Robert S. Turner

Role of the posterior parietal cortex in updating reaching movements to a visual target

The exact role of posterior parietal cortex (PPC) in visually directed reaching is unknown. We propose that, by building an internal representation of instantaneous hand location, PPC computes a dynamic motor error used by motor centers to correct the ongoing trajectory. With unseen right hands, five subjects pointed to visual targets that either remained stationary or moved during saccadic eye movements. Transcranial magnetic stimulation (TMS) was applied over the left PPC during target presentation. Stimulation disrupted path corrections that normally occur in response to target jumps, but had no effect on those directed at stationary targets. Furthermore, left-hand movement corrections were not blocked, ruling out visual or oculomotor effects of stimulation.

Toward a more culturally sensitive DSM-IV. Psychoreligious and psychospiritual problems

In theory, research, and practice, mental health professionals have tended to ignore or pathologize the religious and spiritual dimensions of life. This represents a type of cultural insensitivity toward individuals who have religious and spiritual experiences in both Western and non-Western cultures. After documenting the “religiosity gap” between clinicians and patients, the authors review the role of theory, inadequate training, and biological primacy in fostering psychiatrys insensitivity. A new Z Code (formerly V Code) diagnostic category is proposed for DSM-IV: psychoreligious or psychospiritual problem. Examples of psychoreligious problems include loss or questioning of a firmly held faith, and conversion to a new faith. Examples of psychospiritual problems include near-death experiences and mystical experiences. Both types of problems are defined, and differential diagnostic issues are discussed. This new diagnostic category would: a) improve diagnostic assessments when religious and spiritual issues are involved; b) reduce iatrogenic harm from misdiagnosis of psychoreligious and psychospiritual problems; c) improve treatment of such problems by stimulating clinical research; and d) encourage clinical training centers to address the religious and spiritual dimensions of human existence.

Microelectrode-guided implantation of deep brain stimulators into the globus pallidus internus for dystonia: techniques, electrode locations, and outcomes

Object. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a promising new procedure for the treatment of dystonia. The authors present their technical approach for placement of electrodes into the GPi in awake patients with dystonia, including the methodology used for electrophysiological mapping of the GPi in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit. Methods. Twenty-three adult and pediatric patients who had various forms of dystonia were included in this study. Baseline neurological status and improvement in motor function resulting from DBS were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Implantation of the DBS lead was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol. Conclusions. Physiologically guided implantation of DBS electrodes in patients with dystonia is technically feasible in the awake state in most cases, with low morbidity rates. Spontaneous discharge rates of GPi neurons in dystonia are similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than by rates. Active electrode locations associated with robust improvement (> 50% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance of 3.7 mm from the pallidocapsular border. Patients with juvenile-onset primary dystonia and those with the tardive form benefited greatly from this procedure, whereas benefits for most secondary dystonias and the adult-onset craniocervical form of this disorder were more modest.

Normalizing motor-related brain activity Subthalamic nucleus stimulation in Parkinson disease

Objective: To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. Methods: Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. Results: For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related “overactivity” compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. Conclusions: Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

From Spiritual Emergency to Spiritual Problem: the Transpersonal Roots of the New DSM-IV Category:

Religious or Spiritual Problem is a new diagnostic category (Code V62.89) in the 1994 Diagnostic and Statistical Manual of Mental Disorders. Although the acceptance of this new category was based on a proposal documenting the extensive literature on the frequent occurrence of religious and spiritual issues in clinical practice, the impetus for the proposal came from transpersonal clinicians whose initial focus was on spiritual emergencies-forms of distress associated with spiritual practices and experiences. The proposal grew out of the work of the Spiritual Emergence Network to increase the competence of mental health professionals in sensitivity to such spiritual issues. This article describes the rationale for this new category, the history of the proposal, transpersonal perspectives on spiritual emergency, types of religious and spiritual problems, differential diagnostic issues, psychotherapeutic approaches, and the likely increase in number of persons seeking therapy for spiritual problems. It also presents the preliminary findings from a database of religious and spiritual problems.

The functional anatomy of parkinsonian bradykinesia.

To investigate the difficulty that patients with Parkinsons disease (PD) have in performing fast movements, we used H(2)(15)O PET to study regional cerebral blood flow (rCBF) associated with performance of a simple predictive visuomanual tracking task at three different velocities. Tracking movements in PD patients (versus tracking with the eyes alone) were associated with a general underactivation of the areas normally activated by the task (sensorimotor cortex contralateral to the moving arm, bilateral dorsal premotor cortices, and ipsilateral cerebellum). Presupplementary motor cortex (pre-SMA) ipsilateral to the moving arm had greater than normal movement-related activations. Increasing movement velocity led to increased rCBF in multiple premotor and parietal cortical areas and basal ganglia in the patients as opposed to the few cerebral locations that are normally velocity-related. The functional correlates of PD bradykinesia are: (1) impaired recruitment of cortical and subcortical systems that normally regulate kinematic parameters of movement such as velocity; and (2) increased recruitment of multiple premotor areas including both regions specialized for visuomotor control (ventral premotor and parietal cortices) and some that are not (pre-SMA). The overactivation of cortical regions observed in patients may be functional correlates of compensatory mechanisms and/or impaired suppression as a facet of the primary pathophysiology of PD.

Context-Dependent Modulation of Movement-Related Discharge in the Primate Globus Pallidus

A selective contribution of the basal ganglia (BG) to memory-contingent motor control has long been hypothesized. The importance of memory context remains an open question, however, for the BG skeletomotor circuit. To investigate this question, we studied the perimovement discharge of a carefully selected group of 74 “arm-related” pallidal cells in two rhesus monkeys. The animals performed three tasks designed to dissociate multiple independent aspects of memory-contingent reaching while controlling movement kinematics. The activity of most neurons (88%) was influenced strongly by the memory demands of a task (remembering “where” or “when” to move), but the population as a whole showed no systematic preference for memory- or sensory-contingent conditions. The effects of memory context were primarily additive with those of movement kinematics (particularly movement direction). Considered separately, decreases and increases in firing had very different context preferences: decreases were nearly always larger for sensory-triggered movements, whereas increases were enhanced most often under memory-contingent conditions (i.e., self-initiated or self-guided movements). A similar pattern of preferences was found for both pallidal segments. The distinct context-specific enhancements of decreases and increases could not be explained as simple sensory responses or as interactions with preparatory or anticipatory processes present before movement initiation. Rather, they appear related to movement execution under specific contexts. Our results lead to the conclusion that movement facilitatory decreases in internal pallidal (GPi) activity are primarily greater under sensory-triggered conditions. GPi increases and their suppressive effects, perhaps on competing activity in pallidal-recipient centers, have increased prevalence under memory-contingent conditions.

Deep Brain Stimulation of the Globus Pallidus Internus in the Parkinsonian Primate: Local Entrainment and Suppression of Low-Frequency Oscillations

Competing theories seek to account for the therapeutic effects of high-frequency deep brain stimulation (DBS) of the internal globus pallidus (GPi) for medically intractable Parkinsons disease. To investigate this question, we studied the spontaneous activity of 102 pallidal neurons during GPiDBS in two macaques rendered parkinsonian by administration of MPTP. Stimulation through macroelectrodes in the GPi (> or =200 microA at 150 Hz for 30 s) reduced rigidity in one animal and increased spontaneous movement in both. Novel artifact subtraction methods allowed uninterrupted single-unit recording during stimulation. GPiDBS induced phasic (78% of cells) or sustained (22%) peristimulus changes in firing in both pallidal segments. A subset of cells responded at short latency (<2 ms) in a manner consistent with antidromic driving. Later phasic increases clustered at 3- to 5-ms latency. Stimulation-induced decreases were either phasic, clustered at 1-3 ms, or sustained, showing no peristimulus modulation. Response latency and magnitude often evolved over 30 s of stimulation, but responses were relatively stable by the end of that time. GPiDBS reduced mean firing rates modestly and only in GPi (-6.9 spikes/s). Surprisingly, GPiDBS had no net effect on the prevalence or structure of burst firing. GPiDBS did reduce the prevalence of synchronized low-frequency oscillations. Some cell pairs became synchronized instead at the frequency of stimulation. Suppression of low-frequency oscillations did not require high-frequency synchronization, however, or even the presence of a significant peristimulus response. In summary, the therapeutic effects of GPiDBS may be mediated by an abolition of low-frequency synchronized oscillations as a result of phasic driving.

The basal ganglia network mediates the planning of movement amplitude

This study addresses the hypothesis that the basal ganglia (BG) are involved specifically in the planning of movement amplitude (or covariates). Although often advanced, based on observations that Parkinsons disease (PD) patients exhibit hypokinesia in the absence of significant directional errors, this hypothesis has been challenged by a recent alternative, that parkinsonian hypometria could be caused by dysfunction of on‐line feedback loops. To re‐evaluate this issue, we conducted two successive experiments. In the first experiment we assumed that if BG are involved in extent planning then PD patients (who exhibit a major dysfunction within the BG network) should exhibit a preserved ability to use a direction precue with respect to normals, but an impaired ability to use an amplitude precue. Results were compatible with this prediction. Because this evidence did not prove conclusively that the BG is involved in amplitude planning (functional deficits are not restricted to the BG network in PD), a second experiment was conducted using positron emission tomography (PET). We hypothesized that if the BG is important for planning movement amplitude, a task requiring increased amplitude planning should produce increased activation in the BG network. In agreement with this prediction, we observed enhanced activation of BG structures under a precue condition that emphasized extent planning in comparison with conditions that emphasized direction planning or no planning. Considered together, our results are consistent with the idea that BG is directly involved in the planning of movement amplitude or of factors that covary with that parameter.

Basal ganglia activity patterns in parkinsonism and computational modeling of their downstream effects

The availability of suitable animal models and the opportunity to record electrophysiologic data in movement disorder patients undergoing neurosurgical procedures has allowed researchers to investigate parkinsonism‐related changes in neuronal firing patterns in the basal ganglia and associated areas of the thalamus and cortex. These studies have shown that parkinsonism is associated with increased activity in the basal ganglia output nuclei, along with increases in burst discharges, oscillatory firing and synchronous firing patterns throughout the basal ganglia. Computational approaches have the potential to play an important role in the interpretation of these data. Such efforts can provide a formalized view of neuronal interactions in the network of connections between the basal ganglia, thalamus, and cortex, allow for the exploration of possible contributions of particular network components to parkinsonism, and potentially result in new conceptual frameworks and hypotheses that can be subjected to biological testing. It has proven very difficult, however, to integrate the wealth of the experimental findings into coherent models of the disease. In this review, we provide an overview of the abnormalities in neuronal activity that have been associated with parkinsonism. Subsequently, we discuss some particular efforts to model the pathophysiologic mechanisms that may link abnormal basal ganglia activity to the cardinal parkinsonian motor signs and may help to explain the mechanisms underlying the therapeutic efficacy of deep brain stimulation for Parkinson’s disease. We emphasize the logical structure of these computational studies, making clear the assumptions from which they proceed and the consequences and predictions that follow from these assumptions.