Hepatitis C virus (HCV) infection has been associated worldwide with hepatocellular carcinoma, liver failure, and cirrhosis.¹ Quiz Ref ID Chronic HCV infection not only affects the liver but also is a risk factor in extrahepatic diseases, such as diabetes, chronic kidney disease, atherosclerosis, coronary artery disease, and stroke.^2-5 Several epidemiologic studies found an association between HCV infection and Parkinson disease (PD),^6-9 and HCV infection has been suggested as a risk factor for PD. However, inconsistent results showing no association between HCV infection and PD have also been reported.¹⁰

Pulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior ( AP ) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction. To investigate whether SICI evaluated with AP and PA conditioning stimuli (CS_PA and CS_AP) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TS_PA). Using two superimposed TMS coils, CS_PA and CS_AP were applied at interstimulus intervals (ISI) of 1–5 ms before a TS_PA, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICI_CSPA3 and SICI_CSAP3) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICI_CSPA2), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICI_CSPA3 and SICI_CSAP3. CS_AP produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CS_AP and CS_PA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICI_CSPA3 or SICI_CSAP3 with other forms of inhibition led to quite different results: SICI_CSPA3 interacted in complex ways with CBI, SAI and SICI_CSPA2, whereas the effect of SICI_CSAP3 appeared to be quite independent of them. Although SICI_CSPA and SICI_CSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICI_CSAP was disinhibited much earlier following the imperative signal than SICI_CSPA. SICI_CSPA appears to activate a different inhibitory pathway to that activated by SICI_CSAP. The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.

Motor cortex (M1) paired-pulse TMS (ppTMS) probes excitatory and inhibitory intracortical dynamics by measurement of motor-evoked potentials (MEPs). However, MEPs reflect cortical and spinal excitabilities and therefore cannot isolate cortical function. Concurrent TMS-EEG has the ability to measure cortical function, while limiting peripheral confounds; TMS stimulates M1, whilst EEG acts as the readout: the TMS-evoked potential (TEP). Whilst varying preconditioning stimulus intensity influences intracortical inhibition measured by MEPs, the effects on TEPs is undefined. TMS was delivered to the left M1 using single-pulse and three, ppTMS paradigms, each using a different preconditioning stimulus: 70%, 80% or 90% of resting motor threshold. Corticospinal inhibition was present in all three ppTMS conditions. ppTMS TEP peaks were reduced predominantly under the ppTMS 70 protocol but less so for ppTMS 80 and not at all for ppTMS 90. There was a significant negative correlation between MEPs and N45 TEP peak for ppTMS 70 reaching statistical trends for ppTMS 80 and 90. Whilst ppTMS MEPs show inhibition across a range of preconditioning stimulus intensities, ppTMS TEPs do not. TEPs after M1 ppTMS vary as a function of preconditioning stimulus intensity: smaller preconditioning stimulus intensities result in better discriminability between conditioned and unconditioned TEPs. We recommend that preconditioning stimulus intensity should be minimized when using ppTMS to probe intracortical inhibition.

Connections between the cerebellum and the cortex play a critical role in learning and executing complex behaviours. Dual-coil transcranial magnetic stimulation (TMS) can be used non-invasively to probe connectivity changes between the lateral cerebellum and motor cortex (M1) using the motor evoked potential as an outcome measure (cerebellar-brain inhibition, CBI). However, it gives no information about cerebellar connections to other parts of cortex. We used electroencephalography (EEG) to investigate whether it was possible to detect activity evoked in any areas of cortex by single-pulse TMS of the cerebellum (cerebellar TMS evoked potentials, cbTEPs). A second experiment tested if these responses were influenced by the performance of a cerebellar-dependent motor learning paradigm. In the first series of experiments, TMS was applied over either the right or left cerebellar cortex, and scalp EEG was recorded simultaneously. Control conditions that mimicked auditory and somatosensory inputs associated with cerebellar TMS were included to identify responses due to non-cerebellar sensory stimulation. We conducted a follow-up experiment that evaluated whether cbTEPs are behaviourally sensitive by assessing individuals before and after learning a visuomotor reach adaptation task. A TMS pulse over the lateral cerebellum evoked EEG responses that could be distinguished from those caused by auditory and sensory artefacts. Significant positive (P80) and negative peaks (N110) over the contralateral frontal cerebral area were identified with a mirrored scalp distribution after left vs. right cerebellar stimulation. The P80 and N110 peaks were replicated in the cerebellar motor learning experiment and changed amplitude at different stages of learning. The change in amplitude of the P80 peak was associated with the degree of learning that individuals retained following adaptation. Due to overlap with sensory responses, the N110 should be interpreted with caution. Cerebral potentials evoked by TMS of the lateral cerebellum provide a neurophysiological probe of cerebellar function that complements the existing CBI method. They may provide novel insight into mechanisms of visuomotor adaptation and other cognitive processes.