Sex differences in fetal brain functional network topology.

The fetal period is a critical stage in brain development, and understanding the characteristics of the fetal brain is crucial. Although some studies have explored aspects of fetal brain functional networks, few have specifically focused on sex differences in brain network characteristics. We adopted the graph theory method to calculate brain network functional connectivity and topology properties (including global and nodal properties), and further compared the differences in these parameters between male and female fetuses. We found that male fetuses showed an increased clustering coefficient and local efficiency than female fetuses, but no significant group differences concerning other graph parameters and the functional connectivity matrix. Our study suggests the existence of sex-related distinctions in the topological properties of the brain network at the fetal stage of development and demonstrates an increase in brain network separation in male fetuses compared with female fetuses.

Patterns of brain dynamic functional connectivity are linked with attention-deficit/hyperactivity disorder-related behavioral and cognitive dimensions.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a clinically heterogeneous neurodevelopmental disorder defined by characteristic behavioral and cognitive features. Abnormal brain dynamic functional connectivity (dFC) has been associated with the disorder. The full spectrum of ADHD-related variation of brain dynamics and its association with behavioral and cognitive features remain to be established. METHODS: We sought to identify patterns of brain dynamics linked to specific behavioral and cognitive dimensions using sparse canonical correlation analysis across a cohort of children with and without ADHD (122 children in total, 63 with ADHD). Then, using mediation analysis, we tested the hypothesis that cognitive deficits mediate the relationship between brain dynamics and ADHD-associated behaviors. RESULTS: We identified four distinct patterns of dFC, each corresponding to a specific dimension of behavioral or cognitive function (r = 0.811-0.879). Specifically, the inattention/hyperactivity dimension was positively associated with dFC within the default mode network (DMN) and negatively associated with dFC between DMN and the sensorimotor network (SMN); the somatization dimension was positively associated with dFC within DMN and SMN; the inhibition and flexibility dimension and fluency and memory dimensions were both positively associated with dFC within DMN and between DMN and SMN, and negatively associated with dFC between DMN and the fronto-parietal network. Furthermore, we observed that cognitive functions of inhibition and flexibility mediated the relationship between brain dynamics and behavioral manifestations of inattention and hyperactivity. CONCLUSIONS: These findings document the importance of distinct patterns of dynamic functional brain activity for different cardinal behavioral and cognitive features related to ADHD.

Brain alterations in sensorimotor and emotional regions associated with temporomandibular disorders.

OBJECTIVES: Temporomandibular disorders (TMD) are characterized by sensorimotor and psychological dysfunction, with evidence revealing the implication of a dysfunctional central nervous system. Previous magnetic resonance imaging (MRI) studies have reported brain alterations in TMD, but most studies focused on either structure or function by a single modality of MRI and investigated static functional connectivity (FC) in TMD. By combining structural and functional MRI data, the present study aimed to identify brain regions with structural abnormalities in TMD patients and examine static and dynamic FC seeded by these regions to investigate structural brain alterations and related disrupted FC underlying the pathophysiology of TMD. METHODS: We recruited 30 TMD patients and 20 healthy controls who underwent 3.0 T MRI scanning with T1-weighted images using a three-dimensional magnetization-prepared rapid gradient-echo sequence and resting state functional images using a gradient-echo echo-planar imaging sequence. Cortical thickness, volume, surface area, and subcortical volume were calculated, where brain areas with significant structural between-group differences were treated as seeds for static and dynamic FC analyses. RESULTS: In this preliminary study, we found between-group alterations in sensorimotor regions including decreased cortical thickness in the right sensorimotor cortex as well as decreased volume in the left putamen and associated reduced dynamic FC with the anterior midcingulate cortex; and alterations in emotion processing and regulation regions including decreased volume/surface area in the left posterior superior temporal gyrus and associated increased dynamic FC with the precuneus in TMD patients than controls, having all p < 0.05 with corrections for multiple comparisons. CONCLUSION: Our findings of structural and functional abnormalities in brain regions implicated in sensorimotor and emotional functions provided evidence for the biopsychosocial model of TMD and facilitated our understanding of the pathophysiological mechanism underlying TMD. The associations between neuroimaging results and clinical measurements of TMD warrant further exploration.

Altered brain functional network dynamics in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a debilitating and disabling neuropsychiatric disorder, whose neurobiological basis remains unclear. Although traditional static resting-state magnetic resonance imaging (rfMRI) studies have found aberrant functional connectivity (FC) in OCD, alterations in whole-brain FC and topological properties in the context of brain dynamics remain relatively unexplored. The rfMRI data of 29 patients with OCD and 40 healthy controls were analyzed using group independent component analysis to obtain independent components (ICs) and a sliding-window approach to generate dynamic functional connectivity (dFC) matrices. dFC patterns were clustered into three reoccurring states, and state transition metrics were obtained. Then, graph-theory methods were applied to dFC matrices to calculate the variability of network topological organization. The occurrence of a state (State 1) with the highest modularity index and lowest mean FC between networks was increased significantly in OCD, and the fractional time in brain State 1 was positively correlated with anxiety level in patients. State 1 was characterized by having positive connections within default mode (DMN) and salience networks (SAN), and negative coupling between the two networks. Additionally, ICs belonging to DMN and SAN showed lower temporal variability of nodal degree centrality and efficiency in patients, which was related to longer illness duration and higher current obsession ratings. Our results provide evidence of clinically relevant aberrant dynamic brain activity in OCD. Increased functional segregation among networks and impaired functional flexibility in connections among brain regions in DMN and SAN may play important roles in the neuropathology of OCD.

The neuro-pathophysiology of temporomandibular disorders-related pain: a systematic review of structural and functional MRI studies.

Chronic pain surrounding the temporomandibular joints and masticatory muscles is often the primary chief complaint of patients with temporomandibular disorders (TMD) seeking treatment. Yet, the neuro-pathophysiological basis underlying it remains to be clarified. Neuroimaging techniques have provided a deeper understanding of what happens to brain structure and function in TMD patients with chronic pain. Therefore, we performed a systematic review of magnetic resonance imaging (MRI) studies investigating structural and functional brain alterations in TMD patients to further unravel the neurobiological underpinnings of TMD-related pain. Online databases (PubMed, EMBASE, and Web of Science) were searched up to August 3, 2019, as complemented by a hand search in reference lists. A total of 622 papers were initially identified after duplicates removed and 25 studies met inclusion criteria for this review. Notably, the variations of MRI techniques used and study design among included studies preclude a meta-analysis and we discussed the findings qualitatively according to the specific neural system or network the brain regions were involved in. Brain changes were found in pathways responsible for abnormal pain perception, including the classic trigemino-thalamo-cortical system and the lateral and medial pain systems. Dysfunction and maladaptive changes were also identified in the default mode network, the top-down antinociceptive periaqueductal gray-raphe magnus pathway, as well as the motor system. TMD patients displayed altered brain activations in response to both innocuous and painful stimuli compared with healthy controls. Additionally, evidence indicates that splint therapy can alleviate TMD-related symptoms by inducing functional brain changes. In summary, MRI research provides important novel insights into the altered neural manifestations underlying chronic pain in TMD.

Altered dynamic functional and effective connectivity in drug-naive children with Tourette syndrome.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder characterized by repetitive, stereotyped, involuntary tics, the neurological basis of which remains unclear. Although traditional resting-state MRI (rfMRI) studies have identified abnormal static functional connectivity (FC) in patients with TS, dynamic FC (dFC) remains relatively unexplored. The rfMRI data of 54 children with TS and 46 typically developing children (TDC) were analyzed using group independent component analysis to obtain independent components (ICs), and a sliding-window approach to generate dFC matrices. All dFC matrices were clustered into two reoccurring states, the state transition metrics were obtained. We conducted Granger causality and nodal topological analyses to further investigate the brain regions that may play the most important roles in driving whole-brain switching between different states. We found that children with TS spent more time in state 2 (PFDR < 0.001), a state characterized by strong connectivity between ICs, and switched more quickly between states (PFDR = 0.025) than TDC. The default mode network (DMN) may play an important role in abnormal state transitions because the FC that changed the most between the two states was between the DMN and other networks. Additionally, the DMN had increased degree centrality, efficiency and altered causal influence on other networks. Certain alterations related to executive function (r = -0.309, P < 0.05) and tic symptom ratings (r = 0.282; 0.413, P < 0.05) may represent important aspects of the pathophysiology of TS. These findings facilitate our understanding of the neural basis for the clinical presentation of TS.

Structural and functional alterations in the brains of patients with anisometropic and strabismic amblyopia: a systematic review of magnetic resonance imaging studies.

Amblyopia is the most common cause of vision loss in children and can persist into adulthood in the absence of effective intervention. Previous clinical and neuroimaging studies have suggested that the neural mechanisms underlying strabismic amblyopia and anisometropic amblyopia may be different. Therefore, we performed a systematic review of magnetic resonance imaging studies investigating brain alterations in patients with these two subtypes of amblyopia; this study is registered with PROSPERO (registration ID: CRD42022349191). We searched three online databases (PubMed, EMBASE, and Web of Science) from inception to April 1, 2022; 39 studies with 633 patients (324 patients with anisometropic amblyopia and 309 patients with strabismic amblyopia) and 580 healthy controls met the inclusion criteria (e.g., case-control designed, peer-reviewed articles) and were included in this review. These studies highlighted that both strabismic amblyopia and anisometropic amblyopia patients showed reduced activation and distorted topological cortical activated maps in the striate and extrastriate cortices during task-based functional magnetic resonance imaging with spatial-frequency stimulus and retinotopic representations, respectively; these may have arisen from abnormal visual experiences. Compensations for amblyopia that are reflected in enhanced spontaneous brain function have been reported in the early visual cortices in the resting state, as well as reduced functional connectivity in the dorsal pathway and structural connections in the ventral pathway in both anisometropic amblyopia and strabismic amblyopia patients. The shared dysfunction of anisometropic amblyopia and strabismic amblyopia patients, relative to controls, is also characterized by reduced spontaneous brain activity in the oculomotor cortex, mainly involving the frontal and parietal eye fields and the cerebellum; this may underlie the neural mechanisms of fixation instability and anomalous saccades in amblyopia. With regards to specific alterations of the two forms of amblyopia, anisometropic amblyopia patients suffer more microstructural impairments in the precortical pathway than strabismic amblyopia patients, as reflected by diffusion tensor imaging, and more significant dysfunction and structural loss in the ventral pathway. Strabismic amblyopia patients experience more attenuation of activation in the extrastriate cortex than in the striate cortex when compared to anisometropic amblyopia patients. Finally, brain structural magnetic resonance imaging alterations tend to be lateralized in the adult anisometropic amblyopia patients, and the patterns of brain alterations are more limited in amblyopic adults than in children. In conclusion, magnetic resonance imaging studies provide important insights into the brain alterations underlying the pathophysiology of amblyopia and demonstrate common and specific alterations in anisometropic amblyopia and strabismic amblyopia patients; these alterations may improve our understanding of the neural mechanisms underlying amblyopia.

Controllability of Functional Brain Networks and Its Clinical Significance in First-Episode Schizophrenia.

BACKGROUND AND HYPOTHESIS: Disrupted control of brain state transitions may contribute to the diverse dysfunctions of cognition, emotion, and behavior that are fundamental to schizophrenia. Control theory provides the rationale for evaluating brain state transitions from a controllability perspective, which may help reveal the brain mechanism for clinical features such as cognitive control deficits associated with schizophrenia. We hypothesized that brain controllability would be altered in patients with schizophrenia, and that controllability of brain networks would be related to clinical symptomatology. STUDY DESIGN: Controllability measurements of functional brain networks, including average controllability and modal controllability, were calculated and compared between 125 first-episode never-treated patients with schizophrenia and 133 healthy controls (HCs). Associations between controllability metrics and clinical symptoms were evaluated using sparse canonical correlation analysis. STUDY RESULTS: Compared to HCs, patients showed significantly increased average controllability (PFDR = .023) and decreased modal controllability (PFDR = .023) in dorsal anterior cingulate cortex (dACC). General psychopathology symptoms and positive symptoms were positively correlated with average controllability in regions of default mode network and negatively associated with average controllability in regions of sensorimotor, dorsal attention, and frontoparietal networks. CONCLUSIONS: Our findings suggest that altered controllability of functional activity in dACC may play a critical role in the pathophysiology of schizophrenia, consistent with the importance of this region in cognitive and brain state control operations. The demonstration of associations of functional controllability with psychosis symptoms suggests that the identified alterations in average controllability of brain function may contribute to the severity of acute psychotic illness in schizophrenia.

Shared and Disorder-Specific Alterations of Brain Temporal Dynamics in Obsessive-Compulsive Disorder and Schizophrenia.

BACKGROUND: Obsessive-compulsive disorder (OCD) and schizophrenia have distinct but also overlapping symptoms. Few studies have examined the shared and disorder-specific disturbances in dynamic brain function in the 2 disorders. STUDY DESIGN: Resting-state functional magnetic resonance imaging data of 31 patients with OCD and 49 patients with schizophrenia, all untreated, and 45 healthy controls (HCs) were analyzed using spatial group independent component (IC) analysis. Time-varying degree centrality patterns across the whole brain were clustered into 3 reoccurring states, and state transition metrics were obtained. We further explored regional temporal variability of degree centrality for each IC across all time windows. STUDY RESULTS: Patients with OCD and patients with schizophrenia both showed decreased occurrence of a state having the highest centrality in the sensorimotor and auditory networks. Additionally, patients with OCD and patients with schizophrenia both exhibited reduced dynamics of degree centrality in the superior frontal gyrus than controls, while dynamic degree centrality of the cerebellum was lower in patients with schizophrenia than with OCD and HCs. Altered dynamics of degree centrality nominally correlated with symptom severity in both patient groups. CONCLUSIONS: Our study provides evidence of transdiagnostic and clinically relevant functional brain abnormalities across OCD and schizophrenia in neocortex, as well as functional dynamic alterations in the cerebellum specific to schizophrenia. These findings add to the recognition of overlap in neocortical alterations in the 2 disorders, and indicate that cerebellar alterations in schizophrenia may be specifically important in schizophrenia pathophysiology via impact on cerebellar thalamocortical circuitry.

Recent advances in psychoradiology.

Psychiatry, as a field, lacks objective markers for diagnosis, progression, treatment planning, and prognosis, in part due to difficulties studying the brainin vivo, and diagnoses are based on self-reported symptoms and observation of patient behavior and cognition. Rapid advances in brain imaging techniques allow clinical investigators to noninvasively quantify brain features at the structural, functional, and molecular levels. Psychoradiology is an emerging discipline at the intersection of psychiatry and radiology. Psychoradiology applies medical imaging technologies to psychiatry and promises not only to improve insight into structural and functional brain abnormalities in patients with psychiatric disorders but also to have potential clinical utility. We searched for representative studies related to recent advances in psychoradiology through May 1, 2022, and conducted a selective review of 165 references, including 75 research articles. We summarize the novel dynamic imaging processing methods to model brain networks and present imaging genetics studies that reveal the relationship between various neuroimaging endophenotypes and genetic markers in psychiatric disorders. Furthermore, we survey recent advances in psychoradiology, with a focus on future psychiatric diagnostic approaches with dimensional analysis and a shift from group-level to individualized analysis. Finally, we examine the application of machine learning in psychoradiology studies and the potential of a novel option for brain stimulation treatment based on psychoradiological findings in precision medicine. Here, we provide a summary of recent advances in psychoradiology research, and we hope this review will help guide the practice of psychoradiology in the scientific and clinical fields.

Impaired dynamic functional brain properties and their relationship to symptoms in never treated first-episode patients with schizophrenia.

Studies of dynamic functional connectivity (dFC) and topology can provide novel insights into the neurophysiology of brain dysfunction in schizophrenia and its relation to core symptoms of psychosis. Limited investigations of these disturbances have been conducted with never-treated first-episode patients to avoid the confounds of treatment or chronic illness. Therefore, we recruited 95 acutely ill, first-episode, never-treated patients with schizophrenia and examined brain dFC patterns relative to healthy controls using resting-state functional magnetic resonance imaging and a sliding-window approach. We compared the dynamic attributes at the group level and found patients spent more time in a hypoconnected state and correspondingly less time in a hyperconnected state. Patients demonstrated decreased dynamics of nodal efficiency and eigenvector centrality (EC) in the right medial prefrontal cortex, which was associated with psychosis severity reflected in Positive and Negative Syndrome Scale ratings. We also observed increased dynamics of EC in temporal and sensorimotor regions. These findings were supported by validation analysis. To supplement the group comparison analyses, a support vector classifier was used to identify the dynamic attributes that best distinguished patients from controls at the individual level. Selected features for case-control classification were highly coincident with the properties having significant between-group differences. Our findings provide novel neuroimaging evidence about dynamic characteristics of brain physiology in acute schizophrenia. The clinically relevant atypical pattern of dynamic shifting between brain states in schizophrenia may represent a critical aspect of illness pathophysiology underpinning its defining cognitive, behavioral, and affective features.

Microstructural white matter abnormalities in pediatric and adult obsessive-compulsive disorder: A systematic review and meta-analysis.

OBJECTIVE: To identify the most prominent and replicable fractional anisotropy (FA) alterations of white matter associated with obsessive-compulsive disorder (OCD) in tract-based spatial statistics (TBSS) studies. METHODS: We reviewed previous TBSS studies (n = 20) in OCD and performed a meta-analysis (n = 16) of FA differences. RESULTS: No between-group differences in FA were detected in the pooled meta-analysis. However, reduced FA was identified in the genu and anterior body of corpus callosum (CC) in adult OCD. FA reductions in the anterior body of CC were associated with a later age of onset in adult patients with OCD. For pediatric OCD, decreased FA in earlier adolescence and increased FA in later adolescence were seemingly related to an altered trajectory of brain maturation. CONCLUSIONS: Absent in the pooled sample but robust in adults, disrupted microstructural organization in the anterior part of CC indicates a bias of deficits toward connections in interhemispheric connections of rostral neocortical regions, which could lead to deficits of interhemispheric communication and thus contribute to cognitive and emotional deficits in adult OCD. The correlation between FA in the anterior body of CC and older illness onset suggests that patients with later adult onset of illness may represent a biologically distinct subgroup. For pediatric OCD, alterations in neurodevelopmental maturation may contribute to inconsistent patterns of FA alteration relative to controls during adolescence. While most studies of OCD have emphasized alterations of within hemisphere fronto-striatal circuits, these results indicate that between hemisphere connectivity of this circuitry may also represent important pathophysiology of the illness.

Altered spontaneous activity and effective connectivity of the anterior cingulate cortex in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder whose neurobiological basis remains unclear. Magnetic resonance imaging (MRI) studies have reported functional and structural alterations of the anterior cingulate cortex (ACC) in OCD. In this study, we explored the functional activity of subregions of the ACC and effective connectivity (EC) between ACC subregions and the whole brain in OCD. We used a Granger causality analysis (GCA) to identify the direction of information flow and whether the impact of that flow was excitatory or inhibitory. We performed resting-state functional MRI in 31 patients with OCD and 36 healthy controls and analyzed the amplitude of low-frequency fluctuation (ALFF) and coefficient-based GCA. The left pregenual ACC (pACC) in patients with OCD showed decreased ALFF relative to controls. There was significantly decreased excitatory output from the left pACC to both right dorsal superior frontal gyrus (dSFG) and left precuneus in patients compared with controls. Patients also had decreased inhibitory input to left pACC from left ventral SFG and left thalamus and caudate relative to controls. Results were similar in drug-naive patients and those with prior but not current psychopharmacological treatment. In patients, path coefficients of GCA from left pACC to right dSFG showed significant negative correlations with obsession and anxiety ratings. Decreased spontaneous neural activity and altered EC of pACC with widely distributed cortical circuitry, and associations with clinical ratings highlight the importance of pACC functional alteration in OCD.