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Biomedical subjects

Adam M Brickman

Publications and source records attributed to Adam M Brickman.

At least 37 records · Page 2Linked to original sources

Subcortical hyperintensities impact cognitive function among a select subset of healthy elderly.

Previous studies have examined the impact of subcortical hyperintensities (SH), a proxy measure of cerebrovascular disease, on the cognitive abilities of otherwise healthy older adults. However, there remains a limited understanding as to what extent this MRI marker of pathological processes explains the decline in specific cognitive functions that occur nearly ubiquitously with advanced age, especially in relation to other age-related imaging markers. In the present study we compared cognitive abilities between a sample of 53 older healthy adults (age range=50-79) and a sample of 53 younger adults (age range=21-40). As expected, the older group performed significantly worse on most cognitive measures compared to the younger group. Frontal volume and total grey matter volume were also significantly reduced among the older individuals compared to the younger individuals. SH volume was consistently associated with cognitive function in older adults, though, this relationship was evident only for a relatively small subset of older individuals with the most severe SH. These data suggest that the relationship between SH and cognition in the elderly is driven by a subset of individuals who may be in the earliest stages of vascular cognitive impairment. Further, the findings suggest that cognitive aging is largely determined by factors other than SH for most older adults.

Adolescent↗

Age-dependent change in executive function and gamma 40 Hz phase synchrony.

Decline in cognitive function is well recognized, yet few neurophysiological correlates of age-related cognitive decline have been identified. In this study we examined the impact of age on neurocognitive function and Gamma phase synchrony among 550 normal subjects (aged 11-70). Gamma phase synchrony was acquired to targets in the auditory oddball paradigm. The two tasks of executive function were switching of attention and an electronic maze. Subjects were divided into four age groups, which were balanced for sex. We hypothesized that reduced cognitive performance among older healthy individuals would be associated with age-related changes in gamma phase synchrony. Results showed a significant decrease in executive function in the oldest (51-70 years) age group. ANOVAs of age-by-frontal Gamma synchrony also showed a significant effect of age on Gamma phase synchrony in the left frontal region that corresponded modestly to the age effect found on executive task performance, with reduced performance associated with increased gamma synchrony. The results indicate that age-related changes in cognitive function evident among elderly individuals may in part be related to decreased ability to integrate information and this may be reflected as a compensatory increase in gamma synchrony in frontal regions of the brain.

Adolescent↗

Apathy is associated with volume of the nucleus accumbens in patients infected with HIV.

Apathy refers to a reduction in self-initiated behavior, and it is commonly reported by patients infected with human immunodeficiency virus (HIV). It remains unclear whether apathy among HIV patients reflects a direct effect of the virus on subcortical brain circuits or a secondary neuropsychiatric symptom. In the present study we examined the relationship between ratings of apathy and quantitative analysis of the nucleus accumbens (NA), a subcortical brain structure that regulates initiation of behavioral activation. Twelve HIV-positive individuals without dementia were administered the Marin Apathy Scale and underwent neuroimaging. Voxel-based quantification of the nucleus accumbens was completed using a segmentation protocol. Results of our study revealed that increased ratings of apathy were significantly correlated with lower volume of the nucleus accumbens. By contrast, ratings of depression were unrelated to either apathy or nucleus accumbens volume. These findings provide preliminary evidence that apathy reflects direct involvement of the central nervous system in patients with HIV.

Adult↗

Correlations between MRI-assessed volumes of the thalamus and cortical Brodmann's areas in schizophrenia.

BACKGROUND: We compared the thalamic-cortical volumetric correlational patterns in patients with schizophrenia and normal comparison subjects, and evaluated their relations to outcome. METHODS: High-resolution MR images were acquired in patients with schizophrenia (n=106) and normal comparison subjects (n=42). Patients were divided into good-outcome (n=52) and poor-outcome (Kraepelinian, n=54) subtypes based on their ability for self-care. Correlations between the relative gray and white matter volumes of the individual cortical Brodmann's areas and five dorsoventral levels of the thalamus were assessed. RESULTS: Compared to normal subjects, schizophrenia patients lacked significant thalamic gray matter volume correlations with the prefrontal and medial temporal cortical regions in the right hemisphere, and with frontal, cingulate, posterior parietal and occipital regions in the left hemisphere, while normal white matter volume cortical-thalamic correlations along the cingulate gyrus and in the temporal lobe were not found in schizophrenia patients in both hemispheres. In contrast to both normal comparison subjects and good-outcome group, schizophrenia patients with poor outcomes showed significant bilateral gray matter volume correlations between the dorsal thalamus and ventral prefrontal cortex, while the group differences in the white matter volume correlations were mostly restricted to the cingulate arch. CONCLUSIONS: Whereas patients with schizophrenia exhibit deficiencies in cortical-thalamic correlational patterns, poor outcome is associated with abnormal interregional correlations not observed in either normal subjects or patients with good outcomes. This latter finding may be explained by a core neurodevelopmental disturbance that results in aberrant cortical-thalamic connectivity in poor-outcome schizophrenia.

Adult↗

Thalamus size and outcome in schizophrenia.

The size of the thalamus was assessed in 106 patients with schizophrenia and 42 normal controls using high-resolution magnetic resonance imaging. The thalamus was traced at five axial levels proportionately spaced from dorsal to ventral directions. Patients with schizophrenia had significantly smaller thalamic areas at more ventral levels. Thalamic size was positively associated with frontal lobe and temporal lobe size. The effects were most marked in the patients with poorer clinical outcome (i.e., "Kraepelinian" patients). These findings are consistent with post-mortem and MRI measurement suggesting reduction in volume of the pulvinar, which occupies a large proportion of the ventral thalamus and which has prominent connections to the temporal lobe.

Adult↗

Neuropsychological functioning in first-break, never-medicated adolescents with psychosis.

The purpose of the current study was to examine neuropsychological functioning in a group of never-medicated first-break adolescents with psychosis. It is the first report of cognition in a sample of adolescents with psychosis in which all patients were drug-naive. Twenty-nine adolescent patients (mean age = 16.07; SD = 2.00; 15 male and 14 female patients) experiencing their first psychotic episode and 17 age-matched and sex-matched normal volunteers (mean age = 16.88; SD = 2.39; 9 male and 8 female subjects) were recruited and assessed with a neuropsychological battery. Measures of attention, memory, language, executive functioning, perceptual motor processing, and motor speed were obtained. Psychiatric symptomatology, estimated verbal IQ, and parental socioeconomic status were also determined. Patients with psychosis were significantly more impaired than normal volunteers; effect sizes were greatest in the areas of executive functioning, attention, and memory, and significantly smaller in areas of language, perceptual motor processing, and motor speed. The pattern was not altered when differences in verbal IQ and parental socioeconomic status were controlled. Sex and age interactions indicated that younger male patients were particularly impaired. The findings demonstrate neuropsychological deficits in adolescents with psychosis and suggest that cognitive deficits are core symptoms in psychotic disorders.

Adolescent↗

Abnormal glucose metabolism in the mediodorsal nucleus of the thalamus in schizophrenia.

OBJECTIVE: Three thalamic nuclei--the mediodorsal nucleus, pulvinar, and centromedian nucleus--each have unique reciprocal circuitry with cortical and subcortical areas known to be affected in schizophrenia. To determine if the disorder is also associated with dysfunction in the mediodorsal nucleus, pulvinar, and centromedian nucleus, relative glucose metabolism in these regions was measured in a large group of unmedicated patients with schizophrenia. METHOD: [18F]-deoxyglucose positron emission tomography (PET) and matching T1-weighted magnetic resonance imaging (MRI) scans were obtained for 41 unmedicated patients with schizophrenia and 60 age- and sex-matched healthy subjects. The PET and MRI images for each subject were coregistered, and the whole thalamus, mediodorsal nucleus, pulvinar, and centromedian nucleus were traced on the MRI image. Relative glucose metabolism in these regions was assessed. RESULTS: Patients with schizophrenia showed significantly lower relative glucose metabolism in the mediodorsal nucleus and the centromedian nucleus and significantly higher relative glucose metabolism in the pulvinar, compared with the healthy subjects. Lower relative glucose metabolism in the total thalamus, mediodorsal nucleus, and pulvinar was associated with greater overall clinical symptoms as measured by the Brief Psychiatric Rating Scale. Lower relative glucose metabolism in the pulvinar was associated with more hallucinations and more positive symptoms, while lower relative glucose metabolism in the mediodorsal nucleus was associated with more negative symptoms. CONCLUSIONS: The findings suggest that patients with schizophrenia exhibit dysfunction in thalamic subdivisions with distinct cortical connections and that these thalamic subdivisions have specific associations with clinical symptoms.

Adolescent↗

Depression in autopsy-confirmed dementia with Lewy bodies and Alzheimer's disease.

Depression has frequently been cited as a manifestation of dementia with Lewy bodies (DLB). Previous studies have suggested an increase of depression in patients with DLB, compared to those with Alzheimer's disease (AD). The purpose of this study was to examine depressive symptomatology in nursing home residents, from a consecutive series of DLB (n=16) and AD (n=39) autopsy-confirmed cases. Subjects received standard neuropathological analysis and postmortem chart review for clinical assessment of depression. Depressive symptomatology did not differ between the AD and DLB groups, and there was no significant relationship between depression and cortical or subcortical Lewy body (LB) count in the locus ceruleus or substantia nigra. This study suggests that the presence or absence of depression cannot be used to distinguish between AD and DLB. Furthermore, depressive symptomatology in DLB does not appear to be related to severity of cortical or subcortical LB pathology.

Aged↗

Caudate and putamen volumes in good and poor outcome patients with schizophrenia.

Magnetic resonance images of 37 patients with schizophrenia and 37 age- and sex-matched volunteers were acquired. The caudate nucleus and putamen were traced on axial slices from the most superior extent of the caudate to the most inferior point where the caudate and putamen merge. Two subtypes of schizophrenia were compared, the Kraepelinian subtype (n=13), characterized by an unremitting and severe course, and the non-Kraepelinian subtype (n=24), characterized by a remitting course and some periods of self-care. Patients with good outcome schizophrenia had larger relative mean putamen size (0.0129) than poor outcome patients (0.0123) or normal controls (0.0121), but not caudate size. This enlargement was most marked for the dorsal putamen and right hemisphere. Striatal size was not related to whether patients were currently being treated with atypical or typical neuroleptics or whether they had been predominantly treated with typical or atypical neuroleptics over the past 3 years. This suggests the possibility that the expansion of putamen size may be a physiological correlate of neuroleptic responsiveness or that small putamen size at disease onset may be a predictor of outcome.

Adult↗

Distinct serial position profiles and neuropsychological measures differentiate late life depression from normal aging and Alzheimer's disease.

Geriatric depression is associated with cognitive deficits that share similar features with Alzheimer's disease (AD) and normal aging. This study examined cognitive profiles and serial position effects in patients with geriatric depression (N=20) or AD (N=32) and in elderly controls (N=18). Groups were compared on two measures of serial position of the California Verbal Learning Test (CVLT), scaled scores and regional scores. Newly devised regional scores measure the percentage of items recalled as a function of the possible number of items presented from three regions of the list. Regional scores significantly differentiated depressed from control groups, with reduction of recalled items from the middle region. Scaled scores distinguished the depression from the AD groups on primacy and recency regions, with the characteristic recency effect seen in the AD group. Deficits in regional scores of the middle region are discussed in the context of lower resources in depression.

Aged↗

Magnetic resonance imaging of mediodorsal, pulvinar, and centromedian nuclei of the thalamus in patients with schizophrenia.

BACKGROUND: Postmortem and magnetic resonance imaging (MRI) data have suggested volume reductions in the mediodorsal (MDN) and pulvinar nuclei (PUL) of the thalamus. The centromedian nucleus (CMN), important in attention and arousal, has not been previously studied with MRI. METHODS: A sample of 41 patients with schizophrenia (32 men and 9 women) and 60 healthy volunteers (45 men and 15 women) underwent assessment with high-resolution 1.2-mm thick anatomical MRI. Images were differentiated to enhance the edges and outline of the whole thalamus, and the MDN, PUL, and CMN were outlined on all slices by a tracer masked to diagnostic status. RESULTS: Significantly smaller volumes of the MDN and PUL were found in patients with schizophrenia compared with controls. Volume relative to brain size was reduced in all 3 nuclei; differences in relative reduction did not differ among the nuclei. The remainder of the thalamic volume (whole thalamus minus the volume of the 3 delineated nuclei) was not different between schizophrenic patients and controls, indicating that the volume reduction was specific to these nuclei. Volume relative to brain size was reduced in all 3 nuclei and remained significant when only patients who had never been exposed to neuroleptic medication (n = 15) were considered. For the MDN, women had larger relative volumes than men among controls, but men had larger volumes than women among schizophrenic patients. CONCLUSIONS: Three association regions of the thalamus that have reciprocal connectivity to schizophrenia-associated regions of the cortex have significantly smaller volumes on MRI in patients with schizophrenia.

Adolescent↗

Selective attention, inhibition for repeated events and hemispheric specialization.

When two visual events appear consecutively in the same spatial location, our response to the second event is slower than to the first. This inhibition for repeated events may reflect a bias toward sampling novel locations, a bias useful for exploring visual space. It has been shown that the left hemisphere is more specialized in selective attentional processes than the right one. The aim of the present experiment was to test if this hemispheric specialization for selective attention may also affect the inhibition for repeated events. For this purpose, we asked 11 normal subjects to perform an identity-based discrimination task in which the target to be detected could appear alone or surrounded by flanking letters, in the left or in the right visual field. Results show that inhibition for repeated events is present only when selective attention is required and when the task is performed in the right specialized visual field.

Adult↗

Striatal size, glucose metabolic rate, and verbal learning in normal aging.

The striatum has recently been implicated as an area that may mediate age-associated cognitive decline because of diminution of volume and functional activity. We used 18F-fluorodeoxyglucose (FDG) with positron emission tomography (PET) and high-resolution magnetic resonance imaging (MRI) to examine the effects of age on striatal glucose metabolic rate and size in 70 healthy, normal subjects. During the FDG tracer uptake period, subjects performed a serial verbal learning task, based on the California Verbal Learning Test. PET images were co-registered to the MR images. The interrelations among striatal glucose metabolic rate, size, and performance on the verbal learning task were examined with repeated-measures analysis of variance and correlational analysis. As age increased, relative glucose metabolic rate (GMR) increased in the putamen and decreased in the caudate. Female subjects had lower relative GMR than male subjects in the caudate, but equal in the putamen. Striatal size remained relatively constant across the lifespan in men but was lower in women aged 50-70 than in men. While there were significant associations between striatal activity and performance on the uptake task, these findings were mostly accounted for by age. The findings are consistent with our earlier report on the same cohort that demonstrated an age-related shift from anterior to posterior cortical metabolism, as the putamen receives primarily posterior cortical input and the caudate receives relatively more anterior cortical input. Findings of significant involvement of striatal functioning in verbal learning are most likely accounted for by age and suggest an age-related shift from anterior to posterior circuitry in the human telencephalon.

Adult↗

MRI assessment of gray and white matter distribution in Brodmann's areas of the cortex in patients with schizophrenia with good and poor outcomes.

OBJECTIVE: High-resolution magnetic resonance imaging (MRI) was used to compare cortical gray and white matter and CSF volumes in schizophrenia patients with poor outcomes, schizophrenia patients with good outcomes, and healthy comparison subjects. METHOD: T(1)-weighted, 1.2-mm-thick MR images were acquired for 37 patients with schizophrenia and 37 healthy, age- and sex-matched comparison subjects. The patients were assigned to subgroups with poor outcomes (N=13) and good outcomes (N=24) on the basis of clinical characteristics. Poor-outcome patients were those who were continuously hospitalized or completely dependent on others for basic needs, were unemployed, and had severe negative symptoms and severe formal thought disorder. The MR images were reoriented to standard position parallel to the anterior commissure-posterior commissure line and segmented into CSF, gray matter, and white matter tissue types. The tissue types were assigned to Brodmann's areas by using the Perry postmortem histological atlas, and tissue-type volumes in the three subject groups were compared. RESULTS: Compared to the healthy subjects, the overall patient group had a significantly smaller mean cortical gray matter volume and significantly larger mean CSF volume, especially in the frontal lobe and left temporal lobe. The smaller frontal lobe volume in schizophrenia was confirmed for unadjusted volumes and for volumes with adjustment for whole brain volumes. Compared to patients with good outcomes, patients with poor outcomes (Kraepelinian schizophrenia) had significantly smaller gray matter volumes in the temporal and occipital lobes, but no difference between groups was found for total frontal lobe volume. Only 21% of the healthy subjects had volumes 0.5 standard deviations below the mean for healthy subjects in any area of the frontal or temporal lobes, compared with 62% of poor-outcome patients. CONCLUSIONS: Poor outcome in patients with schizophrenia may be associated with a more posterior distribution (posteriorization) of gray matter deficits across widely distributed cortical regions.

Activities of Daily Living↗

Acoustical analysis of posed prosodic expressions: effects of emotion and sex.

Prosodic expression is an important channel of emotional communication and can be assessed through computerized acoustical analysis. Fundamental frequency (F0) is the most commonly studied acoustic measure and considered the best index of perceived pitch. In this study, we examined two factors that can influence prosodic expression, sex and emotion type. A special feature is the use of a neutral expression as a control measure. We also described procedures for eliciting posed prosodic expression via an experimental task from the New York Emotion Battery. Subjects were healthy men (n=10) and women (n=9), matched for age (M=29.2 yr.) and education (M=15.6 yr.). Subjects were asked to intone neutral-content sentences with happy, sad, and neutral prosody. F0 mean and standard deviation were measured using the Computerized Speech Lab program. Initial findings indicated that women produced significantly higher F0 values than did men and that happy sentences were produced with significantly higher F0 values than were sad sentences. When semitone conversions were applied and neutral prosody was subtracted out, differences remained for emotion type but not for sex. Findings are discussed in terms of implications for the assessment and treatment of prosody in clinical populations.

Adult↗

Longitudinal assessment of patient dependence in Alzheimer disease.

BACKGROUND: The Dependence Scale measures the amount of assistance patients with dementia require in performing daily activities. Validity and reliability of this scale have been demonstrated, but the progression throughout long periods in patients with Alzheimer disease (AD) has not previously been examined. OBJECTIVE: To determine the longitudinal course of patient dependence in a cohort of prospectively followed AD patients. METHODS: Two hundred thirty AD patients enrolled in the Predictors Study were followed up prospectively at 6-month intervals for an average of 6.5 visits. The Dependence Scale was administered to a caregiver, and patients were assessed with the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale. Dependence level and the additive sum of the Dependence Scale items were considered for analysis. RESULTS: Generalized estimating equations to regression analyses were used to determine that both Dependence Scale scores and dependence level significantly decline with time. By covarying mMMSE scores and self-care deficits factor scores of the Blessed Dementia Rating Scale, generalized estimating equations analysis also demonstrated that change in patient dependence was independent of global cognitive decline and other measures of activities of daily living, respectively. CONCLUSIONS: This study shows the validity of the Dependence Scale and demonstrated that dependency in AD significantly declines with time independent of global cognition and other self-care deficits. The scale is a valuable instrument for outcomes research, efficacy trials, and behavioral research in AD.

Activities of Daily Living↗

The prevalence, diagnosis and treatment of depression in dementia patients in chronic care facilities in the last six months of life.

OBJECTIVE: To assess the prevalence, diagnosis and treatment of depression among dementia patients and normal controls in chronic care facilities in the last six months of life. METHOD: We reviewed perimortal data concerning dementia severity, depressive symptoms and diagnoses, and medication use for 279 dementia patients and 24 normal controls brought to autopsy through an Alzheimer's Disease Resource Center. RESULTS: Major depression was highly prevalent among both dementia patients and normal controls in chronic care facilities in the last six months of life. This depression was under-diagnosed by physicians. Documentation of depressive symptoms by medical support staff has improved over time. However, physician diagnosis of depression has not improved. Recognition of depression was significantly lower for patients with severe dementia. Depression was under-treated in both dementia patients and normal controls, although treatment rates may be increasing. Anxiolytics and hypnotics were often used in lieu of, or in addition to, antidepressant therapy. CONCLUSIONS: Major depression was highly prevalent in both dementia patients and normal controls, indicating that depression is an important issue for the elderly in the last six months of life irrespective of cognitive status. Under-diagnosis of depression may be an important clinical issue. As physician diagnosis of depression has not improved with time, further physician training and/or awareness initiatives may be warranted. Depression, a treatable cause of excess morbidity and mortality, was undertreated in all groups studied. However, treatment rates may be improving. The prevalent use of anxiolytics and hypnotics for depressed patients is problematic.

Aged↗

Emotional processing deficits in individuals with unilateral brain damage.

This article presents a review of the neural mechanisms underlying emotional processing deficits (EPDs) in individuals with unilateral brain damage. First, key theoretical issues pertaining to the neuropsychology of emotion are presented. These include parameters of emotional processing, the componential approach, emotional domains, and hypotheses regarding hemispheric specialization for emotion. Second, the literature on hemispheric asymmetries for emotion is reviewed in terms of processing mode (perception and expression) and communication channel (facial, prosodic-intonational, and lexical-verbal). Studies involving normal adults and individuals with right- or left-sided brain damage are reviewed. Third, recent findings identifying the role of the right hemisphere in emotional processing are described. The article is concluded by aligning these new data with findings from the general literature, providing added support for the right-hemisphere emotion hypothesis.

Adult↗