Default Connectivity Research Articles

M193. CHANGES IN THEORY OF MIND DETECTED IN SCHIZOPHRENIA SPECTRUM DISORDERS- A LITERATURE REVIEW

BackgroundTheory of mind (ToM) is a core feature of the social functioning because it influences the way an individual perceive other people’s mental states, and because responses to social cues are shaped by one’s ToM. Patients diagnosed with schizophrenia spectrum disorders (SSD) often present cognitive symptoms as part of their clinical manifestations, and there is a controversy about the relation of ToM deficiencies and more general cognitive features of schizophrenia and related disorders [1]. In order to find data that may clarify if ToM deficiencies are part of the schizophrenia cognitive dimension, or if they precede the onset of psychosis and simply coexist with other symptoms met in this type of disorders, a literature analysis was conducted.MethodsThis review included papers published between January 2000 and August 2019 in the main electronic databases (PubMed, Cochrane, EMBASE, CINAHL). Keywords used for database search were “schizophrenia spectrum disorders”, “schizophrenia”, “schizoaffective disorder”, “delusional disorder”, or “schizophreniform disorder” and “theory of mind”. There was included no age limit, and no exclusion criteria referred to the duration of the disorder.ResultsA number of 93 papers resulted after the primary search, but only 17 remained after de-duplication and application of inclusion/exclusion criteria. A study with young adults diagnosed with first episode of schizophrenia and matched controls (n=128) suggested that ToM deficits are partly independent of other cognitive functions [1]. Another study (n=1630 children 11–12 years old) reported specific alterations in ToM may be associated with specific types of psychotic experiences, and exaggerated type of ToM may index risk for developing psychosis and paranoid delusions in particular [2]. Adolescents who were genetically at high risk for schizophrenia had social skills impairments but no ToM deficits in a study [3]. Also, there is evidence for ToM deficits in the healthy relatives of schizophrenics, patients with delusional disorder, and individual with high schizotypy scores [4]. The hyper-connectivity in SSD has been confirmed on functional magnetic resonance imaging and default connectivity is correlated to and predictive of theory of mind performance [5]. A significant number of papers (n=10) did not formulate any clear argument to support the independent versus secondary status of the ToM deficits in relation to the SSD cognitive dimension.DiscussionToM deficiencies are important elements that have been associated with the social skills and functioning in patients with SSD, although it is not clear if these elements exist independently from other cognitive symptoms. Relatives of patients with SSD may present ToM deficits, and data exist about the correlation between ToM abnormalities and several positive symptoms of the SSD. However, more well designed trials are needed in order to confirm the association between ToM impairments and SSD.ReferencesLindgren M, Torniainen-Holm M, Heiskanen I, et al. Theory of mind in a first-episode psychosis population using the Hinting Task. Psychiatry Res 2018;263:185–192.Clemmensen L, van Os J, Skovgaard AM, et al. Hyper-Theory-of-Mind in children with psychotic experiences. PLoS ONE 2014;9(11):e113082.Gibson CM, Penn DL, Prinstein MJ, et al. Social skills and social cognition in adolescents at genetic risk for psychosis. Schizophr Res 2010;122(1–3):179–184.Bora M. Theory of mind in schizophrenia spectrum disorders. Turkish Journal of Psychiatry 2009;20(3):269–81.Mothersill O, Tangney N, Morris DW, et al. Further evidence of alerted default network connectivity and association with theory of mind ability in schizophrenia. Schizophr Res 2017;184:52–58.

Modulation of Resting Connectivity Between the Mesial Frontal Cortex and Basal Ganglia.

Background: The mesial prefrontal cortex, cingulate cortex, and the ventral striatum are key nodes of the human mesial fronto-striatal circuit involved in decision-making and executive function and pathological disorders. Here we ask whether deep wide-field repetitive transcranial magnetic stimulation (rTMS) targeting the mesial prefrontal cortex (MPFC) influences resting state functional connectivity.Methods: In Study 1, we examined functional connectivity using resting state multi-echo and independent components analysis in 154 healthy subjects to characterize default connectivity in the MPFC and mid-cingulate cortex (MCC). In Study 2, we used inhibitory, 1 Hz deep rTMS with the H7-coil targeting MPFC and dorsal anterior cingulate (dACC) in a separate group of 20 healthy volunteers and examined pre- and post-TMS functional connectivity using seed-based and independent components analysis.Results: In Study 1, we show that MPFC and MCC have distinct patterns of functional connectivity with MPFC–ventral striatum showing negative, whereas MCC–ventral striatum showing positive functional connectivity. Low-frequency rTMS decreased functional connectivity of MPFC and dACC with the ventral striatum. We further showed enhanced connectivity between MCC and ventral striatum.Conclusions: These findings emphasize how deep inhibitory rTMS using the H7-coil can influence underlying network functional connectivity by decreasing connectivity of the targeted MPFC regions, thus potentially enhancing response inhibition and decreasing drug-cue reactivity processes relevant to addictions. The unexpected finding of enhanced default connectivity between MCC and ventral striatum may be related to the decreased influence and connectivity between the MPFC and MCC. These findings are highly relevant to the treatment of disorders relying on the mesio-prefrontal-cingulo-striatal circuit.

Brain resting-state networks in adolescents with high-functioning autism: Analysis of spatial connectivity and temporal neurodynamics.

IntroductionAutism spectrum disorder (ASD) is mainly characterized by functional and communication impairments as well as restrictive and repetitive behavior. The leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, which can be assessed using functional magnetic resonance imaging (fMRI). Even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic, or resting‐state, connectivity. Global default connectivity in individuals with autism versus controls is not well characterized, especially for a high‐functioning young population. The aim of this study is to test whether high‐functioning adolescents with ASD (HFA) have an abnormal resting‐state functional connectivity.Materials and MethodsWe performed spatial and temporal analyses on resting‐state networks (RSNs) in 13 HFA adolescents and 13 IQ‐ and age‐matched controls. For the spatial analysis, we used probabilistic independent component analysis (ICA) and a permutation statistical method to reveal the RSN differences between the groups. For the temporal analysis, we applied Granger causality to find differences in temporal neurodynamics.ResultsControls and HFA display very similar patterns and strengths of resting‐state connectivity. We do not find any significant differences between HFA adolescents and controls in the spatial resting‐state connectivity. However, in the temporal dynamics of this connectivity, we did find differences in the causal effect properties of RSNs originating in temporal and prefrontal cortices.ConclusionThe results show a difference between HFA and controls in the temporal neurodynamics from the ventral attention network to the salience‐executive network: a pathway involving cognitive, executive, and emotion‐related cortices. We hypothesized that this weaker dynamic pathway is due to a subtle trigger challenging the cognitive state prior to the resting state.

Further evidence of alerted default network connectivity and association with theory of mind ability in schizophrenia

BackgroundResting-state functional magnetic resonance imaging (rs-fMRI) has repeatedly shown evidence of altered functional connectivity of large-scale networks in schizophrenia. The relationship between these connectivity changes and behaviour (e.g. symptoms, neuropsychological performance) remains unclear. MethodsFunctional connectivity in 27 patients with schizophrenia or schizoaffective disorder, and 25 age and gender matched healthy controls was examined using rs-fMRI. Based on seed regions from previous studies, we examined functional connectivity of the default, cognitive control, affective and attention networks. Effects of symptom severity and theory of mind performance on functional connectivity were also examined. ResultsPatients showed increased connectivity between key nodes of the default network including the precuneus and medial prefrontal cortex compared to controls (p<0.01, FWE-corrected). Increasing positive symptoms and increasing theory of mind performance were both associated with altered connectivity of default regions within the patient group (p<0.01, FWE-corrected). DiscussionThis study confirms previous findings of default hyper-connectivity in schizophrenia spectrum patients and reveals an association between altered default connectivity and positive symptom severity. As a novel find, this study also shows that default connectivity is correlated to and predictive of theory of mind performance. Extending these findings by examining the effects of emerging social cognition treatments on both default connectivity and theory of mind performance is now an important goal for research.

P.1.c.004 Study of the effects of alpha-lipoic acid, benfotiamine and combined vitamin preparation on pain and inflammation in rats

Resting-state functional magnetic resonance imaging (rs-fMRI) has repeatedly shown evidence of altered functional connectivity of large-scale networks in schizophrenia. The relationship between these connectivity changes and behaviour (e.g. symptoms, neuropsychological performance) remains unclear.Functional connectivity in 27 patients with schizophrenia or schizoaffective disorder, and 25 age and gender matched healthy controls was examined using rs-fMRI. Based on seed regions from previous studies, we examined functional connectivity of the default, cognitive control, affective and attention networks. Effects of symptom severity and theory of mind performance on functional connectivity were also examined.Patients showed increased connectivity between key nodes of the default network including the precuneus and medial prefrontal cortex compared to controls (p < 0.01, FWE-corrected). Increasing positive symptoms and increasing theory of mind performance were both associated with altered connectivity of default regions within the patient group (p < 0.01, FWE-corrected).This study confirms previous findings of default hyper-connectivity in schizophrenia spectrum patients and reveals an association between altered default connectivity and positive symptom severity. As a novel find, this study also shows that default connectivity is correlated to and predictive of theory of mind performance. Extending these findings by examining the effects of emerging social cognition treatments on both default connectivity and theory of mind performance is now an important goal for research.

Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia.

We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.