Group Differences In Connectivity Research Articles

Resting-state functional connectivity in deaf and hearing individuals and its link to executive processing

Sensory experience shapes brain structure and function, and it is likely to influence the organisation of functional networks of the brain, including those involved in cognitive processing. Here we investigated the influence of early deafness on the organisation of resting-state networks of the brain and its relation to executive processing. We compared resting-state connectivity between deaf and hearing individuals across 18 functional networks and 400 ROIs. Our results showed significant group differences in connectivity between seeds of the auditory network and most large-scale networks of the brain, in particular the somatomotor and salience/ventral attention networks. When we investigated group differences in resting-state fMRI and their link to behavioural performance in executive function tasks (working memory, inhibition and switching), differences between groups were found in the connectivity of association networks of the brain, such as the salience/ventral attention and default-mode networks. These findings indicate that sensory experience influences not only the organisation of sensory networks, but that it also has a measurable impact on the organisation of association networks supporting cognitive processing. Overall, our findings suggest that different developmental pathways and functional organisation can support executive processing in the adult brain.

PTSD and comorbid MDD is associated with activation of the right frontoparietal network

There is growing evidence of abnormalities in intrinsic functional connectivity (FC) in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). However, there has been less work on the commonly occurring co-presentation of PTSD and MDD. Characterising intrinsic FC abnormalities in this clinical population is important for understanding how they may contribute towards impairments underpinned by different networks. Participants were mothers enroled in the Drakenstein Child Health Study from Western Cape, South Africa. Mothers between 18 and 50 years of age were recruited and divided into 4 groups: PTSD, MDD, PTSD with MDD, and healthy controls. Participants underwent resting-state fMRI at the 18-month postpartum time point. Functional connectivity within and between higher order cognitive control networks, including the salience, dorsal attention, frontoparietal, and default mode networks were compared across the 4 groups. PTSD with comorbid MDD was associated with greater intrinsic FC within the R FPAR, relative to controls and the mono-diagnostic groups. Intrinsic FC differences were observed within the default mode network for the MDD group. No group differences in connectivity between networks were observed. Differential intrinsic connectivity in participants with comorbidity are consistent with evidence that such individuals have more severe illness and require more robust intervention.

Thalamocortical functional connectivity in youth with attention-deficit/hyperactivity disorder.

Few studies have empirically tested the relationships between anatomically defined thalamic nuclei and functionally defined cortical networks, and little is known about their implications in attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate the functional connectivity of the thalamus in youth with ADHD, using both anatomically and functionally defined thalamic seed regions. Resting-state functional MRIs obtained from the publicly available ADHD-200 database were analyzed. Thalamic seed regions were defined functionally and anatomically based on Yeo's 7 resting-state-network parcellation atlas and the AAL3 atlas, respectively. Functional connectivity maps of the thalamus were extracted, and thalamocortical functional connectivity was compared between youth with and without ADHD. Using the functionally defined seeds, significant group differences in thalamocortical functional connectivity and significant negative correlations between thalamocortical connectivity and ADHD symptom severity were observed within the boundaries of corresponding large-scale networks. However, in the analysis using the anatomically defined thalamic seeds, significant group differences in connectivity and significant positive correlations were observed outside the expected boundaries of major anatomic projections. The thalamocortical connectivity originating from the lateral geniculate nuclei of the thalamus was significantly correlated with age in youth with ADHD. The small sample size and smaller proportion of girls were limiting factors. Thalamocortical functional connectivity based on the intrinsic network architecture of the brain appears to be clinically relevant in ADHD. The positive association between thalamocortical functional connectivity and ADHD symptom severity may represent a compensatory process recruiting an alternative neural network.

Combined electrophysiological and morphological phenotypes in patients with genetic generalized epilepsy and their healthy siblings.

Genetic generalized epilepsy (GGE) is characterized by aberrant neuronal dynamics and subtle structural alterations. We evaluated whether a combination of magnetic and electrical neuronal signals and cortical thickness would provide complementary information about network pathology in GGE. We also investigated whether these imaging phenotypes were present in healthy siblings of the patients to test for genetic influence. In this cross-sectional study, we analyzed 5min of resting state data acquired using electroencephalography (EEG) and magnetoencephalography (MEG) in patients, their siblings, and controls, matched for age and sex. We computed source-reconstructed power and connectivity in six frequency bands (1-40Hz) and cortical thickness (derived from magnetic resonance imaging). Group differences were assessed using permutation analysis of linear models for each modality separately and jointly for all modalities using a nonparametric combination. Patients with GGE (n=23) had higher power than controls (n=35) in all frequencies, with a more posterior focus in MEG than EEG. Connectivity was also increased, particularly in frontotemporal and central regions in theta (strongest in EEG) and low beta frequencies (strongest in MEG), which was eminent in the joint EEG/MEG analysis. EEG showed weaker connectivity differences in higher frequencies, possibly related to drug effects. The inclusion of cortical thickness reinforced group differences in connectivity and power. Siblings (n=18) had functional and structural patterns intermediate between those of patients and controls. EEG detected increased connectivity and power in GGE similar to MEG, but with different spectral sensitivity, highlighting the importance of theta and beta oscillations. Cortical thickness reductions in GGE corresponded to functional imaging patterns. Our multimodal approach extends the understanding of the resting state in GGE and points to genetic underpinnings of the imaging markers studied, providing new insights into the causes and consequences of epilepsy.

Atypical Intrinsic Hemispheric Interaction Associated with Autism Spectrum Disorder Is Present within the First Year of Life.

Autism spectrum disorder (ASD) is characterized by atypical connectivity lateralization of functional networks. However, previous studies have not directly investigated if differences in specialization between ASD and typically developing (TD) peers are present in infancy, leaving the timing of onset of these differences relatively unknown. We studied the hemispheric asymmetries of connectivity in children with ASD and infants later meeting the diagnostic criteria for ASD. Analyses were performed in 733 children with ASD and TD peers and in 71 infants at high risk (HR) or normal risk (NR) for ASD, with data collected at 1 month and 9 months of age. Comparing children with ASD (n = 301) to TDs (n = 432), four regions demonstrated group differences in connectivity: posterior cingulate cortex (PCC), posterior superior temporal gyrus, extrastriate cortex, and anterior prefrontal cortex. At 1 month, none of these regions exhibited group differences between ASD (n = 10), HR-nonASD (n = 15), or NR (n = 18) infants. However, by 9 months, the PCC and extrastriate exhibited atypical connectivity in ASD (n = 11) and HR-nonASD infants (n = 24) compared to NR infants (n = 22). Connectivity did not correlate with symptoms in either sample. Our results demonstrate that differences in network asymmetries associated with ASD risk are observable prior to the age of a reliable clinical diagnosis.

Cognitive Profiles of Amyotrophic Lateral Sclerosis Differ in Resting-State Functional Connectivity: An fMRI Study.

BackgroundHalf of all amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) patients are classified as cognitively impaired, of which 10% have frontotemporal dementia (FTD), and an additional 40% suffer from a frontotemporal syndrome not severe enough to be described as dementia (cognitively impaired/ALSci). As changes in cerebral function measured by resting-state magnet resonance imaging (rs-fMRI) are known in ALS, we investigated whether group differences in resting-state functional connectivity (RSFC) networks could be observed between ALS patients with different cognitive profiles against healthy controls (HC). Furthermore, we correlated cognition and motor functioning with network connectivity.MethodsHealthy controls, 69, and 97 ALS patients underwent functional MRI scanning and cognitive assessment. The ALS patients were categorized as non-impaired (ALSni; n = 68), cognitively impaired (ALSci; n = 21), and ALS-FTD (n = 8). Group differences in connectivity of the default mode network (DMN), motor network (MN), and ventral attention network (VAN) were investigated using a full-factorial model; correlations between global cognitive performance, shifting, and motor symptom severity were established using Pearson’s correlation.ResultsAt a liberal alpha level of uncorrected p < 0.005 and a cluster size exceeding 20 voxels, we found widespread decreases in functional connectivity in all three networks when comparing ALS patients to HC. Similar patterns of hypoconnectivity in the bilateral motor cortices and frontotemporal emerged when comparing the ALSci and ALS-FTD patients to those not cognitively impaired. Hyperconnectivity in the DMN temporal gyrus correlated with worse global cognition; moreover, hyperconnectivity in the VAN thalamus, insula, and putamen correlated with worse shifting ability. Better-preserved motor function correlated with higher MN connectivity. Only the motor-related effects prevailed at a more conservative significance level of pFDR< 0.001.ConclusionResting-state functional connectivity differs between cognitive profiles of ALS and is directly associated with clinical presentation, specifically with motor function, and cognitive shifting.

Dynamic Causal Modelling of the Reduced Habituation to Painful Stimuli in Migraine: An EEG Study.

A consistent finding in migraine is reduced cortical habituation to repetitive sensory stimuli. This study investigated brain dynamics underlying the atypical habituation to painful stimuli in interictal migraine. We investigated modulations in effective connectivity between the sources of laser evoked potentials (LEPs) from a first to final block of trigeminal LEPs using dynamic causal modelling (DCM) in a group of 23 migraine patients and 20 controls. Additionally, we looked whether the strength of dynamical connections in the migrainous brain is initially different. The examined network consisted of the secondary somatosensory areas (lS2, rS2), insulae (lIns, rIns), anterior cingulate cortex (ACC), contralateral primary somatosensory cortex (lS1), and a hidden source assumed to represent the thalamus. Results suggest that migraine patients show initially heightened communication between lS1 and the thalamus, in both directions. After repetitive stimulations, connection strengths from the thalamus to all somatosensory areas habituated in controls whereas this was not apparent in migraine. Together with further abnormalities in initial connectivity strengths and modulations between the thalamus and the insulae, these results are in line with altered thalamo-cortical network dynamics in migraine. Group differences in connectivity from and to the insulae including interhemispheric connections, suggests an important role of the insulae.

Frontoparietal Network Connectivity During an N-Back Task in Adults With Autism Spectrum Disorder.

BackgroundShort-term and working memory (STM and WM) deficits have been demonstrated in individuals with autism spectrum disorder (ASD) and may emerge through atypical functional activity and connectivity of the frontoparietal network, which exerts top-down control necessary for successful STM and WM processes. Little is known regarding the spectral properties of the frontoparietal network during STM or WM processes in ASD, although certain neural frequencies have been linked to specific neural mechanisms.MethodsWe analysed magnetoencephalographic data from 39 control adults (26 males; 27.15 ± 5.91 years old) and 40 adults with ASD (26 males; 27.17 ± 6.27 years old) during a 1-back condition (STM) of an n-back task, and from a subset of this sample during a 2-back condition (WM). We performed seed-based connectivity analyses using regions of the frontoparietal network. Interregional synchrony in theta, alpha, and beta bands was assessed with the phase difference derivative and compared between groups during periods of maintenance and recognition.ResultsDuring maintenance of newly presented vs. repeated stimuli, the two groups did not differ significantly in theta, alpha, or beta phase synchrony for either condition. Adults with ASD showed alpha-band synchrony in a network containing the right dorsolateral prefrontal cortex, bilateral inferior parietal lobules (IPL), and precuneus in both 1- and 2-back tasks, whereas controls demonstrated alpha-band synchrony in a sparser set of regions, including the left insula and IPL, in only the 1-back task. During recognition of repeated vs. newly presented stimuli, adults with ASD exhibited decreased theta-band connectivity compared to controls in a network with hubs in the right inferior frontal gyrus and left IPL in the 1-back condition. Whilst there were no group differences in connectivity in the 2-back condition, adults with ASD showed no frontoparietal network recruitment during recognition, whilst controls activated networks in the theta and beta bands.ConclusionsOur findings suggest that since adults with ASD performed well on the n-back task, their appropriate, but effortful recruitment of alpha-band mechanisms in the frontoparietal network to maintain items in STM and WM may compensate for atypical modulation of this network in the theta band to recognise previously presented items in STM.

Functional Connectivity in Chronic Nonbothersome Tinnitus Following Acoustic Trauma: A Seed-Based Resting-State Functional Magnetic Resonance Imaging Study.

Background: Tinnitus and its mechanisms are an ongoing subject of interrogation in the neuroscientific community. Although most current models agree that it encompasses multiple structures within and outside the auditory system, evidence provided in the literature suffers from a lack of convergence. To further our understanding of contributions to tinnitus lying outside the auditory system, we explored a new model based on a proprioceptive hypothesis specifically in subjects experiencing chronic nonbothersome tinnitus due to acoustic trauma. The present study addresses the role of the right operculum 3 (OP3) involved in this model. It also investigates classical models of tinnitus. Methods: A seed-based resting-state magnetic resonance imaging study explored the functional connectivity in an acoustic trauma group presenting slight to mild nonbothersome chronic tinnitus and compared it with a control group. Results: Group differences were found with two networks: with the sensorimotor-auditory and the frontoparietal, but not with the default mode network nor the limbic regions. In the auditory pathway, the inferior colliculus displayed group differences in connectivity with the right superior parietal lobule. Exploratory analysis elicited a significant increase in connectivity between two seeds in the right OP3 and two mirror regions of the dorsal prefrontal cortex, thought to correspond to the human homologue of the premotor ear-eye field bilaterally and the inferior parietal lobule involved in proprioception, in the tinnitus group. Conclusions: These new findings support the view that acoustic trauma tinnitus could bear a proprioceptive contribution and that a permanent cognitive control is required to filter out this chronic phantom percept.

When worry may be good for you: Worry severity and limbic-prefrontal functional connectivity in late-life generalized anxiety disorder

BackgroundLate-life generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older adults. However, its neural markers have received relatively little attention. In this study, we explored the association between worry severity and limbic-prefrontal connectivity during emotional reactivity in late-life GAD. MethodsWe recruited 16 anxious (GAD) and 20 non-anxious (HC) older adults to perform the faces/shapes emotional reactivity task during functional magnetic resonance imaging (fMRI). We investigated the functional connectivity of both the amygdala and the bed nucleus of stria terminalis (BNST) with the prefrontal cortex (PFC) using generalized psychophysiological interaction (gPPI) analysis. We tested for (1) group differences in connectivity, (2) association between worry severity and connectivity, and (3) interaction between group and worry severity and its association with connectivity. ResultsAmygdala-PFC and BNST-PFC functional connectivity were associated with worry severity in an inverse U-shape, and was independent of depression severity, global anxiety, neuroticism, and general cognitive function. LimitationsOur limitations include slightly skewed PSWQ distributions, lack of non-anxious individuals with high worry, small sample size, and low depression comorbidity in a sample of late-life GAD that may not generalize to GAD in younger populations. ConclusionsThis suggests that moderate worry is associated with maximum engagement of the limbic-PFC connectivity, while severe worry is associated with failure of the limbic-PFC emotional regulation circuit. This may explain the aberrant and exaggerated responses to negative stimuli observed in participants with pathological worry.

Functional Connectivity of the Striatum in Schizophrenia and Psychotic Bipolar Disorder

BackgroundThe striatum is abnormal in schizophrenia and possibly represents a common neurobiological mechanism underlying psychotic disorders. Resting-state functional magnetic resonance imaging studies have not reached a consensus regarding striatal dysconnectivity in schizophrenia, although these studies generally find impaired frontoparietal and salience network connectivity. The goal of the current study was to clarify the pattern of corticostriatal connectivity, including whether corticostriatal dysconnectivity is transdiagnostic and extends into psychotic bipolar disorder. MethodsWe examined corticostriatal functional connectivity in 60 healthy subjects and 117 individuals with psychosis, including 77 with a schizophrenia spectrum illness and 40 with psychotic bipolar disorder. We conducted a cortical seed–based region-of-interest analysis with follow-up voxelwise analysis for any significant results. Further, a striatum seed–based analysis was conducted to examine group differences in connectivity between the striatum and the whole cortex. ResultsCortical region-of-interest analysis indicated that overall connectivity of the salience network with the striatum was reduced in psychotic disorders, which follow-up voxelwise analysis localized to the left putamen. Striatum seed–based analyses showed reduced ventral rostral putamen connectivity with the salience network portion of the medial prefrontal cortex in both schizophrenia and psychotic bipolar disorder. ConclusionsThe current study found evidence of transdiagnostic corticostriatal dysconnectivity in both schizophrenia and psychotic bipolar disorder, including reduced salience network connectivity, as well as reduced connectivity between the putamen and the medial prefrontal cortex. Overall, the current study points to the relative importance of salience network hypoconnectivity in psychotic disorders.

Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression

BackgroundLate-life depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the default mode network (DMN), cognitive control network (CCN), and salience network. However, these findings often derive from small samples, and it is not well understood how network findings relate to clinical and cognitive symptomatology. MethodsWe studied 100 older adults (n = 79 with LLD, n = 21 nondepressed) and collected resting-state functional magnetic resonance imaging, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and salience network) as seeds in seed-to-voxel analysis. We compared connectivity between the depressed and nondepressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance. ResultsLLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ21 = 22.33, p < .001). No significant group differences in connectivity were found for the CCN or salience network. However, in the LLD group, increased CCN connectivity was associated with increased depression severity (Wald χ21 > 20.14, p < .001), greater anhedonia (Wald χ21 = 7.02, p = .008) and fatigue (Wald χ21 = 6.31, p = .012), and poorer performance on tests of episodic memory (Wald χ21 > 4.65, p < .031), executive function (Wald χ21 = 7.18, p = .007), and working memory (Wald χ21 > 4.29, p < .038). ConclusionsLLD is characterized by differences in DMN connectivity, while CCN connectivity is associated with LLD symptomology, including poorer performance in several cognitive domains.

Altered Functional Connectivity of Fronto-Cingulo-Striatal Circuits during Error Monitoring in Adolescents with a History of Childhood Abuse.

Childhood maltreatment is associated with error hypersensitivity. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA) interaction on functional brain connectivity during error processing in medication/drug-free adolescents. Functional connectivity was compared, using generalized psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 22 age- and gender-matched medication-naïve and substance abuse-free adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed an individually adjusted tracking stop-signal task, designed to elicit 50% inhibition failures. During inhibition failures, abused participants relative to healthy controls exhibited reduced connectivity between right and left putamen, bilateral caudate and anterior cingulate cortex (ACC), and between right supplementary motor area (SMA) and right inferior and dorsolateral prefrontal cortex. Abuse-related connectivity abnormalities were associated with longer abuse duration. No group differences in connectivity were observed for successful inhibition. The findings suggest that childhood abuse is associated with decreased functional connectivity in fronto-cingulo-striatal networks during error processing. Furthermore that the severity of connectivity abnormalities increases with abuse duration. Reduced connectivity of error detection networks in maltreated individuals may be linked to constant monitoring of errors in order to avoid mistakes which, in abusive contexts, are often associated with harsh punishment.

Aberrant hemodynamic responses in autism: Implications for resting state fMRI functional connectivity studies.

Functional MRI (fMRI) is modeled as a convolution of the hemodynamic response function (HRF) and an unmeasured latent neural signal. However, HRF itself is variable across brain regions and subjects. This variability is induced by both neural and non-neural factors. Aberrations in underlying neurochemical mechanisms, which control HRF shape, have been reported in autism spectrum disorders (ASD). Therefore, we hypothesized that this will lead to voxel-specific, yet systematic differences in HRF shape between ASD and healthy controls. As a corollary, we also hypothesized that such alterations will lead to differences in estimated functional connectivity in fMRI space compared to latent neural space. To test these hypotheses, we performed blind deconvolution of resting-state fMRI time series acquired from large number of ASD and control subjects obtained from the Autism Brain Imaging Data Exchange (ABIDE) database (N = 1102). Many brain regions previously implicated in autism showed systematic differences in HRF shape in ASD. Specifically, we found that precuneus had aberrations in all HRF parameters. Consequently, we obtained precuneus-seed-based functional connectivity differences between ASD and controls using fMRI as well as using latent neural signals. We found that non-deconvolved fMRI data failed to detect group differences in connectivity between precuneus and certain brain regions that were instead observed in deconvolved data. Our results are relevant for the understanding of hemodynamic and neurochemical aberrations in ASD, as well as have methodological implications for resting-state functional connectivity studies in Autism, and more generally in disorders that are accompanied by neurochemical alterations that may impact HRF shape.

Graph-based analysis of brain connectivity in schizophrenia

The present study evaluated brain connectivity using electroencephalography (EEG) data from 14 patients with schizophrenia and 14 healthy controls. Phase-Locking Value (PLV), Phase-Lag Index (PLI) and Directed Transfer Function (DTF) were calculated for the original EEG data and following current source density (CSD) transformation, re-referencing using the average reference electrode (AVERAGE) and reference electrode standardization techniques (REST). The statistical analysis of adjacency matrices was carried out using indices based on graph theory. Both CSD and REST reduced the influence of volume conducted currents. The largest group differences in connectivity were observed for the alpha band. Schizophrenic patients showed reduced connectivity strength, as well as a lower clustering coefficient and shorter characteristic path length for both measures of phase synchronization following CSD transformation or REST re-referencing. Reduced synchronization was accompanied by increased directional flow from the occipital region for the alpha band. Following the REST re-referencing, the sources of alpha activity were located at parietal rather than occipital derivations. The results of PLV and DTF demonstrated group differences in fronto-posterior asymmetry following CSD transformation, while for PLI the differences were significant only using REST. The only analysis that identified group differences in inter-hemispheric asymmetry was DTF calculated for REST. Our results suggest that a comparison of different connectivity measures using graph-based indices for each frequency band, separately, may be a useful tool in the study of disconnectivity disorders such as schizophrenia.

Reduced functional connectivity between ventromedial prefrontal cortex and insula relates to longer corrected QT interval in HIV+ and HIV− individuals

ObjectiveProlongation of the QT interval, i.e., measure of the time between the start of the Q wave and the end of the T wave, is a precursor to fatal cardiac arrhythmias commonly observed in individuals infected with the Human Immunodeficiency Virus (HIV), and is related to dysregulation of the autonomic nervous system. We investigated the relationship between QT interval length and resting state functional connectivity (rsFC) of the ventromedial prefrontal cortex (VMPFC), a core region of the brain that is involved with cardio-autonomic regulation. MethodEighteen HIV+ men on antiretroviral therapy and with no history of heart disease were compared with 26 HIV-negative control subjects who had similar demographic and cardio-metabolic characteristics. A seed-based rsFC analysis of the right and left VMPFC was performed at the individual subject level, and 2nd-level analyses were conducted to identify the following: group differences in connectivity, brain regions correlating with corrected (QTc) interval length before and after controlling for those group differences, and regions where seed-based rsFC correlates with CD4 count and QTc interval within HIV+ individuals. ResultsHIV-negative adults showed greater rsFC between the VMPFC seed regions and several default mode network structures. Across groups greater rsFC with the left anterior insula was associated with shorter QTc intervals, whereas right posterior insula connectivity with the VMPFC correlated with greater QTc intervals. HIV patients with lower CD4 counts and higher QTc intervals showed greater rsFC between the right VMPFC and the right posterior insula and dorsal cingulate gyrus. ConclusionsThis study demonstrates that QTc interval lengths are associated with distinct patterns of VMPFC rsFC with posterior and anterior insula. In HIV patients, longer QTc interval and lower CD4 count corresponded to weaker VMPFC connectivity with the dorsal striatrum. SignificanceA forebrain control mechanism may be implicated in the suppression of cardiovagal influence that confers risk for ventricular arrhythmias and sudden cardiac death in HIV+ individuals.

Measuring Brain Connectivity via Shape Analysis of fMRI Time Courses and Spectra.

We present a shape matching approach for functional magnetic resonance imaging (fMRI) time course and spectral alignment. We use ideas from differential geometry and functional data analysis to define a functional representation for fMRI signals. The space of fMRI functions is then equipped with a reparameterization invariant Riemannian metric that enables elastic alignment of both amplitude and phase of the fMRI time courses as well as their power spectral densities. Experimental results show significant increases in pairwise node to node correlations and coherences following alignment. We apply this method for finding group differences in connectivity between patients with major depression and healthy controls.

Aberrant activity and connectivity of the posterior superior temporal sulcus during social cognition in schizophrenia

Schizophrenia is associated with significant impairments in social cognition. These impairments have been shown to go along with altered activation of the posterior superior temporal sulcus (pSTS). However, studies that investigate connectivity of pSTS during social cognition in schizophrenia are sparse. Twenty-two patients with schizophrenia and 22 matched healthy controls completed a social-cognitive task for functional magnetic resonance imaging that allows the investigation of affective Theory of Mind (ToM), emotion recognition and the processing of neutral facial expressions. Moreover, a resting-state measurement was taken. Patients with schizophrenia performed worse in the social-cognitive task (main effect of group). In addition, a group by social-cognitive processing interaction was revealed for activity, as well as for connectivity during the social-cognitive task, i.e., patients with schizophrenia showed hyperactivity of right pSTS during neutral face processing, but hypoactivity during emotion recognition and affective ToM. In addition, hypoconnectivity between right and left pSTS was revealed for affective ToM, but not for neutral face processing or emotion recognition. No group differences in connectivity from right to left pSTS occurred during resting state. This pattern of aberrant activity and connectivity of the right pSTS during social cognition might form the basis of false-positive perceptions of emotions and intentions and could contribute to the emergence and sustainment of delusions.

Altered whole-brain connectivity in albinism.

Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc.

Aberrant Hippocampal Connectivity in Unmedicated Patients With Schizophrenia and Effects of Antipsychotic Medication: A Longitudinal Resting State Functional MRI Study.

To better characterize hippocampal pathophysiology in schizophrenia, we conducted a longitudinal study evaluating hippocampal functional connectivity during resting state, using seeds prescribed in its anterior and posterior regions. We enrolled 34 unmedicated patients with schizophrenia or schizoaffective disorder (SZ) and 34 matched healthy controls. SZ were scanned while off medication, then were treated with risperidone for 6 weeks and re-scanned (n = 22). Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. We found significant dysconnectivity with anterior and posterior hippocampal seeds in unmedicated SZ. Baseline connectivity between the hippocampus and anterior cingulate cortex, caudate nucleus, auditory cortex and calcarine sulcus in SZ predicted subsequent response to antipsychotic medications. These same regions demonstrated changes over the 6-week treatment trial that were correlated with symptomatic improvement. Our findings implicate several neural networks relevant to clinical improvement with antipsychotic medications.