Abstract
Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. However, little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC-thalamus network. We collected resting-state fMRI and diffusion-weighted MRI data from 18 patients and 20 healthy controls. We analyzed fronto-thalamic effective connectivity using dynamic causal modeling for cross-spectral densities in a network consisting of the ACC and the left and right medio-dorsal thalamic regions. We studied structural connectivity using fractional anisotropy (FA). We found decreased coupling strength from the right thalamus to the ACC and from the right thalamus to the left thalamus, as well as increased inhibitory intrinsic connectivity in the right thalamus in patients relative to controls. ACC-to-left thalamus coupling strength correlated with the Positive and Negative Syndrome Scale (PANSS) total positive syndrome score and with delusion score. Whole-brain structural analysis revealed several tracts with reduced FA in patients, with a maximum decrease in white matter tracts containing fronto-thalamic and cingulo-thalamic fibers. We found altered effective and structural connectivity within the ACC-thalamus network in SZ. Our results indicate that ACC-thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. We suggest that positive symptoms may arise as a consequence of compensatory measures to imbalanced fronto-thalamic coupling.
Highlights
Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures
We found decreased coupling strength in patients relative to controls from the right thalamus to the anterior cingulate cortex (ACC), and from the right thalamus to the left thalamus, while an increased self-(inhibitory) connectivity in the right thalamus was found in patients relative to controls (Fig. 1a)
The influence of ACC over the thalamus is decreased in SZ (Wagner et al, 2013, 2015), our current results suggest that resting state is characterized by a decreased influence of the right thalamus over the ACC in SZ
Summary
Schizophrenia (SZ) is a complex disorder characterized by a range of behavioral and cognitive symptoms as well as structural and functional alterations in multiple cortical and subcortical structures. SZ is associated with reduced functional network connectivity involving core regions such as the anterior cingulate cortex (ACC) and the thalamus. Little is known whether effective coupling, the directed influence of one structure over the other, is altered during rest in the ACC–thalamus network. Our results indicate that ACC–thalamus network activity at rest is characterized by reduced thalamus-to-ACC coupling. A recent meta-analysis of regional brain volumes in patients with SZ suggested the anterior cingulate cortex (ACC) as a core structure affected by the disorder due to its consistently lower mean volume (Brugger & Howes, 2017). A remarkable body of evidence indicates that ACC dysfunction in SZ might underlie or contribute to psychotic symptoms
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