Neuroscience article

Evidence for impaired cortical inhibition in schizophrenia, using transcranial magnetic stimulation

Zafiris J. Daskalakis, MD , FRCP(C); BruceK. Christensen, PhD, Cpsych; Robert Chen, MBB Chir, MSc, FRCP(C) ; Paul B. Fitzgerald, MBBS, MPM, FRANZCP; Robert B. Zipursky, MD, FRCP (C) ; Shitij Kapur, MD, PhD, FRCP (C)

By Oscar Wiksell

BackgroundEvidence suggest that schizophrenia is a

disorder associated with deficits in cortical inhibition.

This article used 3 different types of TMS to asses cortical inhibition in schizophrenic patients.

Deficits in cortical inhibition have been demonstrated in cognitive, motor, neurophysiologic and neuropathologic studies.

MethodsTranscranial magnetic stimulation non-

invasive technique to excite neurons.

3 types used:◦Paired pulse TMS ◦Cortical silent period◦Transcallosal inhibition

Methods Paired pulse TMS

◦ Stimulating with a lower intensity pulse a few ms, before a higher intensity pulse. Thereby inhibiting size of the motor evoked potential produced by higher intensity pulse.

Cortical silent period◦ Inhibition is reflected by the silent period duration. (duration

of EMG activity cessation following a TMS induced motor evoked potential)

Transcallosal inhibition◦ Involves stimulation of contralateral motor cortex several ms

prior to stimulation of ipsilateral motor cortex. Inhibiting size of motor evoked potential produced by ipsilateral stimulation.

Methods15 unmedicated patients with

schizophrenia.

15 medicated patients.

15 healthy controls.

EMG recordings of the right and left first dorsal interosseus muscle.

Results ppTMS

◦ Unmedicated 31,2% less inhibtion compared to healthy.◦ Medicated 15,64% less inhibtion comared to healthy.

CSP◦ 15,26 ms shorter in unmedicated compared to healthy.◦ 5,38 ms longer in medicated compared to healthy.

TCI◦ Unmedicated 23,25% less inhibition compared to

control.◦ 9,92% less inhibition in medicated compared to healthy.

Conclusion Results demonstrate unmedicated patients with

schizophrenia have significant deficits in CI, compared with healthy controls across all 3 TMS types.

Medication seemed to reduce CI deficits in these patients.

Results demonstrate CI deficits in ppTMS were correlated with severity of psychosis. No other measure of CI was correlated with degree of psychosis.

Disrupted CI may present an important neurophysiologic mechanism responsible for the symptoms in patients with schizophrenia.

ConclusionLimitations to these experiments

◦ CI differencies between umedicated & medicated patients were not significant across all measures. Small effects, limited sample size and large variance in measures.

◦ Not certain if differences observed where truly result of medication effects or related to other variables (duration of illness)

◦ Unclear if differencies in CI in mediated group were related to effects of medication on GABA, dopamine or some other neurotransmitter system.

Thank you!