Subthalamic nucleus stimulation and dysarthria in Parkinson’s disease: a PET study

Abstract

In Parkinson's disease, functional imaging studies during limb motor tasks reveal cerebral activation abnormalities that can be reversed by subthalamic nucleus (STN) stimulation. The effect of STN stimulation on parkinsonian dysarthria has not, however, been investigated using PET. The aim of the present study was to evaluate the effect of STN stimulation on regional cerebral blood flow (rCBF) during speech production and silent articulation in patients with Parkinson's disease. Ten Parkinson's disease patients surgically implanted bilaterally in the STN and with significant improvement of their dysarthria induced by STN stimulation were included. Ten healthy control subjects also participated in this study. Control subjects performed six sessions of [15O]H2O-PET scanning corresponding to three duplicated conditions externally cued by an auditory signal. The conditions were: (i) rest; (ii) production of a short, simple sentence; and (iii) silent articulation of the same sentence. Parkinson's disease patients carried out the six PET sessions twice, i.e., in the ON and OFF STN stimulation states. PET data analysis was performed using statistical parametric mapping (SPM99). In control subjects, speech production (SP) compared with rest was associated with increased rCBF bilaterally in the primary motor cortex (M1) corresponding to the orofacial somatotopy, the supplementary motor area (SMA), the associative auditory cortex and the cerebellar hemispheres. Silent articulation (SA) compared with rest induced a bilateral rCBF increase restricted to the orofacial M1 and cerebellar hemispheres. In Parkinson's disease patients in the OFF stimulation condition, during both SP and SA there was a lack of activation in the right orofacial M1 and in the cerebellum, abnormal increased rCBF in the right superior premotor cortex, and overactivation of the SMA. There was also an abnormal, increased rCBF in the dorsolateral prefrontal cortex (DLPFC) only during SP and increased rCBF in the left insula only during SA. In Parkinson's disease patients ON stimulation, for both SP and SA the activation pattern appeared similar to that in control subjects. In conclusion, our results suggest that parkinsonian dysarthria is associated with altered recruitment of the main motor cerebral regions (orofacial M1, cerebellum), and increased involvement of the premotor and prefrontal cortices (DLPFC, SMA, superior premotor cortex). These abnormal activations are different from those reported during hand motor tasks. They could be a compensatory mechanism, but might also arise directly as part of the pathophysiology of Parkinson's disease. STN stimulation tends to reverse these abnormal activations, which is consistent with the observed improvement of Parkinson's disease dysarthria.

STN‐stimulation in Parkinson's disease restores striatal inhibition of thalamocortical projection

“…Thus Payoux et al [2004] agreed with Ceballos-Baumann et al [1999] that the effect of stimulation is reduction of an abnormally high resting activity in motor cortex and selective activation during motion. We suggest that a similar mechanism can explain how studies of a resting baseline subtracted from the active condition [e.g., Pinto et al, 2004] yield higher activity of the SMA when STN stimulation is on compared to off.…”

“…With correction for multiple comparisons STN stimulation significantly raised glucose metabolism bilaterally in the thalamus but did not reduce motor cortex activity [Hilker et al, 2004], the latter in contrast to most blood flow studies [Hershey et al, 2003;Limousin et al, 1997;Pinto et al, 2004;Thobois et al, 2002]. Hilker et al [2004] O-PET at 5-10 mm, but neuroanatomical differences-especially in the size of the ventricles-can misplace the basal ganglia in the resultant average image during the transformation to Talairach space.…”

“…As plasma halflives of the agonists used by patients in this study ranged from 6 to 24 h, we do not claim that the subjects were completely without benefit of medication. However, we considered it unacceptable for the majority of patients to be without anti-Parkinson medication for longer than 12 h, and at the same time to have the STN stimulator turned off for more than 4 h. The literature gives the preference of 12 h of drug-freedom adopted in this study, e.g., Thobois [2002], Hilker [2004], Zhao et al [2004], Pinto et al [2004], and Payoux et al [2004].…”

Functional MRI with active, fully implanted, deep brain stimulation systems: Safety and experimental confounds

“…Since the first functional imaging investigation of DBS using positron emission tomography (PET) (Limousin 1997) numerous PET and single photon emission computed tomography (SPECT) studies have been reported (e.g. Fukuda 2001, Grafton 2006, Hilker 2004, Pinto 2004, Schroeder 2003, Thobois 2002.…”

Changes induced by levodopa and subthalamic nucleus stimulation on parkinsonian speech

“…2 Functional neuroimaging studies have revealed an underactivation of the main motor cerebral regions (primary motor cortex, cerebellum) and an overactivation of premotor and prefrontal cortices to represent the cerebral basis of parkinsonian dysarthria. 10 The results of surgery in the basal ganglia for the treatment of PD depend on the structure targeted and the surgical technique employed. 11 It has been recognized that lesions of the ventral intermediate nucleus of the thalamus (VIM), 12 the internal globus pallidus (GPi), 13 or subthalamic nucleus (STN), 14 which alleviate PD symptoms, can induce a worsening of speech, 14 -19 especially if surgery is performed bilaterally.…”