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.

Feeling of knowing for names in response to faces.

Participants were asked to recall the names when shown photographs of faces in both a semantic task (Experiment 1) and an episodic task (Experiments 2 and 3). When recall failed, feeling of knowing (FOK) ratings were solicited. In addition, participants reported on the strategies that they used to make their ratings, whether they could recall other pieces of information (the target-accessibility strategy, e.g., Koriat, A. (1993). How do we know that? The accessibility model of the feeling of knowing. Psychological Review, 100, 609-639) or whether the faces simply looked familiar (the cue-familiarity strategy, e.g., Schwartz, B. L., & Metcalfe, J. (1992). Cue familiarity but not target accessibility enhances feeling of knowing ratings. Journal of Experimental Psychology: Learning, Memory, and Cognition, 18, 1074-1083). In all experiments, FOK ratings were fairly accurate in that participants were successful in predicting their performance on a subsequent recognition test. More importantly, participants reported using the cue-familiarity strategy more often, although they gave higher FOK ratings when they reported using the target-accessibility strategy. The FOK ratings that were given using the two strategies were equally accurate.

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.

Temporal dissociation of early lexical access and articulation using a delayed naming task--an FMRI study.

Neuroimaging studies of overt speech hold an important practical advantage allowing monitoring of subject performance, particularly valuable in disorders like aphasia. However, speech production is not a monotonic process but a complex sequence of stages. Levelt and colleagues have described these as roughly corresponding to two originally independent systems--conceptual and sensorimotor--that are linked in the formulation and expression of spoken language. In the initial stages a word is chosen to match a concept (lexical selection); in the later stages the sound and motor patterns are encoded and the word is uttered (articulation). It has been difficult to discriminate these stages using conventional neuroimaging techniques. We designed a functional magnetic resonance imaging study in an attempt to do this, by introducing a latency into a conventional naming paradigm, delaying the articulated response. Our results showed that left hemisphere perisylvian areas were active throughout, interacting with visual and heteromodal areas during early lexical access and with motor and auditory areas during overt articulation. These results are consistent with the broadest version of the Levelt model and with that derived from Chomsky's minimalist program in which a core language system interacts with conceptual-intentional systems and articulatory-perceptual systems during the early and late stages of lexical access respectively.

Neural bases of categorization of simple speech and nonspeech sounds.

Categorization is fundamental to our perception and understanding of the environment. However, little is known about the neural bases underlying the categorization of sounds. Using human functional magnetic resonance imaging (fMRI) we compared the brain responses to a category discrimination task with an auditory discrimination task using identical sets of sounds. Our stimuli differed along two dimensions: a speech-nonspeech dimension and a fast-slow temporal dynamics dimension. All stimuli activated regions in the primary and nonprimary auditory cortices in the temporal cortex and in the parietal and frontal cortices for the two tasks. When comparing the activation patterns for the category discrimination task to those for the auditory discrimination task, the results show that a core group of regions beyond the auditory cortices, including inferior and middle frontal gyri, dorsomedial frontal gyrus, and intraparietal sulcus, were preferentially activated for familiar speech categories and for novel nonspeech categories. These regions have been shown to play a role in working memory tasks by a number of studies. Additionally, the categorization of nonspeech sounds activated left middle frontal gyrus and right parietal cortex to a greater extent than did the categorization of speech sounds. Processing the temporal aspects of the stimuli had a greater impact on the left lateralization of the categorization network than did other factors, particularly in the inferior frontal gyrus, suggesting that there is no inherent left hemisphere advantage in the categorical processing of speech stimuli, or for the categorization task itself.

Temporal dynamics of cortical and subcortical responses to apomorphine in Parkinson disease: an H2(15)O PET study.

H2(15)O positron emission tomography (PET) was used to study the temporal course of central nervous system (CNS) responses to apomorphine in patients with idiopathic Parkinson disease (PD). Agonist-induced changes in regional cerebral blood flow (rCBF) were evaluated within corticostriatal-thalamocortical circuits as well as in regions that extend beyond the standard pathophysiological model for PD. Compared with controls, rCBF was increased in PD patients in subcortical regions including the basal ganglia and cerebellum and both increased and decreased in prefrontal, parietal, sensorimotor, and paralimbic cortical areas. Apomorphine reversed many of these effects and had widespread effects throughout the brain. We evaluated the effects of apomorphine as they changed over time, comparing rCBF before the motor response and at later times when the motor response was maximal. Apomorphine's effects on functional connectivity also changed over time; activity in the ventrolateral thalamus was coupled with that in the SMA and cerebellum at the time of maximum motor response, but not at 45 seconds. Apomorphine affected rCBF in regions commonly considered part of the pathophysiological model of PD (eg, basal ganglia, thalamus, SMA), and other effects were seen in regions outside of the model (eg, cerebellum and superior parietal lobule). Results are discussed in light of this model.