Cognitive deficits in patients with essential tremor.

OBJECTIVE: To assess cognitive and affective functioning in patients with essential tremor (ET). BACKGROUND: ET is traditionally thought to occur in isolation, without other neurologic abnormalities or cognitive changes. Recent evidence of gait disturbance and bradykinesia in these patients suggests that the neurologic abnormalities in ET may be more widespread than was once thought. Cognitive function in these patients has not been the subject of in-depth study. METHODS: Cognitive performance and mood were assessed in 18 consecutive patients with ET and 18 consecutive patients with PD who visited the neurosurgical clinic for surgical treatment of their symptoms. RESULTS: The patients with ET were found to have deficits on tests of verbal fluency, naming, mental set-shifting, verbal memory, and working memory, as well as higher levels of depression. In contrast to these areas of deficit, their performance was better than that of the normative sample on several tests of verbal and nonverbal conceptualization and reasoning. Tremor severity was not correlated with cognitive deficits. Patients with PD had deficits on the same tests that were impaired in the ET group and on tests of visuospatial processes. Direct comparison of the ET and PD groups showed greater impairment in facial perception in the PD group and greater impairment in verbal fluency and working memory in the ET group. CONCLUSION: Patients with ET have deficits in specific aspects of neuropsychological functioning, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests involvement of frontocerebellar circuits in this disease.

Relationship of lesion location to cognitive outcome following microelectrode-guided pallidotomy for Parkinson's disease: support for the existence of cognitive circuits in the human pallidum.

Current models of basal ganglia anatomy posit the existence of multiple parallel, anatomically segregated circuits. Anatomical data from non-human primates suggest that the circuits subserving motor functions are segregated from those subserving cognitive functions. Here we present data that demonstrate that, in humans, motor and cognitive frontosubcortical circuits are segregated. We studied a group of patients with Parkinson's disease undergoing surgical lesioning of the globus pallidus internus for relief of their symptoms. Lesion location along an anteromedial-to-posterolateral axis was found to be related to postsurgical outcome on both cognitive and motor measures. Performance on several neuropsychological measures, including the generation of category exemplars and continuous mental addition, was linearly related to distance along this axis, with anteromedial lesions leading to postsurgical impairment, intermediate lesions having little effect and posterolateral lesions leading to an improvement on several measures. The same relationship was found between memory performance under conditions of proactive interference and lesion location within the globus pallidus internus. In contrast, bradykinesia, assessed as the speed of finger-tapping, had a non-linear relationship to lesion location, intermediate lesions leading to greater postsurgical improvement than lesions in more extreme anteromedial or posterolateral locations. These data demonstrate that the cognitive effects of pallidotomy can be dissociated from the motor effects. These effects depend upon the placement of the lesions within the globus pallidus internus, supporting the segregation of functionally distinct circuits in the human pallidum.

Wisconsin Card Sorting Test performance following head injury: dorsolateral fronto-striatal circuit activity predicts perseveration.

The Wisconsin Card Sorting Test (WCST) has been argued to be a sensitive indicator of frontal lobe function. However, several recent studies have failed to find a consistent relationship between structural damage to this cortical area and perseveration on the test. In the present study, positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose was used to examine the relationship of regional brain metabolism to perseverative responding on the WCST in patients with a history of closed-head injury. An inverse relationship was found between perseverative responses and metabolism in the right, but not the left, dorsolateral prefrontal cortex and caudate nucleus. Perseverative responding was not related to metabolism in several other regions of the frontal lobes and basal ganglia, including the putamen and the frontal poles bilaterally. These data suggest that the functional integrity of the right dorsolateral frontal-subcortical circuit is critical for WCST performance.

Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson's disease.

The purpose of this study was to examine the relationship between lesion location and clinical outcome following globus pallidus internus (GPi) pallidotomy for advanced Parkinson's disease. Thirty-three patients were prospectively studied with extensive neurological examinations before and at 6 and 12 months following microelectrode-guided pallidotomy. Lesion location was characterized using volumetric MRI. The position of lesions within the posteroventral region of the GPi was measured, from anteromedial to posterolateral along an axis parallel to the internal capsule. To relate lesion position to clinical outcome, hierarchical multiple regression analysis was used. The variance in outcome measures that was related to preoperative scores and lesion volume was first calculated, and then the remaining variance attributable to lesion location was determined. Lesion location along the anteromedial-to-posterolateral axis within the GPi influenced the variance in total score on the Unified Parkinson's Disease Rating Scale in the postoperative 'off' period, and in 'on' period dyskinesia scores. Within the posteroventral GPi, anteromedial lesions were associated with greater improvement in 'off' period contralateral rigidity and 'on' period dyskinesia, whereas more centrally located lesions correlated with better postoperative scores of contralateral akinesia and postural instability/gait disturbance. Improvement in contralateral tremor was weakly related to lesion location, being greater with posterolateral lesions. We conclude that improvement in specific motor signs in Parkinson's disease following pallidotomy is related to lesion position within the posteroventral GPi. These findings are consistent with the known segregated but parallel organization of specific motor circuits in the basal ganglia, and may explain the variability in clinical outcome after pallidotomy and therefore have important therapeutic implications.

Variability in lesion location after microelectrode-guided pallidotomy for Parkinson's disease: anatomical, physiological, and technical factors that determine lesion distribution.

OBJECT: To understand the factors that determine the distribution of lesions after microelectrode-guided pallidotomy for Parkinson's disease, the authors quantitatively characterized lesion location in a cohort of patients who were prospectively followed to determine the effects of pallidotomy on clinical outcome. METHODS: Thirty-three patients underwent volumetric magnetic resonance (MR) imaging after surgery to allow quantitative lesion localization in relation to conventional intraventricular landmarks and, alternatively, more anatomically relevant landmarks. The validity of the method was verified in a cohort of postpallidotomy patients who underwent concurrent volumetric and stereotactic MR imaging in an external head frame. Lesions were distributed over a considerable distance in the anteroposterior (8.8 mm) and mediolateral (8.7 mm) dimensions in relation to the anterior commissure and wall of the third ventricle, respectively. Less variation was seen in lesion location in the dorsoventral dimension (4.8 mm) in relation to the intercommissural plane. CONCLUSIONS: Lesion distribution was not random: lesion locations in the anteroposterior and mediolateral dimensions were highly correlated, such that lesions were distributed from anteromedial to posterolateral, parallel to the border of the globus pallidus internus with the obliquely oriented internal capsule. The factors that led to variability in lesion location were variation in third ventricle width and the oblique anteromedial-to-posterolateral course of the internal capsule. This demonstration of variability of lesion location in a cohort of patients who experienced excellent clinical benefits and minimal postoperative complications emphasizes the importance of anatomical variations in determining lesion position and the need for physiological corroboration for correct lesion placement.

Effects of triazolam and ethanol on proactive interference: evidence for an impairment in retrieval inhibition.

The effects of two memory-impairing drugs, ethanol and triazolam, on proactive interference (PI) in memory were studied. Following ingestion of either one of these drugs or a placebo, subjects studied an A-B list (e.g., BEE-WASP) of paired associates, followed by an A-C list (e.g., BEE-HONEY) on the interference trial, and a D-E list (e.g., KING-QUEEN) followed by an A-C list on the control trial. A PI effect was found in the data, such that subjects produced fewer correct second list targets on the interference trial than on the control trial. Neither ethanol nor triazolam was found to influence the size of the PI effect. However, both drugs were found to increase B intrusions on the test of the A-C list, to impair subjects' ability to produce more than one studied response for each cue word, and to impair the subjective experience of retrieved memory information. These data suggest that ethanol and triazolam impair an inhibitory process that normally operates as one component of intentional retrieval, playing an important role in the suppression of unwanted information during a memory task.

Associative priming in word fragment completion: a dissociation between explicit and implicit retrieval processes.

Three experiments investigated associative priming in word fragment completion. In associative priming, the study word that acts as a prime is semantically related in some way to the response word that the subject must produce or respond to at test. For example, a prime might be semantically related to the solution to its paired word fragment (e.g. study "VANILLA", solve fragment "-H-C--A-E" at test, solution is "CHOCOLATE"). Associative priming therefore differs from both repetition and conceptual priming, in which the studied primes are themselves the words that must be produced or responded to at test. In Experiment 1, associative primes were found to influence word fragment completion performance on an explicit test, but not on an implicit test. Experiment 2 demonstrated that the effects of associative primes on explicitly instructed fragment completion cannot be attributed to the specific information about cue-prime relationships that is included in the explicit instructions. Experiment 3 demonstrated that a manipulation of modality, a variable known to disrupt implicit retrieval processes, disrupts repetition priming on an explicit test, but not associative priming. The results of these three experiments suggest that whereas repetition primes are retrieved from memory by both explicit and implicit retrieval processes, associative primes are retrieved by only explicit processes. These data suggest that implicit retrieval processes are cue-dependent processes which automatically retrieve memory information that provides a good match to retrieval cues. Explicit retrieval processes are cue-independent, functioning as an intentional retrieval set to access particular categories or types of memory information.

Automaticity of chronically accessible constructs in person x situation effects on person perception: it's just a matter of time.

Models of Person X Situation influences on social behavior and judgement have invoked two distinct mechanisms: a personality disposition and a situational press. In this study we conceptualized both influences in terms of a single underlying mechanism, construct accessibility. We pitted the characteristic ways that individuals perceive others against situational influences on accessibility (i.e., contextual priming) and tracked over time the relative power of these competing influences on the outcome of an impression-formation task. Subjects possessed either a chronically accessible (chronics) or an inaccessible (nonchronics) construct for either outgoing or inconsiderate behavior. As predicted, as the delay since the priming event lengthened (from 15 to 180 s), chronics were progressively more likely to use the chronically accessible construct instead of the primed alternative construct to categorize an ambiguous target behavior, whereas nonchronics' relative use of the primed and alternative constructs did not change as a function of postpriming delay.