Improved sensory gating of urinary bladder afferents in Parkinson's disease following subthalamic stimulation.

In addition to motor symptoms, patients with Parkinson's disease (PD) show deficits in sensory processing. These deficits are thought to result from deficient gating of sensory information due to basal ganglia dysfunction in PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been shown to improve sensory deficits in PD, e.g. STN-DBS normalizes the perception of urinary bladder filling in patients with PD. This study aimed at investigating how STN-DBS modulates the processing of urinary bladder information to elucidate the (patho-)physiology of sensory gating mechanisms in PD. Nine PD patients with bilateral STN-DBS switched on (STN-DBS ON) or off (STN-DBS OFF) were studied during dynamic bladder filling and an empty bladder condition (for control), while changes in regional cerebral blood flow (rCBF) were measured by PET. Urinary bladder filling led to an increased rCBF in the periaqueductal grey (PAG), the posterior thalamus, the insular cortex as well as in the right frontal cortex and the cerebellum bilaterally. A significant interaction between bladder condition and STN-DBS was observed in the posterior thalamus and the insular cortex, with enhanced modulation of these areas during STN-DBS ON compared to STN-DBS OFF. Furthermore, regression analyses revealed a modulation of the neural activity in the thalamus and the insular cortex by the PAG activity during STN-DBS ON only. Thus, STN-DBS led to a significant enhancement of afferent urinary bladder information processing. The data suggest that STN-DBS facilitates the discrimination of different bodily states by supporting sensory perception and the underlying neural mechanisms. Furthermore, this is the first imaging study, which shows an effect of STN-DBS on sensory gating in PD patients and its neural basis.

Functional interactions during the retrieval of conceptual action knowledge: an fMRI study.

Impaired retrieval of conceptual knowledge for actions has been associated with lesions of left premotor, left parietal, and left middle temporal areas [Tranel, D., Kemmerer, D., Adolphs, R., Damasio, H., & Damasio, A. R. Neural correlates of conceptual knowledge for actions. Cognitive Neuropsychology, 409-432, 2003]. Here we aimed at characterizing the differential contribution of these areas to the retrieval of conceptual knowledge about actions. During functional magnetic resonance imaging (fMRI), different categories of pictograms (whole-body actions, manipulable and nonmanipulable objects) were presented to healthy subjects. fMRI data were analyzed using SPM2. A conjunction analysis of the neural activations elicited by all pictograms revealed ( p<.05, corrected) a bilateral inferior occipito-temporal neural network with strong activations in the right and left fusiform gyri. Action pictograms contrasted to object pictograms showed differential activation of area MT+, the inferior and superior parietal cortex, and the premotor cortex bilaterally. An analysis of psychophysiological interactions identified contribution-dependent changes in the neural responses when pictograms triggered the retrieval of conceptual action knowledge: Processing of action pictograms specifically enhanced the neural interaction between the right and left fusiform gyri, the right and left middle temporal cortices (MT+), and the left superior and inferior parietal cortex. These results complement and extend previous neuropsychological and neuroimaging studies by showing that knowledge about action concepts results from an increased coupling between areas concerned with semantic processing (fusiform gyrus), movement perception (MT+), and temporospatial movement control (left parietal cortex).

Subthalamic stimulation modulates cortical control of urinary bladder in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for off-period motor symptoms and dyskinesias in advanced Parkinson's disease. Clinical studies have shown that STN-DBS also ameliorates urinary bladder function in Parkinson's disease patients by delaying the first desire to void and increasing bladder capacity. This study aimed at investigating the effect of STN-DBS on the neural mechanisms underlying cerebral bladder control. Using PET to measure changes in regional cerebral blood flow (rCBF), 11 patients with bilateral STN-DBS were studied during urodynamic bladder filling in STN-DBS ON and OFF condition. A filled bladder led to a significant increase of rCBF in the anterior cingulate cortex, which was further enhanced during STN-DBS OFF. A significant interaction between bladder state and STN-DBS was observed in lateral frontal cortex with increased rCBF when the bladder was filled during STN-DBS OFF. The data suggest that STN-DBS ameliorates bladder dysfunction and that this modulation may result from facilitated processing of afferent bladder information.

Common and differential neural mechanisms supporting imitation of meaningful and meaningless actions.

Neuropsychological studies indicate that, after brain damage, the ability to imitate meaningful or meaningless actions can be selectively impaired. However, the neural bases supporting the imitation of these two types of action are still poorly understood. Using PET, we investigated in 10 healthy individuals the neural mechanisms of imitating novel, meaningless actions and familiar, meaningful actions. Data were analyzed using SPM99. During imitation, a significant positive correlation (p < .05, corrected) of regional cerebral blood flow with the amount of meaningful actions was observed in the left inferior temporal gyrus only. In contrast, a significant positive correlation (p < .05, corrected) with the amount of meaningless movements was observed in the right parieto-occipital junction. The direct categorical comparison of imitating meaningful (100%) relative to meaningless (100%) actions showed differential increases in neural activity (p < .001, uncorrected) in the left inferior temporal gyrus, the left parahippocampal gyrus, and the left angular gyrus. The reverse categorical comparison of imitating meaningless (100%) relative to meaningful (100%) actions revealed differential increases in neural activity (p < .001, uncorrected) in the superior parietal cortex bilaterally, in the right parieto-occipital junction, in the right occipital-temporal junction (MT, V5), and in the left superior temporal gyrus. Increased neural activity common to imitation of meaningless and meaningful actions compared to action observation was observed in a network of areas known to be involved in imitation of actions including the primary sensorimotor cortex, the supplementary motor area, and the ventral premotor cortex. These results are compatible with the two-route model of action imitation which suggests that there are at least two mechanisms involved in imitation of actions: a direct mechanism transforming a novel action into a motor output, and a semantic mechanism, on the basis of stored memories, that allows reproductions of known actions. Our results indicate that, in addition to shared neural processes, the direct and the semantic mechanisms that underlie action imitation also draw upon differential neural mechanisms. The direct mechanism underlying imitation of meaningless actions differentially involves visuospatial transformation processes as evidenced by activation of areas belonging to the dorsal stream. In contrast, imitation of meaningful actions differentially involves semantic processing as evidenced by activation of areas belonging to the ventral stream.

Left inferior parietal cortex integrates time and space during collision judgments.

Left inferior parietal lobe lesions can cause perturbation of the space-time plans underlying skilled actions. But does the perceptual integration of spatiotemporal information use the same neural substrate or is the role of the left inferior parietal cortex restricted to visuomotor transformations? We use fMRI and a collision judgment paradigm to examine whether the left inferior parietal cortex integrates temporal and spatial variables in situations in which no complex action and no visuomotor transformation is required. We used a perceptual task in which healthy subjects indicated by simple button presses whether two moving objects (of the same or different size) would or would not collide with each other. This task of interest was contrasted with a control task that employed the same stimuli and identical motor responses but in which the size of the two moving objects had to be compared. To assess putative differential eye-movement effects both tasks were performed with and without central fixation. Analysis of the fMRI data (employing a random-effects model and SPM99) showed that collision judgments (relative to size judgments) provoked a significant increase in neural activity in the left inferior parietal cortex (supramarginal gyrus) only. These results show that left inferior parietal cortex is involved in the integration of perceptual spatiotemporal information and thus provide a neural correlate for the use of space-time plans (whose perturbation can lead to apraxia as originally hypothesized by Liepmann). Furthermore, the data suggest that the left supramarginal gyrus combines temporal and spatial variables more widely than previously supposed.