Treatment of ballism and pseudobulbar affect with sertraline.

BACKGROUND: The pathogenesis of ballism is uncertain and may involve more than one mechanism; treatment is not always efficacious. OBJECTIVE: To provide evidence of a nondopaminergic mechanism and the potential for a prompt and nearly complete response to a serotonergic agent. METHODS: Report of 2 separate trials of sertraline hydrochloride in a single patient. RESULTS: Complete remission of symptoms within 48 hours of each drug trial. CONCLUSION: Sertraline may offer an alternative with a better adverse effect profile than dopamine receptor blockers in the treatment of patients with ballism.

Basal ganglia dysfunction, working memory, and sentence comprehension in patients with Parkinson's disease.

To investigate the role of the basal ganglia in working memory and sentence comprehension, 14 patients with Parkinson's disease (PD) were administered experimental measures of semantic and phonological working memory, and a measure of sentence comprehension, while receiving dopaminergic medications and after a period of withdrawal from these medications. An age- and education- matched control group (N=14) received the same measures. Comparison with control subjects revealed deficits in patients with PD in sentence processing regardless of medication status, but no deficits in working memory. In contrast to previous studies, withdrawal of dopaminergic medications had no significant impact on task- related working memory functions or on sentence comprehension. Results suggest that basal ganglia dysfunction does not solely account for sentence comprehension deficits seen in PD.

A neuropsychological outcome study of a child's left pericallosal arteriovenous malformation with occult fornix lesion.

Pericallosal arteriovenous malformations are rarely reported, particularly in children. Moreover, few arteriovenous malformation studies report thorough neuropsychological outcome data for assessing post-surgical functioning. This case report provides a longitudinal study of a boy who initially presented for neuropsychological testing at the age of 8 years and 1 month, following polyvinyl alcohol embolization, two craniotomies and resections and stereotactic radiosurgery for a pericallosal arteriovenous malformation involving nearly all of the corpus callosum. Follow-up magnetic resonance imaging also indicated absence of the left fornix. Functioning has been assessed over 7 years. Neuropsychological measures identified a consistent pattern of verbally mediated cognitive and memory deficits, with relatively spared visual perceptual and visual motor functioning. No evidence of a split-brain syndrome was found. The findings are consistent with insult to dominant hemisphere language and memory systems, provide an interesting example of neurodevelopmental compensation for significant early brain insult, and may provide insight into functions subserved by the fornix.

Phonology: a review and proposals from a connectionist perspective.

A parallel distributed processing (PDP) model of phonological processing is developed, including components to support repetition, auditory processing, comprehension, and language production. From the performance of the PDP reading model of Plaut, McClelland, Seidenberg, and Patterson (1996), it is inferred that the acoustic-articulatory motor pattern associator that supports repetition provides the basis for phonological sequence knowledge. From the observation that many patients make phonemic paraphasic errors in language production, as in repetition, it is argued that there must be a direct link between distributed concept representations (lexical semantic knowledge) and this network representation of sequence knowledge. In this way, both lexical semantic and phonotactic constraints are brought to bear on language production. The literature on phonological function in normal subjects (slip-of-the-tongue corpora) and in patients with aphasia is critically reviewed from this perspective. The relationship between acoustic and articulatory motor representations in the process of phonetic perception is considered. Repetition and reproduction conduction aphasia are reviewed in detail and extended consideration is given to the representation of auditory verbal short-term memory in the model. Finally, the PDP model is reconciled with information processing models of phonological processing, including that of Lichtheim, and with current knowledge of the anatomic localization of phonological processing. Although no simulations of the model were run, a number of simulation studies are proposed.

Increased discrimination of "false memories" in autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) have impaired ability to use context, which may manifest as alterations of relatedness within the semantic network. However, impairment in context use may be more difficult to detect in high-functioning adults with ASD. To test context use in this population, we examined the influence of context on memory by using the "false memory" test. In the false memory task, lists of words were presented to high-functioning subjects with ASD and matched controls. Each list consists of words highly related to an index word not on the list. Subjects are then given a recognition test. Positive responses to the index words represent false memories. We found that individuals with ASD are able to discriminate false memory items from true items significantly better than are control subjects. Memory in patients with ASD may be more accurate than in normal individuals under certain conditions. These results also suggest that semantic representations comprise a less distributed network in high-functioning adults with ASD. Furthermore, these results may be related to the unusually high memory capacities found in some individuals with ASD. Research directed at defining the range of tasks performed superiorly by high-functioning individuals with ASD will be important for optimal vocational rehabilitation.

Conceptual apraxia in probable Alzheimer's disease as demonstrated by the Florida Action Recall Test.

Patients with probable Alzheimer's disease (AD) often have difficulties associated with semantic knowledge. Therefore, conceptual apraxia, a defect of action semantics and mechanical knowledge, may be an early sign of this disease. The Florida Action Recall Test (FLART), developed to assess conceptual apraxia, consists of 45 line drawings of objects or scenes. The subject must imagine the proper tool to apply to each pictured object or scene and then pantomime its use. Twelve participants with Alzheimer's disease (NINCDS-ADRDA criteria) and 21 age- and education-matched controls were tested. Nine Alzheimer's disease participants scored below a 2-standard-deviation cutoff on conceptual accuracy, and the three who scored above the cutoff were beyond a 2-standard-deviation cutoff on completion time. The FLART appears to be a sensitive measure of conceptual apraxia in the early stages of Alzheimer's disease.

Alterations in the functional anatomy of reading induced by rehabilitation of an alexic patient.

OBJECTIVE: The goal of the study was to measure regional cerebral blood flow (CBF) in a stroke patient with acquired phonologic alexia before and after therapy using the Auditory Discrimination in Depth (ADD) program. BACKGROUND: After rehabilitation of acquired language disorders, functional imaging can detect activity in brain structures that do not mediate language during normal conditions. However, the anatomic correlates of recovery or rehabilitation from acquired reading disorders are largely undescribed. METHODS: Cerebral SPECT scans were obtained before and after the intervention with Auditory Discrimination in Depth. The first and last activation tasks necessitated that the patient read nonwords during radionuclide uptake. Another (control) scan was acquired during performance of a nonlinguistic task shortly before the end of the ADD program. RESULTS: Before therapy, the right hemisphere was inactive during nonword reading relative to the nonlinguistic task. After treatment, nonword reading increased cerebral blood flow in the posterior right perisylvian cortices homologous to the dominant hemisphere areas engaged by reading. Brain activity also increased in Broca's area of both hemispheres. CONCLUSIONS: Dyslexia rehabilitation may facilitate right-hemisphere cortical networks in the reading process and increase engagement of phonologic articulatory motor representations in Broca's area.

Effects of left frontal transcranial magnetic stimulation on depressed mood, cognition, and corticomotor threshold.

BACKGROUND: The pathophysiology of depression may include synaptic hypoactivity of left prefrontal cortex. Several groups of investigators have described improved mood associated with rapid transcranial magnetic stimulation (rTMS) but have not looked for possible cognitive side effects associated with left prefrontal magnetic stimulation. METHODS: We measured the effects of left prefrontal rTMS on mood, cognition, and motor evoked potential threshold in 10 patients with medication-resistant major depression. RESULTS: In a 2-week open trial of left prefrontal rTMS off antidepressant medications, scores on the Hamilton Rating Scale for Depression and the Beck Depression Inventory decreased by 41% and 40%, respectively. After resuming pre-rTMS antidepressant medication, improvement in mood was still significant at 1 and 3 months later. rTMS had no adverse effects on neuropsychological performance. rTMS treatments were associated with significant decreases in motor evoked potential threshold in the 9 of 10 patients who remained off psychotropic medications during the 2-week treatment period. CONCLUSIONS: These preliminary data suggest that left prefrontal rTMS is safe and improves mood in patients with medication-resistant major depression. Changes in motor evoked potential threshold suggest that prefrontal rTMS may alter brain activity at sites remote from the stimulation. Double-blind, sham-controlled studies are needed.

The effect of semantic and emotional context on written recall for verbal language in high functioning adults with autism spectrum disorder.

OBJECTIVE: Several deficits have been proposed to account for cognitive impairment in autism including an inability to comprehend the perspectives of others ("theory of mind"), an inability to process emotional information, and difficulty drawing together diverse information in context ("central coherence"). Because context (central coherence) and emotion can influence memory, a study was designed to show if autism spectrum disorder was associated with impaired utilisation of context and emotion in recall; and if impairments in theory of mind processing would influence recall in autism spectrum disorder. METHODS: Ten high functioning subjects with autism spectrum disorder and 13 age and IQ matched controls were tested using recall tests. In the first coherence memory test, subjects listened to a series of word lists that were in varying degrees of syntactic and semantic (coherent) order and were asked to recall the words. In the second coherence memory test, subjects listened to stories consisting of sentences that were, or were not, in logical (coherent) order. In the emotional memory test, the subjects listened to sentences that were highly emotional or non-emotional. In the theory of mind test, the subjects listened to stories requiring varying levels of understanding of the perspectives of others. RESULTS: There were no significant differences between groups in recall of coherent versus incoherent word lists, nor was there a significant difference between groups in recall of coherent versus incoherent stories. However, the control subjects recalled more of the emotional than non-emotional sentences, whereas the autism spectrum disorder group did not show such a difference. No significant difference existed in recall of stories requiring varying levels of understanding of the perspectives of others among subjects with autism spectrum disorder, and subjects with autism spectrum disorder did not differ from control subjects in the influence of theory of mind content on story recall. CONCLUSION: The study shows that memory in high functioning adults with autism spectrum disorder is facilitated by emotional content to a lesser degree than it is facilitated by coherence. Therefore, impairments in emotional processing cannot be considered as simply an effect of the "weak central coherence" theory in autism spectrum disorder. Whereas the reasons for this emotional deficit are unknown, evidence of abnormalities of the limbic structures in autism spectrum disorder may provide an anatomical explanation.

Functional imaging: heterogeneity in task strategy and functional anatomy and the case for individual analysis.

To learn more about the functional anatomy of language, the authors used [99mTc]HMPAO single photon emission computed tomography (SPECT) functional imaging to study nonword rhyming, lexical-semantics and syntax. The authors did not find any task-related differences in cerebral blood flow using region-by-region analysis of variance. This led them to examine individual subject's task-related patterns of cerebral blood flow. This analysis revealed regions of interest with little or no change but also regions with changes as great as 30%. There was marked subject-to-subject variability in the pattern of blood flow, which precluded statistically significant results using analysis of variance. An alternative analytic strategy based on numbers of subjects exceeding a minimum threshold task-related change in cerebral blood flow was tested and shows promise in identifying commonalities and differences in individual task-related blood flow patterns. The authors conclude that the complex and difficult to interpret pattern of blood flow changes observed in this study reflect in considerable part the combined effects of variability in task strategy, owing in part to insufficiently constrained task performance, and variability in functional anatomy. The authors also tested the differences in results achieved with simple normalization and analysis of covariance approaches and found them to be insignificant.

Subcortical aphasia.

We critically review the literature on subcortical aphasia, suggest that a number of traditional concepts regarding mechanisms of aphasia are inconsistent with now abundant data, and propose several new hypotheses. The absence of aphasia in 17 reported cases of dominant hemisphere striatocapsular infarction and the finding of nearly every conceivable pattern of language impairment in 33 different reported cases of striatocapsular infarction provide strong evidence against a major direct role of the basal ganglia in language and against disconnection or diaschisis as mechanisms of nonthalamic subcortical aphasia. However, detailed consideration of the vascular events leading to striatocapsular infarction strongly suggests that associated linguistic deficits are predominantly related to sustained cortical hypoperfusion and infarction not visible on structural imaging studies. Thalamic disconnection, as may occur with striatocapsular infarcts with extension to the temporal stem and putamenal hemorrhages, may also contribute to the language deficits in some patients. Review of the literature on thalamic infarction, in conjunction with previously unreported anatomic details of four cases, suggests that what infarcts in the tuberothalamic artery territory and the occasional infarcts in the paramedian artery territory associated with aphasia have in common is damage to the frontal lobe-inferior thalamic peduncle-nucleus reticularis-center median system that may be involved in regulating the thalamic gate in attentional processes. Disruption of attentional gating in the pulvinar and lateral posterior nuclei resulting from such lesions may impair selection of specific neuronal networks in the projection field of these nuclei that serve as the substrate for lexical-semantic function, which is in effect a disruption of a type of working memory, as defined by Goldman-Rakic. We define this as a defect of selective engagement.

Resting and stimulated states in functional imaging studies: evidence of differences in attentional and intentional set.

In a [99mTc]-hexamethylpropyleneamine oxime single photon emission computed tomography study of cerebral blood flow (CBF) in a visual activation paradigm (awake, eyes closed versus eyes open viewing a reversing checkerboard pattern), the authors systematically measured previously observed qualitative alterations in frontal blood flow associated with visual stimulation (experiment 1). They confirmed a trend toward reductions in CBF throughout precentral cortex that approached significance in areas 9 and 46, in conjunction with significant increases in CBF in postcentral cortices, including visual association area PO, and areas 3-1-2, 22, and 23. The authors posited that these changes may be related to differences in attentional and intentional state in the eyes-closed and eyes-open conditions. Such differences should be associated with alterations in motor preparedness, leading to changes in response times and to alterations in thalamocortical gating of somatosensory information, which in turn lead to changes in somatosensory-evoked potential amplitudes. In experiment 2, the authors measured simple motor response times to a 1500-Hz tone stimulus and early components of somatosensory-evoked potentials under the same experimental conditions. In the visual stimulation condition, there was a significant increase in the evoked potential amplitude (t = 2.686, p = 0.021), and a significant decrease in response time (t = -2.464, p = 0.031). These observations provided tentative support for their hypothesis. The authors also demonstrated the major effect of normalization assumptions on regional blood flow measurements.

Gaze related enhancement of hemispheric blood flow in a stroke patient.

OBJECTIVE: A patient with a right posterior cerebral artery territory infarction and a left superior quadrantanopia exhibited improvement on various visual tasks including Goldmann perimetry during extreme right gaze. The phenomenon was investigated by functional imaging of cerebral blood flow. METHODS: [(99m)Tc]HMPAO SPECT was carried out while the patient gazed to the right and to the left at an 8 Hz flash stimulus. RESULTS: When compared with left gaze, photic stimulation during right gaze was associated with an up to 39.8% increase in regional cerebral blood flow in the damaged right hemisphere, including Brodmann's areas 3-1-2, 7, 21, 22, 39, and 40. CONCLUSIONS: These gaze related alterations in function and synaptic activity suggest the engagement of a novel arousal-like mechanism that may account in part for comparable findings in patients with neglect and other disorders, and may have relevance to rehabilitation.

Adynamic aphasia: a transcortical motor aphasia with defective semantic strategy formation.

Adynamic aphasia is a form of transcortical motor aphasia characterized by sparse but otherwise normal spontaneous speech that may improve when concepts are introduced by external stimuli. Akinesia, impaired concept formation, inertia of concept generation, a defective semantic network, damage or impaired access to the verbal output lexicon, and defective semantic strategy formation have been proposed to account for this disorder. We studied a patient with adynamic aphasia and frontal lobe systems dysfunction due to bilateral striatocapsular infarctions. The patient was not akinetic but did demonstrate inertia of concept generation that could be overcome with prompting. However, prompting did not improve the number of concepts generated. He demonstrated a generally intact verbal lexicon and semantic network and normal lexical priming. However, his ability to sort closely related items into different classes without prior cuing regarding the nature of the classes was defective. Although his verbal memory was normal, he appeared to use a serial rather than a semantic strategy to recall items. Finally, despite normal lexical priming, he was impaired on a letter fluency task. These results most clearly demonstrate a defect in semantic strategy formation but indicate an additional and possibly related deficit in concept formation and a partial deficit in lexical strategy formation. All of these deficits appear to reflect impairment in the hierarchical organization of knowledge specific to the task at hand. This appears to be a key component of executive functions supported by frontal lobe systems.

Tapping, talking and the thalamus: possible influence of the intralaminar nuclei on basal ganglia function.

A patient with a discrete lesion of the left, intralaminar thalamic, nuclei exhibited a paradoxical finding with regard to finger-tapping. Normal subjects typically reduce their tapping rate when performing simultaneous verbal activity. Tapping was impaired in our patient's contralesional hand on baseline trials; however, performing the controlled oral word association (COWA) task, while finger-tapping, normalized her deficit. Subsequent experiments showed that motoric tasks rather than cognitive aspects of the COWA task were critical in potentiating finger-tapping performance. A SPECT study performed at rest revealed focal perfusion asymmetries in motor and premotor cortices. Because the caudal intralaminar nuclei project heavily to the striatum, striatal deafferentiation may account for these asymmetries. These observations provide some insight into the influences of the caudal intralaminar thalamic nuclei on basal ganglia function and the basal ganglia's influence on motor gating.

Diagnostic approach to central and peripheral nervous system vasculitis.

The diagnosis of vasculitis is first and foremost a clinical one. Correct diagnosis requires a high index of suspicion coupled with knowledge of the manifestations of other disorders that may masquerade as vasculitis. Treatment of vasculitis requires prolonged use of drugs with the potential for serious side effects. Whereas the prompt initiation of definitive treatment is a very high priority, there is also substantial risk of inappropriately treating self-limited and more benign disorders mimicking vasculitis. This has been a particular problem with primary angiitis of the central nervous system. Laboratory studies, particularly tissue biopsy, provide a crucial adjunct to clinical diagnosis.