Common and unique responses to dopamine agonist therapy and deep brain stimulation in Parkinson's disease: an H(2)(15)O PET study.

BACKGROUND: Dopamine agonist therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are antiparkinsonian treatments that act on a different part of the basal ganglia-thalamocortical motor circuitry, yet produce similar symptomatic improvements. OBJECTIVE/HYPOTHESIS: The purpose of this study was to identify common and unique brain network features of these standard treatments. METHODS: We analyzed images produced by H(2)(15)O positron emission tomography (PET) of patients with Parkinson's disease (PD) at rest. Nine patients were scanned before and after injection of apomorphine, and 11 patients were scanned while bilateral stimulators were off and while they were on. RESULTS: Both treatments produced common deactivations of the neocortical sensorimotor areas, including the supplementary motor area, precentral gyrus, and postcentral gyrus, and in subcortical structures, including the putamen and cerebellum. We observed concomitant activations of the superior parietal lobule and the midbrain in the region of the substantia nigra/STN. We also detected unique, treatment-specific changes with possible motor-related consequences in the basal ganglia, thalamus, neocortical sensorimotor cortex, and posterolateral cerebellum. Unique changes in nonmotor regions may reflect treatment-specific effects on verbal fluency and limbic functions. CONCLUSIONS: Many of the common effects of these treatments are consistent with the standard pathophysiologic model of PD. However, the common effects in the cerebellum are not readily explained by the model. Consistent deactivation of the cerebellum is interesting in light of recent reports of synaptic pathways directly connecting the cerebellum and basal ganglia, and may warrant further consideration for incorporation into the model.

Selective left, right and bilateral stimulation of subthalamic nuclei in Parkinson's disease: differential effects on motor, speech and language function.

Deep brain stimulation (DBS) of the subthalamic nucleus improves the motor symptoms of Parkinson's disease, but may produce a worsening of speech and language performance at rates and amplitudes typically selected in clinical practice. The possibility that these dissociated effects might be modulated by selective stimulation of left and right STN has never been systematically investigated. To address this issue, we analyzed motor, speech and language functions of 12 patients implanted with bilateral stimulators configured for optimal motor responses. Behavioral responses were quantified under four stimulator conditions: bilateral DBS, right-only DBS, left-only DBS and no DBS. Under bilateral and left-only DBS conditions, our results exhibited a significant improvement in motor symptoms but worsening of speech and language. These findings contribute to the growing body of literature demonstrating that bilateral STN DBS compromises speech and language function and suggests that these negative effects may be principally due to left-sided stimulation. These findings may have practical clinical consequences, suggesting that clinicians might optimize motor, speech and language functions by carefully adjusting left- and right-sided stimulation parameters.

Laryngeal reflex responses are not modulated during human voice and respiratory tasks.

The laryngeal adductor response (LAR) is a protective reflex that prevents aspiration and can be elicited either by electrical stimulation of afferents in the superior laryngeal nerve (SLN) or by deflection of mechanoreceptors in the laryngeal mucosa. We hypothesized that because this reflex is life-sustaining, laryngeal muscle responses to sensory stimuli would not be suppressed during volitional laryngeal tasks when compared to quiet respiration. Unilateral electrical superior laryngeal nerve stimulation was used to elicit early (R1) and late (R2) responses in the ipsilateral thyroarytenoid muscle in 10 healthy subjects. The baseline levels of muscle activity before stimulation, R1 and R2 response occurrence and the integrals of responses were measured during each task: quiet inspiration, prolonged vowels, humming, forced inhalation and effort closure. We tested whether R1 response integrals during tasks were equal to either: (1) baseline muscle activity during the task added to the response integral at rest; (2) the response integral at rest minus the baseline muscle activity during the task; or (3) the response integral at rest. R1 response occurrence was not altered by task from rest while fewer R2 responses occurred only during effort closure and humming compared to rest. Because the R1 response integrals did not change from rest, task increases in motor neuron firing did not alter the LAR. These findings demonstrate that laryngeal motor neuron responses to sensory inputs are not gated during volitional tasks confirming the robust life-sustaining protective mechanisms provided by this airway reflex.

Alterations in CNS activity induced by botulinum toxin treatment in spasmodic dysphonia: an H215O PET study.

Speech-related changes in regional cerebral blood flow (rCBF) were measured using H(2)(15)O positron-emission tomography in 9 adults with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (BTX) injection and 10 age- and gender-matched volunteers without neurological disorders. Scans were acquired at rest and during production of continuous narrative speech and whispered speech. Speech was recorded during scan acquisition for offline quantification of voice breaks, pitch breaks, and percentage aperiodicity to assess correlations between treatment-related changes in rCBF and clinical improvement. Results demonstrated that speech-related responses in heteromodal sensory areas were significantly reduced in persons with ADSD, compared with volunteers, before the administration of BTX. Three to 4 weeks after BTX injection, speech-related responses were significantly augmented in these regions and in left hemisphere motor areas commonly associated with oral-laryngeal motor control. This pattern of responses was most strongly correlated with the objective measures of clinical improvement (decreases in the frequency of voice breaks, pitch breaks, and percentage aperiodicity). These data suggest a pathophysiological model for ADSD in which BTX treatment results in more efficient cortical processing of sensory information, making this information available to motor areas that use it to more effectively regulate laryngeal movements.

Immediate and sustained changes in tongue movement with an experimental palatal "fistula": a case study.

OBJECTIVE: To determine the immediate and longer-term effect(s) on tongue movement following the placement of an experimental opening through a palatal obturator (replicate of subject's prosthesis) worn by an adult male with an unrepaired cleft of the hard and soft palate. METHODS: Tongue movements associated with an anterior experimental opening of 20 mm(2) were examined under three conditions: a control condition in which the subject wore the experimental obturator completely occluded, a condition immediately after drilling the experimental openings through the obturator, and a condition after 5 days in which the subject wore the experimental obturator with the experimental opening. An Electromagnetic Articulograph was used for obtaining tongue movements during speech. RESULTS: The findings partly revealed that the immediate introduction of a perturbation to the speech system (experimental fistula) had a temporary effect on tongue movement. After sustained perturbation (for 5 days), the system normalized (going back toward control condition's behavior). Perceptual data were consistent with kinematic tongue movement direction in most of the cases. CONCLUSIONS: Although the immediate response can be interpreted as indicative of the subject's attempts to move the tongue toward the opening to compensate for air loss, the findings following a sustained perturbation indicate that with time, other physiological adjustments (such as respiratory adjustments, for example) may help reestablish the requirements of a pressure-regulating system.

The effects of speech therapy and pharmacological treatments on voice and speech in Parkinson s disease: a review of the literature.

The purpose of this paper was to examine the effects of speech therapy and various pharmacological treatment approaches on the voice and speech of persons with Parkinson s disease (PD). Approximately 80% of PD patients have voice and speech problems including reduced vocal intensity, reduced vocal pitch, monopitch and monoloudness, and imprecise articulation. Research prior to 1970's had not demonstrated significant improvements following speech therapy. However, recent research has shown that speech therapy (when persons with PD are optimally medicated) has proven to be the most efficacious therapeutic method for improving voice and speech function. Across research studies, pharmacological methods of treatment in isolation do not appear to significantly improve voice and speech function in PD. In a single subject study, however, the dopamine agonist Mirapex was shown to have beneficial effects on vocal intensity. Possible explanations for the differential responses to treatment are discussed. It is suggested that the goal of future studies should be investigations of the effects of combined treatment approaches.