Neuroplasticity in depressed individuals compared with healthy controls

Abstract

Several lines of evidence suggest that neuroplasticity is impaired in depression. This study aimed to compare neuroplasticity in 23 subjects with DSM-IV major depressive episode and 23 age- and gender-matched healthy controls, using an objective test that is independent of subject effort and motivation. Neuroplasticity was assessed in the motor cortex using a brain stimulation paradigm known as paired associative stimulation (PAS), which induces transient changes in motor cortical function. Motor cortical excitability was assessed before and after PAS using single-pulse transcranial magnetic stimulation (TMS) to induce motor evoked potentials (MEPs) in a hand muscle. After PAS, MEP amplitudes significantly increased in healthy controls compared with depressed subjects (P=0.002). The functional significance of motor cortical changes was assessed using a motor learning task-a computerized version of the rotor pursuit task. Healthy controls also performed better on motor learning (P=0.02). BDNF blood levels and genotype were assayed to determine any relationship with motor cortical plasticity. However, PAS results did not correlate with motor learning, nor appear to be related to BDNF measures. The significance of these findings is that it provides one of the first direct demonstrations of reduced neuroplasticity in depressed subjects, using an objective test.

Figure 1

Experimental design. Motor evoked potentials (MEPs) were elicited to measure motor cortex excitability before and after a period of conditioning stimulation, which comprised 13 min of repeated paired brain and peripheral nerve stimulation (PAS, paired associative stimulation).

Figure 2

(a) Group data (mean±SEM) showing the time course of changes in the amplitude of motor evoked potentials (MEPs) after conditioning stimulation (PAS) in depressed subjects (crosses) and healthy controls (filled circles). MEP amplitudes were normalized to baseline values for each subject. (b) Mean normalized MEP amplitudes after PAS conditioning stimulation in depressed subjects on medication (DEP-med; n=17), depressed subjects without medication (DEP-no-med; n=6), and healthy controls (HC; n=23). The seven post-PAS time points shown in panel (a) are collapsed into single group values. Means and standard errors are shown.

Figure 3

Comparison of time on target on the rotor pursuit task in the depressed cohort (DEP, crosses) and healthy controls (HC, filled circles). Time on target in each test block was normalized to the baseline block. Mean and standard errors are shown. Increasing time on target indicates motor learning.