Functional and structural alterations in the cingulate motor area relate to decreased fronto-striatal coupling in major depressive disorder with psychomotor disturbances

Benny Liberg, Paul Klauser, Ian H Harding, Mats Adler, Christoffer Rahm, Johan Lundberg, Thomas Masterman, Caroline Wachtler, Tomas Jonsson, Maria Kristoffersen-Wiberg, Christos Pantelis, Björn Wahlund, Benny Liberg, Paul Klauser, Ian H Harding, Mats Adler, Christoffer Rahm, Johan Lundberg, Thomas Masterman, Caroline Wachtler, Tomas Jonsson, Maria Kristoffersen-Wiberg, Christos Pantelis, Björn Wahlund

Abstract

Psychomotor disturbances are a classic feature of major depressive disorders. These can manifest as lack of facial expressions and decreased speech production, reduced body posture and mobility, and slowed voluntary movement. The neural correlates of psychomotor disturbances in depression are poorly understood but it has been suggested that outputs from the cingulate motor area (CMA) to striatal motor regions, including the putamen, could be involved. We used functional and structural magnetic resonance imaging to conduct a region-of-interest analysis to test the hypotheses that neural activation patterns related to motor production and gray matter volumes in the CMA would be different between depressed subjects displaying psychomotor disturbances (n = 13) and matched healthy controls (n = 13). In addition, we conducted a psychophysiological interaction analysis to assess the functional coupling related to self-paced finger-tapping between the caudal CMA and the posterior putamen in patients compared to controls. We found a cluster of increased neural activation, adjacent to a cluster of decreased gray matter volume in the caudal CMA in patients compared to controls. The functional coupling between the left caudal CMA and the left putamen during finger-tapping task performance was additionally decreased in patients compared to controls. In addition, the strength of the functional coupling between the left caudal CMA and the left putamen was negatively correlated with the severity of psychomotor disturbances in the patient group. In conclusion, we found converging evidence for involvement of the caudal CMA and putamen in the generation of psychomotor disturbances in depression.

Keywords: bipolar disorder; cingulate cortex; cingulate motor area; major depression; psychomotor disturbances; putamen; striatum.

Figures

Figure 1
Figure 1
The image shows the structural and functional imaging findings in the left caudal cingulate motor area (CMA) and putamen regions connected to caudal motor regions in the frontal lobe. The first row shows the contrast parameter estimates reflecting how patients activate the caudal cingulate motor regions more than healthy controls (Z > 2.3, p = 0.05, corrected) during self-paced finger-tapping. The second row shows decreased gray matter volume in the left CMA of patients (T > 2.5, p = 0.05, corrected). The third row shows the decreased functional coupling of the left CMA and left posterior putamen regions connected to caudal motor regions in the frontal lobe during self-paced finger-tapping (p = 0.02, corrected). Metrics (mean) from clusters of between-group differences in the left caudal CMA and posterior putamen were retrieved using masks comprising 356 voxels/2848 mm3 from the functional magnetic resonance imaging analysis, 941 voxels/3176 mm3 from the voxel-based morphometry analysis, and 31 voxels/248 mm3 from the psychophysiological interaction analysis.
Figure 2
Figure 2
The image shows the localization of structural and functional imaging findings in the left caudal cingulate motor. Left is left in the image. The red cluster represents increased functional activation in patients compared to controls (Z > 2.3, p = 0.05, corrected). The blue cluster represents gray matter volume decreases in patients compared to controls (T > 2.5, p = 0.05, corrected). The purple voxels represent the overlap between function and structural findings.
Figure 3
Figure 3
The image shows the binarized region of interest masks defining the left caudal cingulate motor area and the left putamen regions connected to caudal motor regions in the frontal lobe.

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