Motor cortical excitability and clinical response to rTMS in depression

doi:10.1016/j.jad.2003.09.014

Journal of Affective Disorders

Volume 82, Issue 1, 1 October 2004, Pages 71-76

https://doi.org/10.1016/j.jad.2003.09.014 Get rights and content

Abstract

Background: The relationship between frontal lobe activity in the left and right hemispheres and the pathophysiology of depression remains unclear. In addition, it is uncertain whether levels of frontal or motor cortical excitability relate to clinical response to treatment modalities. We aimed to explore whether motor cortical excitability as assessed with single and paired pulse transcranial magnetic stimulation (TMS) could be used to predict the response to treatment with repetitive TMS (rTMS) applied to the left or right prefrontal cortex. Methods: Motor thresholds, cortical excitability and cortical inhibition (CI) were assessed prior to a trial of rTMS in patients with treatment resistant depression. Results: There was no consistent pattern of differences in hemispheric activity, although there was a relationship between the degree of psychopathology and cortical excitability (right hemisphere) and an inverse relationship between inhibitory activity and clinical response (left hemisphere). Conclusions: The study does not support a simple model of laterality in motor cortical excitability in depression. The TMS measures used in this study appear to be of limited use in the prediction of clinical response to rTMS.

Introduction

Changes in activity levels in frontal cortical regions have been widely implicated in the pathophysiology of depression. It has been suggested that depression is accompanied by a relative reduction in left prefrontal cortical (PFC) activity compared to activity in the contralateral hemisphere. This has been supported by imaging studies indicating left frontal hypoactivity (Baxter et al., 1989) and right sided hyperactivity (Abou-Saleh et al., 1999) and EEG studies that show left–right prefrontal alpha EEG asymmetry (Davidson and Meltzer-Brody, 1999). Differences in cortical activity in depressed subjects have also been demonstrated in transcranial magnetic stimulation (TMS) studies of the motor cortex. For example, Meada et al. assessed bilateral motor cortical excitability in a small group of depressed subjects and a group of normal controls (Maeda et al., 2000). They found a greater resting motor threshold (RMT) on the left in the patient group and differences in paired pulse curves suggesting lowered left and greater right sided excitability in the patients compared to the control group.

Paired pulse TMS (ppTMS) has been extensively used over recent years to assess motor cortical excitability in various neuropsychiatric disorders (for example Daskalakis et al., 2002, Fitzgerald et al., 2002). In ppTMS a supra-threshold stimulus is paired with a preceding sub-threshold stimulus and the response to the paired stimuli may be increased (facilitation) or decreased (inhibition) depending on the interstimulus interval (ISI) (Kujirai et al., 1993). Inhibitory cortical activity can also be measured through the recording of the cortical silent period (CSP) which is a period of suppression of tonic motor activity produced following the induction of a descending motor evoked potential (MEP). The objective of this study was to assess cortical excitability in a sample of patients involved in a treatment trial with repetitive TMS (rTMS) for major depression. We aimed to investigate differences between the left and right motor cortex and whether cortical excitability levels would predict clinical response to rTMS.

Section snippets

Subjects

Patients were included in this study who participated in a clinical trial of rTMS. The design of the trial and outcome data have been reported separately (Fitzgerald et al., 2003). In brief, 60 patients with treatment resistant depression (54 patients—major depressive episode, 6—bipolar I disorder) were enrolled and randomized to either a sham condition, high frequency left prefrontal active rTMS (LA) or low frequency right prefrontal active rTMS (RA). All patients received 10 daily sessions of

Results

All subjects tolerated the procedures without difficulty. Measurements were not able to be performed in a number of subjects due to technical difficulties with the ppTMS equipment. The complete data set was available for 55 subjects enrolled in the clinical trial.

Discussion

Our study found an indication of reduced motor cortical excitability in the left hemisphere of subjects with depression (increased CI, lower RMT levels) especially in subjects rated with higher CORE scores of melancholia although we did not find a clear and consistent pattern of altered excitability over several TMS measures. We also found a relationship between excitability in the right hemisphere and the severity of psychopathology. In addition, the study's findings suggested a relationship

Acknowledgements

The study was supported by a National Health and Medical Research Council grant (143651) and a grant from The Stanley Medical Research Institute. We would like to thank the patients whose participation was essential in the successful completion of the study. We would also like to thank Dr. Marlies Largerberg and Dr. James Zurek who assisted with the provision of rTMS during the clinical trial.

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We performed a systematic review and extracted data to perform meta-analyses of interhemispheric asymmetry of motor cortex excitability, assessed with TMS, across different mood disorders and in healthy subjects. Additionally, potential predictors of interhemispheric asymmetry were explored.
Asymmetry of resting motor threshold (MT) among healthy volunteers was significant, favoring lower right relative to left-hemisphere excitability. MT was also significantly asymmetric in major depressive disorder (MDD), but with lower excitability of the left -hemisphere, when compared to the right, no longer observed in recovered patients. Findings on intracortical facilitation were similar. The few trials including bipolar depression revealed similar trends for imbalance, but with lower right hemisphere excitability, relative to the left.
There is interhemispheric asymmetry of motor cortical excitability in MDD, with lower excitability on left when compared to right-side. Interhemispheric asymmetry, with lower right relative to left-sided excitability, was found for bipolar depression and was also suggested for healthy volunteers, in a pattern that is clearly distinct from MDD.
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Citation Excerpt :
Little is known about the predictive value of TMS neurophysiologic measures. A trend was observed toward a worse reaction to HF-rTMS treatment in patients with a longer cortical silent period and a higher motor threshold on the right primary motor area (Fitzgerald et al., 2004). The group of patients examined consisted of 54 unipolar and six bipolar patients.
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Research reportMotor cortical excitability and clinical response to rTMS in depression

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Acknowledgements

J. Affect. Disord

Psychiatry Res. Neuroimaging

Biol. Psychiatry

J. Neurol. Sci

Neuropsychologia

Electroencephalogr. Clin. Neurophysiol

Reduction of prefrontal cortex glucose metabolism common to three types of depression

Arch. Gen. Psychiatry

An inventory for measuring depression

Arch. Gen. Psychiatry

Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation

Arch. Gen. Psychiatry

The underrecognition and undertreatment of depression: what is the breadth and depth of the problem?

J. Clin. Psychiatry

Research report
Motor cortical excitability and clinical response to rTMS in depression