Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia

Abstract

The thalamus plays a central and dynamic role in information transmission and processing in the brain. Multiple studies reveal increasing association between schizophrenia and dysfunction of the thalamus, in particular the medial dorsal nucleus (MDN), and its projection targets. The medial dorsal thalamic connections to the prefrontal cortex are of particular interest, and explicit in vivo evidence of this connection in healthy humans is sparse. Additionally, recent neuroimaging evidence has demonstrated disconnection among a variety of cortical regions in schizophrenia, though the MDN thalamic prefrontal cortex network has not been extensively probed in schizophrenia. To this end, we have examined thalamo-anterior cingulate cortex connectivity using detection of low-frequency blood oxygen level dependence fluctuations (LFBF) during a resting-state paradigm. Eleven schizophrenic patients and 12 healthy control participants were enrolled in a study of brain thalamocortical connectivity. Resting-state data were collected, and seed-based connectivity analysis was performed to identify the thalamocortical network. First, we have shown there is MDN thalamocortical connectivity in healthy controls, thus demonstrating that LFBF analysis is a manner to probe the thalamocortical network. Additionally, we have found there is statistically significantly reduced thalamocortical connectivity in schizophrenics compared with matched healthy controls. We did not observe any significant difference in motor networks between groups. We have shown that the thalamocortical network is observable using resting-state connectivity in healthy controls and that this network is altered in schizophrenia. These data support a disruption model of the thalamocortical network and are consistent with a disconnection hypothesis of schizophrenia.

Fig. 1.

Thalamocortical Connectivity During Rest. All voxels thresholded at P ≤.0025 (uncorrected), cluster extend k ≥10 voxels. Images are shown in neurological convention. (A) Correlations to seed placed in left MDN of thalamus for healthy controls. (B) Correlations to seed placed in right MDN thalamus for healthy controls. (C) Correlations to seed placed in left MDN thalamus for schizophrenic participants. (D) Correlations to seed placed in right MDN thalamus for schizophrenic participants.

Fig. 2.

Greater Medial Dorsal Thalamocortical Connectivity in Healthy Controls Compared With Schizophrenic Patients During Rest. All voxels thresholded at P≤.0025 (uncorrected), cluster extent k≥10 voxels. (A) Correlations to seed placed in left medial dorsal nucleus (MDN) of thalamus. (B) Correlations to seed placed in right MDN thalamus.

Fig. 3.

Motor Cortex Connectivity During Rest. All voxels thresholded at P ≤.0025 (uncorrected), cluster extent k ≥10 voxels. (A) Left hemisphere for healthy controls. (B) Right hemisphere for healthy controls. (C) Left hemisphere for schizophrenic patients. (D) Right hemisphere for schizophrenic patients.

Fig. 4.

Voxel Counts Present in Brodman Areas When Varying Left (A) and Right (B) MDN Seed Placement in Healthy Controls. Columns are organized as follows: dorsal values first, then original MDN seed location, and then ventral regions. +xindicates toward the left and –x indicates toward the right. Columns are further organized as lateral columns first (+x for left plot and –x for right plot) and then medial columns (–x for left and +x for right plots, respectively). Rostral indicated by +y and caudal with –y.

Fig. 5.

Gray Matter Likelihood for Region of Interest Placement for Left and Right Seeds, Respectively. Student t test (unequal variance) for seed voxel gray matter difference between controls and patients: left MDN thalamus P = .198; right MDN thalamus P = .309. ±x and ±y labeling follows that as figure 4.