Exploring the effects of transcranial direct current stimulation on thalamo-cortical connectivity; implications for therapeutic interventions on prolonged disorders of consciousness

Aloi, Davide (2024). Exploring the effects of transcranial direct current stimulation on thalamo-cortical connectivity; implications for therapeutic interventions on prolonged disorders of consciousness. University of Birmingham. Ph.D.

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Abstract

Prolonged disorders of consciousness (PDOC) are a medical condition characterised by heterogeneous brain atrophies. PDOC are clinically defined by an impairment of consciousness in one or more of its two components (i.e., awareness and wakefulness). Options for the rehabilitation of such disorders are limited, and restricted to disability management rather than treatment. Different neuroimaging studies revealed a subgroup of PDOC patients characterised by a lack of wakefulness and a partially (or fully) preserved awareness (i.e., Cognitive Motor Dissociation, CMD). Interestingly, the lack of behavioural responsiveness present in patients with CMD has been linked to a partial reduction of coupling in two key areas of the motor network, namely the thalamus and the primary motor cortex (M1). Recent evidence shows that Transcranial Direct Current Stimulation (tDCS) - a non-invasive brain stimulation technique - might have a potential therapeutic effect. This notwithstanding, the literature is highly inconsistent, and the neural basis of such putative therapeutic effects is still unknown.

This thesis proposes a new therapeutic direction that directly targets the mechanisms underlying the lack of responsiveness in PDOC. Using Dynamic Causal Modelling (DCM), I explored the effects of tDCS on motor-network dynamics during command-following in three functional Magnetic Resonance Imaging (fMRI) experiments conducted on healthy individuals. In Chapter 4, I administered a single session of M1-tDCS (Experiment 1) and of cerebellar-tDCS (Experiment 2). In Chapter 5, I investigated the effects of five M1-tDCS sessions paired with passive mobilisation (Experiment 3). Additionally, in Chapter 6, I utilised magnetic resonance imaging (MRI) structural scans from the above experiments to model tDCS-induced electric fields and investigated the relationship between current density and connectivity changes following stimulation. Overall, I demonstrated that cathodal cerebellar- tDCS can selectively modulate thalamo-cortical connectivity during command-following in a polarity-specific manner (Experiment 2), while M1-tDCS reduced self-inhibition in the thalamus and M1 (Experiment 1 and 3, respectively). Therefore, I propose that the tDCS protocols used in this thesis could help sustain PDOC rehabilitation either by directly modulating thalamo-cortical connectivity or by reducing thalamic and M1 self-inhibition. Moreover, the relationship between current density metrics and effective connectivity following tDCS suggests that considering stimulation parameters based on subjects' electric field models might help mitigate inter-individual differences in tDCS effectiveness. Lastly, I tested the methods employed throughout the thesis on a PDOC patient in a multi-session multi- modal tDCS study. It is noteworthy that the data collection was restricted to one patient due to the impact of COVID-19.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):