The Cerebellum in Temporal Prediction: Insights from Neurophysiology to Dystonia Pathophysiology

This project aims to provide novel insights into the cerebellum’s causal role in orchestrating complex cognitive processes that optimize behaviour, focusing on the multifaceted construct of temporal prediction (TP). Starting by exploring this ability in healthy subjects to understand cerebellar-dependent modulation, we then reframed temporal prediction in the context of cervical dystonia, offering a new perspective on its pathophysiology. We first explored, in Chapter 1, key models of time perception and prediction, emphasizing the cerebellum’s role and the influence of emotional states on temporal distortions. Chapter 2 presented cervical dystonia as a pathophysiological framework for studying temporal prediction, highlighting its network-based pathophysiology and the cerebellum’s possible contribution to altered temporal processing. Finally, Chapter 3 outlined research methods used to investigate cerebellar function (i.e., Transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS)), underscoring their relevance for understanding and treating disorders like dystonia and ataxias. Building on these findings, we first used tDCS to modulate cerebellar activity and test its effect on context-dependent temporal prediction in healthy subjects (Chapter 4, Experiment 1). We then examined cerebellar connectivity during rhythmic and single-interval temporal prediction tasks, via the Cerebellar-Brain Inhibition protocol (CBI) (Chapter 5, Experiment 2), and then we explored how emotional state impacts temporal prediction (Chapter 6, Experiment 3). In the last part of the thesis, we present data related to dystonia and the cerebellum. Particularly, we explored the TP ability in cervical dystonia patients (Chapter 7, Experiment 4). Lastly, Chapter 8, Experiment 5 used the Cerebellar Cognitive Affective Syndrome (CCAS) scale to define the cognitive profile of cervical dystonia patients. The Appendix includes two studies on vibro-tactile stimulation (VTS) as a potential neuromodulation method for symptom relief in cervical dystonia. Our results demonstrate that perturbing cerebellar activity with cathodal tDCS alters temporal prediction ability (Experiment 1). Further, we found a significant reduction of CBI during the task, compared to CBI recorded at rest, in the single-interval context during task preparation, highlighting the cerebellum's context-dependent role in temporal prediction (Experiment 2). We have also presented compelling new evidence highlighting the malleability of temporal prediction (Experiment 3), finding that negative emotions, such as fear, can influence temporal prediction, as shown by decreased reaction times when the target stimulus was a fearful face (Experiment 3). In cervical dystonia, patients exhibited selective impairments in memory-based temporal prediction, confirming cerebellar involvement in dystonia's pathophysiology (Experiment 4). Additionally, using the Cerebellar Cognitive Affective Syndrome Scale (CCAS-S), we mapped a cognitive profile for CD patients, shedding light on cerebellar-related cognitive alterations (Experiment 5). Collectively, this work highlights the need to characterize the cerebellum-dependent underlying function by investigating cognitive processes that stem from integrative mechanisms within the cerebellum, like temporal prediction. Understanding how the cerebellum integrates cognitive and motor processes for prediction will not only enhance our knowledge of its unique contribution to brain function but also open new avenues for targeted interventions in clinical settings.