FACTORS INFLUENCING THE INDUCTION OF NEUROPLASTIC CHANGES IN HUMAN MOTOR CORTEX

Abstract

The human primary motor cortex {(M1)} undergoes structural andfunctional change throughout life by a process known asneuroplasticity. Techniques which artificially induceneuroplastic changes are seen as potential adjunct therapiesfor neurological conditions reliant on neuroplasticity forrecovery of function. Unfortunately, the reportedimprovements in function when these techniques have beenused in combination with regular rehabilitation have so farbeen inconsistent. One reason attributed to this is thelarge variability in effectiveness of these techniques ininducing neuroplastic change. This thesis has investigatedfactors influencing the effectiveness and reproducibility ofneuroplasticity induction in human M1 using severalexperimental paradigms. The effectiveness andreproducibility of inducing neuroplasticity in human M1using two variants of a paired associative stimulation {(PAS)}protocol was investigated in the first set of experiments{(Chapter} 2). Both protocols repeatedly paired a peripheralelectrical stimulus to the median nerve of the left wristwith single-pulse transcranial magnetic stimulation {(TMS)}delivered 25 ms later to the contralateral M1. Neuroplasticchanges were quantified by comparing the amplitude of themuscle evoked potential {(MEP)} recorded in abductor pollicisbrevis {(APB)} muscle by suprathreshold {TMS} prior to andfollowing {PAS.} With both protocols, neuroplasticityinduction was more effective, and the responses acrosssessions more reproducible, if the experiments wereperformed in the afternoon compared to the morning.Subsequent experiments confirmed the time of day modulationof {PAS-induced} neuroplasticity by repeatedly testingtwenty-five subjects on two separate occasions, once in themorning (8 am), and once in the evening (8 pm) {(Chapter} 3).Time of day was also shown to modulate {GABAergic} inhibitionin M1. In a further set of experiments, a double-blind,placebo-controlled study demonstrated that artificiallyelevated circulating cortisol levels (with a single oraldose of hydrocortisone) inhibits {PAS-induced} neuroplasticityin the evening (8 pm), indicating that the time of daymodulation of neuroplasticity induction with {PAS} is due, atleast in part, to differences in circulating cortisol levels{(Chapter} 3). The cortical circuits that are modulated by {PAS}have also been shown to be important in motor learning.Therefore, the final set of experiments, described inChapter 4, investigated whether motor-training-relatedchanges in motor performance (and cortical excitability)following a ballistic motor training task are also modulatedby time of day. Twenty-two subjects repeatedly abductedtheir left thumb with maximal acceleration for thirtyminutes during two experimental sessions (morning (8 am) andevening (8 pm)) on separate occasions. Motor trainingimproved motor performance, and increased corticalexcitability, however these changes were independent of timeof day. It may be that the motor training task and/oroutcome measures used were not sufficiently sensitive todetect a subtle time of day effect of motor training onmotor performance. Alternatively, the normally functioningmotor system may be able to compensate for changes incortical excitability to maintain optimal motor performance.These findings have important implications for therapiesreliant on neuroplasticity for recovery of function, andindicate that rehabilitation may be most effective whencirculating cortisol levels are low.