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dc.contributor.advisorWinn, Philip
dc.contributor.authorGut, Nadine Katrin
dc.coverage.spatialxvii, 281en_US
dc.description.abstractBased on the belief that it is a locomotor control structure, the pedunculopontine tegmental nucleus (PPTg) has been considered a potential target for deep brain stimulation (DBS) for Parkinson’s disease (PD) patients with symptoms refractory to medication and/or stimulation of established target sites. To date, a number of patients have been implanted with PPTg electrodes with mostly disappointing results. Exact target site in PPTg, possible mechanisms of PPTg-DBS and likely potential benefits need to be systematically explored before consideration of further clinical application. The research described here approaches these questions by (i) investigating the role of the PPTg in gait per se; (ii) developing a refined model of PD that mimics the underlying pathophysiology by including partial loss of the PPTg itself; (iii) adapting a wireless device to let rats move freely while receiving DBS; and (iv) investigating the effect of DBS at different sites in the PPTg on gait and posture in the traditional and refined model of PD. Underlining the concern that understanding the PPTg as a locomotor control structure is inadequate, the experiments showed that neither partial nor complete lesions of PPTg caused gait deficits. The refined model showed hardly any differences compared to the standard one, but the effect of DBS in each was very different, highlighting the need to take degeneration in the PPTg into consideration when investigating it as a DBS target. The differential results of anterior and posterior PPTg-DBS show the critical importance of intra-PPTg DBS location: Anterior PPTg electrodes caused severe freezing and worsened gait while some gait parameters improved with stimulation of posterior PPTg. The results suggest mechanisms of PPTg-DBS beyond the proposed activation of over-inhibited PPTg neurons, including aggravation of already dysfunctional inhibitory input by anterior PPTg-DBS and activation of ascending projections from posterior PPTg to the forebrain.en_US
dc.publisherUniversity of St Andrews
dc.subjectPedunculopontine tegmental nucleusen_US
dc.subjectDeep brain stimulationen_US
dc.subjectParkinson's diseaseen_US
dc.subjectBasal gangliaen_US
dc.subjectFreezing of gaiten_US
dc.subject.lcshBrain stimulationen_US
dc.subject.lcshMesencephalic tegmentumen_US
dc.subject.lcshParkinson's disease--Treatmenten_US
dc.titleModelling the effects of deep brain stimulation in the pedunculopontine tegmental nucleus in Parkinson’s diseaseen_US
dc.contributor.sponsorMedical Research Council (MRC)en_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US
dc.publisher.departmentSchool of Psychology and Neuroscienceen_US

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