Peter H. Weiss

Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD

The authors retrospectively compared 1-year results of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN; n = 16) and internal pallidum (GPi) (n = 11) in advanced PD and found about equal improvements in “off” period motor symptoms, dyskinesias, and fluctuations. STN stimulation reduced medication requirements by 65% and required significantly less electrical power. These advantages contrasted with a need for more intensive postoperative monitoring and a higher incidence of adverse events related to levodopa withdrawal.

Line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI

Objective: To use functional MRI (fMRI) to determine which brain regions are implicated when normal volunteers judge whether pretransected horizontal lines are correctly bisected (the Landmark test). Background: Manual line bisection and a variant thereof involving perceptual judgments of pretransected lines (the Landmark test) are widely used to assess unilateral visuospatial neglect in patients with neurologic disease. Although unilateral (left) neglect most often results from lesions to right temporoparietal cortex, the normal functional anatomy of the Landmark test has not been convincingly demonstrated. Methods: fMRI was carried out in 12 healthy right-handed male volunteers who judged whether horizontal lines were correctly prebisected. In the control task, subjects detected whether the horizontal lines contained a transection mark irrespective of the position of that mark. Response was by two-choice key press: on half the trials, subjects used the right, and on half, the left hand. Statistical analysis of evoked blood oxygenation level-dependent responses, measured with echoplanar imaging, employed statistical parametric mapping. Results: Performing the Landmark task showed neural activity (p < 0.05, corrected) in the right superior posterior and right inferior parietal lobe, early visual processing areas bilaterally, the cerebellar vermis, and the left cerebellar hemisphere. Only the latter area showed a significant interaction with hand used. Conclusions: The right hemispheric dominance observed in inferior parietal cortex is consistent with the results of lesion studies. Right superior parietal cortex, vermis, and left cerebellar hemisphere have not been implicated in neglect, but all appear to play a cognitive role in the Landmark task.

Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space—The roles of Brodmann areas 44 and 45

We investigated neural activations underlying a verbal fluency task and cytoarchitectonic probabilistic maps of Brocas speech region (Brodmanns areas 44 and 45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging (fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412 (1999) 319] and developed a method to combine both data sets. In the fMRI experiment, verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from predefined categories. A factorial design was used with factors verbal class (semantic vs. overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44 and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo fMRI and postmortem MR data were warped to a common reference brain using a new elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about intersubject variability were calculated for both areas and superimposed on the functional data, which showed the involvement of left hemisphere areas with verbal fluency relative to the baseline. Semantic relative to overlearned fluency showed greater involvement of left area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so differentially. Left area 45 is more involved in semantic aspects of language processing, while area 44 is probably involved in high-level aspects of programming speech production per se. The combination of functional data analysis with a new elastic warping tool and cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved in language.

Crossmodal Processing of Object Features in Human Anterior Intraparietal Cortex: An fMRI Study Implies Equivalencies between Humans and Monkeys

The organization of macaque posterior parietal cortex (PPC) reflects its functional specialization in integrating polymodal sensory information for object recognition and manipulation. Neuropsychological and recent human imaging studies imply equivalencies between human and macaque PPC, and in particular, the cortex buried in the intraparietal sulcus (IPS). Using functional MRI, we tested the hypothesis that an area in human anterior intraparietal cortex is activated when healthy subjects perform a crossmodal visuo-tactile delayed matching-to-sample task with objects. Tactile or visual object presentation (encoding and recognition) both significantly activated anterior intraparietal cortex. As hypothesized, neural activity in this area was further enhanced when subjects transferred object information between modalities (crossmodal matching). Based on both the observed functional properties and the anatomical location, we suggest that this area in anterior IPS is the human equivalent of macaque area AIP.

The Neural Basis of Vertical and Horizontal Line Bisection Judgments: An fMRI Study of Normal Volunteers

Bisection of horizontal lines is used as a clinical test of spatial cognition in patients with left visuospatial neglect after right hemisphere lesions. Bisection of vertical lines has also been employed, albeit less frequently. Interestingly, normal subjects often bisect horizontal lines too far left and vertical lines too high. We used fMRI to investigate whether vertical/horizontal stimulus orientation interacts with the neural mechanisms associated with line bisection judgments (the Landmark task). For control of orientation per se, subjects performed a visual detection task with the same stimuli. Statistical analysis of evoked BOLD responses employed SPM99. The Landmark task increased neural activity (P < 0.05, corrected) in the superior and inferior parietal lobes bilaterally, though predominantly on the right; early visual processing areas bilaterally; and cerebellar vermis, left cerebellar hemisphere, anterior cingulate, and prefrontal cortex bilaterally. Vertical lines (relative to horizontal lines and vice versa) increased neural activity in early visual processing areas, consistent with differential retinotopic stimulation. In addition, vertical lines activated right parietooccipital and superior posterior parietal cortex bilaterally. No significant interactions between the neural mechanisms associated with task and stimuli were observed. Increased neural activation in parietal and parietooccipital cortex associated with vertical lines may reflect increased attentional demands associated with this stimulus orientation. The right hemispheric dominance observed in posterior parietal during the Landmark task irrespective of stimulus orientation is consistent with lesion studies. Our results suggest that the behavioral patterns observed in normal subjects and neurological patients result from different stimulus effects rather than differential task demands.

Performing allocentric visuospatial judgments with induced distortion of the egocentric reference frame: an fMRI study with clinical implications.

The temporary improvement of visuospatial neglect during galvanic vestibular stimulation (Scand. J. Rehabil. Med. 31 (1999)117) may result from correction of the spatial reference frame distorted by the responsible lesion. Prior to an investigation of the neural basis of this effect in neurological patients, exploration of the neural mechanisms underlying such procedures in normals is required to provide insight into the physiological basis thereof. Despite their clinical impact, the neural mechanisms underlying the interaction of galvanic (and other) vestibular manipulations with visuospatial processing (and indeed the neural bases of how spatial reference frames are computed in man) remain to be clarified. We accordingly used fMRI in normal volunteers to investigate the effect of galvanically induced interference with the egocentric spatial reference frame on the neural processes underlying allocentric visuospatial (line bisection) judgments. A significant specific interaction of galvanic vestibular stimulation with the neural mechanisms underlying allocentric visuospatial judgments was observed in right posterior parietal and ventral premotor cortex only. Activation of these areas previously found to be damaged in visuospatial neglect suggests that these effects reflect the increased processing demands when compensating for the distorted egocentric spatial reference frame while maintaining accurate performance during the allocentric spatial task. These results thus implicate right posterior parietal and right ventral premotor cortex in the computation of spatial reference frames. Furthermore, our data imply a specific physiological basis for the temporary improvement of visuospatial neglect in patients with right hemisphere lesions during galvanic vestibular stimulation and may thus impact upon the rehabilitation of neglect: understanding the interaction of galvanic vestibular stimulation with allocentric visuospatial judgments in healthy volunteers may lead to the more effective deployment of such techniques in neurological patients.

Neural basis of pantomiming the use of visually presented objects

UNLABELLED Neuropsychological studies of patients suffering from apraxia strongly imply a left hemisphere basis for skillful object use, the neural mechanisms of which, however, remain to be elucidated. We therefore carried out a PET study in 14 healthy human volunteers with the aim to isolate the neural mechanisms underlying the sensorimotor transformation of object-triggers into skilled actions. We employed a factorial design with two factors ( RESPONSE naming, pantomiming; and TRIGGER: actions, objects) and four conditions (IA: imitating the observed pantomime; IO: pantomiming the use of the object shown; NA: naming the observed pantomime; NO: naming the object shown). The design thus mainly aims at investigating the interaction [i.e. (IO-IA)-(NO-NA)] which allows the assessment of increased neural activity specific to the sensorimotor transformation of object-triggers into skilled actions. The results (P < 0.05, corrected) showed that producing a wide range of skilled actions triggered by objects (controlled for perceptual, motor, semantic, and lexical effects) activated left inferior parietal cortex. The data provide an explanation for why patients with lesions including left parietal cortex suffer from ideational apraxia as assessed by impaired object use and pantomining to visually presented objects.

Gender differences in the functional neuroanatomy of emotional episodic autobiographical memory

Autobiographical memory is based on interactions between episodic memory contents, associated emotions, and a sense of self‐continuity along the time axis of ones life. The functional neuroanatomy subserving autobiographical memory is known to include prefrontal, medial and lateral temporal, as well as retrosplenial brain areas; however, whether gender differences exist in neural correlates of autobiographical memory remains to be clarified. We reanalyzed data from a previous functional magnetic resonance imaging (fMRI) experiment to investigate gender‐related differences in the neural bases of autobiographical memories with differential remoteness and emotional valence. On the behavioral level, there were no significant gender differences in memory performance or emotional intensity of memories. Activations common to males and females during autobiographical memory retrieval were observed in a bilateral network of brain areas comprising medial and lateral temporal regions, including hippocampal and parahippocampal structures, posterior cingulate, as well as prefrontal cortex. In males (relative to females), all types of autobiographical memories investigated were associated with differential activation of the left parahippocampal gyrus. By contrast, right dorsolateral prefrontal cortex was activated differentially by females. In addition, the right insula was activated differentially in females during remote and negative memory retrieval. The data show gender‐related differential neural activations within the network subserving autobiographical memory in both genders. We suggest that the differential activations may reflect gender‐specific cognitive strategies during access to autobiographical memories that do not necessarily affect the behavioral level of memory performance and emotionality. Hum Brain Mapping 24:313–324, 2005.

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.

Identifying Human Parieto-Insular Vestibular Cortex Using fMRI and Cytoarchitectonic Mapping

The parieto‐insular vestibular cortex (PIVC) plays a central role in the cortical vestibular network. Although this region was first defined and subsequently extensively studied in nonhuman primates, there is also ample evidence for a human analogue in the posterior parietal operculum. In this study, we functionally and anatomically characterize the putative human equivalent to macaque area PIVC by combining functional magnetic resonance imaging (fMRI) of the cortical response to galvanic vestibular stimulation (GVS) with probabilistic cytoarchitectonic maps of the human parietal operculum. Our fMRI data revealed a bilateral cortical response to GVS in posterior parieto‐insular cortex. Based on the topographic similarity of these activations to primate area PIVC, we suggest that they constitute the functionally defined human equivalent to macaque area PIVC. The locations of these activations were then compared to the probabilistic cytoarchitectonic maps of the parietal operculum (Eickhoff et al. [ 2005a ]: Cereb Cortex, in press; Eickhoff et al. [ 2005c ]: Cereb Cortex, in press), whereby the functionally defined PIVC matched most closely the cytoarchitectonically defined area OP 2. This activation of OP 2 by vestibular stimulation and its cytoarchitectonic features, which are similar to other primary sensory areas, suggest that area OP 2 constitutes the human equivalent of macaque area PIVC. Hum Brain Mapp, 2005.