Biomedical subjects

A Pfefferbaum

Publications and source records attributed to A Pfefferbaum.

At least 73 records · Page 4Linked to original sources

PubMed1998

Structural MRI correlates of recognition memory in Alzheimer's disease.

Neuroimaging and lesion studies have demonstrated that hippocampal volume correlates with memory performance, but material-specific lateralization of this structure-function relationship has been inconsistent. This MRI study examined the relative contributions of left and right temporal lobe volumes to verbal and nonverbal recognition memory in a group of 20 Alzheimer's disease (AD) patients. There was a significant relationship between extent of right hippocampal and right temporal gray matter tissue volume deficit and performance on the face recognition subtest of the Warrington Recognition Memory Test. The face recognition test correlated with right hemisphere volume but not to left, indicating a material-specific relationship between brain structure and function in this patient group. Right temporal horn volume did not account for a significant proportion of variance in face recognition memory. Although word recognition was not significantly correlated with either left or right hippocampal volume in the total group, there was a strong correlation between left hippocampal volume and word recognition memory in the female AD patients. Thus, face recognition shows a material specific relationship with select lateralized hippocampal and temporal cortical volumes in AD patients, regardless of gender, whereas the verbal recognition-left-hippocampal volume relationship may be mediated by gender.

Adult↗

PubMed1998

A profile of cortical gray matter volume deficits characteristic of schizophrenia.

Quantitative magnetic resonance imaging (MRI) studies from our laboratory have reported that patients with schizophrenia show a widespread cortical gray matter volume deficit, which is especially pronounced in the prefrontal and anterior superior temporal cortices. The present study compared two separate samples of schizophrenic patients -- 71 men from a Veterans Administration (VA) hospital and a sample of 57 severely ill men from a state hospital (SH) -- in an effort to test whether the pattern of brain volume abnormalities previously observed in VA schizophrenic patients can be generalized to other groups of schizophrenic patients. MRI-derived brain volumes of gray matter, white matter and sulcal cerebrospinal fluid (CSF) in six cortical regions, and CSF in the lateral and third ventricles were computed. All MRI volumes were adjusted for normal variation in head size and age and were expressed as standardized Z-scores, which also permitted structures of different sizes to be compared directly. The two schizophrenic groups displayed similar patterns of volume abnormalities: cortical gray matter but not white matter volume deficits that were widespread but especially notable in the prefrontal and temporal regions. The regional gray matter deficits in the SH group were generally greater than those in the VA group, particularly in the prefrontal and posterior superior temporal regions. Both schizophrenic groups had abnormally large volumes of the cortical sulci and lateral and third ventricles; however, the SH group showed greater enlargements, the most prominent occurring in the ventricles and temporal sulci. The overlapping patterns of cortical gray matter deficits in the two groups provide evidence for generality of this pattern of regional brain volume abnormalities in schizophrenia.

Adult↗

PubMed1998

Differential contributions of cognitive and motor component processes to physical and instrumental activities of daily living in Parkinson's disease.

Patients with Parkinson's disease (PD) become dependent upon caregivers because motor and cognitive disabilities interfere with their ability to carry out activities of daily living (ADLs). However, PD patients display diverse motor and cognitive symptoms, and it is not yet known which are most responsible for ADL dysfunction. The purpose of this study was to identify the contributions that specific cognitive and motor functions make to ADLs. Executive functioning, in particular sequencing, was a significant independent predictor of instrumental ADLs whereas simple motor functioning was not. By contrast, simple motor functioning, but not executive functioning, was a significant independent predictor of physical ADLs. Dementia severity, as measured by the Dementia Rating Scale, was significantly correlated with instrumental but not physical ADLs. The identification of selective relationships between motor and cognitive functioning and ADLs may ultimately provide a model for evaluating the benefits and limitations of different treatments for PD.

Journal Article↗

PubMed1997

Quantification of cerebellar structures with MRI.

Methodological issues have limited neuroimaging studies of cerebellar structures. In this article we describe a method that addresses some of these limitations and phantom studies that examine the validity of the image manipulations. We compared volumes derived from 3D Spoiled Gradient Recalled Acquisition MR images sliced with respect to three different alignment methods: one based on cerebellar landmarks, another on cerebral landmarks and a third on the plane of acquisition. Examination of coefficients of variation, coefficients of error and convergent validity suggests that although regional cerebellar volumes based on cerebellar landmarks provide the best estimates of the true volumes, observed differences between volume measurements from alignments based on cerebellar or cerebral landmarks were generally not significant and were inconsequential. In this case, the measure was improved with alignment along local, relevant cerebellar landmarks. A set of phantom experiments showed that realignment, reslicing and interpolation in 3-dimensional image processing exerted, at most, trivial distortion on the estimates of actual object volumes.

Adult↗

PubMed1997

Deficits in multiple systems of working memory in schizophrenia.

Working memory, the ability to hold and manipulate information 'on-line' in a temporary memory store, is impaired in schizophrenia. This impairment may be characterized within the framework of two opposing theoretical models: (1) central executive as coordinator of component processes of working memory or (2) multiple independent systems of spatial and object memory. In order to test which of these models better explains the working memory deficit of schizophrenia, 14 schizophrenic patients and 12 age- and gender-matched control subjects performed tests of spatial memory (dot location), object memory (shapes, color dots) and a dual paradigm (dot location + shapes). If schizophrenia impairs the central executive, a group-by-task interaction would demonstrate excessively worse performance on the dual than single tasks in schizophrenics relative to controls; however, the absence of an interaction would be consistent with deficits in the multiple working memory systems. The schizophrenic group was significantly impaired on all measures, and both the schizophrenic and control performance was worse on the dual than the single tasks. Despite the schizophrenic group performance deficits on the single tasks, the extent of such deficit did not appear additive and contributive to the dual tasks. The lack of a group-by-task interaction provided no support for the central executive model of dysfunction. Rather, the results uphold the model of working memory deficits arising from compromise of multiple (here spatial and object), relatively independent systems, both of which are affected in schizophrenia.

Adult↗

PubMed1997

Combined event-related fMRI and EEG evidence for temporal-parietal cortex activation during target detection.

Target detection is the process of bringing a salient stimulus into conscious awareness. Target detection evokes a prominent event-related potential (ERP) component (P3) in the electroencephalogram (EEG). We combined the high spatial resolution of functional magnetic resonance imaging (fMRI) with the high temporal resolution of EEG to investigate the neural generators of the P3. Event-related brain activation (ERBA) and ERPs were computed by time-locked averaging of fMRI and EEG, respectively, recorded using the same paradigm in the same subjects. Target detection elicited significantly greater ERBAs bilaterally in the temporal-parietal cortex, thalamus and anterior cingulate. Spatio-temporal modelling of ERPs based on dipole locations derived from the ERBAs indicated that bilateral sources in the temporal-parietal cortex are the main generators of the P3. The findings provide convergent fMRI and EEG evidence for significant activation of the temporal-parietal cortex 285-610 ms after stimulus onset during target detection. The methods developed here provide a novel multimodal neuroimaging technique to investigate the spatio-temporal aspects of processes underlying brain function.

Adult↗

PubMed1997

Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease.

OBJECTIVE: To examine whether each of the 5 Mattis Dementia Rating Scale (DRS) scores related to magnetic resonance imaging-derived volumes of specific cortical or limbic brain regions in patients with Alzheimer disease (AD). DESIGN: Relations between DRS measures and regional brain volume measures were tested with bivariate and multivariate regression analyses. SETTING: The Aging Clinical Research Center of the Stanford (Calif) University Department of Psychiatry and Behavioral Science and the Geriatric Psychiatry Rehabilitation Unit of the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. PATIENTS AND OTHER PARTICIPANTS: Fifty patients with possible or probable AD. Magnetic resonance imaging data from 136 healthy control participants, age 20 to 84 years, were used to correct brain volumes for normal variation arising from intracranial volume and age. MAIN OUTCOME MEASURES: The DRS scores and volumes of regional cortical gray matter and of the hippocampus. RESULTS: Memory scores of the patients with AD were selectively related to hippocampal volumes. Attention and construction scores were related to several anterior brain volume measures, with attention showing a significantly greater association to right than left hemisphere measures. Initiation/perseveration scores were not significantly correlated with any measure of regional gray matter volume, but performance was related to prefrontal sulcal widening, with a greater association with the left than right sulcal volume. CONCLUSIONS: Certain DRS subtests are predictably correlated with selective regional brain volumes in AD. The specific relation between memory and hippocampal volumes and the nonsignificant relations between memory and regional cortical volumes suggest a dissociation between cortical and hippocampal contributions to explicit memory performance.

Adult↗

PubMed1997

Structural magnetic resonance imaging abnormalities in men with severe chronic schizophrenia and an early age at clinical onset.

BACKGROUND: Early age at onset of schizophrenia often signifies a more severe form of the illness. However, the relationship between age at onset and brain abnormalities has not been established. We assessed temporal-limbic morphometry in severely ill men with chronic schizophrenia who had a relatively early onset of illness and examined the relationships among regional brain volumes, clinical symptoms, and age at illness onset. METHOD: Temporal lobe, superior temporal gyrus, hippocampus, temporal horn, lateral ventricles, third ventricle, and frontoparietal volumes were measured on magnetic resonance imaging data from 56 schizophrenic men (mean [SD] age at illness onset, 16.6 [4.2] years) recruited from a state hospital and 52 age- and range-matched healthy control men. RESULTS: Patients had significantly smaller gray matter volumes in the temporal lobe, superior temporal gyrus, and frontoparietal regions; smaller temporal lobe white matter volumes; and larger cerebrospinal fluid volumes for temporal lobe sulci and the 3 ventricular measures. There were no group differences in hippocampal volumes. Psychotic symptom subscores from the Brief Psychiatric Rating Scale were selectively correlated with smaller left posterior superior temporal gyrus gray matter volumes. None of the brain measurements were significantly correlated with age at illness onset. CONCLUSIONS: Data from this unique sample of severely ill schizophrenic men emphasize a pattern of structural abnormalities involving the cortex, but not the hippocampus, in schizophrenia. Furthermore, these data support theories suggesting that superior temporal gyrus abnormalities contribute selectively to psychotic symptoms and that the extent of structural abnormalities is unrelated to age of clinical symptom onset.

Adolescent↗

PubMed1997

Patterns of content, contextual, and working memory impairments in schizophrenia and nonamnesic alcoholism.

This study used tests of content memory (item recognition of words and abstract designs), context memory (order recognition of verbal and nonverbal items), and working memory (recognition at a short retention interval) to examine patterns of performance in 27 schizophrenic patients, 52 chronic alcoholic patients, and 66 healthy control participants. When performance was age- and IQ-adjusted the schizophrenia group was significantly impaired in item and order recognition of verbal and nonverbal material; the alcoholic group was impaired only in order recognition for both material types. Item- and order-recognition deficits in the schizophrenia group were greatest at the shortest retention intervals, a pattern previously observed in patients with Parkinson's disease, suggesting a prominence of a working memory deficit in schizophrenia.

Adult↗

PubMed1997

Cortical and hippocampal volume deficits in temporal lobe epilepsy.

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.

Adolescent↗

PubMed1997

Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics.

This study used magnetic resonance imaging to quantify the extent and pattern of tissue volume deficit and cerebrospinal fluid volume enlargement in younger versus older chronic alcoholics relative to normal controls. In the present analysis, we divided our previously reported group of 62 alcoholic men into a younger group (n = 33, age mean = 37.5 +/- 4.5, and range = 26 to 44 years) and an older group (n = 29, age mean = 52.7 +/- 6.0, and range = 45 to 63 years) to examine whether, in addition to extent, the two age groups differed in pattern of tissue type and regional brain volume abnormalities quantified with magnetic resonance imaging. Brain volumes were adjusted for normal variation in head size and age established from a group of healthy controls and were expressed as Z-scores. The younger group had significant cortical gray, but not white, matter volume deficits and sulcal and ventricular enlargement relative to age-matched controls. The older group had volume deficits in both cortical gray and white matter and sulcal and ventricular enlargement that significantly exceeded the younger alcoholic group. An analysis of six cortical regions revealed that, although both age groups had gray matter volume deficits throughout the cortex, the older alcoholic group had a selectively more severe deficit in prefrontal gray matter relative to the younger alcoholic group. Similarly, the cortical white matter volume deficit in the older alcoholics was especially severe in the prefrontal and frontal regions. The differences in brain dysmorphology between the two alcoholic groups cannot easily be attributed to potential alcohol history differences typically related to age because the two groups had similar disease durations and amounts of lifetime alcohol consumption. These results provide in vivo evidence that the frontal lobes are especially vulnerable to chronic alcoholism in older men.

Adult↗

PubMed1997

Similar extent of brain dysmorphology in severely ill women and men with schizophrenia.

OBJECTIVE: The purpose of this study was to determine whether women with chronic, severe schizophrenia manifest a widespread deficit in cortical gray matter and ventricular enlargement similar to that seen in men with schizophrenia and whether this deficit is related to age at onset of illness, length of illness, or current illness severity. METHOD: Volumetric measures of head size, cortical gray matter, white matter and sulci, and lateral and third ventricles were obtained from magnetic resonance images of chronic inpatient schizophrenic women (N = 19) and men (N = 18) and healthy comparison women (N = 19) and men (N = 18). Sex and group differences were assessed by using a two-factor analysis of variance of brain measures. Age was entered as a covariate in assessments of associations between brain measures and age at onset and length of illness. RESULTS: The schizophrenic patients as a group had less cortical gray matter but comparable white matter and significantly more lateral and third ventricular CSF than the comparison group. Compared to the combined groups of men, women, regardless of diagnosis, had smaller heads, less cortical gray and white matter, and less sulcal, lateral, and third ventricular CSF. There were no group-by-sex interactions, suggesting that in schizophrenia these aspects of gross volumetric morphology in male and female brains are affected equally. There was no relationship between cortical gray matter deficit or ventricular enlargements and age at symptom onset or length of illness in either men or women with schizophrenia, when variance due to age was accounted for statistically. CONCLUSIONS: The process that contributes to cortical gray matter deficit in schizophrenia appears to affect men and women to a similar extent.

Adult↗

PubMed1996

The effect of stimulus-response incompatibility on P3 latency depends on the task but not on age.

To help identify the loci of age-related slowing of cognitive processing, the effects of stimulus-response (S-R) incompatibility and stimulus degradation on P3 latency and reaction time (RT) were assessed in ten young and ten elderly women. Subjects saw the words right, left, RIGHT, or LEFT in tasks which required responses to (1) the meaning of the word (WORD) (2) its case (CASE) and (3) both (CASE/WORD). Each task was tested with regular and degraded stimuli. On half the trials, the stimulus and response were incompatible. Although RTs and P3s of elderly subjects were slower, especially RTs in CASE/WORD, stimulus degradation and S-R incompatibility did not differentially affect the two groups, suggesting that cognitive processing of older subjects is not especially prolonged in perceptual and response-related stages. For both groups RTs and P3s were task dependent and were prolonged by degradation and S-R incompatibility. Incompatibility delayed RTs in WORD and CASE/WORD but P3s in WORD only. Thus, young and elderly subjects show qualitatively similar psychophysiological and behavioral indicators of processing speed.

Adult↗

PubMed1996

Gray matter deficits in young onset schizophrenia are independent of age of onset.

This study examined whether the degree of brain dysmorphology observable in adulthood was related to onset age of schizophrenic symptoms. Brain magnetic resonance imaging (MRI) scans were acquired in 57 men with schizophrenia, whose age at MRI was 19-53 years, and whose symptom onset ranged from age 7 to 29 years; all were inpatients in a state hospital. Volumes of intracranial space, cortical gray matter (GM) and white matter (WM), and cerebrospinal fluid (CSF) in lateral and third ventricles and cortical sulci were derived from MRI scans and corrected by regression analysis for variations attributable to age and head size, quantified in a control sample of healthy community volunteers. The schizophrenic patients had larger volumes of cortical and ventricular CSF and smaller volumes of cortical GM but not WM than age-matched controls, whether or not volumes were adjusted for head size and age norms. Age of onset did not correlate with any of the five age-adjusted brain measures. Neither current age, length of illness, nor symptom severity correlated with age-normalized volumes of cortical GM, sulcal CSF, or ventricular CSF. These observations are consistent with the theory that brain structure deficits 1) first develop prior to symptom onset (perhaps during the prenatal and/or early childhood process of GM development); 2) probably establish a vulnerability to subsequent dysfunctionality; but 3) are nonprogressive.

Adult↗

PubMed1996

Slow wave sleep and computed tomographic measures of brain morphology in schizophrenia.

To test the hypothesis that slow wave sleep in schizophrenia is inversely correlated with ventricular system volume, polysomnography and computed tomographic (CT) brain imaging were carried out in 14 psychiatric patients who met Research Diagnostic Criteria for schizophrenia (h = 11) or schizoaffective disorder (n = 3). Three measures of ventricular system volume were analyzed: (1) raw ventricular volume expressed in cm3; (2) ventricle-to-brain ratio; and (3) ventricular volume corrected for normal variation in age and head size expressed as a standardized (z) score. All three quantifications of ventricular volume were significantly and inversely correlated with visually scored measures of stage 3 and stage 4 sleep. This finding suggests that the etiology of slow wave sleep deficits in schizophrenia is related either directly or indirectly to underlying brain dysmorphology.

Adult↗

PubMed1996

Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia.

This study examined whether the neuropsychological deficits observed in patients with schizophrenia were related to cortical gray matter volume deficits in these patients. All subjects were men and included 34 patients with DSM-III-R Schizophrenia and 47 age-matched healthy controls. Subjects received a battery of 21 tests, assessing four different functional domains: executive functions, short-term memory and production, declarative memory, and motor ability. MRI volumes were corrected for normal variation in head size and age, and neuropsychological test scores were corrected for normal variation in age. The schizophrenic group had significantly smaller cortical gray matter volumes (p < .05) and lower test scores in all functional domain than the control group (p = .0001). Within the schizophrenic group, lower scores in each domain were significantly correlated with smaller total cortical gray matter volumes; however, no predictable relationships were observed between neuropsychological test performance and the volumes of specific cortical regions.

Adult↗

PubMed1996

Cortical gray matter volume deficits in schizophrenia: a replication.

We sought to replicate an earlier finding of widespread deficit in cortical gray matter in schizophrenia by testing new samples of 22 schizophrenic patients and 27 controls between the ages of 21-46 years. Brain values for both patients and controls were standardized against age and head size norms derived from a larger control group (n = 73) spanning a wider age range (21-70). Compared to the new age-matched controls, the new schizophrenic sample showed a deficit in gray matter volume affecting the cortex as a whole and enlargement of the lateral and third ventricles. Thus, widespread cortical gray matter deficit is a replicable feature of the brain dysmorphology of schizophrenia in young to middle-aged men.

Adult↗

PubMed1996

Neuroimaging and the cognitive neuroscience of schizophrenia.

The Carmel Workshop on Cognitive Psychophysiology began in 1980, and the focus of the 1996 workshop was on schizophrenia. Research into schizophrenia is in the midst of a period of unparalleled advance, driven in large part, by improvements in neuroimaging technology that make detailed examination of in vivo brain structure and function possible. Neuroimaging studies may help provide a bridge between investigations demonstrating molecular and cellular abnormalities in schizophrenia and those demonstrating cognitive dysfunction. The workshop brought together experts in different neuroimaging modalities to present the strengths and advantages of each, as well as the insights each modality might bring into normal and schizophrenic cognitition. It began with a series of tutorials to inform participants of the state of the art in various disciplines. It then broke into four panels, each given a very specific topic assignment related to neuroimaging and/or the cognitive neuroscience of schizophrenia. After 1 1/2 days of discussion, each panel reported its conclusions to the workshop. Group I presented cellular models of the pathophysiology of schizophrenia. Group II examined experimental paradigms for studying cognitive function and schizophrenia. Group III examined technical issues in image processing and combining data across different modalities. Group IV sought to survey the current state of knowledge about the pathophysiology of schizophrenia. The conclusions of each of the groups are presented in this report.

California↗