Human verbal working memory impairments associated with thalamic damage.

Although animal studies, human neuroimaging studies, and numerous theoretical models suggest possible contributions of the thalamus to working memory, there are very few reported deficits in human working memory following thalamic lesions. The present study examined working memory performance in six individuals with isolated thalamic stroke and found evidence of impairment on a number of working memory span tasks, but not on a forward digit-span measure. Examination of additional aspects of working memory performance (e.g., spatial and object working memory), analysis of subjects with other sites of thalamic stroke, and functional neuroimaging suggest a role of the thalamus in working memory.

Hypersexuality and hemiballism due to subthalamic infarction.

OBJECTIVE: A 70-year-old right-handed man presented with a subthalamic infarction followed by persistent hypersexuality and hemiballism. A lacunar infarction 1 cm in diameter was observed on magnetic resonance imaging. We hypothesized that metabolic abnormalities would be detected in cortical areas related to his neurobehavioral symptoms. BACKGROUND: Statistical validation of the regional metabolic changes that may relate to neuropsychiatric symptoms has been elusive. Relating metabolic changes to neuropsychiatric symptoms is especially important in unique neurobehavioral cases. METHOD: Quantitative fluorodeoxyglucose positron emission tomography was obtained for a single-subject comparison with scans from 60 healthy subjects. RESULTS: Substantial glucose hypometabolism (p <0.001, uncorrected; [df = 56]) was identified in the subthalamic nucleus at the site of the lacunar infarction. Hypermetabolism (p <0.01) was identified within the basal forebrain and temporal lobes, anterior cingulate and medial prefrontal cortices (areas previously associated with hypersexuality), and striatum (p <0.001) ipsilateral to the stroke (areas known to relate to hemiballism). CONCLUSIONS: Single-subject statistical parametric mapping may improve our understanding of unique neurobehavioral cases.

Event-related potentials correlate with task-dependent glucose metabolism.

Cognitive processing is associated with brain electrical activity that is reflected in event-related potentials (ERP). ERP during a target detection task, and regional cerebral glucose metabolism (CMRglc) measured simultaneously, may be influenced by the same neurophysiologic processes. We tested the hypothesis that ERP factors could be directly correlated with CMRglc to derive functional brain maps of brain activity at 120, 160, 200, 280, and 400 ms following stimulus presentation in a target detection task. We controlled for the potential confounding effects of age, sex, and task accuracy, and correlate target-related and nontarget-related ERP separately. Increases and decreases in CMRglc at each time point were identified with statistical parametric mapping (P < 0.001, uncorrected). The 120- and 160-ms maps were the same for target and nontarget processing, while maps for 280 and 400 ms clearly distinguished between targets and nontargets. Extrinsic (early) cognitive processes that depend mainly on stimulus characteristics show less variation based on stimulus meaning (i.e., letter vs shape; target vs nontarget) than later (intrinsic) cognitive processes. These early effects are lateralized to the left hemisphere, for negative ERP factors, and positive ERP-PET correlations are more likely than negative ERP-PET correlations. Thus, brain areas related to task processing impact both ERP and CMRglc measures, suggesting a shared neurophysiologic mechanism for negative ERP factors and increased CMRglc. Direct statistical analysis of these two measures using statistical parametric mapping provides high spatial and temporal resolution in multisubject experiments, while requiring only a single (18)FDG PET scan per subject.

Cortical deficits in multiple sclerosis on the basis of subcortical lesions.

Patients suffering from multiple sclerosis have a high frequency of cognitive deficits usually attributable to demyelination and axonal loss in the subcortical white matter. Neurologic abnormalities referable to cortical function are uncommon but have been described. The present study describes three patients with clinically definite MS with deficits in cognitive function referable to cortical location. Two of the patients underwent positron emission tomography and showed profound cortical hypometabolism adjacent to subcortical white matter lesions seen on MRI. This paper points out that neurologic deficits referable to cortical sites may be caused by subcortical white matter lesions and that cognitive dysfunction in patients with MS may progress rapidly in the absence of motoria deficits or other evidence of clinical deterioration. Multiple Sclerosis (2000) 6 50 - 55

Cortical activity related to accuracy of letter recognition.

Previous imaging and neurophysiological studies have suggested that the posterior inferior temporal region participates in tasks requiring the recognition of objects, including faces, words, and letters; however, the relationship between accuracy of recognition and activity in that region has not been systematically investigated. In this study, positron emission tomography was used to estimate glucose metabolism in 60 normal adults performing a computer-generated letter-recognition task. Both a region of interest and a voxel-based method of analysis, with subject state and trait variables statistically controlled, found task accuracy to be: (1) negatively related to metabolism in the left ventrolateral inferior temporal occipital cortex (Brodmann's area 37, or ventrolateral BA 37) and (2) positively related to metabolism in a region of the right ventrolateral frontal cortex (Brodmann's areas 47 and 11, or right BA 47/11). Left ventrolateral BA 37 was significantly related both to hits and to false alarms, whereas the right BA 47/11 finding was related only to false alarms. The results were taken as supporting an automaticity mechanism for left ventrolateral BA 37, whereby task accuracy was associated with automatic letter recognition and in turn to reduced metabolism in this extrastriate area. The right BA 47/11 finding was interpreted as reflecting a separate component of task accuracy, associated with selectivity of attention broadly and with inhibition of erroneous responding in particular. The findings are interpreted as supporting the need for control of variance due to subject and task variables, not only in correlational but also in subtraction designs.

Depressive symptoms in Alzheimer disease: assessment and determinants.

Depression is difficult to assess in Alzheimer disease (AD) and controversy surrounds the prevalence, etiology, and characteristics of mood alterations in patients with this disorder. We used a variety of standardized instruments to assess mood changes in 33 patients with AD. The frequency of depression ranged from 6 to 30%, depending on the diagnostic criteria employed. No relationship was found between patient depression and dementia severity, self-awareness of cognitive deficits (as measured by a memory self-rating scale), or mood of the caregiver. Delusional patients had higher scores on mood rating scales than nondelusional patients. The results suggest that depression in AD is not severe and is unrelated to patient self-awareness of illness. We hypothesize that the cholinergic deficit of AD may ameliorate depressive symptoms.

p(C) analysis facilitates dementia diagnosis.

A modified receiver operating characteristic (ROC) analysis technique was applied to a sample of 161 consecutive volunteers seen in a dementia clinic. Clinical, imaging, neuropsychological, and laboratory evaluation guided experienced clinicians in clinical diagnosis, taken as the "gold standard." Two symptom inventories, the Hachinski Ischemic Score and the Dementia of the Alzheimer's Type Inventory, were obtained by clinicians who were blind to final clinical diagnosis; scores on these inventories correlate with the likelihoods of multi-infarct dementia and Alzheimer's disease, respectively. A disjunctive sequential testing strategy was analyzed such that subthreshold scores on the first test identified patients for whom the second test was considered. Both tests were analyzed at all possible cutoff-point combinations and in both possible testing sequences. Diagnoses based on these tests were compared with the clinical "gold standard" diagnoses to determine the accuracy of the testing procedures. The best strategy correctly classified 154/161 (95.6%) of the dementia patients and required cutoff points (5 for the HIS and 10 for the Dementia of the Alzheimer's Type Inventory) that were lower than those usually recommended for either test used alone (i.e., 7 and 14, respectively). The Hachinski Ischemic Score--then Dementia of the Alzheimer's Type Inventory testing sequence was superior to the reverse strategy. A sensitivity analysis (varying prevalences of Alzheimer's disease, multi-infarct dementia, and other dementias) revealed similar test performances across a wide range of prevalences. These data suggest that simple clinical tests that take approximately 30 minutes to administer can produce diagnostic classifications of dementia that are similar to those of clinicians experienced in dementia diagnosis.

Dementia diagnosis and therapy in the elderly.

Dementia is a devastating personal tragedy, a cause of tremendous family strife, and a significant societal dilemma both medically and economically. Appropriate evaluation and therapy of medical complications, underlying causes of intellectual compromise, and non-cognitive behavioral disturbances are important goals. Comprehensive psychological, social, and legal support complement the medical management of these patients. Research to identify the underlying pathophysiology of and to devise more effective therapies for all aspects of these syndromes is an important priority. The physician who intervenes effectively for the elderly patient with dementia is a valuable asset to patients, families and, indirectly, society.