Project description:BACKGROUND:Impairment in episodic memory is one of the most robust findings in schizophrenia. Disruptions of fronto-temporal functional connectivity that could explain some aspects of these deficits have been reported. Recent work has identified abnormal hippocampal function in unmedicated patients with schizophrenia (SZ), such as increased metabolism and glutamate content that are not always seen in medicated SZ. For these reasons, we hypothesized that altered fronto-temporal connectivity might originate from the hippocampus and might be partially restored by antipsychotic medication. METHODS:Granger causality methods were used to evaluate the effective connectivity between frontal and temporal regions in 21 unmedicated SZ and 20 matched healthy controls (HC) during performance of an episodic memory retrieval task. In 16 SZ, effective connectivity between these regions was evaluated before and after 1-week of antipsychotic treatment. RESULTS:In HC, significant effective connectivity originating from the right hippocampus to frontal regions was identified. Compared to HC, unmedicated SZ showed significant altered fronto-temporal effective connectivity, including reduced right hippocampal to right medial frontal connectivity. After 1-week of antipsychotic treatment, connectivity more closely resembled the patterns observed in HC, including increased effective connectivity from the right hippocampus to frontal regions. CONCLUSIONS:These results support the notion that memory disruption in schizophrenia might originate from hippocampal dysfunction and that medication restores some aspects of fronto-temporal dysconnectivity. Patterns of fronto-temporal connectivity could provide valuable biomarkers to identify new treatments for the symptoms of schizophrenia, including memory deficits.
Project description:People with schizophrenia exhibit impaired social cognitive functions, particularly emotion regulation. Abnormal activations of the ventral medial prefrontal cortex (vMPFC) during emotional tasks have been demonstrated in schizophrenia, suggesting its important role in emotion processing in patients. We used the resting-state functional connectivity approach, setting a functionally relevant region, the vMPFC, as a seed region to examine the intrinsic functional interactions and communication between the vMPFC and other brain regions in schizophrenic patients. We found hypo-connectivity between the vMPFC and the medial frontal cortex, right middle temporal lobe (MTL), right hippocampus, parahippocampal cortex (PHC) and amygdala. Further, there was a decreased strength of the negative connectivity (or anticorrelation) between the vMPFC and the bilateral dorsal lateral prefrontal cortex (DLPFC) and pre-supplementary motor areas. Among these connectivity alterations, reduced vMPFC-DLPFC connectivity was positively correlated with positive symptoms on the Positive and Negative Syndrome Scale, while vMPFC-right MTL/PHC/amygdala functional connectivity was positively correlated with the performance of emotional regulation in patients. These findings imply that communication and coordination throughout the brain networks are disrupted in schizophrenia. The emotional correlates of vMPFC connectivity suggest a role of the hypo-connectivity between these regions in the neuropathology of abnormal social cognition in chronic schizophrenia.
Project description:OBJECTIVE:Cognitive remediation is emerging as an effective psychosocial intervention for addressing untreated cognitive and functional impairments in persons with schizophrenia, and might achieve its benefits through neuroplastic changes in brain connectivity. This study seeks to examine the effects of cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a randomized controlled trial with individuals in the early course of schizophrenia. METHOD:Stabilized, early course outpatients with schizophrenia or schizoaffective disorder (N = 41) were randomly assigned to CET (n = 25) or an active enriched supportive therapy (EST) control (n = 16) and treated for 2 years. Functional MRI data were collected annually, and pseudo resting-state functional connectivity analysis was used to examine differential changes in fronto-temporal connectivity between those treated with CET compared with EST. RESULTS:Individuals receiving CET evidenced significantly less functional connectivity loss between the resting-state network and the left dorsolateral prefrontal cortex as well as significantly increased connectivity with the right insular cortex compared to EST (all corrected p < .01). These neural networks are involved in emotion processing and problem-solving. Increased connectivity with the right insula significantly mediated CET effects on improved emotion perception (z' = -1.96, p = .021), and increased connectivity with the left dorsolateral prefrontal cortex mediated CET-related improvements in emotion regulation (z' = -1.71, p = .052). CONCLUSIONS:These findings provide preliminary evidence that CET, a psychosocial cognitive remediation intervention, may enhance connectivity between frontal and temporal brain regions implicated in problem-solving and emotion processing in service of cognitive enhancement in schizophrenia.
Project description:Hallucinations may arise from an imbalance between sensory and higher cognitive brain regions, reflected by alterations in functional connectivity. It is unknown whether hallucinations across the psychosis continuum exhibit similar alterations in functional connectivity, suggesting a common neural mechanism, or whether different mechanisms link to hallucinations across phenotypes. We acquired resting-state functional MRI scans of 483 participants, including 40 non-clinical individuals with hallucinations, 99 schizophrenia patients with hallucinations, 74 bipolar-I disorder patients with hallucinations, 42 bipolar-I disorder patients without hallucinations, and 228 healthy controls. The weighted connectivity matrices were compared using network-based statistics. Non-clinical individuals with hallucinations and schizophrenia patients with hallucinations exhibited increased connectivity, mainly among fronto-temporal and fronto-insula/cingulate areas compared to controls (P?<?0.001 adjusted). Differential effects were observed for bipolar-I disorder patients with hallucinations versus controls, mainly characterized by decreased connectivity between fronto-temporal and fronto-striatal areas (P?=?0.012 adjusted). No connectivity alterations were found between bipolar-I disorder patients without hallucinations and controls. Our results support the notion that hallucinations in non-clinical individuals and schizophrenia patients are related to altered interactions between sensory and higher-order cognitive brain regions. However, a different dysconnectivity pattern was observed for bipolar-I disorder patients with hallucinations, which implies a different neural mechanism across the psychosis continuum.
Project description:This prospective study examined the course of neurological soft signs (NSS) in patients with first-episode schizophrenia and its relationship with negative symptoms and cognitive functions. One hundred and forty-five patients with first-episode schizophrenia were recruited, 29 were classified as having prominent negative symptoms. NSS and neuropsychological measures were administered to all patients and 62 healthy controls at baseline. Patients were then followed-up prospectively at six-month intervals for up to a year. Patients with prominent negative symptoms exhibited significantly more motor coordination signs and total NSS than patients without prominent negative symptoms. Patients with prominent negative symptoms performed worse than patients without negative symptoms in working memory functions but not other fronto-parietal or fronto-temporal functions. Linear growth model for binary data showed that the prominent negative symptoms were stable over time. Despite general improvement in NSS and neuropsychological functions, the prominent negative symptoms group still exhibited poorer motor coordination and higher levels of NSS, as well as poorer working memory than patients without prominent negative symptoms. Two distinct subtypes of first-episode patients could be distinguished by NSS and prominent negative symptoms.
Project description:Research on empathy in schizophrenia has relied on dated self-report scales that do not conform to contemporary social neuroscience models of empathy. The current study evaluated the structure and correlates of the recently-developed Questionnaire of Cognitive and Affective Empathy (QCAE) in schizophrenia. This measure, whose structure and validity was established in healthy individuals, includes separate scales to assess the two main components of empathy: Cognitive Empathy (assessed by two subscales) and Affective Empathy (assessed by three subscales). Stable outpatients with schizophrenia (n = 145) and healthy individuals (n = 45) completed the QCAE, alternative measures of empathy, and assessments of clinical symptoms, neurocognition, and functional outcome. Exploratory and confirmatory factor analyses provided consistent support for a two-factor solution in the schizophrenia group, justifying the use of separate cognitive and affective empathy scales in this population. However, one of the three Affective Empathy subscales was not psychometrically sound and was excluded from further analyses. Patients reported significantly lower Cognitive Empathy but higher Affective Empathy than controls. Among patients, the QCAE scales showed significant correlations with an alternative self-report empathy scale, but not with performance on an empathic accuracy task. The QCAE Cognitive Empathy subscales also showed significant, though modest, correlations with negative symptoms and functional outcome. These findings indicate that structure of self-reported empathy is similar in people with schizophrenia and healthy subjects, and can be meaningfully compared between groups. They also contribute to emerging evidence that some aspects of empathy may be intact or hyper-responsive in schizophrenia.
Project description:Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives.We investigated resting state functional magnetic resonance imaging in 70 schizophrenia and 64 psychotic bipolar probands, their respective first-degree relatives (n = 70 and 52), and 118 healthy subjects. We used independent component analysis to identify components representing various resting state networks and assessed spatial aspects of functional connectivity within all networks. We first investigated group differences using five-level, one-way analysis of covariance (ANCOVA), followed by post hoc t tests within regions displaying ANCOVA group differences and correlation of such functional connectivity measures with symptom ratings to examine clinical relationships.Seven networks revealed abnormalities (five-level one-way ANCOVA, family-wise error correction p < .05): A) fronto-occipital, B) midbrain/cerebellum, C) frontal/thalamic/basal ganglia, D) meso/paralimbic, E) posterior default mode network, F) fronto-temporal/paralimbic and G) sensorimotor networks. Abnormalities in networks B and F were unique to schizophrenia probands. Furthermore, abnormalities in networks D and E were common to both patient groups. Finally, networks A, C, and G showed abnormalities shared by probands and their relative groups. Negative correlation with Positive and Negative Syndrome Scale negative and positive scores were found in regions within network C and F respectively, and positive correlation with Positive and Negative Syndrome Scale negative scores was found in regions in network D among schizophrenia probands only.Schizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes.
Project description:To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD).In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest.The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects.Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease.
Project description:Empathy is an important component of human relationships, yet the neural mechanisms that facilitate empathy are unclear. The broad construct of empathy incorporates both cognitive and affective components. Cognitive empathy includes mentalizing skills such as perspective-taking. Affective empathy consists of the affect produced in response to someone else's emotional state, a process which is facilitated by simulation or "mirroring." Prior evidence shows that mentalizing tasks engage a neural network which includes the temporoparietal junction, superior temporal sulcus, and medial prefrontal cortex. On the other hand, simulation tasks engage the fronto-parietal mirror neuron system (MNS) which includes the inferior frontal gyrus (IFG) and the somotosensory related cortex (SRC). Here, we tested whether neural activity in these two neural networks was related to self-reports of cognitive and affective empathy in daily life. Participants viewed social scenes in which the shift of direction of attention of a character did or did not change the character's mental and emotional state. As expected, the task robustly activated both mentalizing and MNS networks. We found that when detecting the character's change in mental and emotional state, neural activity in both networks is strongly related to cognitive empathy. Specifically, neural activity in the IFG, SRC, and STS were related to cognitive empathy. Activity in the precentral gyrus was related to affective empathy. The findings suggest that both simulation and mentalizing networks contribute to multiple components of empathy.
Project description:We aim to investigate the effect of fronto-temporal transcranial direct current stimulation (tDCS) on the interactions among functional networks and its association with psychotic symptoms. In this pilot study, we will determine possible candidate functional networks and an adequate sample size for future research. Seven schizophrenia patients with treatment-refractory auditory hallucinations underwent tDCS twice daily for 5 days. Resting-state fMRI data and measures of the severity of psychotic symptoms were acquired at baseline and after completion of the tDCS sessions. At baseline, decreased functional network interaction was negatively correlated with increased hallucinatory behavior. After tDCS, the previously reduced functional network connectivity significantly increased. Our results showed that fronto-temporal tDCS could possibly remediate aberrant hallucination-related functional network interactions in patients with schizophrenia.