REducing SPEECH-related Side-effects of Deep Brain Stimulation in Parkinson's Disease Via Automated Speech Analysis

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment of L-dopa sensitive motor symptoms of Parkinson's disease (PD) but its effects on speech are equivocal. Although some aspects of speech might improve with STN-DBS, stimulation-induced dysarthria represents one of the most common side effects, with a prevalence of up to 90%. Worsening of speech can neutralize the motor benefits of STN-DBS in terms of overall benefit in quality of life. STN-DBS induced dysarthria is not understood in sufficient detail that would allow its prevention or sustained reduction. The human ear is too limited in quantifying subtle changes in speech and to differentiate between parkinsonian and stimulation induced dysarthria. The investigators' objective is to improve L-dopa sensitive PD-related dysarthria and at the same time reduce DBS-induced speech disorders with the help of automated acoustic analysis in patients with STN-DBS-induced dysarthria.

In Part 1, the investigators' aim is to identify the most sensitive and specific speech variables for STN-DBS-related improvement of parkinsonian dysarthria and STN-DBS-induced speech-related side-effects, by application of an automated acoustic speech analysis technique. Patients with STN-DSB induced dysarthria will be examined in their medication ON state. Where possible the study will also be performed in the medication OFF state (after an overnight withdrawal of their PD medication). In both states, speech analysis will be performed in the stimulation OFF and ON states, as well as with increasing stimulation amplitudes.

In Part 2, the investigators' aim at investigating the anatomical and pathophysiological substrates of STN-DBS induced changes in speech production, by establishing stimulation maps. Stimulation maps highlight effective regions of stimulation and can help clinicians to navigate and program DBS steering the current towards the target region that improves speech (here a priori the sensorimotor STN for improving parkinsonian speech together with other parkinsonian signs), while avoiding current diffusion to regions identified as potentially worsening speech.

Part 3 is explorative. The investigators' hypothesize, that selected speech variables in automated speech analysis (as identified in part 1+2) are more sensitive to improvement of STN-DBS induced dysarthria, than ratings of three blinded speech-therapists. Again patients with STN-DBS induced dysarthria will be recruited to this study (willing participants of part 1+2 and patients who did not participate in part 1+2 will be included). The investigators will assess dysarthria by automated speech analysis, expert ratings and subjective ratings, before (at baseline visit) and at two time points (at V1 between 0-6 weeks after baseline and at V2 between 6-12 weeks after V1) after measures are taken to reduce stimulation induced dysarthria. Measures to reduce STN-DBS induced dysarthria will include all DBS settings that are routinely applied in daily clinical practice for dysarthria reduction. DBS-settings will be performed on both DBS-leads and patients will be in the medication ON state.

• Part 1: Subjective rating of the quality of speech [Time frame: At visit 1 (baseline visit) and visit 2 (≤4 weeks)]
• Part 1: Assessment parkinsonism contralateral to the tested DBS lead [Time frame: At visit 1 (baseline visit) and visit 2 (≤4 weeks)]
• Part 1: Clinical assessment of possible side effects [Time frame: At visit 1 (baseline visit) and visit 2 (≤4 weeks)]
• Part 3: Subjective rating of the quality of speech [Time frame: At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)]
• Part 3: Assessment of motoric symptoms [Time frame: At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)]
• Part 3: Clinical assessment of possible side effects [Time frame: At baseline visit, visit 1 (0-6 weeks after baseline) and visit 2 (6-12 weeks after visit 1)]