abstract

۱٫ Introduction

۲٫ Methods and materials

۳٫ Results

۴٫ Discussion

CRediT authorship contribution statement

Declaration of Competing Interest

Acknowledgements

References

Abstract

 Objective
Altered interhemispheric connectivity is implicated in the pathophysiology of schizophrenia (SCZ) and major depressive disorder (MDD) and may account for deficits in lateralized cognitive processes. We measured transcranial magnetic stimulation evoked interhemispheric signal propagation (ISP), a non-invasive measure of transcallosal connectivity, and hypothesized that the SCZ and MDD groups will have increased ISP compared to healthy controls.

Methods
We evaluated ISP over the dorsolateral prefrontal cortex in 34 patients with SCZ and 34 patients with MDD compared to 32 age and sex-matched healthy controls.

Results
ISP was significantly increased in patients with SCZ and patients with MDD compared to healthy controls but did not differ between patient groups. There were no effects of antidepressant, antipsychotic, and benzodiazepine medications on ISP and our results remained unchanged after re-analysis with a region of interest method.

Conclusion
Altered ISP was found in both SCZ and MDD patient groups. This indicates that disruptions of interhemispheric signaling processes can be indexed with ISP across psychiatric populations.

Significance
These findings enhance our knowledge of the physiological mechanisms of interhemispheric imbalances in SCZ and MDD, which may serve as potential treatment targets in future patients.

Introduction

     Interhemispheric functional asymmetry is disrupted in psychiatric disorders such as schizophrenia (SCZ) and major depressive disorder (MDD) (Garcia-Toro et al., 2001, Ribolsi et al., 2009). In SCZ, deficits of lateralized sensorimotor and cognitive processes are linked to impaired cerebral specialization and interhemispheric communication (David, 1994, Whitford et al., 2010), in accordance with the disconnection hypothesis (Friston, 1999). Meanwhile, patients with MDD typically present with deficits in mood, emotion, and cognitive processing which also rely on hemispheric lateralization (Davidson, 2002). The corpus callosum is the largest white matter connective pathway in the brain and plays a critical role in interhemispheric connectivity, particularly for the lateralization of cognitive and perceptual processes (Gazzaniga, 2000). Transcallosal connectivity relies on a complex interplay of excitatory and inhibitory processes involving glutamate release from callosal axon terminals (Kawaguchi, 1992) and GABAergic neurotransmission initiated by local inhibitory interneurons in the contralateral hemisphere. Functional impairments of lateralized processes may reflect an underlying imbalance between excitatory and inhibitory signaling processes in the two hemispheres.

Results

۳٫۱٫ ISP

     The ANOVA yielded a significant effect of group on ISP (F (2,97) = 7.24, p = 0.001). Post-hoc t-test comparisons revealed increased ISP in SCZ patients than in healthy controls (t(64) = – 3.642, p = 0.002; Bonferroni corrected p < 0.05; d’ = ۰٫۹۰) and in MDD patients compared to healthy controls (t(64) = -3.311, p = 0.01; Bonferroni corrected p < 0.05; d’ = ۰٫۸۲) (Fig. 1). We found no differences in ISP between SCZ patients and MDD patients (t(66) = -0.545, p = 1.00, d’ = ۰٫۱۳) (Fig. 1). The group mean topoplots and rectified TEPs are shown in Fig. 2. To evaluate whether elevated ISP was also extended to remote regions, we measured ISP in the T7 and T8 regions and found no significant differences between groups (F(2,97) = 0.20, p = 0.82).

۳٫۲٫ Correlation with symptom severity

     There was a trending correlation between ISP values and the HRSD scores for patients with MDD (r = 0.334, p = 0.054), suggesting that increased depression severity may be related to higher levels of signal transmission to the unstimulated hemisphere. For patients with SCZ, the total BPRS score and summed factor BPRS were used to determine the relationship between clinical severity with ISP. There was no correlation between ISP values with the total BPRS score (r = -0.005, p = 0.979), affective symptoms (r = 0.255, p = 0.145), psychotic symptoms (r =