Peter Drummond

Abstract
Resting tremor—involuntary and rhythmic shaking that usually occurs in the limbs—is the most common presenting motor symptom in Parkinson’s disease (PD). Tremor is not associated with the severity of dopamine depletion in the basal ganglia, and dopaminergic medication, which is used primarily to target dopamine depletion in the basal ganglia, has limited efficacy in reducing tremor. This suggests that other brain regions might underpin tremor in PD. Intracortical inhibition within the primary motor cortex (M1) has been implicated in tremor: intracortical inhibition in M1 is lower in PD than controls, higher motor cortex GABA is associated with lower tremor severity in PD, and pharmacological increases in GABA activity reduce tremor severity in PD. A combined intermittent theta-burst stimulation (iTBS)—gamma transcranial alternating current stimulation (tACS) protocol has been shown to increase short-interval intracortical inhibition (SICI) in PD. Therefore, in the current study, we examined M1 excitability, SICI, and resting tremor before and after real and sham iTBS-tACS. In a within-subjects design, we tested 19 participants (13 male; mean age 66 years) with idiopathic, tremor-dominant PD OFF medication. M1 excitability increased after real but not sham iTBS-tACS. There was no change in SICI after either real or sham iTBS-tACS. Resting tremor in the extensor carpi radialis showed a trend to increase after sham but not real iTBS, indicating that real iTBS-tACS might have prevented resumption of tremor activity in PD participants OFF medication. These findings provide preliminary evidence that iTBS-tACS induced long-term potentiation-like plasticity in M1 in tremor-dominant PD, which could influence tremor severity. However, further research is needed to examine the time-course of iTBS-tACS-induced changes in M1 excitability and tremor severity. If iTBS-tACS can reduce tremor, it could offer an alternative, or supplementary, treatment to levodopa medication for people with tremor-dominant PD.

Research Category and Technology and Methods
Clinical Research: 10. Transcranial Magnetic Stimulation (TMS)

Background
Chronic pain (CP) and PTSD often co-occur, leading to increased symptom severity, anxiety, depression, disability, and opioid use. Reduced cardiac vagal activity (CVA) and emotion regulation (ER) are both observed within these patients, which is indicated to induce heightened anxiety when faced with pain or trauma reminders. Thus, we aim to specifically target CVA via heart rate variability biofeedback (HRVBF), which to our knowledge has yet to be evaluated in comorbid patients exhibiting CP and PTSD. Additionally, via high frequency data sampling, the trajectories of CVA and ER during HRVBF will be assessed, elucidating potential mechanisms driving clinical benefits.

Methods
This study utilises a six-week randomized waitlist control HRVBF intervention, with a three-month follow-up, in a target sample of N=80, diagnosed with CP and PTSD. Based on the role of CVA in pain, PTSD and ER, we hypothesize that HRVBF will improve symptom severity and enhance ER. Daily HRV and ER assessments, as well as laboratory testing of breathing patterns and HRV at multiple time points throughout the intervention allows for in-depth mediation analysis to infer potential causal relationships between CVA and ER during biofeedback.

Discussion
This study aids in developing new treatment protocols for comorbid CP and PTSD. Furthermore, whilst the association between CVA and ER is well documented, causal relationships during HRVBF have thus far not been delineated. The high data sampling approach provides the opportunity to clarify their interaction in the progression of CP and PTSD.