Cortical inhibition in symptomatic and remitted mania compared to healthy subjects: A cross‐sectional study

Abstract

Objectives: Transcranial magnetic stimulation (TMS)-derived cortical reactivity studies provide a unique opportunity to non-invasively study gamma amino butyric acid (GABA)-mediated inhibitory neurotransmission in bipolar disorder (BD). Earlier studies were conducted in smaller samples and on patients who were on medications that can potentially confound the results. We aimed to study short-interval (SICI) and longinterval intracortical inhibition (LICI) in medication-naïve/free symptomatic (manic) BD patients (n=39), first episode mania (FEM) patients who had recently (≤6 months) remitted with treatment (remitted FEM; n = 28) and healthy subjects (HSs; n = 45). Methods:Resting motor threshold (RMT), stimulation intensity to elicit a 1-mV motor evoked potential (MEP) (SI 1 mV ), SICI and LICI were measured in three groups using single-and paired-pulse TMS.Results: Motor thresholds were higher in the manic BD and HS groups compared to the remitted FEM group (P < .001). SICI was lower (P = .026) but LICI was higher (P = .044) in the manic BD and remitted FEM groups compared to the HS group.Conclusions: Lower motor thresholds in remitted FEM perhaps reflect the effect of treatment, and could be studied as potential prognostic neuromarkers. Inverse findings for SICI (reduced) and LICI (increased) in BD indicate a possible differential involvement of the GABA A and GABA B subreceptor systems. These could be trait markers as they are impaired in both mania and euthymia.

A Systematic Review of Long-Interval Intracortical Inhibition as a Biomarker in Neuropsychiatric Disorders

“…Possible explanations and supporting evidence of enhanced LICI in bipolar disorder comes from the studies showing manic symptoms triggered with baclofen and elevated GABA/Creatine ratio in anterior cingulate cortex of patients with BD (38). These results might be affected by study flaws such as larger manic sample and medication naïve condition (36) or small sample size (35).…”

“…Prior studies measuring LICI in patients with bipolar disorder (BD) used TMS-EMG to investigate motor cortex activity ( (36). Possible explanations and supporting evidence of enhanced LICI in bipolar disorder comes from the studies showing manic symptoms triggered with baclofen and elevated GABA/Creatine ratio in anterior cingulate cortex of patients with BD (38).…”

Elevated mirror neuron system activity in bipolar mania: Evidence from a transcranial magnetic stimulation study

“…This effectively controls for and nullifies the effect of a possible overall hyperexcitable cortical state. Moreover, even after controlling for the baseline cortical reactivity group differences, patients demonstrated greater motor cortical facilitation during action‐observation, during the SICI and LICI paradigms. That is to say, despite demonstrating the opposite patterns of baseline abnormalities (low SICI and high LICI), putative MNS‐activity in the patient group was higher than that in the healthy subjects.…”

Motor Resonance During Action Observation and Its Relevance to Virtual Clinical Consultations: Observational Study Using Transcranial Magnetic Stimulation

“…Further, the time effect was not significant for LICI; a similar lack of MEP facilitation and therefore motor resonance was noted with the LICI paradigm in our earlier study [ 17 ]. This might partly be due to the more robust inhibition of MEP observed in the GABA B (metabotropic)-mediated LICI as opposed to the less pronounced inhibition of MEP in the GABA A (ionotropic)-mediated SICI [ 24 ].…”