FPN are associated with the pathophysiology of schizophrenia. However, how intra-modular biochemical disruptions lead to inter-modular dysfunction of the FPN, remains unclear. In this study, we aim to investigate alterations in the modular functional-metabolic coupling of the FPN, in patients with schizophrenia. Methods: We combined resting-state functional magnetic resonance imaging (rs-fMRI) and magnetic resonance spectroscopy (MRS) technology and acquired multimodal neuroimaging data in 20 patients with schizophrenia and 26 healthy controls. For the MRS, the dorsolateral prefrontal cortex (DLPFC) region within the FPN was explored. Metabolites including gamma aminobutyric acid (GABA), N-aspart-acetyl (NAA) and glutamate + glutamine (Glx) were quantified, using LCModel software. A graph theoretical approach was applied for functional modular parcellation. The relationship between inter/intra-modular connectivity and metabolic concentration was examined using the Pearson correlation analysis. Moreover, correlations with schizophrenia symptomatology were investigated by the Spearman correlation analysis. Results: The functional topological network consisted of six modules in both subject groups, namely, the default mode, frontoparietal, central, hippocampus, occipital, and subcortical modules. Inter-modular connectivity between the frontoparietal and central modules, and the frontoparietal and the hippocampus modules was decreased in the patient group compared to the healthy controls, while the connectivity within the frontoparietal modular increased in the patient group. Moreover, a positive correlation between the frontoparietal and central module functional connectivity and the NAA in the DLPFC was found in the healthy control group (r = 0.614, p = 0.001), but not in the patient group. Significant functional dysconnectivity between the frontoparietal and limbic modules was correlated with the clinical symptoms of patients. Conclusions: This study examined the links between functional connectivity and the neuronal metabolic level in the DLPFC of SCZ. Impaired functional connectivity of the frontoparietal areas in SCZ, may be partially explained by a neurochemical-functional connectivity decoupling effect. This disconnection pattern can further provide useful insights in the cognitive and perceptual impairments of schizophrenia in future studies.

Pallidal deep brain stimulation combined with capsulotomy for Tourette's syndrome with psychiatric comorbidity.

OBJECTIVE: A current challenge is finding an effective and safe treatment for severely disabled patients with Tourette's syndrome (TS) and comorbid psychiatric disorders, in whom conventional treatments have failed. The authors aimed to evaluate the utility of globus pallidus internus deep brain stimulation (GPi-DBS) combined with bilateral anterior capsulotomy in treating these clinically challenging patients. METHODS: The authors conducted a retrospective review of the clinical history and outcomes of 10 severely disabled patients with treatment-refractory TS and a psychiatric comorbidity, who had undergone GPi-DBS combined with bilateral anterior capsulotomy in their hospital. At the time of surgery, patients presented mainly with obsessive-compulsive disorder and affective disorders. Clinical outcome assessments of tic and psychiatric symptoms, as well as of general adaptive functioning and quality of life, were performed at the time of surgery and at 6, 12, and between 24 and 96 months postsurgery. RESULTS: After surgery, all patients showed significant progressive improvements in tic and psychiatric symptoms, along with improvements in general adaptive functioning and quality of life. Tic alleviation reached 64% at 12 months and 77% at the last follow-up on the Yale Global Tic Severity Scale. At the final follow-up, patients had functionally recovered and displayed no or only mild tic and psychiatric symptoms. All patients tolerated treatment reasonably well, with no serious side effects. CONCLUSIONS: GPi-DBS combined with bilateral anterior capsulotomy seems to offer major clinical benefits to severely disabled patients with otherwise treatment-refractory TS and psychiatric comorbidities.

Dissociable Frontostriatal Connectivity: Mechanism and Predictor of the Clinical Efficacy of Capsulotomy in Obsessive-Compulsive Disorder.

BACKGROUND: Little is known about the neural mechanism and response variability underlying neurosurgical interventions for intractable obsessive-compulsive disorder (OCD). METHODS: Of 81 OCD patients screened for capsulotomy identified in our institutional database, 36 patients with clinical assessment before and after capsulotomy and imaging data (9 of 36 patients without postoperative imaging data used as an independent test group), and 29 healthy control subjects were retrospectively recruited. Twenty of 36 patients (56%) responded to the lesion procedure (determined as a ≥35% reduction in Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score). Seed-based (i.e., ventral and dorsal caudate, medial dorsal thalamus, and ventral and dorsal putamen) resting-state functional connectivity was used to examine alterations in frontostriatal circuitry after capsulotomy. RESULTS: The Y-BOCS score significantly decreased (p < .001) after capsulotomy in OCD patients. Functional connectivity between the ventral striatum/nucleus accumbens and the dorsal anterior cingulate cortex was reduced (p < .05, corrected) after the surgical procedure. Moreover, change in connectivity significantly correlated with alteration in Y-BOCS score (r = .41, p = .033). In addition, preoperative connectivity between the dorsal caudate and the dorsal anterior cingulate cortex could differentiate nonresponders from responders and predict changes in Y-BOCS score (R2 = .23, F1,25 = 7.56, p = .011), which was generalized in an independent test group. CONCLUSIONS: We demonstrated that restoration of ventral frontostriatal connectivity was associated with clinical improvement in refractory OCD, suggesting a therapeutic mechanism of capsulotomy. Moreover, preoperative variations in dorsal frontostriatal connectivity predicted clinical response, which may offer a predictor of treatment outcome.

Dynamic Network Communication in the Human Functional Connectome Predicts Perceptual Variability in Visual Illusion.

Ubiquitous variability between individuals in visual perception is difficult to standardize and has thus essentially been ignored. Here we construct a quantitative psychophysical measure of illusory rotary motion based on the Pinna-Brelstaff figure (PBF) in 73 healthy volunteers and investigate the neural circuit mechanisms underlying perceptual variation using functional magnetic resonance imaging (fMRI). We acquired fMRI data from a subset of 42 subjects during spontaneous and 3 stimulus conditions: expanding PBF, expanding modified-PBF (illusion-free) and expanding modified-PBF with physical rotation. Brain-wide graph analysis of stimulus-evoked functional connectivity patterns yielded a functionally segregated architecture containing 3 discrete hierarchical networks, commonly shared between rest and stimulation conditions. Strikingly, communication efficiency and strength between 2 networks predominantly located in visual areas robustly predicted individual perceptual differences solely in the illusory stimulus condition. These unprecedented findings demonstrate that stimulus-dependent, not spontaneous, dynamic functional integration between distributed brain networks contributes to perceptual variability in humans.

Target-specific deep brain stimulation of the ventral capsule/ventral striatum for the treatment of neuropsychiatric disease.

Deep brain stimulation (DBS) is a well-established therapy for Parkinson's disease and other movement disorders. An accumulating body of evidence supports the extension of DBS application for the treatment of refractory psychiatric disorders. The ventral capsule/ventral striatum (VC/VS) is the most common anatomical target for obsessive-compulsive disorder (OCD), addiction, and depression. However, no specific electrode is available for the clinical targeting of these areas for DBS. According to the anatomical features of the VC/VS, a novel electrode was developed for simultaneous and independently programmed stimulation of the nucleus accumbens (NAc) and the anterior limb of the internal capsule (ALIC). This VC/VS-specific electrode has the potential to enhance stimulus intensity, provide independent and flexible target stimulation.