Impaired inter-hemispheric facilitatory connectivity in schizophrenia

Clinica Psichiatrica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology (Impact Factor: 3.1). 03/2011; 122(3):512-7. DOI: 10.1016/j.clinph.2010.08.013
Source: PubMed


To investigate the inter-hemispheric connections between the dorsal premotor cortex (dPM) and contralateral primary motor cortex (M1) in schizophrenia.
Sixteen medicated, nine unmedicated schizophrenia patients and 20 healthy age-matched subjects were studied by twin-coil Transcranial Magnetic Stimulation. To activate distinct facilitatory and inhibitory transcallosal pathways between dPM and the contralateral M1, the intensity of dPM stimulation was adjusted to be either suprathreshold (110% of resting motor threshold) or subthreshold (80% of active motor threshold). Interstimulus intervals between conditioning stimulus and test stimulus were 6, 8 and 15 ms.
Schizophrenia patients had comparable efficacy of the inhibitory pathway. On the other hand, medicated patients showed less facilitation of contralateral M1 following dPM stimulation at 80% of active motor threshold, at interstimulus interval=8 ms. The individual amount of facilitation induced by dPM conditioning at 80% of active motor threshold at interstimulus interval=8 ms correlated negatively with negative symptoms.
Inter-hemispheric facilitatory dPM-M1 connectivity is selectively altered in schizophrenia.
This study produced evidence that dPM-M1 connectivity is dysfunctional and that correlates with negative symptoms. These results converge with previous studies which strongly hypothesize that inter- and intra-hemispheric connectivity disturbances may play a major role in schizophrenia.

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Available from: Giacomo Koch
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    • "Cortical inhibition deficit has previously been suggested as one potential pathophysiological mechanism in schizophrenia (Freedman et al., 1983). More recent studies, using transcranial magnetic stimulation, have shown broad evidence of reduced intra and inter-hemispheric cortical inhibition in SZP (Koch et al., 2008; Ribolsi et al., 2011; Wobrock et al., 2008). Antipsychotic treatment has been shown to modulate functional connectivity and represents potentially serious confound (Lui et al., 2010), however SQ + and SQ− do not differ significantly in the dose of antipsychotics, therefore we can assume the differences in connectivity between groups are not due to antipsychotics. "
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    • "Many studies have demonstrated impaired inter-areal connectivity in schizophrenia patients. For instance, the application of both single- and double-pulse transcranial magnetic stimulation (TMS) designs has demonstrated defective facilitatory and inhibitory connections between left and right primary motor cortices and between other areas of the motor system in schizophrenia patients [4, 6, 16, 19, 34, 36]. Another approach testing inter-hemispheric connectivity involves applying a plasticity-inducing stimulation protocol to one cortical area and investigating the excitability changes at both the site of the stimulation and in more remote interconnected sites [35, 39]. "
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    • "The inhibitory connection between both primary motor cortices (M1), which is discussed to be mediated by corpus callosum pathways, was found to be deficient in schizophrenia patients [5]. One further study supported the idea of an altered interhemispheric connection, revealing a selectively impaired facilitatory connectivity between the left dorsal premotor cortex and the right M1 [34]. As a third disrupted interhemispheric pathway, the connection between right cerebellum and left M1 was shown to be deficient in schizophrenia patients [6], indicating a disrupted direct cerebellar-M1 connection or an abnormal cerebellar inhibitory output. "
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