Biomedical subjects

A Pfefferbaum

Publications and source records attributed to A Pfefferbaum.

At least 19 recordsLinked to original sources

PubMed1999

P300 amplitude is related to clinical state in severely and moderately ill patients with schizophrenia.

BACKGROUND: Relationships between illness severity and neurobiologic abnormalities in schizophrenia were studied in subpopulations varying in clinical severity. METHODS: Auditory ERPs were collected from 28 severely ill, chronically hospitalized schizophrenic men from a state hospital; 29 moderately ill inpatient and outpatient schizophrenic men from a veterans hospital; and 30 healthy male subjects from the community as controls. Clinical symptoms were evaluated in patients using the Brief Psychiatric Rating Scale (BPRS). RESULTS: Both schizophrenic patient groups had smaller P300 amplitude than the control subjects. Severely ill patients had smaller P300s than moderately ill patients and scored higher on three BPRS factor scores as well as BPRS Total. Among severely ill patients, P300 amplitude was unrelated to clinical symptoms. Among moderately ill patients, P300 was related to Withdrawal/Retardation, Anxiety/Depression, and BPRS Total. After combining patients, Thinking Disturbance emerged as an additional correlate of P300. Group differences in P300 could not be accounted for by group differences in symptom severity using analysis of covariance. CONCLUSIONS: Reduced P300 amplitude marks the diagnosis of schizophrenia, but also reflects individual differences in severity, including positive symptoms. Previous failures to find relationships between positive symptoms and P300 may have been due to a restricted range of clinical severity.

Acute Disease↗

PubMed1999

Failures of automatic and strategic processing in schizophrenia: comparisons of event-related brain potential and startle blink modification.

Noises elicit startle blinks that are inhibited when immediately (approximately 100 ms) preceded by non-startling prepulses, perhaps reflecting automatic sensory gating. Startle blinks are facilitated when preceded by prepulses at longer lead intervals, perhaps reflecting strategic processes. Event-related brain potentials (ERPs) and startle blinks were used to investigate the well-documented prepulse inhibition failure in schizophrenia. Blinks and ERPs were recorded from 15 schizophrenic men and 20 age-matched controls to noises alone and to noises preceded by prepulses at 120 (PP120), 500 (PP500) and 4000 ms (PP4000) lead intervals. Neither blinks nor any of the ERP components elicited by the noise alone differentiated schizophrenics from controls, although responses to noises were modified by prepulses differently in the two groups. With the N1 component of the ERP, patients showed normal inhibition but lacked facilitation, and with P2, patients lacked inhibition, but showed normal facilitation. With reflex blinks and P300, inhibition was seen in both groups, but no facilitation. These results suggest that different neural circuits are involved in blink and cortical reflections of startle modification in schizophrenics and controls, with both automatic and strategic processes being impaired in schizophrenia.

Acoustic Stimulation↗

PubMed1999

Severity of schizophrenia and magnetic resonance imaging abnormalities: a comparison of state and veterans hospital patients.

BACKGROUND: The relationship between illness severity and neuroanatomical abnormalities in schizophrenia remains unclear. The purpose of this study was to test whether the pattern and extent of brain volume abnormalities differed between two patient groups, distinguished by their overall severity and clinical course of schizophrenia. METHODS: Subjects were 56 severely ill, chronically hospitalized schizophrenic men from Napa State Hospital (SH-SZ), 44 moderately ill, acutely hospitalized schizophrenic men from the Palo Alto Veterans Administration Health Care System (VA-SZ), and 52 healthy male control subjects. Temporolimbic, ventricular, and frontoparietal volumes, quantified from 3-mm coronal spin-echo magnetic resonance images and adjusted for cerebral volume and age, were compared using analysis of variance. RESULTS: Compared to control subjects, both SZ groups had smaller (p < .05) temporal lobe and frontoparietal gray matter volumes and larger ventricles and temporal sulci. Whereas SH-SZ had more pronounced cerebrospinal fluid and frontoparietal abnormalities relative to VA-SZ; VA-SZ had greater temporal lobe gray matter deficits. Neither patients group had hippocampal or cerebral volume deficits relative to control subjects. There were no differences between diagnostic subtypes. CONCLUSIONS: The magnitude of volume abnormalities in schizophrenia varies with respect to disease severity and to brain region, but disease severity is not associated with anatomically distinct subgroups.

Adult↗

PubMed1999

Cerebrospinal fluid glutamate inversely correlates with positive symptom severity in unmedicated male schizophrenic/schizoaffective patients.

BACKGROUND: Recent hypotheses have suggested that diminished brain glutamate may be of importance in the neurochemical basis of schizophrenia. METHODS: We assayed cerebrospinal fluid for glutamate and obtained clinical symptom ratings in 19 medication-free (except p.r.n. chloral hydrate) schizophrenic or schizoaffective (typically with significant schizophrenic qualities) male inpatients. RESULTS: Ratings of positive symptoms were significantly inversely correlated (rs = -.457, p < .05, one-tailed test) with glutamate concentrations. Hallucinatory behavior was strongly correlated (rs = -.621, p < .01, one-tailed test) with glutamate. A subset of 11 patients consented to a second lumbar puncture (LP) after treatment with haloperidol (typically 15 or 20 mg/day) for 2-4 weeks. Haloperidol treatment did not alter glutamate concentrations. No correlations were noted between glutamate and symptoms in the medicated subsample. Though approximately half the patients received chloral hydrate during the 72 hours prior to the unmedicated LP, the correlations between positive symptoms and glutamate in the patients who received no chloral hydrate prior to the LP were quite similar to those found in the overall sample. CONCLUSIONS: The results provide further support for the potential importance of glutamate in the neurochemical basis of schizophrenia.

Adult↗

PubMed1999

In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) and normal aging result in cortical gray matter volume deficits. The extent to which the remaining cortex is functionally compromised can be estimated in vivo with magnetic resonance spectroscopic imaging. OBJECTIVE: To assess the effects of age and dementia on gray matter and white matter concentrations of 3 metabolites visible in the proton spectrum: N-acetyl compounds, present only in living neurons; creatine plus phosphocreatine, reflecting high-energy phosphate metabolism; and choline, increasing with membrane synthesis and degradation. METHOD: Fifteen healthy young individuals, 19 healthy elderly individuals, and 16 patients with AD underwent 3-dimensional magnetic resonance spectroscopic imaging and memory and language testing. RESULTS: Gray matter N-acetyl compound concentrations (signal intensity corrected for the amount of brain tissue contributing to the magnetic resonance spectroscopic imaging signal) was significantly reduced only in patients with AD, even though both the AD and elderly control groups had substantial gray matter volume deficits relative to the young control group. Both the healthy elderly and AD groups had abnormally high gray matter creatine plus phosphocreatine concentrations. Gray matter choline concentrations were higher in the elderly than the younger controls, and even higher in the AD group than in the elderly control group. Functional significance of these findings was supported by correlations between poorer performance on recognition memory tests and lower gray matter N-acetyl compounds in elderly controls and higher gray matter creatine plus phosphocreatine and choline concentrations in patients with AD. CONCLUSION: Cortical gray matter volume deficits in patients with AD are accompanied by disease-related increases in gray matter choline concentrations suggestive of cellular degeneration and reduced N-acetyl compound concentrations, with possible effects on behavioral function.

Adult↗

PubMed1999

Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging.

BACKGROUND: Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo. METHODS: Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging. RESULTS: Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions. CONCLUSIONS: Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.

Adult↗

PubMed1999

In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: effects of normal aging.

Volumetric proton magnetic resonance spectroscopic imaging (MRSI) was used to generate brain metabolite maps in 15 young and 19 elderly adult volunteers. All subjects also had structural MR scans, and a model, which took into account the underlying structural composition of the brain contributing to each metabolite voxel, was developed and used to estimate the concentration of the N-acetyl-moiety (NAc), creatine (Cr), and choline (Cho) in gray matter and white matter. NAc concentration (signal intensity per unit volume of brain) was higher in gray than white matter and did not differ between young and old subjects despite significant gray matter volume deficits in the older subjects. To the extent that NAc is an index of neuronal integrity, the available gray matter appears to be intact in these older healthy adults. Cr concentrations were much higher in gray than white matter and significantly higher in the old than young subjects. Cho concentration in gray matter was also significantly higher in old than young subjects. Independent determination of metabolite values rather than use of ratios is essential for characterizing age-related changes in brain MRS metabolites.

Adult↗

PubMed1998

Association between regional brain volumes and clozapine response in schizophrenia.

BACKGROUND: Clozapine has shown considerable therapeutic promise in the treatment of schizophrenia; however, the clinical risks and initial high treatment costs associated with its administration motivate the search to identify patients who will best respond. Neuroimaging studies have suggested that prefrontal sulcal prominence may be a predictor of nonresponsiveness. METHODS: We used magnetic resonance imaging (MRI) to test whether volumes in any cortical regions of the brain were associated with symptom improvement with clozapine treatment. The 21 schizophrenic men studied were clinically evaluated during treatment with typical neuroleptics (baseline) and after a mean of 6.2 months treatment with clozapine (final dose 300-900, median = 562 mg/day). At least a 20% improvement on total Brief Psychiatric Rating Scale (BPRS) was seen in 47.6% of the schizophrenics. Clinical improvement was regressed on baseline differences in clinical severity, and the residual scores were related to MRI values. RESULTS: Patients with larger anterior superior temporal lobe cerebrospinal fluid volumes (primarily sylvian fissure) showed greater improvement on total BPRS and withdrawal/retardation symptoms. CONCLUSIONS: Even schizophrenics with significant brain dysmorphology can have a positive clinical response to clozapine.

Adult↗

PubMed1998

Differential activation of dorsal basal ganglia during externally and self paced sequences of arm movements.

The basal ganglia are thought to be critically involved in motor control. However, the relative contributions of the various sub-components are not known. Although, in principle, functional magnetic resonance imaging (fMRI) provides adequate resolution to image the basal ganglia at the spatial scale of the individual nuclei, activating these nuclei with fMRI has proven to be difficult. Here we report two tasks, involving externally and self paced sequences of arm movements, which resulted in significant activation of contralateral posterior (post-commissural) putamen and globus pallidus. This activation did not significantly differ between the tasks. In contrast, significant activation of the contralateral and ipsilateral anterior caudate and anterior putamen was observed only during externally paced arm movements. These results suggest a dissociation in the roles of the anterior and posterior dorsal basal ganglia: the anterior caudate and putamen may be involved in sensory to motor mapping and the posterior putamen and globus pallidus may be involved in the motor response itself. The findings support the hypothesis that the basal ganglia may be involved in gating sensory influences onto motor areas.

Adult↗

PubMed1998

Patterns of regional cortical dysmorphology distinguishing schizophrenia and chronic alcoholism.

BACKGROUND: This study used magnetic resonance imaging (MRI) to compare the extent and pattern of tissue volume deficit and cerebrospinal fluid volume enlargement in chronic alcoholics and schizophrenics. METHODS: The subjects included 62 detoxified chronic alcoholics (26-63 years), 71 schizophrenics (23-63 years), and 73 controls spanning the adult age range (21-70 years). MRI volumes were adjusted for normal variation in head size and age established from the control group. RESULTS: Both patient groups showed widespread cortical gray matter volume deficits compared with controls, but only the alcoholics had white matter volume deficits. The schizophrenics had significantly greater volume deficits in the prefrontal and anterior superior temporal gray matter than in the more posterior cortical regions. By contrast, the deficits in the alcoholics were relatively homogeneous across the cortex. For white matter, the deficits in the alcoholics were greatest in the prefrontal and temporal-parietal regions. Although both patient groups had abnormally larger cortical sulci and lateral and third ventricles than the controls, the alcoholics had significantly larger sulcal volumes in the frontal, anterior, and posterior parietal-occipital regions than the schizophrenics. CONCLUSIONS: This quantitative MRI study revealed different patterns of regional cortical volume abnormalities in schizophrenics and alcoholics. The schizophrenic group exhibited cortical gray matter volume deficits of modestly greater magnitude than that observed in the alcoholic group, and the alcoholics but not the schizophrenics exhibited cortical white matter volume deficits.

Adult↗

PubMed1998

A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval.

BACKGROUND: We report on structural brain changes during a 5-year period in healthy control and alcoholic men. METHODS: Alcoholic patients (n = 16), from an initial group of 58 who underwent brain magnetic resonance imaging scanning while in treatment, were rescanned with the same acquisition sequence approximately 5 years later. Control subjects (n = 28) spanning the same age range also were scanned twice at a comparable interval. Changes in brain volume were corrected for error due to differences in head placement between scans and expressed as slopes (cubic centimeters per year), percentage of change over baseline for the control subjects, and standardized change for the alcoholic patients. The alcoholic patients varied considerably in the percentage of time that symptoms of alcohol dependence were present and in the amount of alcohol consumed during follow-up. RESULTS: The cortical gray matter diminished in volume over time in the control subjects, most prominently in the prefrontal cortex, while the lateral and third ventricles enlarged. The alcoholic patients showed similar age-related changes with a greater rate of gray matter volume loss than the control subjects in the anterior superior temporal lobe. The amount of alcohol consumed during follow-up predicted the rate of cortical gray matter volume loss, as well as sulcal expansion. The rate of ventricular enlargement in alcoholic patients who maintained virtual sobriety was comparable to that in the control subjects. CONCLUSIONS: During a 5-year period, brain volume shrinkage is exaggerated in the prefrontal cortex in normal aging with additional loss in the anterior superior temporal cortex in alcoholism. The association of cortical gray matter volume reduction with alcohol consumption over time suggests that continued alcohol abuse results in progressive brain tissue volume shrinkage.

Aging↗

PubMed1998

Proton magnetic resonance spectroscopic imaging of cortical gray and white matter in schizophrenia.

OBJECTIVE: To apply in vivo proton magnetic resonance spectroscopy imaging estimates of N-acetylaspartate (NAA), a neuronal marker, to clarify the relative contribution of neuronal and glial changes to the widespread volume deficit of cortical gray matter seen in patients with schizophrenia with magnetic resonance images. METHODS: Ten male veterans meeting criteria of the DSM-IV, for schizophrenia and 9 healthy age-matched men for comparison were scanned using spectroscopic, anatomical, and field-map sequences. Instrument and collection variables were standardized to allow an estimation of comparable values for NAA, choline, and creatine for all subjects. Metabolite values from each voxel on 3 upper cortical slices were regressed against the gray tissue proportion of that voxel to derive estimates of gray and white matter NAA, creatine, and choline concentrations. RESULTS: The volume of cortical gray matter was reduced in patients with schizophrenia, but NAA signal intensity from a comparable region was normal. In contrast, the volume of cortical white matter was normal in patients with schizophrenia, but NAA signal intensity from a comparable region was reduced. CONCLUSIONS: The lack of reduction in gray matter NAA signal intensity suggests that the cortical gray matter deficit in these patients involved both neuronal and glial compartments rather than a neurodegenerative process in which there is a decrease in the neuronal relative to the glial compartment. Reduced white matter NAA signal intensity without a white matter volume deficit may reflect abnormal axonal connections.

Adult↗

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↗

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↗