Disordered volition

The subjective nature of volition and the absence of any clear criteria to define precisely when it occurs make speaking about ‘disordered’ volition difficult. However, certain neurological pathologies are characterised by disorders of voluntary movement. The neural abnormalities that accompany such pathologies are by now well known. One might reasonably suppose that divergences in these underlying mechanisms should manifest as altered experiences of volition. Patients who show abnormal patterns of

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action initiation, maintenance and termination are therefore a useful population in which to study the phenomena associated with volition.

Parkinson’s disease (PD) is characterised by reduced and slower voluntary

movements compared to healthy populations (Goetz et al., 2008). Cognitive impairments in PD include an increase in impulse control disorders (Weintraub, David, Evans, Grant, & Stacy, 2015), apathy (Starkstein et al., 1992) and depression (Cummings, 1992).

The primary site of pathology is the substantia nigra, where PD patients show severe loss of dopaminergic projection neurons relative to healthy individuals (Braak & Braak, 2000). However, even from the earliest stages of the disease, this loss is associated with impaired function beyond the substantia nigra. The systems affected are varied.

Research has largely focussed on disorders in dopaminergic pathways in the limbic system, however other cell types including cholinergic, GABAergic and glutaminergic neurons are also typically implicated (Jellinger, 1991).

Lesions in the limbic system, particularly the transentorhinal region, have wide-reaching consequences in PD (Braak et al., 1994). Damage in entorhinal and hippocampal areas, as well as the amygdala, interrupts normal communication from these sites to cortical and subcortical regions. Learning, memory, emotion regulation and motor function are all typically affected (Braak et al., 1996).

Relevant to the experience of voluntary actions, diminished dopaminergic projection to the SMA have been shown to reduce both the occurrence and speed of self-generated movements (Jahanshahi et el., 1995). Given the involvement of the SMA and pre-SMA, it

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seems reasonable to assume that neural markers associated with the motor symptoms of PD may be detectable in changes to the readiness potential (RP).

RP studies of PD have typically measured the amplitude or latency of the negative going pre-motor potential. Results have differed considerably between studies (Barrett, Shibasaki, & Neshige, 1986; Dick et al., 1987; Jahanshashi et al., 1995; Shibasaki et al., 1980), however this may reflect methodological differences, particularly in the administration of dopaminergic medication. A recent review (Georgiev, Lange, Seer, Kopp, & Jahanshahi, 2016) suggests that the most consistent finding from among 14 relevant studies was a reduction in the amplitude of the early stage RP. The authors further noted that the diminished amplitude could be increased by the administration of dopaminergic medication (Feve, Bathien, & Rondot, 1992; Dick et al., 1987).

A recent study (Tabu et al., 2015) examined the awareness of action intentions in PD using a Libet task. Participants were elderly (mean age of 67 for males, 70 for females), mildly impaired according to established criteria (Goetz et al., 2008) and completed the task having not taken dopaminergic medication for at least 12 hours. Patients showed a much later W judgement (awareness of intention to act) relative to healthy controls, while M judgements (awareness of acting) and S judgements (awareness of a sensory event) were unaffected. The authors concluded that due to the relatively mild impairment of the cohort, these results were unlikely to be the sole product of cognitive deficits.

It is tempting to conclude that reduced levels of dopamine (DA) may have driven delayed intention awareness alongside diminished movement control. Tabu and colleagues did not test patients while on dopaminergic intervention, so results from their study cannot be used to defend this viewpoint. Furthermore, this hypothesis is not

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supported by results from patients with Tourette’s syndrome (Moretto et al., 2011), described below.

Tourette’s syndrome is characterised by involuntary movements and vocalisations

called tics that typically appear in late childhood and often continue into adulthood. The ability to control tics varies both between individuals and within individuals over the lifespan (Robertson et al., 2009). Tics are a particularly unique case of ‘unwanted’

movement in that they are not described as fully automatic (like reflex movements).

Patients often report ‘urges’ prior to a tic, and many patients learn to control tics as they move from adolescence into adulthood (Jackson et al., 2011). Tics are therefore experienced as involuntary, but are mediated by the voluntary motor system. It is particularly interesting to note that RPs may be observed prior to tic movements, however this is rare and the RPs are shorter in duration compared those of fully intended movements in healthy controls (van der Salm et al., 2012).

Ganos and colleagues (2015) predicted that increased neural noise preceding movements in Tourette’s syndrome would result in a later subjective experience of action initiation. They reasoned that a less reliable signal around the usual time of RP onset would require a more conservative threshold for the detection of volition. Indeed, Moretto and colleagues (2011) previously observed significantly later action awareness in Tourette’s syndrome compared to healthy controls. Ganos et al., using the Libet method in a study on 27 adolescents, failed to replicate Moretto et al., but found that patient reports of volition were indeed influenced by features of the pathology.

Specifically, although age and severity of tics was not systematically related to a delayed awareness of intention, patients who experience strong pre-tic urges also reported a later intention to act. Similarly, patients who had good control of their tics, showed a

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much earlier awareness of intention. The authors concluded that volition arises as the brain learns to discriminate neural noise related to pre-motor preparation.

Importantly, Tourette’s syndrome is a hyper-dopaminergic condition; so reduced DA levels cannot explain delayed awareness of intentions.

It therefore remains to be determined whether disorders implicating dopamine, such as Tourette’s syndrome and PD, are associated with delayed intention awareness due to one common or several distinct neural processes. One of the objectives of this thesis is to investigate this question by comparing the action awareness of PD patients with healthy controls. Critically, the presence of DA-related symptoms in patients will also be manipulated in three separate experiments using medication and deep brain stimulation (DBS). These interventions will be more fully introduced in the relevant sections of chapters 2 & 3.