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Biomedical subjects

Thomas W McAllister

Publications and source records attributed to Thomas W McAllister.

At least 19 recordsLinked to original sources
PubMed2006

Mechanisms of working memory dysfunction after mild and moderate TBI: evidence from functional MRI and neurogenetics.

Cognitive complaints are a frequent source of distress and disability after mild and moderate traumatic brain injury (TBI). While there are deficits in several cognitive domains, many aspects of these complaints and deficits suggest that problems in working memory (WM) play an important role. Functional imaging studies in healthy individuals have outlined the neural substrate of WM and have shown that regions important in WM circuitry overlap with regions commonly vulnerable to damage in TBI. Use of functional MRI (fMRI) in individuals with mild and moderate TBI suggests that they can have problems in the activation and allocation of WM, and several lines of evidence suggest that subtle alterations in central catecholaminergic sensitivity may underlie these problems. We review the evidence from fMRI and neurogenetic studies that support the role of catecholaminergic dysregulation in the etiology of WM complaints and deficits after mild and moderate TBI.

Brain Injuries↗
PubMed2006

Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury.

There is currently a lack of evidence-based guidelines to guide the pharmacological treatment of neurobehavioral problems that commonly occur after traumatic brain injury (TBI). It was our objective to review the current literature on the pharmacological treatment of neurobehavioral problems after traumatic brain injury in three key areas: aggression, cognitive disorders, and affective disorders/anxiety/ psychosis. Three panels of leading researchers in the field of brain injury were formed to review the current literature on pharmacological treatment for TBI sequelae in the topic areas of affective/anxiety/ psychotic disorders, cognitive disorders, and aggression. A comprehensive Medline literature search was performed by each group to establish the groups of pertinent articles. Additional articles were obtained from bibliography searches of the primary articles. Group members then independently reviewed the articles and established a consensus rating. Despite reviewing a significant number of studies on drug treatment of neurobehavioral sequelae after TBI, the quality of evidence did not support any treatment standards and few guidelines due to a number of recurrent methodological problems. Guidelines were established for the use of methylphenidate in the treatment of deficits in attention and speed of information processing, as well as for the use of beta-blockers for the treatment of aggression following TBI. Options were recommended in the treatment of depression, bipolar disorder/mania, psychosis, aggression, general cognitive functions, and deficits in attention, speed of processing, and memory after TBI. The evidence-based guidelines and options established by this working group may help to guide the pharmacological treatment of the person experiencing neurobehavioral sequelae following TBI. There is a clear need for well-designed randomized controlled trials in the treatment of these common problems after TBI in order to establish definitive treatment standards for this patient population.

Aggression↗
PubMed2006

Increased brain activation during working memory in cognitively intact adults with the APOE epsilon4 allele.

OBJECTIVE: Altered patterns of brain activity during cognitive tasks have been demonstrated using functional magnetic resonance imaging (fMRI) in mild cognitive impairment and Alzheimer's disease. However, there have been few studies of adults at genetic risk for Alzheimer's disease prior to the onset of symptoms. The purpose of this study was to determine whether brain activation patterns associated with working memory differ as a function of apolipoprotein E (APOE) genotype in cognitively intact adults. METHOD: Participants were cognitively intact, healthy adults who completed genotyping, comprehensive neuropsychological testing, and structural and functional neuroimaging. Twenty-two participants had the APOE epsilon3/epsilon3 genotype, and 13 participants had the APOE epsilon3/epsilon4 genotype. The study employed an auditory verbal N-back task to probe working memory-related brain activity. RESULTS: The epsilon3/epsilon3 and epsilon3/epsilon4 groups did not differ in demographic characteristics, cognitive ability, mood, or in-scanner task performance. The epsilon3/epsilon4 group showed greater activity during working memory in the medial frontal and parietal regions bilaterally and in the right dorsolateral prefrontal cortex. There were no regions in which the epsilon3/epsilon3 group showed greater activation than the epsilon3/epsilon4 group. CONCLUSIONS: These results indicate that differences in brain activity are evident in cognitively intact individuals who are at risk for late-onset Alzheimer's disease by virtue of their APOE allele status. As neuroprotective interventions become available, early detection will increase in importance. The combination of genetic and functional neuroimaging strategies may prove useful for monitoring individuals at risk for Alzheimer's disease before the onset of cognitive symptoms.

Adult↗
PubMed2005

The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among disorders of mood and affect. Proceedings of a roundtable meeting.

This monograph summarizes the proceedings of a roundtable meeting convened to discuss pseudobulbar affect (PBA). Two didactic lectures were presented followed by a moderated discussion among 11 participants. Post-meeting manuscript development synthesized didactic- and discussion-based content ad incorporated additional material from the neuroscience literature. A conceptual framework with which to distinguish between disorders of mood and affect is presented first, and disorders of affect regulation are then reviewed briefly. A detailed description of the most common of these disorders, PBA, is the focus of the remainder of the monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA are reviewed, and current and emerging methods of evaluation and treatment of persons with PBA are discussed. The material presented in this monograph will help clinicians better recognize, diagnose, and treat PBA, and will form a foundation for understanding and interpreting future studies of this condition.

Diagnosis, Differential↗
PubMed2005

Effect of the dopamine D2 receptor T allele on response latency after mild traumatic brain injury.

OBJECTIVE: The authors tested the hypothesis that the dopamine D2 receptor T allele (formerly described as the A1 allele) would be associated with poorer performance on memory and attention tasks following mild traumatic brain injury. METHOD: Thirty-nine patients with mild traumatic brain injury and 27 comparison subjects were genotyped. All subjects completed memory and attention tests, including the California Verbal Learning Test recognition task and the Continuous Performance Test. RESULTS: In both groups the T allele was associated with poorer performance on the California Verbal Learning Test recognition task. There was also a significant diagnosis-by-allele interaction on measures of response latency (Continuous Performance Test): the subjects with mild traumatic brain injury and the T allele had the worst performance. CONCLUSIONS: Genetic polymorphisms modulating central dopaminergic tone can affect cognitive outcome following mild traumatic brain injury.

Adult↗
PubMed2004

Cognitive effects of cytotoxic cancer chemotherapy: predisposing risk factors and potential treatments.

Increasing evidence suggests that systemic cancer chemotherapy can have significant long-term effects on cognition, particularly on verbal learning, memory, attention, and speed of information processing. These deficits can be a source of significant distress to survivors. There is much less known about the mechanisms, predisposing vulnerabilities, and treatment of these deficits. We will summarize current knowledge of chemotherapy-associated cognitive deficits. Emerging theories about the role of selected genetic polymorphisms in heightening the vulnerability to chemotherapy-induced cognitive decline will be described.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Neuropsychiatric syndromes in adults with intellectual disability: issues in assessment and treatment.

The purpose of this article is to present a survey of important neuropsychiatric issues and recent findings regarding the evaluation and treatment of neuropsychiatric symptoms and syndromes in patients with intellectual disability (ID). The cause of ID, environmental or genetic, can be determined in few patients. Etiology is idiopathic in most patients. ID and psychiatric illness are not mutually exclusive; individuals with ID have increased rates of psychiatric illness. Although recognition of significant axis I psychopathology is important, not all challenging behaviors in persons with ID will have a clear axis I diagnosis. Psychologic, behavioral, and environmental treatments are appropriate measures, but pharmacotherapy often is needed. Our experience has shown us that the more severe, disruptive, and dangerous the behavior, the stronger the indication for empirical drug treatment trials. Community-based models of support with neuropsychiatric intervention can be a potent therapeutic combination in the management of challenging behaviors in individuals with ID.

Adult↗
PubMed2004

Working memory deficits after traumatic brain injury: catecholaminergic mechanisms and prospects for treatment -- a review.

PRIMARY OBJECTIVE: To review the neural circuitry and neurochemistry of working memory and outline the evidence for working memory deficits after traumatic brain injury, and the evidence for the use of catecholaminergic agents in the amelioration of these deficits. Current knowledge gaps and research needs are identified. MAIN OUTCOMES AND RESULTS: Impairments in working memory are a core component of the cognitive deficits associated with traumatic brain injury. Recent progress in understanding the neural circuitry and neurochemistry of working memory suggests that catecholamines play a central role in the activation and regulation of working memory and thus lays a framework in which to consider the use of catecholaminergic agents (dopaminergic and alpha-2 adrenergic agonists) in the treatment of specific cognitive deficits after traumatic brain injury. CONCLUSIONS: The combined methods of cognitive neuroscience, functional brain imaging and neuropharmacology are proposed as an excellent method for studying working memory deficits. A strong rationale exists for the targeted use of catecholaminergic agonists in the treatment of working memory deficits after traumatic brain injury.

Adrenergic alpha-Agonists↗
PubMed2004

Apathy in schizophrenia: reduced frontal lobe volume and neuropsychological deficits.

OBJECTIVE: Apathy is a common negative symptom in schizophrenia. The authors investigated neuropsychological performance and regional brain volumes in schizophrenia patients with high versus low levels of apathy. METHOD: Schizophrenia patients with low apathy levels (N=18) and high apathy levels (N=20) and 12 healthy comparison subjects completed neuropsychological testing as well as magnetic resonance imaging scanning to obtain lobar volumes after total intracranial volume was controlled. RESULTS: The high apathy group scored lower than comparison subjects on rapid visuomotor sequencing and verbal learning/recall. The high apathy group had lower performance IQ scores than the low apathy and comparison groups. Only the high apathy group showed significantly reduced bilateral frontal lobe volumes relative to comparison subjects; both schizophrenia patient groups showed bilateral temporal lobe volume reductions. CONCLUSIONS: The present findings are consistent with studies in other disorders showing frontal lobe involvement in apathy.

Adult↗
PubMed2003

Genetic polymorphisms in the expression and treatment of neuropsychiatric disorders.

Recent advances in molecular genetics have greatly increased the understanding of the pathophysiology of certain neurobehavioral disorders and the core symptoms of these disorders. This paper reviews key concepts important in understanding the genetics of neuropsychiatric disorders, and gives an overview of several different types of genetic disorders, including trinucleotide repeat disorders, and functional polymorphisms of monoamine neurotransmitter systems.

Animals↗
PubMed2003

Complex partial seizures and depression.

A long-recognized association exists between epilepsy and affective disturbance, especially depression. People with complex partial seizures that result from temporal lobe seizure foci are highly vulnerable to psychiatric disorders. Accurate diagnosis of such disorders is an important key to treatment. Interictal depression or dysphoria is the most clinically significant problem of this type. Pharmacotherapeutic treatments that have positive effects in other types of depressive illness are also effective for depression associated with epilepsy. Electroconvulsive therapy is helpful to some patients with depression that is refractory to drug treatment or psychotherapy. Surgical resection of seizure foci may lead to psychiatric improvement for some individuals, but can also have psychiatric complications.

Anticonvulsants↗
PubMed2002

Functional magnetic resonance imaging: emerging clinical applications.

Functional magnetic resonance imaging (fMRI) is a relatively new and noninvasive method of functional brain mapping. Functional MRI is increasingly being applied to the study of neuropsychiatric disorders, including schizophrenia, Alzheimer's disease, traumatic brain injury, and others. Particularly noteworthy are findings related to plasticity in the adult human brain. Despite the promise of fMRI for improving the conceptualization, assessment, and treatment of neuropsychiatric disorders, important technical and scientific issues remain. Future research will address integrating fMRI with other emerging neuroimaging techniques.

Brain↗
PubMed2002

Evaluation and treatment of postconcussive symptoms.

Postconcussive symptoms such as headache, dizziness, irritability, and difficulties with memory and attention are reported frequently after traumatic brain injuries (TBI) of all severities. The etiology of these symptoms in individuals with mild TBI has been a subject of some controversy with theories ranging from neural damage to malingering. Furthermore, although the term postconcussive syndrome is commonly used clinically and in the scientific literature, it is not clear that postconcussive symptoms constitute a syndrome per se. Instead, it may be the case that the various symptoms that commonly co-occur after TBI are relatively independent consequences of a single neurological event. In other words, because the locations and severity of injury vary between individuals despite ostensibly similar injuries, it follows that there should be variations in symptom type and severity between individuals as well. This article reviews the sequelae and natural course of recovery from mild TBI, the evidence regarding both persistent postconcussive symptoms and the postconcussive syndrome, and outlines an approach to the assessment and treatment of individuals with these symptoms after TBI.

Brain Injuries↗