Fong, Po-Yu; (2023) Intracortical and cerebellar cortical inhibition in human. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Cortical inhibition is an essential feature of cortical circuitry and function that is mediated by the inhibitory neurotransmitter GABA. Transcranial magnetic stimulation (TMS) has been used for many years to explore cortical inhibition in the motor cortex. However, the technique is limited to describing inhibition of corticospinal volleys evoked by a second TMS pulse, meaning that we are uncertain how inhibition affects other circuits or even areas of the cortex. The experiments in this thesis describe how to combine TMS with EEG and behavioural tasks to investigate more widely the nature of cortical inhibition. In the first experiment motor cortex inhibition sufficient to suppress the amplitude of corticospinal volleys (i.e. short-interval intracortical inhibition, SICI) produced phasic gamma desynchronization over the motor cortex, consistent with reduced excitability of multiple circuits. The second experiment tested how the cortex responds to extracortical inhibitory input from the cerebellum which is conventionally studied in the motor cortex using cerebellar cortical inhibition (CBI). The results showed that TMS of the cerebellum sufficient to produce motor cortex CBI, evoked an EEG potential (cbTEP) characterised by a positive wave over the contralateral frontal region (P80). The latency of the cbTEP is much greater than the 5-10 ms expected from motor cortex CBI. They therefore may result from rebound discharge after cerebellar TMS-induced Purkinje cell inhibition. Since the amplitude of the cbTEP changed during the course of cerebellar visuomotor learning, this may reflect a cerebellar contribution to higher-level cognitive processing. For comparison with the SICI experiment, in which both a conditioning and test TMS pulse were applied, we studied the EEG response after cerebellar stimulation plus a test TMS pulse. There was significant suppression of potentials over motor cortex from early to late latencies, replicating the laterality of CBI, with asymmetrical N100 after test stimuli to the left and right motor cortex. A time-frequency analysis revealed phasic desynchronization across multiple frequency bands, different from the finding in SICI. The final experiment investigated how SICI and CBI circuits interact with one another. Careful probing of SICI with PA (posterior-anterior) and AP (anterior-posterior) conditioning TMS pulses showed that SICI consisted of two distinct and independent cortical inhibitory circuits, which interacted differently with CBI (and also short-latency afferent inhibition, SAI). SICI produced by a PA conditioning stimulus interacted in complex ways with CBI and SAI, whereas AP-induced SICI appeared to be quite independent. In conclusion, the experiments highlight the differences in circuits activated by the conditioning pulse in SICI and CBI and give further insight into how they interact with each other. They also confirm the utility of combining EEG and EMG methodologies to study human brain physiology.

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