Altered effective connectivity within an oculomotor control network in individuals with schizophrenia.
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ABSTRACT:
SUBMITTER: Lehet M
PROVIDER: S-EPMC8313596 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The ability to rapidly stop or change a planned action is a critical cognitive process that is impaired in schizophrenia. The current study aimed to examine whether this impairment reflects familial vulnerability to schizophrenia across two experiments comparing unaffected first-degree relatives to healthy controls. First, we examined performance on a saccadic stop-signal task that required rapid inhibition of an eye movement. Then, in a different sample, we investigated behavioral and neural responses (using fMRI) during a stop-signal task variant that required rapid modification of a prepared eye movement. Here, we examined differences between relatives and healthy controls in terms of activation and effective connectivity within an oculomotor control network during task performance. Like individuals with schizophrenia, the unaffected relatives showed behavioral evidence for more inefficient inhibitory processes. Unlike previous findings in individuals with schizophrenia, however, the relatives showed evidence for a compensatory waiting strategy. Behavioral differences were accompanied by more activation among the relatives in task-relevant regions across conditions and group differences in effective connectivity across the task that were modulated differently by the instruction to exert control over a planned saccade. Effective connectivity parameters were related to behavioral measures of inhibition efficiency. The results suggest that individuals at familial risk for schizophrenia were engaging an oculomotor control network differently than controls and in a way that compromises inhibition efficiency.
| S-EPMC8467791 | biostudies-literature
Project description:BackgroundImpairments in social cognition have been described in schizophrenia and relate to core symptoms of the disorder. Social cognition is subserved by a network of brain regions, many of which have been implicated in schizophrenia. We hypothesized that deficits in connectivity between components of this social brain network may underlie the social cognition impairments seen in the disorder.MethodsWe investigated brain activation and connectivity in a group of individuals with schizophrenia making social judgments of approachability from faces (n = 20), compared with a group of matched healthy volunteers (n = 24), using functional magnetic resonance imaging. Effective connectivity from the amygdala was estimated using the psychophysiological interaction approach.ResultsWhile making approachability judgments, healthy participants recruited a network of social brain regions including amygdala, fusiform gyrus, cerebellum, and inferior frontal gyrus bilaterally and left medial prefrontal cortex. During the approachability task, healthy participants showed increased connectivity from the amygdala to the fusiform gyri, cerebellum, and left superior frontal cortex. In comparison to controls, individuals with schizophrenia overactivated the right middle frontal gyrus, superior frontal gyrus, and precuneus and had reduced connectivity between the amygdala and the insula cortex.DiscussionWe report increased activation of frontal and medial parietal regions during social judgment in patients with schizophrenia, accompanied by decreased connectivity between the amygdala and insula. We suggest that the increased activation of frontal control systems and association cortex may reflect a compensatory mechanism for impaired connectivity of the amygdala with other parts of the social brain networks in schizophrenia.
| S-EPMC3885300 | biostudies-literature
Project description:Functional connectivity is one of the most widely used tools for investigating brain changes due to schizophrenia. Previous studies have identified abnormal functional connectivity in schizophrenia patients at the resting state brain network level. This study tests the existence of functional connectivity effects at whole brain and domain levels. Domain level refers to the integration of data from several brain networks grouped by their functional relationship. Data integration provides more consistent and accurate information compared to an individual brain network. This work considers two domain level measures: functional connectivity strength and randomness. The first measure is simply an average of connectivities within the domain. The second measure assesses the unpredictability and lack of pattern of functional connectivity within the domain. Domains with less random connectivity have higher chance of exhibiting a biologically meaningful connectivity pattern. Consistent with prior observations, individuals with schizophrenia showed aberrant domain connectivity strength between subcortical, cerebellar, and sensorial brain areas. Compared to healthy volunteers, functional connectivity between cognitive and default mode domains showed less randomness, while connectivity between default mode-sensorial areas showed more randomness in schizophrenia patients. These differences in connectivity patterns suggest deleterious rewiring trade-offs among important brain networks.
| S-EPMC6664085 | biostudies-literature
Project description:Abnormal functional brain connectivity could be considered an endophenotype of psychosis in schizophrenia. Identifying candidate endophenotypes may serve as a tool for elucidating its biological and neural mechanisms. The present study investigated the similarities and differences of features of brain network connectivity between patients and their first-degree relatives. Independent component analysis was conducted on imaging data collected from 34 healthy controls, 33 schizophrenia patients, and 30 unaffected first-degree relatives. The correlation between functional connectivity with neurocognitive performance and clinical symptoms were calculated. Abnormalities of between-network connectivity largely overlapped in patients and first-degree relatives, but the extent of such abnormalities was relatively minor in relatives. Negative connectivity between language networks and executive control networks was impaired in schizophrenia patients and their first-degree relatives, and this decreased connectivity was correlated with performance in language processing. Similar impairments were found in high-visual network and executive network coupling, and this decreased connection was correlated with the severity of positive symptoms in patients. The results indicated that abnormal functional connectivity within and between perceptual systems (i.e., high-visual and language) and executive control networks was related to the generic risk of schizophrenia, which makes it a potential endophenotype for schizophrenia.
| S-EPMC5511161 | biostudies-literature
Project description:Research on brain activity in schizophrenia has shown that changes in the function of any single region cannot explain the range of cognitive and affective impairments in this illness. Rather, neural circuits that support sensory, cognitive, and emotional processes are now being investigated as substrates for cognitive and affective impairments in schizophrenia, a shift in focus consistent with long-standing hypotheses about schizophrenia as a disconnection syndrome. Our goal was to further examine alterations in functional connectivity within and between the default mode network and three cognitive control networks (frontal-parietal, cingulo-opercular, and cerebellar) as a basis for such impairments.Resting state functional magnetic resonance imaging was collected from 40 individuals with DSM-IV-TR schizophrenia, 31 siblings of individuals with schizophrenia, 15 healthy control subjects, and 18 siblings of healthy control subjects while they rested quietly with their eyes closed. Connectivity metrics were compared between patients and control subjects for both within- and between-network connections and were used to predict clinical symptoms and cognitive function.Individuals with schizophrenia showed reduced distal and somewhat enhanced local connectivity between the cognitive control networks compared with control subjects. Additionally, greater connectivity between the frontal-parietal and cerebellar regions was robustly predictive of better cognitive performance across groups and predictive of fewer disorganization symptoms among patients.These results are consistent with the hypothesis that impairments of executive function and cognitive control result from disruption in the coordination of activity across brain networks and additionally suggest that these might reflect impairments in normal pattern of brain connectivity development.
| S-EPMC3081915 | biostudies-literature
Project description:ObjectiveWe hypothesized that compared to healthy controls, long-term abstinent substance dependent individuals (SDI) will differ in their effective connectivity between large-scale brain networks and demonstrate increased directional information from executive control to interoception-, reward-, and habit-related networks. In addition, using graph theory to compare network efficiencies we predicted decreased small-worldness in SDI compared to controls.Methods50 SDI and 50 controls of similar sex and age completed psychological surveys and resting state fMRI. fMRI results were analyzed using group independent component analysis; 14 networks-of-interest (NOI) were selected using template matching to a canonical set of resting state networks. The number, direction, and strength of connections between NOI were analyzed with Granger Causality. Within-group thresholds were p<0.005 using a bootstrap permutation. Between group thresholds were p<0.05, FDR-corrected for multiple comparisons. NOI were correlated with behavioral measures, and group-level graph theory measures were compared.ResultsCompared to controls, SDI showed significantly greater Granger causal connectivity from right executive control network (RECN) to dorsal default mode network (dDMN) and from dDMN to basal ganglia network (BGN). RECN was negatively correlated with impulsivity, behavioral approach, and negative affect; dDMN was positively correlated with impulsivity. Among the 14 NOI, SDI showed greater bidirectional connectivity; controls showed more unidirectional connectivity. SDI demonstrated greater global efficiency and lower local efficiency.ConclusionsIncreased effective connectivity in long-term abstinent drug users may reflect improved cognitive control over habit and reward processes. Higher global and lower local efficiency across all networks in SDI compared to controls may reflect connectivity changes associated with drug dependence or remission and requires future, longitudinal studies to confirm.
| S-EPMC5077096 | biostudies-literature
Project description:Analyzing the schizophrenia connectome can identify illness-related alterations in connectivity across the brain. An important question that remains unanswered is whether connectivity alterations are already evident at the onset of illness, before treatment with antipsychotic medication and possible influences of neuroprogressive or secondary alterations related to chronic illness duration. In the present study, diffusion tensor imaging and deterministic fiber tractography were performed with 137 antipsychotic-naive first-episode schizophrenia patients and 113 matched healthy controls. Using graph theoretic analysis, groups were compared in global and regional measurements and modularity of white matter connectivity. Compared with controls, the patients showed significantly decreased total connection strength. Furthermore, patients demonstrated significantly decreased connections within and between brain modules. Several local brain regions within association cortex exhibited reduced nodal centralities and abnormal participant coefficient or intra-module degree, some of which were correlated with illness duration and overall functional disability. In never-treated schizophrenia patients, networks showed a less effective organizational pattern of white matter pathways. White matter disconnectivity occurred not only within but also between multiple modules, shedding light on the deficits of anatomical network organization early in the course of schizophrenia.
| S-EPMC5814807 | biostudies-other
Project description:BackgroundImpaired eye movements in multiple sclerosis (MS) are common and could represent a non-invasive and accurate measure of (dys)functioning of interconnected areas within the complex brain network. The aim of this study was to test whether altered saccadic eye movements are related to changes in functional connectivity (FC) in patients with MS.MethodsCross-sectional eye movement (pro-saccades and anti-saccades) and magnetoencephalography (MEG) data from the Amsterdam MS cohort were included from 176 MS patients and 33 healthy controls. FC was calculated between all regions of the Brainnetome atlas in six conventional frequency bands. Cognitive function and disability were evaluated by previously validated measures. The relationships between saccadic parameters and both FC and clinical scores in MS patients were analysed using multivariate linear regression models.ResultsIn MS pro- and anti-saccades were abnormal compared to healthy controls A relationship of saccadic eye movements was found with FC of the oculomotor network, which was stronger for regional than global FC. In general, abnormal eye movements were related to higher delta and theta FC but lower beta FC. Strongest associations were found for pro-saccadic latency and FC of the precuneus (beta band β = -0.23, p = .006), peak velocity and FC of the parietal eye field (theta band β = -0.25, p = .005) and gain and FC of the inferior frontal eye field (theta band β = -0.25, p = .003). Pro-saccadic latency was also strongly associated with disability scores and cognitive dysfunction.ConclusionsImpaired saccadic eye movements were related to functional connectivity of the oculomotor network and clinical performance in MS. This study also showed that, in addition to global network connectivity, studying regional changes in MEG studies could yield stronger correlations.
| S-EPMC8503580 | biostudies-literature
Project description:Antipsychotic treatment resistance affects a third of people with schizophrenia and the underlying mechanism remains unclear. We used an fMRI emotion-yoked reward learning task, allied to prefrontal cortical glutamate levels, to explain the role of cognitive control in differentiating treatment-resistant from responsive patients. We investigated how reward learning is disrupted at the network level in 21 medicated treatment-responsive and 20 medicated treatment-resistant patients with schizophrenia compared with 24 healthy controls (HC). Dynamic Causal Modelling assessed how effective connectivity between regions in a cortico-striatal-limbic network is disrupted in each patient group compared to HC. Connectivity was also examined with respect to symptoms, salience and anterior cingulate (ACC) glutamate levels measured from the same region of the ACC. We found that ACC connectivity differentiated these patient groups, with responsive patients exhibiting increased top-down connectivity from ACC to sensory regions and reduced ACC drive to the striatum, while resistant patients showed altered connectivity within the ACC itself. In these resistant patients, the ACC drive to striatum was positively correlated with their symptom severity. ACC glutamate levels were found to correlate with ACC control over sensory regions in responsive patients but not in resistant patients. We suggest a central non-dopaminergic impairment that impacts cognitive control networks in treatment-resistant schizophrenia. This impairment was associated with disrupted reward learning and could be underpinned by aberrant glutamate function. These findings should form the focus of future treatment strategies (e.g. glutamatergic targets and giving clozapine earlier) in resistant patients.
| S-EPMC8044714 | biostudies-literature
Project description:Background/objectivesNeuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.Subjects/methodsFifty healthy, premenopausal women, 19 overweight and obese (high BMI=26-38?kg?m(-2)) and 31 lean (BMI=19-25?kg?m(-2)) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.ResultsGMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.ConclusionsOverweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors.
| S-EPMC4314578 | biostudies-literature