Functional and Anatomical Connectivity Abnormalities in Cognitive Division of Anterior Cingulate Cortex in Schizophrenia

<div><h3>Introduction</h3><p>Current pathophysiological theories of schizophrenia highlight the role of altered brain functional and anatomical connectivity. The cognitive division of anterior cingulate cortex (ACC-cd) is a commonly reported abnormal brain region in schizophrenia for its importance in cognitive control process. The aim of this study was to investigate the functional and anatomical connectivity of ACC-cd and its cognitive and clinical manifestation significance in schizophrenia by using the resting-state functional magnetic resonance imaging (fMRI) and the diffusion tensor imaging (DTI).</p> <h3>Methods</h3><p>Thirty-three medicated schizophrenics and 30 well-matched health controls were recruited. Region-of-interest (ROI)-based resting-state functional connectivity analysis and Tract-Based Spatial Statistics (TBSS) were performed on 30 patients and 30 controls, and 24 patients and 29 controls, respectively. The Pearson correlation was performed between the imaging measures and the Stroop performance and scores of the Positive and Negative Syndrome Scale (PANSS), respectively.</p> <h3>Results</h3><p>Patients with schizophrenia showed significantly abnormal in the functional connectivity and its hemispheric asymmetry of the ACC-cd with multiple brain areas, e.g., decreased positive connectivity with the bilateral putamen and caudate, increased negative connectivity with the left posterior cingulated cortex (PCC), increased asymmetry of connectivity strength with the contralateral inferior frontal gyrus (IFG). The FA of the right anterior cingulum was significantly decreased in patients group (<em>p</em> = 0.014). The abnormal functional and structural connectivity of ACC-cd were correlated with Stroop performance and the severity of the symptoms in patients.</p> <h3>Conclusions</h3><p>Our results suggested that the abnormal connectivity of the ACC-cd might play a role in the cognitive impairment and clinical symptoms in schizophrenia.</p> </div

Hemispheric asymmetry of functional network abnormalities in patients with schizophrenia.

<p>(A) Brain regions showing significantly altered hemispheric asymmetry of functional connectivity of ACC-cd in patients with schizophrenia. (B) <i>Z</i>-values of peak voxel for the contralateral and ipsilateral IFG in the left and right ACC-cd networks in both groups. (1) Increased asymmetry in contralateral IFG. (2) Increased asymmetry in ipsilateral IFG. (3) Increased asymmetry in contralateral IPL. (4) Lost asymmetry in Mid-FG. IFG, inferior frontal gyrus; IPL, inferior parietal lobule; Mid-FG, middle frontal gyrus. *p<0.05; **p<0.001.</p

Brain regions showing significantly altered connectivity in positive functional networks and negative functional networks with LACC-cd and RACC-cd in patients with schizophrenia.

<p>In the positive networks, cool color indicates decreased or lost positive connectivity in patients. In the negative networks, cool color indicates increased negative connectivity, and warm color indicates decreased or lost negative connectivity. Color bar indicates the t-value. Puta, putamen; Caud, caudate; ACC, anterior cingulate cortex; MFG, medial prefrontal gyrus; Tha, thalamus; IFG, inferior frontal gyrus; PCu, precuneus; PCC, posterior cingulate cortex; IPL, inferior parietal lobule; SMC, sensorimotor cortex.</p

Brain regions showing significant differences for functional connectivity of LACC-cd in patients with schizophrenia compared with healthy controls.

<p>BA, Brodmann area;</p>a<p>The peak voxel in MNI coordinates.</p>b<p>Minimum cluster size: 10 voxels (270 mm³).</p

Brain regions showing significant hemispheric asymmetry of functional connectivity with ACC-cd.

<p>Hemispheric asymmetry of functional network of ACC-cd in healthy controls (A) and patients with schizophrenia (B). The foci in the right side show significant asymmetric functional connectivity with their ipsilateral ACC-cd, and foci in the left side show significant asymmetric functional connectivity with their contralateral ACC-cd. Color bar indicates the t-value. IH, ipsilateral hemisphere; CH, contralateral hemisphere; Dec, declive; IFG, inferior frontal gyrus; dPCC, dorsal posterior cingulate cortex; IPL, inferior parietal lobe; SMA, supplementary motor ares; PMA, premotor area; PCu, precuneus.</p

Brain regions showing significant differences for hemispheric asymmetry of functional connectivity with ACC-cd in patients with schizophrenia compared with healthy controls.

<p>BA, Brodmann area.</p>a<p>The peak voxel in MNI coordinates.</p>b<p>The positive or negative sign of <i>x</i> coordinate has been omitted to avoid confusion, because it does not indicate right or left hemisphere in the table.</p>c<p>Minimum cluster size: 13 voxels (351 mm³).</p

Correlation coefficient between ACC-cd functional networks and clinical measures and Stroop performance in patients with schizophrenia.

a<p>Regions with significantly altered functional connectivity with ACC-cd in patients with schizophrenia. P and N in blanket denote the positive and negative networks, respectively; A denotes the asymmetry of functional connectivity of ACC-cd. “↑” denotes the increased connectivity strength in patients; “↓” denotes the decreased connectivity strength in patients. Puta, putamen; PCu, precuneus; mPFC, medial prefrontal cortex; Tha, thalamus; PCC, posterior cingulate cortex; SMC, sensorimotor cortex; Con-IFG, contralateral inferior frontal gyrus; AI, asymmetry index.</p>*<p>p<0.05,</p>**<p>p<0.01.</p

Demographic, clinical and behavior details.

a<p>Sample size in control and schizophrenia groups were 29 and 29, respectively. PANSS_T, total score of PANSS; PANSS_P, score of PANSS positive subscale; PANSS_N, score of PANSS negative subscale; PANSS_G, score of PANSS general psychopathology subscale.</p

Brain regions showing significant differences for functional connectivity of RACC-cd in patients with schizophrenia compared with healthy controls.

<p>BA, Brodmann area;</p>a<p>The peak voxel in MNI coordinates.</p>b<p>Minimum cluster size: 10 voxels (270 mm³).</p

The regions of interest (ROIs) for anterior cingulum.

<p>The blue and red regions indicate the left and right anterior cingulum respectively. The green regions indicate the mean FA skeleton for all participants.</p