Dopaminergic control of speech production in Parkinson's disease–an fMRI study

Introduction: Early on in Parkinson`s disease (PD), patients show hypophonia with the characteristic soft and uniform voice that is not responsive to dopaminergic treatment¹. This speech pathology could result from reduced feedforward drive due to hypokinesia or from ineffective sensorimotor integration² due to insufficient filtering in corticobasal circuits³. More general, akinesia could result from impaired cognitive planning, motor preparation, or both. We thus tested whether PD patients planned less efficiently prior to motor preparation by comparing preparation for covert and overt speech production using functional imaging.

Methods: 20 PD patients (on 200mg levodopa and off medication, Hoehn & Yahr I and II) and 20 matched controls participated in the study. During fMRI scanning at 3T, participants read written sentences, preceded by 2–4s by an auditory cue, indicating whether the following phrase had to be read silently or overtly with normal intonation. After standard pre-processing (SPM8), we tested the interaction between condition (overt vs. covert) and group (on, off and control) separately for preparation and execution (ANOVA). Psychophysiological interactions of overt>covert reading were compared between groups separately for preparation and execution. All results are significant at p<0.001, uncorrected.

Results and Discussion: Hypokinesia relates to functional hypo-connectivity in corticostriatal loops during cognitive preparation for motor production, which normalizes upon dopamine administration. During actual speech production, hypophonia manifests in decreased use of auditory feedback and increased activity in the feedforward processing left inferior frontal gyrus and dorsal premotor cortex. Therefore we speculate that PD patients’ speech deteriorates to incomprehensible levels when prefrontal cortices and thus compensatory feedforward commands are affected by the progressive disease.

Literatur: 1. Romito LM et al., (2010) J Neurol 257, 298-304 2. Hickok G et al., (2011) Neuron 69, 407-422 3. Mink JW, (1996) Progress Neurobiol 50, 381-425