Altered Functional Connectivity Research Articles

Mecp2 deletion results in profound alterations of developmental and adult functional connectivity.

As a regressive neurodevelopmental disorder with a well-established genetic cause, Rett syndrome and its Mecp2 loss-of-function mouse model provide an excellent opportunity to define potentially translatable functional signatures of disease progression, as well as offer insight into the role of Mecp2 in functional circuit development. Thus, we applied widefield optical fluorescence imaging to assess mesoscale calcium functional connectivity (FC) in the Mecp2 cortex both at postnatal day (P)35 in development and during the disease-related decline. We found that FC between numerous cortical regions was disrupted in Mecp2 mutant males both in juvenile development and early adulthood. Female Mecp2 mice displayed an increase in homotopic contralateral FC in the motor cortex at P35 but not in adulthood, where instead more posterior parietal regions were implicated. An increase in the amplitude of connection strength, both with more positive correlations and more negative anticorrelations, was observed across the male cortex in numerous functional regions. Widespread rescue of MeCP2 protein in GABAergic neurons rescued none of these functional deficits, nor, surprisingly, the expected male lifespan. Altogether, the female results identify early signs of disease progression, while the results in males indicate MeCP2 protein is required for typical FC in the brain.

Language impairment in Parkinson's disease: fMRI study of sentence reading comprehension.

Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04). Using PPI, we found a statistically significant difference between the PwPD and the HC in connectivity from the right striatum to the supplementary motor area [SMA, (4 8 53)] for non-canonical sentences. This PPI connectivity was negatively correlated with the ToSC accuracy of non-canonical sentences in the PwPD. Our results showed disturbed sentence reading comprehension in the PwPD with altered task-dependent functional connectivity from the right striatum to the SMA, which supports the synchronization of the temporal and sequential aspects of language processing. The study revealed that subcortical-cortical networks (striatal-frontal loop) in PwPD are compromised, leading to impaired comprehension of syntactically complex sentences.

Molecular and network-level mechanisms explaining individual differences in autism spectrum disorder.

The mechanisms underlying phenotypic heterogeneity in autism spectrum disorder (ASD) are not well understood. Using a large neuroimaging dataset, we identified three latent dimensions of functional brain network connectivity that predicted individual differences in ASD behaviors and were stable in cross-validation. Clustering along these three dimensions revealed four reproducible ASD subgroups with distinct functional connectivity alterations in ASD-related networks and clinical symptom profiles that were reproducible in an independent sample. By integrating neuroimaging data with normative gene expression data from two independent transcriptomic atlases, we found that within each subgroup, ASD-related functional connectivity was explained by regional differences in the expression of distinct ASD-related gene sets. These gene sets were differentially associated with distinct molecular signaling pathways involving immune and synapse function, G-protein-coupled receptor signaling, protein synthesis and other processes. Collectively, our findings delineate atypical connectivity patterns underlying different forms of ASD that implicate distinct molecular signaling mechanisms.

Disrupted voxel-mirrored homotopic connectivity in congenital nystagmus using resting-state fMRI.

Idiopathic congenital nystagmus (CN) is a rare eye disease that can cause early blindness (EB). CN deficits are observed most frequently with oculomotor dysfunction; however, it is still unclear what neuromechanics underly CN with EB. Based on that visual experience requires the functional integration of both hemispheres, we hypothesized that CN adolescents with EB might exhibit impaired interhemispheric synchrony. Our study aimed to investigate the interhemispheric functional connectivity alterations using voxel-mirrored homotopic connectivity (VMHC) and their relationships with clinical features in CN patients. This study included 21 patients with CN and EB, and 21 sighted controls (SC), who were matched for sex, age and educational level. The 3.0 T MRI scan and ocular examination were performed. The VMHC differences were examined between the two groups, and the relationships between mean VMHC values in altered brain regions and clinical variables in the CN group were evaluated by Pearson correlation analysis. Compared with the SC group, the CN had increased VMHC values in the bilateral cerebellum posterior and anterior lobes/cerebellar tonsil/declive/pyramis/culmen/pons, middle frontal gyri (BA 10) and frontal eye field/superior frontal gyri (BA 6 and BA 8). No particular areas of the brain had lower VMHC values. Furthermore, no correlation with the duration of disease or blindness could be demonstrated in CN. Our results suggest the existence of interhemispheric connectivity changes and provide further evidence for the neurological basis of CN with EB.

Functional connectivity alterations in traumatic brain injury patients with late seizures

PTE is a neurological disorder characterized by recurrent and spontaneous epileptic seizures. PTE is a major public health problem occurring in 2–50% of TBI patients. Identifying PTE biomarkers is crucial for the development of effective treatments. Functional neuroimaging studies in patients with epilepsy and in epileptic rodents have observed that abnormal functional brain activity plays a role in the development of epilepsy. Network representations of complex systems ease quantitative analysis of heterogeneous interactions within a unified mathematical framework. In this work, graph theory was used to study resting state functional magnetic resonance imaging (rs-fMRI) and reveal functional connectivity abnormalities that are associated with seizure development in traumatic brain injury (TBI) patients. We examined rs-fMRI of 75 TBI patients from Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) which aims to identify validated Post-traumatic epilepsy (PTE) biomarkers and antiepileptogenic therapies using multimodal and longitudinal data acquired from 14 international sites. The dataset includes 28 subjects who had at least one late seizure after TBI and 47 subjects who had no seizures within 2 years post-injury. Each subject’s neural functional network was investigated by computing the correlation between the low frequency time series of 116 regions of interest (ROIs). Each subject’s functional organization was represented as a network consisting of nodes, brain regions, and edges that show the relationship between the nodes. Then, several graph measures concerning the integration and the segregation of the functional brain networks were extracted in order to highlight changes in functional connectivity between the two TBI groups. Results showed that the late seizure-affected group had a compromised balance between integration and segregation and presents functional networks that are hyperconnected, hyperintegrated but at the same time hyposegregated compared with seizure-free patients. Moreover, TBI subjects who developed late seizures had more low betweenness hubs.

Brain dysconnectivity with heart failure.

Structural brain damage associated with heart failure is well described; however, little is known about associated changes in various specific brain functions that bear immediate clinical relevance. A satisfactory pathophysiological link between heart failure and decline in cognitive function is still missing. In the present study, we aim to detect functional correlates of heart failure in terms of alterations in functional brain connectivity (quantified by functional magnetic resonance imaging) related to cognitive performance assessed by neuropsychological testing. Eighty patients were post hoc grouped into subjects with and without coronary artery disease. The coronary artery disease patients were further grouped as presenting with or without heart failure according to the guidelines of the European Society of Cardiology. On the basis of resting-state functional magnetic resonance imaging, brain connectivity was investigated using network centrality as well as seed-based correlation. Statistical analysis aimed at specifying centrality group differences and potential correlations between centrality and heart failure-related measures including left ventricular ejection fraction and serum concentrations of N-terminal fragment of the pro-hormone brain-type natriuretic peptide. The resulting correlation maps were then analysed using a flexible factorial model with the factors 'heart failure' and 'cognitive performance'. Our core findings are: (i) A statistically significant network centrality decrease was found to be associated with heart failure primarily in the precuneus, i.e. we show a positive correlation between centrality and left ventricular ejection fraction as well as a negative correlation between centrality and N-terminal fragment of the pro-hormone brain-type natriuretic peptide. (ii) Seed-based correlation analysis showed a significant interaction between heart failure and cognitive performance related to a significant decrease of precuneus connectivity to other brain regions. We obtained these results by different analysis approaches indicating the robustness of the findings we report here. Our results suggest that the precuneus is a brain region involved in connectivity decline in patients with heart failure, possibly primarily or already at an early stage. Current models of Alzheimer's disease-having pathophysiological risk factors in common with cerebrovascular disorders-also consider reduced precuneus connectivity as a marker of brain degeneration. Consequently, we propose that heart failure and Alzheimer's disease exhibit partly overlapping pathophysiological paths or have common endpoints associated with a more or less severe decrease in brain connectivity. This is further supported by specific functional connectivity alterations between the precuneus and widely distributed cortical regions, particularly in patients showing reduced cognitive performance.

Regional superficial amygdala resting-state functional connectivity in adults infers childhood maltreatment severity.

Childhood maltreatment (CM) is a potential risk factor for some neuropsychiatric disorders in adulthood (e.g. depression and anxiety) and alters trajectories of brain development. Accumulating evidence suggests that functional connectivity of the limbic system, especially the amygdala, is highly associated with childhood maltreatment, although not all studies have found this. These inconsistent results may be due to differential alterations of amygdala resting-state functional connectivity (rsFC) following childhood maltreatment. Our aim was to investigate the relationship between the rsFC of amygdala subregions and CM severity, as well as to develop a stable rsFC-based model for inferring the severity of CM. In this study, we employed the Childhood Trauma Questionnaire (CTQ) to assess CM severity in each individual. We explored the relationship between the rsFC of amygdala subregions (i.e. centromedial -CMA, basolateral -BLA, superficial-SFA amygdala) and CM experience in a discovery dataset of n=110 healthy Chinese participants by linear multiple regression analysis. Subsequent dimensional and categorical approach were performed to elucidate the relationship between rsFCs and CM severity and CM subtypes, respectively. A support vector regression model was then conducted to validate the associations between rsFCs and total CTQ scores. Moreover, we also verified the model into another independent replication dataset (n=38). Our findings suggested that childhood maltreatment was negatively associated with rsFC between the right superficial amygdala and perigenual anterior cingulate cortex (pgACC)/postcentral gyrus (PCG) but not the other two amygdala subregions. Moreover, SFA-pgACC coupling was more associated with physical neglect whereas the SFA-PCG was more related to emotional neglect. In addition, supervised machine learning confirmed that using these two rsFCs as predictors could stably estimate continuous maltreatment severity in both discovery and replication datasets. The current study supports that the rsFCs of superficial amygdala are related to childhood maltreatment and which may be a potential biomarker for the effects of childhood maltreatment-related psychiatric disorders (i.e. depression and anxiety).

Association of Brain Microstructure and Functional Connectivity With Cognitive Outcomes and Postnatal Growth Among Early School–Aged Children Born With Extremely Low Birth Weight

Postnatal growth may be associated with longitudinal brain development in children born preterm. To compare brain microstructure and functional connectivity strength with cognitive outcomes in association with postnatal growth among early school-aged children born preterm with extremely low birth weight. This single-center cohort study prospectively enrolled 38 children 6 to 8 years of age born preterm with extremely low birth weight: 21 with postnatal growth failure (PGF) and 17 without PGF. Children were enrolled, past records were retrospectively reviewed, and imaging data and cognitive assessments occurred from April 29, 2013, through February 14, 2017. Image processing and statistical analyses were conducted through November 2021. Postnatal growth failure in the early neonatal period. Diffusion tensor images and resting-state functional magnetic resonance images were analyzed. Cognitive skills were tested using the Wechsler Intelligence Scale; executive function was assessed based on a composite score calculated from the synthetic composite of the Children's Color Trails Test, STROOP Color and Word Test, and Wisconsin Card Sorting Test; attention function was evaluated using the Advanced Test of Attention (ATA); and the Hollingshead Four Factor Index of Social Status-Child was estimated. Twenty-one children born preterm with PGF (14 girls [66.7%]), 17 children born preterm without PGF (6 girls [35.3%]), and 44 children born full term (24 girls [54.5%]) were recruited. Attention function was less favorable in children with PGF than those without PGF (mean [SD] ATA score: children with PGF, 63.5 [9.4]; children without PGF, 55.7 [8.0]; P = .008). Significantly lower mean (SD) fractional anisotropy in the forceps major of the corpus callosum (0.498 [0.067] vs 0.558 [0.044] vs 0.570 [0.038]) and higher mean (SD) mean diffusivity in the left superior longitudinal fasciculus-parietal bundle (8.312 [0.318] vs 7.902 [0.455] vs 8.083 [0.393]; originally calculated as millimeter squared per second and rescaled 10 000 times as mean diffusivity × 10 000) were seen among children with PGF compared with children without PGF and controls, respectively. Decreased resting-state functional connectivity strength was observed in the children with PGF. The mean diffusivity of the forceps major of the corpus callosum significantly correlated with the attention measures (r = 0.225; P = .047). Functional connectivity strength between the left superior lateral occipital cortex and both superior parietal lobules correlated with cognitive outcomes of intelligence (right superior parietal lobule, r = 0.262; P = .02; and left superior parietal lobule, r = 0.286; P = .01) and executive function (right superior parietal lobule, r = 0.367; P = .002; and left superior parietal lobule, r = 0.324; P = .007). The ATA score was positively correlated with functional connectivity strength between the precuneus and anterior division of the cingulate gyrus (r = 0.225; P = .048); however, it was negatively correlated with functional connectivity strength between the posterior cingulate gyrus and both superior parietal lobules (the right superior parietal lobule [r = -0.269; P = .02] and the left superior parietal lobule [r = -0.338; P = .002]). This cohort study suggests that the forceps major of the corpus callosum and the superior parietal lobule were vulnerable regions in preterm infants. Preterm birth and suboptimal postnatal growth could have negative associations with brain maturation, including altered microstructure and functional connectivity. Postnatal growth may be associated with differences in long-term neurodevelopment among children born preterm.

Applying Functional Imaging to Clinical Practice: Are We Making Progress Toward Its Promise?

Applying Functional Imaging to Clinical Practice: Are We Making Progress Toward Its Promise?

Abnormal cerebellum connectivity patterns related to motor subtypes of Parkinson’s disease

Cerebellar dysfunction may substantially contribute to the clinical symptoms of Parkinson’s disease (PD). The role of cerebellar subregions in tremors and gait disturbances in PD remains unknown. To investigate alterations in cerebellar subregion volumes and functional connectivity (FC), as well as FC between the dentate nucleus (DN) and ventral lateral posterior nucleus (VLp) of the thalamus, which are potentially involved in different PD motor subtypes. We conducted morphometric and resting-state functional connectivity analyses in various cerebellar subregions in 22 tremor-dominant (TD)-PD and 35 postural instability gait difficulty dominant (PIGD)-PD patients and 38 sex- and age-matched healthy controls (HCs). The volume and FC alterations in various cerebellar subregions and the neural correlates of these changes with the clinical severity scores were investigated. The PIGD-PD group showed greater FC between the right motor cerebellum (CBMm) and left postcentral gyrus than the HC group, and a higher FC was associated with less severe PIGD symptoms. In contrast, the TD-PD group had decreased FC between the right DN and left VLp compared with the PIGD-PD and HC groups, and lower FC was associated with worse TD symptoms. Furthermore, the PIGD-PD group had higher FC between the left DN and left inferior temporal gyrus than the TD-PD group. Morphometric analysis revealed that the TD-PD group showed a significantly higher volume of left CBMm than the HC group. Our findings point to differential alteration patterns in cerebellar subregions and offer a new perspective on the pathophysiology of motor subtypes of PD.

Exploring the Restoration of Brain Connectivity during Weight Normalization in Severe Anorexia Nervosa

Abstract Anorexia nervosa is a persistent and often difficult to treat eating disorder with significant physical and mental health consequences. While it is known that the disorder is associated with alterations in brain functional connectivity during the phase of acute underweight, the effect of weight normalization on brain connectivity remains unclear. This talk focuses on the recovery of intrinsic brain connectivity during weight normalization in severe anorexia nervosa, presenting data from a longitudinal study. Using resting-state functional magnetic resonance imaging, we assessed brain connectivity at three different stages of inpatient treatment. Our findings indicate that patients with severe anorexia nervosa have weaker intrinsic connectivity and altered network topology, which do not improve during treatment. These persistent disruptions in brain networks suggest that severe anorexia nervosa may have long-term effects on the way the brain processes information, even after weight is restored. Disclosure of Interest None Declared

Transdiagnostic and Disorder-Specific Resting-State Functional Network Alterations in Alcohol Use Disorder, Schizophrenia, Bipolar Affective Disorder and Obsessive-Compulsive Disorder

Introduction The ICD and DSM diagnostic categories do not represent entirely distinct entities because several cognitive impairments are shared across psychiatric disorders. Such shared cognitive impairments are hypothesized to be caused by common neurobiological substrates, one of which is transdiagnostic alterations in functional network connectivity (FNC). Objectives To investigate and compare the within-network functional connectivity (WNFC) and between-network functional connectivity (BNFC) in alcohol use disorder (AUD), schizophrenia (SCZ), bipolar affective disorder (BPAD), obsessive-compulsive disorder (OCD) and healthy controls (HC) using resting-state fMRI employing a data-driven exploratory approach. Methods The current study was a secondary analysis of data from the ADBS project in India. After pre-processing of fMRI data, a spatially and temporally constrained group-independent component analysis in the GIFT toolbox was performed using the NeuroMark templates to generate 53 independent components (ICs). These components were divided into seven functional domains including subcortical (SC), auditory (AU), sensorimotor (SM), visual (VI), cognitive-control (CC), default-mode (DM), and cerebellar (CB). To investigate the FNC correlations associated with group status (patients or HC) univariate models were applied which were subjected to corrections for multiple comparisons at an alpha=0.05 significance level using the FDR. Results The overall sample size was 249 [AUD=35, SCZ=44, BPAD=48, OCD=53, and HC=69]. Transdiagnostic WNFC alterations largely involved dysconnectivity in the CC, DM, and SC domains, resulting in ICs with both increased and decreased WNFC. Transdiagnostic BNFC alterations were primarily in the form of increased connectivity of the SC domain with various cortical domains whereas reduced connectivity was noted between AU, VI, SM, and CB domains. There was AUD-specific hyperconnectivity in the CC domain and SCZ-specific hyperconnectivity in the DM domain, and dysconnectivity in the SC domain. BPAD-specific hyperconnectivity was identified in DM and SC domains in addition to increased connectivity between CB and SM domains and decreased connectivity between CB and SC domains. All results were significant at p ≤ 0.05; [FDR] q= 0.05. Conclusions Our transdiagnostic WNFC alterations corresponded to the central executive network, default mode network, salience network, and CSTC loop, which provided transdiagnostic evidence for the triple network model of psychopathology and underlined the relevance of subcortical dysconnectivity in this model. Furthermore, our BNFC changes showed subcortical hyperconnectivity with many cortical networks, underscoring its relevance as a potential target for transdiagnostic therapeutic interventions. Disclosure of Interest None Declared

Neuroplasticity Following Stroke from a Functional Laterality Perspective: A fNIRS Study.

To explore alterations of resting-state functional connectivity (rsFC) in sensorimotor cortex following strokes with left or right hemiplegia considering the lateralization and neuroplasticity. Seventy-three resting-state functional near-infrared spectroscopy (fNIRS) files were selected, including 26 from left hemiplegia (LH), 21 from right hemiplegia (RH) and 26 from normal controls (NC) group. Whole-brain analyses matching the Pearson correlation were used for rsFC calculations. For right-handed normal controls, rsFC of motor components (M1 and M2) in the left hemisphere displayed a prominent intensity in comparison with the right hemisphere (p < 0.05), while for stroke groups, this asymmetry has disappeared. Additionally, RH rather than LH showed stronger rsFC between left S1 and left M1 in contrast to normal controls (p < 0.05), which correlated inversely with motor function (r = -0.53, p < 0.05). Regarding M1, rsFC within ipsi-lesioned M1 has a negative correlation with motor function of the affected limb (r = -0.60 for the RH group and -0.43 for the LH group, p < 0.05). The rsFC within contra-lesioned M1 that innervates the normal side was weakened compared with that of normal controls (p < 0.05). Stronger rsFC of motor components in left hemisphere was confirmed by rs-fNIRS as the "secret of dominance" for the first time, while post-stroke hemiplegia broke this cortical asymmetry. Meanwhile, a statistically strengthened rsFC between left S1 and M1 only in right-hemiplegia group may act as a compensation for the impairment of the dominant side. This research has implications for brain-computer interfaces synchronizing sensory feedback with motor performance and transcranial magnetic regulation for cortical excitability to induce cortical plasticity.

Resting-state Fronto-limbic Connectivity in Unipolar Depressive Patients as a Predictor for Sporadic Conversion to (Hypo)mania

IntroductionPatients with a bipolar disorder (BD) may experience one or several episodes of major depression before transitioning into a manic phase. Given that treatment with common antidepressants may exacerbate symptoms of mania in patients with BD, initial diagnosis of major depressive disorder (MDD) is a significant issue affecting BD patients. Currently, a family history of BD is used as an early identifier for BD, but as genetic factors associated with BD confer susceptibility to a wide range of psychiatric illnesses, this approach lacks specificity. Thus, there is a pressing need for a biomarker which specifically predicts development of bipolar symptoms in patients with MDD, rather than a trait vulnerability to psychiatric disorderObjectives The aim of this study is to assess alterations in fronto-limbic function that exist prior to the manifestation of the first manic episode in BD patients without familial predisposition for BD.MethodsTo identify a biomarker for conversion to BD we performed a study in a naturalistic sample of MDD patients without a familial risk for BD, which were followed for 9 years. We used a seed-based functional connectivity analysis to assess differences in resting-state fronto-limbic connectivity between MDD patients who converted to BD during the follow-up period (n = 11), and non-converting MDD patients (n = 56).ResultsClusters of significantly reduced functional connectivity were found in the fronto-limbic network of prospective converters relative to non-converters.ConclusionsFindings suggest that alterations of fronto-limbic functional connectivity during episodes of depression predate and associate with conversion to BD later in life, in the absence of familial risk. These fronto-limbic functional connectivity disturbances may be of interest for diagnosing early-stage BD, and may offer insight in the mechanisms that drive conversion in the absence of familial predisposition. Findings from this study need to be verified through large-scale longitudinal imaging studies in naturalistic cohorts of MDD patients.Disclosure of InterestNone Declared

Exploring structural and functional alterations in drug-naïve obsessive-compulsive disorder patients: An ultrahigh field multimodal MRI study.

Brain structural and functional alterations have been reported in obsessive-compulsive disorder (OCD) patients; however, these findings were inconsistent across studies due to several limitations, including small sample sizes, different inclusion/exclusion criteria, varied demographic characteristics and symptom dimensions, comorbidity, and medication status. Prominent and replicable neuroimaging biomarkers remain to be discovered. This study explored the gray matter structure, neural activity, and white matter microstructure differences in 40 drug-naïve OCD patients and 57 matched healthy controls using ultrahigh field 7.0T multimodal magnetic resonance imaging, which increased the spatial resolution and detection power. We also evaluated correlations among different modalities, imaging features and clinical symptoms. Drug-naïve OCD patients exhibited significantly increased gray matter volume in the frontal cortex, especially in the orbitofrontal cortex, as well as volumetric reduction in the temporal lobe, occipital lobe and cerebellum. Increased neural activities were observed in the cingulate gyri and precuneus. Increased temporal-middle cingulate and posterior cingulate-precuneus functional connectivities and decreased frontal-middle cingulate connectivity were further detected. Decreased fractional anisotropy values were found in the cingulum-hippocampus gyrus and inferior fronto-occipital fascicle in OCD patients. Moreover, significantly altered imaging features were related to OCD symptom severity. Altered functional and structural neural connectivity might influence compulsive and obsessive features, respectively. Altered structure and function of the classical cortico-striato-thalamo-cortical circuit, limbic system, default mode network, visual, language and sensorimotor networks play important roles in the neurophysiology of OCD.

Reduced cerebello-cerebral functional connectivity correlates with disease severity and impaired white matter integrity in Friedreich ataxia

Friedreich ataxia (FRDA) is a rare, inherited neurodegenerative disease characterised in most cases by progressive and debilitating motor dysfunction. Degeneration of cerebellar white matter pathways have been previously reported, alongside indications of cerebello-cerebral functional alterations. In this work, we examine resting-state functional connectivity changes within cerebello-cerebral circuits, and their associations with disease severity (Scale for the Assessment and Rating of Ataxia [SARA]), psychomotor function (speeded and paced finger tapping), and white matter integrity (diffusion tensor imaging) in 35 adults with FRDA and 45 age and sex-matched controls. Voxel-wise seed-based functional connectivity was assessed for three cerebellar cortical regions (anterior lobe, lobules I-V; superior posterior lobe, lobules VI-VIIB; inferior posterior lobe, lobules VIIIA-IX) and two dentate nucleus seeds (dorsal and ventral). Compared to controls, people with FRDA showed significantly reduced connectivity between the anterior cerebellum and bilateral pre/postcentral gyri, and between the superior posterior cerebellum and left dorsolateral PFC. Greater disease severity correlated with lower connectivity in these circuits. Lower anterior cerebellum-motor cortex functional connectivity also correlated with slower speeded finger tapping and less fractional anisotropy in the superior cerebellar peduncles, internal capsule, and precentral white matter in the FRDA cohort. There were no significant between-group differences in inferior posterior cerebellar or dentate nucleus connectivity. This study indicates that altered cerebello-cerebral functional connectivity is associated with functional status and white matter damage in cerebellar efferent pathways in people with FRDA, particularly in motor circuits.

Alterations in BNST Intrinsic Functional Connectivity in Early Abstinence from Alcohol Use Disorder.

Maintaining abstinence from alcohol use disorder (AUD) is extremely challenging, partially due to increased symptoms of anxiety and stress that trigger relapse. Rodent models of AUD have identified that the bed nucleus of the stria terminalis (BNST) contributes to symptoms of anxiety-like behavior and drug-seeking during abstinence. In humans, however, the BNST's role in abstinence remains poorly understood. The aims of this study were to assess BNST network intrinsic functional connectivity in individuals during abstinence from AUD compared to healthy controls and examine associations between BNST intrinsic functional connectivity, anxiety and alcohol use severity during abstinence. The study included resting state fMRI scans from participants aged 21-40years: 20 participants with AUD in abstinence and 20 healthy controls. Analyses were restricted to five pre-selected brain regions with known BNST structural connections. Linear mixed models were used to test for group differences, with sex as a fixed factor given previously shown sex differences. BNST-hypothalamus intrinsic connectivity was lower in the abstinent group relative to the control group. There were also pronounced sex differences in both the group and individual analyses; many of the findings were specific to men. Within the abstinent group, anxiety was positively associated with BNST-amygdala and BNST-hypothalamus connectivity, and men, not women, showed a negative relationship between alcohol use severity and BNST-hypothalamus connectivity. Understanding differences in connectivity during abstinence may help explain the clinically observed anxiety and depression symptoms during abstinence and may inform the development of individualized treatments.

Dissociable brainstem functional connectivity changes correlate with objective and subjective vigilance decline after total sleep deprivation in healthy male subjects.

The maintenance of vigilance relies on the activation of the cerebral cortex by the arousal system centered on the brainstem. Previous studies have suggested that both objective and subjective vigilance are susceptible to sleep deprivation. This study aims to explore the alterations in brainstem arousal system functional connectivity (FC) and its involvement in these two types of vigilance decline following total sleep deprivation (TSD). Thirty-seven healthy male subjects underwent two counterbalanced resting-state fMRI scans, once in rested wakefulness (RW) and once after 36 h of TSD. The pontine tegmental area and caudal midbrain (PTA-cMidbrain), the core regions of the brainstem arousal system, were chosen as the seeds for FC analysis. The difference in PTA-cMidbrain FC between RW and TSD conditions was then investigated, as well as its associations with objective vigilance measured by psychomotor vigilance task (PVT) and subjective vigilance measured by Stanford Sleepiness Scale. The sleep-deprived subjects showed increased PTA-cMidbrain FC with the thalamus and cerebellum and decreased PTA-cMidbrain FC with the occipital, parietal, and sensorimotor regions. TSD-induced increases in PVT reaction time were negatively correlated with altered PTA-cMidbrain FC in the dorsolateral prefrontal cortex, extrastriate visual cortex, and precuneus. TSD-induced increases in subjective sleepiness were positively correlated with altered PTA-cMidbrain FC in default mode regions including the medial prefrontal cortex and precuneus. Our results suggest that different brainstem FC patterns underlie the objective and subjective vigilance declines induced by TSD.

Association between decreased interhemispheric functional connectivity of the insula and duration of illness in recurrent depression

ObjectiveTo investigate the altered interhemispheric functional connectivity in the resting state in patients with recurrent major depressive disorder (MDD). MethodsVoxel-mirrored homotopic connectivity (VMHC), a measure of the functional connectivity between any pair of symmetrical interhemispheric voxels, and pattern classification were examined in 41 recurrent MDD patients (22 during the depressive state and 19 during the remitted state) and 60 age, sex, and education level-matched healthy controls (HC) using resting-state functional magnetic resonance imaging (fMRI). ResultsCompared with HC, the recurrent MDD patients exhibited decreased VMHC values in the bilateral fusiform, inferior occipital gyrus, posterior insula, precentral gyrus, precuneus, superior temporal gyrus, and thalamus. A significant negative correlation between the VMHC value of the bilateral posterior insula and illness duration in recurrent MDD was identified. Support vector machine (SVM) analysis showed that VMHC in the fusiform and posterior insula could be used to distinguish recurrent MDD patients from HC with a sensitivity and accuracy >0.6. ConclusionOur findings revealed a reduction in the resting-state brain activity across several neural networks in patients with recurrent MDD, including within the posterior insula. Lower VMHC values in the posterior insula were associated with longer illness duration, suggesting that impairment in interhemispheric synchronization within the salience network may be due to the accumulated pathology of depression and may contribute to future depression relapse. VMHC changes in the posterior insula may serve as a potential imaging marker to discriminate recurrent MDD patients from HC.

Altered dynamic functional connectivity associates with post-traumatic stress disorder.

Research has been looking into neural pathophysiology of post-traumatic stress disorder (PTSD) and dynamic functioning connectivity (dFC) applying resting state functional magnetic resonance imaging (rs-fMRI). Previous studies showed that PTSD related impairments are associated with alterations distributed across different brain regions and disorganized functional connectivity, especially in Default Mode Network and the cerebellar area. In this study, we specifically looked into dFC on a whole brain level, and we focused on critical regions such as DMN and cerebellum. To explore the characteristics of dFC among patients with PTSD, we collected rs-fMRI data from 27 PTSD patients and 30 healthy controls. The study also added a control group of 33 trauma-exposed individuals to further look into trauma impact. Utilizing group spatial independent component analysis (ICA), the dynamic properties on whole brain level were detected with sliding time window approach, and k-means clustering. Two reoccurring FC "States" were identified, with connections being more concentrated on a within-network level in one state and more strongly inter-connected in the other state. Abnormalities in dFC were found within DMN, between DMN and cerebellum, and between DMN and visual network for PTSD patients. The findings were in accordance with the study hypothesis that the dFC alterations might point to deficits in emotional modulation and dysfunctional self-referential thought. Abnormalities in dFC among PTSD patients might also be indicators of PTSD symptoms including depression and anxiety, hypervigilance, impaired cognitive functioning and self-referential information processing.