Cortical Inhibitory Dysfunction in Bipolar Disorder: A Study Using Transcranial Magnetic Stimulation

Objective: Neuroanatomic evidence suggests that patients with bipolar disorder (BD) have impaired cortical inhibition (CI). However, there is little in vivo neurophysiological evidence supporting the occurrence of such impairments in this disorder. Using 3 transcranial magnetic stimulation paradigms, known as short-interval CI (SICI), cortical silent period (SP), and interhemispheric inhibition (IHI), the authors measured inhibition in the motor cortex. Method: Fifteen patients with BD and 15 healthy subjects were enrolled. Short-interval CI involves stimulating with a subthreshold pulse a few milliseconds before a suprathreshold pulse, thereby inhibiting the size of the motor-evoked potential (MEP) produced by the suprathreshold pulse. In the SP paradigm, inhibition is reflected by the SP duration (ie, the duration of electromyographic activity cessation following a transcranial magnetic stimulation-induced MEP). Interhemispheric inhibition involves a subthreshold conditioning stimulus applied to the right motor cortex several milliseconds before a suprathreshold test stimulus is applied to the left motor cortex which inhibits the size of the MEP produced by the test stimulus by 50% to 75%. Results: Patients with BD demonstrated deficits in all 3 paradigms: SICI (F1,28 = 5.55, P = 0.03; Cohen d = 0.86), SP (F1,28 = 5.24, P = 0.03; Cohen d = 0.84), and IHI (F1,28 = 3.41, P = 0.02; Cohen d = 0.77) compared with healthy volunteers with a large effect size. Conclusions: Our study supports the hypothesis that CI is decreased in BD. Further understanding of the neurophysiology of such deficiencies may help to elucidate future treatment options.