Transcranial Magnetic Stimulation for Parkinson’s Disease and Stroke Speech Rehabilitation

Aphasia is recognised as a common and debilitating communication impairment, as a result of a stroke lesion. Language deficits in aphasia transpire as a result of damage to the primary language centres in the human cortex. Specifically, anterior cortical lesions result in expressive language deficits, termed non-fluent aphasia (Broca’s type aphasia). Persons who suffer from aphasia, even in its mildest form, describe the impairment in communication as a significant impediment to activities of daily living. The recovery of language function commonly occurs in the weeks and months subsequent to stroke as a result of spontaneous recovery, often attributed to reperfusion of the stroke-affected cortical regions. Despite this, many patients are left with chronic, persisting longer term aphasic language deficits. Presently employed behavioural language interventions afford insufficient language outcomes for many patients, particularly those with chronic impairments. Therefore, there is an identifiable need to expedite investigations to source alternative and/or adjunct therapies to advance language rehabilitation for persons with chronic aphasia. Transcranial Magnetic Stimulation (TMS) has recently been applied to cortical targets in persons with chronic non-fluent aphasia, resulting in positive language outcomes attained from explorations on small patient samples. Researchers postulate that inhibitory forms of TMS applied to a homologous language site, in the right hemisphere (RH), may reduce maladaptive neural patterns in chronic aphasic patients, improving neural activity in the language dominant left hemisphere (LH). To date there is modest evidence, at best, to support this notion. TMS is foreseen as a potential therapeutic adjunct to language therapy to remediate language impairment. Hence, the primary aim of this thesis is to provide objective insight into the short and long-term effects of Transcranial Magnetic Stimulation applied to the chronic non-fluent aphasic brain via the application of thorough measurements pertaining to behavioural language and semantic based event-related brain potentials (ERP). Twelve persons with non-fluent aphasia were treated using a protocol of low frequency (1Hz) repetitive Transcranial Magnetic Stimulation of 20 minutes duration for 10 days. Stimulation was guided by a state-of-the-art neuronavigational system, the Stealth Station Treon. The patient cohort was randomly assigned to receive placebo (sham condition) stimulation or experimental stimulation. All patients were at least 6 months post-stroke, with the majority 1-3 years post-stroke at the time of stimulation. Standardised behavioural language assessments and event-related brain potentials (ERP) measures of the semantic response N400 were taken at baseline (pre-stimulation), 1 week, 2 months and 8 months post stimulation to monitor language and neurophysiological outcomes subsequent to stimulation. Previous experimental studies report the most prominent language improvements for measures of picture naming subsequent to TMS. Thus, the primary outcome measures for the present intervention were targeted subtests from the Boston Diagnostic Aphasia Examination (BDAE) and the Boston Naming Test (BNT), testing specific expressive language performance. Extending on previous investigations, specific monitoring of picture naming accuracy and latency was also incorporated using a standardised subset of pictures to elucidate the longitudinal effects of stimulation on naming measures. Additional outcomes of spontaneous speech and receptive language were integrated to examine and characterise more generalised language effects as a result of stimulation. Behavioural language measures illustrated significantly higher performance for patients receiving experimental rTMS compared to the placebo form, on measures of picture naming at 1 week, 2 months and 8 months post stimulation. More significant differences between the groups were demonstrated over time (i.e. at 8 months post stimulation) compared to pre-stimulation measures. Supplementary improvements in expressive language, including picture description and repetition were also reported on longitudinal measures after stimulation. Minor improvements in receptive language performance were also noted across the testing period. Although novel, the empirically based measures supporting the presence of receptive language improvements subsequent to stimulation postulate wider reaching effects of TMS on bilateral neural language networks, with significant ramifications for future therapeutic applications. A further intention of this thesis was to investigate the neurophysiological influence of TMS on semantic processing through the measurement of the ERP (N400) responses. Measures of mean amplitude, peak amplitude, area and latency were recorded over the course of 8 months post stimulation. The interim outcomes at 1 week post stimulation demonstrated no significant differences between the experimental and placebo. A significantly heightened amplitude of response was found for the real stimulation when compared to the placebo group at 2 months post stimulation. At 8 months subsequent to stimulation, significant differences between the active and placebo group were found on all measures of N400. This evidence advocates for the presence of a treatment effect pertaining to rTMS on lexical-semantic processing in chronic aphasia. The longitudinal experiments presented in this thesis considerably expand on preceding investigations. An increased and more diversified sample size of persons with aphasia was examined in the current studies, with the incorporation of a placebo control aphasic group (sham stimulation) as a comparative measure of behavioural and neurophysiological performance. Of significance, placebo methods of TMS inform the potential behavioural and somatosensory effects of TMS. In addition, these experiments are the first published to date applying ERP as a measure of lexical-semantic change post TMS. The characterisation of language outcomes subsequent to rTMS may have a cogent role in clinical rehabilitation of language post-stroke. Further implementation of TMS in experimental research may prompt the development of protocols for clinical trials, utilising rTMS as an adjunct to existing speech pathology interventions to provide the most auspicious language outcomes for aphasic patients.

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