Default Mode Network Aberrant Connectivity Associated with Neurological Soft Signs in Schizophrenia Patients and Unaffected Relatives

Abstract

Brain connectivity and neurological soft signs (NSS) are reportedly abnormal in schizophrenia and unaffected relatives, suggesting they might be useful neurobiological markers of the illness. NSS are discrete sensorimotor impairments thought to correspond to deviant brain development. Although NSS support the hypothesis that schizophrenia involves disruption in functional circuits involving several hetero modal association areas, little is known about the relationship between NSS and brain connectivity. We explored functional connectivity abnormalities of the default mode network (DMN) related to NSS in schizophrenia. A cross-sectional study was performed with 27 patients diagnosed with schizophrenia, 23 unaffected relatives who were unrelated to the schizophrenia subjects included in the study, and 35 healthy controls. Subjects underwent magnetic resonance imaging scans including a functional resting-state acquisition and NSS evaluation. Seed-to-voxel and independent component analyses were used to study brain connectivity. NSS scores were significantly different between groups, ranging from a higher to lower scores for patients, unaffected relatives, and healthy controls, respectively (analysis of variance effect of group F = 56.51, p < 0.001). The connectivity analysis revealed significant hyperconnectivity in the fusiform gyrus, insular and dorsolateral prefrontal cortices, inferior and middle frontal gyri, middle and superior temporal gyri, and posterior cingulate cortex [minimum p-family wise error (FWE) < 0.05 for all clusters] in patients with schizophrenia as compared with in controls. Also, unaffected relatives showed hyperconnectivity in relation to controls in the supramarginal association and dorsal posterior cingulate cortices (p-FWE < 0.05 for all clusters) in patients with schizophrenia as compared with in controls. Also, unaffected relatives showed hyperconnectivity in relation to controls in the supramarginal association and dorsal posterior cingulate cortices (p-FWE = 0.001) and in the anterior prefrontal cortex (42 voxels, p-FWE = 0.047). A negative correlation was found between left caudate connectivity and NSS [p-FWE = 0.044, cluster size (k) = 110 voxels]. These findings support the theory of widespread abnormal connectivity in schizophrenia, reinforcing DMN hyperconnectivity and NSS as neurobiological markers of schizophrenia. The results also indicate the caudate nucleus as the gateway to the motor consequences of abnormal DMN connectivity.

Reduced Resting-State Connectivity in the Precuneus is correlated with Apathy in Patients with Schizophrenia

“…This result is consistent with two previous studies that employed the same ICA method to investigate rs-fMRI spatial maps and reported decreased functional connectivity within the DMN in patients with schizophrenia 17,18 and thus supports the dysconnection hypothesis 3,4 . The present result of decreased connectivity within the DMN also supplements the inconsistent literature of previous ICA studies that observed both decreases and increases [20][21][22] , only increases 19 as well as no differences in the spatial maps of the DMN at all [23][24][25] . In the context of previous inconclusive findings we would like to emphasize that we included more patients in the reported analysis (N = 35) than previous rs-fMRI studies employing ICA.…”

“…Rs-fMRI studies employing different methodological approaches have shown various functional alterations in this DMN in patients diagnosed with schizophrenia 8,11,16 . Studies that applied the data-driven method of ICA to resting-state fMRI data of patients diagnosed with schizophrenia and healthy controls reported mixed functional connectivity results within the spatial maps of the DMN including decreases 17,18 , increases 19 , both increases and decreases [20][21][22] , and no differences [23][24][25] between the groups.…”

Modeling Social Sensory Processing During Social Computerized Cognitive Training for Psychosis Spectrum: The Resting-State Approach

“…We suggest that improvers express, stronger than maintainers, the psychosis endophenotype that is characterized by increased connectivity of DMN ( 55 ). The distinct lack of DMN suppression in our ROP improvers subsample replicates a large body of studies that observed increased connectivity at rest in schizophrenia within the DMN hubs and between DMN hubs and extra-DMN areas ( 55 ).…”

Neurological Soft Signs and Brain Abnormalities in Schizophrenia: A Literature Review

“…A negative correlation was found between left caudate connectivity and NSS. The study was limited by small sample size and examiners' bias [ 44 ].…”