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Modulating writing skill learning in Parkinson’s disease: novel insights into the effects of dopaminergic medication and transcranial direct current stimulation

Book - Dissertation

Parkinson's disease (PD) is a neurodegenerative disorder causing slowness and decreased movement size, affecting writing performance. Current available treatments for PD patients are unable to slow down the course of the disease, can induce motor fluctuations and offer only limited symptomatic relief. Motor relearning may partially alleviate the functional impact of PD. Transcranial direct current stimulation (tDCS) has the potential to boost motor learning even more. Therefore, the aim of this project was to get better insight in the neurophysiological and behavioral representations of motor learning of writing skills and its interactions with tDCS and dopaminergic medication in PD. As a first step, we explored the discriminative ability of a short and simple timed tapping task on a smartphone to distinguish between the ON-OFF medication states in 32 patients. Task performance was measured during 7 days in the home setting at well-defined times after medication intake. Results revealed that tapping outcomes (i.e. frequency and inter-tap distance) on average were able to distinguish OFF from ON performance, both at 1 and 3 hours after medication intake. We also found excellent test-retest reliability within one day and learning effects over the 7 days. The most optimal discriminative ON-OFF accuracy for tapping frequency with the dominant hand was found at 1 hour after medication intake, after familiarization with the task (day 2) and before reaching a ceiling effect in learning (day 5). Despite the fact that we also showed a need for remote supervision, our overall compliance outcomes pointed to a great potential for this smartphone-based tapping task to detect daily medication response in PD. Subsequently, we explored whether an innovative writing task discriminated between 32 people with and 31 without PD-pathology and detected the effects of dopaminergic medication intake. A novel finding of this study was that PD patients OFF-medication not only showed decreased writing sizes compared to HC, but that particularly their up-stroke, and not their down-stroke, of writing was affected. Interestingly, dopaminergic medication improved overall writing amplitudes and the upstroke continuation in a letter sequence, but this occurred at the cost of the down-stroke trajectory. The impact of dopaminergic medication on writing performance was thus more complex than anticipated and direction-specific. In the next part, we conducted a pilot study and investigated whether 1 session of concurrent tDCS during training affected upper limb freezing and writing sequential up-and-down strokes in ten patients with PD compared to ten healthy controls (HC). We found that tDCS as applied to the primary motor cortex, compared to sham stimulation, relieved the number of freezing episodes during writing. We also found a subgroup-dependent variability in response to stimulation, as indicated by a beneficial effect of tDCS on stroke characteristics in the patients who reported freezing episodes in daily life but not in those without such episodes. Next, the effects of tDCS were analyzed on the consolidation of learning writing skills and cortical excitability. We showed that, compared to sham stimulation, tDCS improved writing performance by increasing writing size and velocity. Most importantly, benefits were sustained when patients received tDCS in the trained and untrained tasks on the tablet as well as for writing on paper unlike when receiving sham stimulation. The study was underpowered to reveal meaningful effects of the tDCS-boosted intervention on motor cortex excitability. Finally, the effects of writing training combined with tDCS versus sham on the primary motor cortex (M1) were investigated on the consolidation of writing skills as well as on the cortical excitability in M1 in the ON and OFF medication state. We recruited 39 patients and conducted a randomized blinded and sham-controlled study. We showed that tDCS improved consolidation after writing training as evidenced by retention and transfer of the learning increments as well as by the better ability to execute continued learning during a second training session, particularly when patients were ON medication. We also found that medication had a direct impact on writing performance but did not improve learning. Furthermore, after training the cortical inhibition was significantly increased in the tDCS compared to the sham group. Hence, these results provide robust evidence for tDCS-mediated consolidation of writing skills. Overall, this doctoral project provides the first robust knowledge on the added value of incorporating tDCS and smartphone-based ON-OFF assessments in the field of PD rehabilitation.
Publication year:2022