title: Pathomechanisms and compensatory efforts related to Parkinsonian speech.
abstract: Voice and speech in Parkinson's disease (PD) patients are classically affected by a hypophonia, dysprosody, and dysarthria. The underlying pathomechanisms of these disabling symptoms are not well understood. To identify functional anomalies related to pathophysiology and compensation we compared speech-related brain activity and effective connectivity in early PD patients who did not yet develop voice or speech symptoms and matched controls. During fMRI 20 PD patients ON and OFF levodopa and 20 control participants read 75 sentences covertly, overtly with neutral, or with happy intonation. A cue-target reading paradigm allowed for dissociating task preparation from execution. We found pathologically reduced striato-prefrontal preparatory effective connectivity in early PD patients associated with subcortical (OFF state) or cortical (ON state) compensatory networks. While speaking, PD patients showed signs of diminished monitoring of external auditory feedback. During generation of affective prosody, a reduced functional coupling between the ventral and dorsal striatum was observed. Our results suggest three pathomechanisms affecting speech in PD: While diminished energization on the basis of striato-prefrontal hypo-connectivity together with dysfunctional self-monitoring mechanisms could underlie hypophonia, dysarthria may result from fading speech motor representations given that they are not sufficiently well updated by external auditory feedback. A pathological interplay between the limbic and sensorimotor striatum could interfere with affective modulation of speech routines, which affects emotional prosody generation. However, early PD patients show compensatory mechanisms that could help improve future speech therapies.
authors: Cognitive Neuroscience Group, Brain Imaging Center, Goethe University, Frankfurt, Germany ; Department of Neurology, Goethe University, Frankfurt, Germany.
authors: Christiane
authors: C
authors: Arnold
authors: Johannes
authors: J
authors: Gehrig
authors: Suzana
authors: S
authors: Gispert
authors: Carola
authors: C
authors: Seifried
authors: Christian A
authors: CA
authors: Kell
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001676:Biofeedback, Psychology; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007980:Levodopa / Q000627:therapeutic use; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D011571:Psychoacoustics; D011932:Reading; D013064:Speech Disorders / Q000209:etiology / Q000473:pathology*; D014832:Voice Disorders / Q000209:etiology / Q000473:pathology*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D010100:Oxygen
keywords: AC, auditory cortex; CN, caudate nucleus; COMT, catechol-O-methyltransferase; CON, control participant; DAT1, dopamine transporter; DLPFC, dorsolateral prefrontal cortex; Dysarthria; Dysarthrophonia; EPI, echo-planar imaging; FWE, family-wise error; Functional MRI; GLM, general linear model; HRF, hemodynamic response function; Hypophonia; IFG, inferior frontal gyrus; LSVT, Lee Silverman Voice Treatment; PD, Parkinson's disease; PPI, psycho-physiological interaction; PUT, putamen; Parkinson's disease; ROI, region of interest; SEM, standard error of the mean; SMA, supplementary motor area; SPL, superior parietal lobule; STS, superior temporal sulcus; SVC, small volume correction; Speech production; T, Tesla; UPDRS, Unified Parkinson's Disease Rating Scale; dPMC, dorsal premotor cortex; dstriatum, dorsal striatum; fMRI, functional magnetic response imaging; mPFC, medial prefrontal cortex; vstriatum, ventral striatum