LTD-like central motor plasticity is not compromised in multiple sclerosis patients

Background: Compensation of brain injury in multiple sclerosis (MS) may be based on neuronal plasticity. Plasticity of neuronal connections likely involves both enhancement and depression of synaptic efficacy. We previously showed that expression of rapid onset excitability increasing, LTP-like motor plasticity remains intact in MS. However, it remains unknown if excitability decreasing, LTD-like plasticity is compromised in MS patients. This question is of interest, because in a functional magnetic resonance study (fMRI), MS-patients specifically failed to exhibit task-specific reductions, but not enhancements, of activation in some cortical regions while in another recent fMRI study regional brain activation by right hand tapping decayed over consecutive runs at a similar rate in MS-patients and controls.

Methods: We used theta-burst stimulation (TBS) to examine LTD-like central motor plasticity in 15 patients with stable MS (age 33.6±10.2 years; 9 women; EDSS 2.3±1.8) and age-matched healthy controls. MS patients and controls received bursts (50Hz) of three subthreshold biphasic magnetic stimuli repeated at 5Hz for 40s over the hand area of the left primary motor cortex (M1). Additional sham stimulation (2% of the maximal stimulator output) over M1 served as a control condition in healthy subjects. Corticospinal excitability was probed by evoking MEPs in the abductor pollicis brevis (APB) muscle by single suprathreshold monophasic stimuli over M1 before and after TBS. Force level control was assessed in an isometric right thumb abduction task. Eight blocks (30 abductions each) were acquired before, four blocks after TBS.

Results: Subthreshold TBS over M1 reduced MEP amplitudes in the contralateral APB (MS patients, 81±24%, controls, 68±23%). The magnitude of this effect was not statistically different between MS patients and controls (p=0.167). Post-TBS right thumb force level control was impaired for a duration of at least 5min in MS patients (delta=2.4±4.3) and controls (2.4±3.3, p=0.980). In healthy controls, sham stimulation had no effect on either MEP amplitudes or force level control.

Conclusions: The present findings suggest that LTD-like plasticity remain largely intact in MS patients. Along with previous observations these observations suggest that synaptic plasticity is not compromised in mild-to-moderately affected MS patients. This substantiates the notion that rehabilitation efforts may need to focus on mechanisms supporting the later rather than the early stages of central motor plasticity. The fact that TBS over M1 temporarily affected force production performance in MS patients to a similar degree as in control subjects suggests that activation of non-canonical motor regions, as previously demonstrated to occur in MS patients, does not render M1 in MS patients more resistant to inference than M1 of healthy controls.