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Biomedical subjects

A Pfefferbaum

Publications and source records attributed to A Pfefferbaum.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia.

Mammillary body and cerebellar atrophy have been described as postmorten neuropathologic markers of Korsakoff's syndrome. This study examined whether shrinkage in the mammillary bodies and cerebellum is present consistently in amnesic chronic alcoholics during life and whether the degree of abnormality in these patients differs from that in nonamnesic alcoholic and healthy controls. The severity of shrinkage in the mammillary bodies, cerebellar hemispheres, and cerebellar vermis visualizable on MRI scans was rated on a three-point scale in 33 chronic nonamnesic alcoholics, 9 amnesic alcoholics, and 20 healthy controls. Although both alcoholic groups showed significant mammillary body and cerebellar shrinkage relative to controls, the two patient groups did not differ from each other. Furthermore, four of eight amnesic patients in our sample did not demonstrate clinically significant mammillary body atrophy. These results suggest that alcoholism is associated with mammillary body and cerebellar tissue volume loss but do not provide evidence that these markers distinguish accurately between amnesic and nonamnesic patients. In addition, they suggest that visualizable mammillary body atrophy is not necessary for the development of amnesia in alcoholic patients.

Adult↗

Relationship between alcohol withdrawal seizures and temporal lobe white matter volume deficits.

A previous magnetic resonance imaging study from our laboratory reported significant temporal lobe volume deficits in cortical gray matter, white matter, and anterior hippocampus in chronic alcoholic men relative to controls. In the present study, we reexamined these data and asked whether withdrawal seizure history was predictive of either the hippocampal or the extrahippocampal volume deficits. A review of the medical charts indicated that 11 alcoholics had experienced one or more alcohol-related seizures and 35 were seizure-free; no patient had a seizure disorder unrelated to alcohol. The two alcoholic groups did not differ significantly in age, education, alcohol consumption variables, premorbid intelligence, Memory Quotient, Trail Making, or detection of hidden figures. Although each alcoholic group showed significant bilateral volume deficits of the anterior hippocampus and frontal-parietal and temporal gray matter, relative to controls, the seizure group had significantly smaller temporal lobe white matter volumes than either the control or the seizure-free groups; the latter two groups did not differ from each other. Both alcoholic groups, however, had white matter volume deficits in the frontal-parietal region. Thus, the seizure group accounted for the white matter volume deficits in the temporal lobe previously reported in the full sample of alcoholics. It seems, then, that reduced white matter volume in the temporal lobes may be either a risk factor for or sequela of alcohol withdrawal seizures.

Adult↗

Thinning of the corpus callosum in older alcoholic men: a magnetic resonance imaging study.

A brain image averaging technique was applied to three-dimensional magnetic resonance images to identify visually detectable brain volume abnormalities in chronically alcoholic men, compared with healthy control men. This technique, which was based on pixel-by-pixel statistical probability mapping, revealed a dramatic reduction in the area of the corpus callosum in older alcoholics (age 45 years or older), relative to age-matched controls. Subsequent analysis used anatomical landmarks to outline the borders of midsagittal sections of the corpus callosum in a larger group of alcoholics and controls, who spanned the adult age range from 23 to 71 years. This analysis revealed significant reduction, most prominent in the genu and body, of total callosal area in the alcoholic group relative to the control group; the results were the same whether raw area measures or head size plus age adjusted measure were analyzed. Significant thinning of the callosal body in alcoholics is usually attributed to the relatively rare, nutritional-deficient condition, Marchiafava-Bignami disease. However, callosal thinning was present in vivo in chronic alcoholics without clinical symptoms of severe liver disease, amnesia, or alcoholic dementia. These data suggest that chronic alcoholism can be characterized by a continuum of graded brain dysmorphology, rather than classical alcoholic-related subsyndromes, such as Marchiafava-Bignami disease.

Adult↗

White matter MR hyperintensities in adult patients with congenital rubella.

PURPOSE: To observe and quantify white matter hyperintensities on MR images in adults with schizophrenialike symptoms who had had congenital rubella, in order to elucidate the neuropathologic sequelae of this perinatal viral infection and to explore the potential relationship of these lesions to schizophrenia. METHODS: Eleven deaf adult patients with documented prenatal rubella virus infection and schizophrenialike symptoms were compared with 19 age-matched patients with early-onset schizophrenia who did not have congenital rubella and with 18 age-matched control subjects. All MR images (obtained at 1.5 T) were evaluated by a neuroradiologist who was blinded to diagnosis and were rated for white matter lesions on a five-point scale: 0 = no lesions; 1 = 1 lesion less than 1 mm in diameter; 2 = 1 to 4 lesions 1 mm or greater; 3 = 5 to 10 lesions; 4 = more than 10 lesions or a single lesion more than 1 cm in diameter. In addition, the white matter hyperintensities were volumed objectively with a manual threshold technique. RESULTS: Ratings of white matter lesions were significantly higher in the rubella patients than in the control subjects: 6 of the 11 patients had ratings greater than 1 compared with 1 of the 18 control subjects and none of the 19 schizophrenic patients. Also, MR images in five rubella patients received ratings at the highest end of the scale of abnormality (3 or 4). The white matter hyperintensities were characterized as bilateral T2 signal hyperintensities in periventricular and subcortical regions, punctate or linear in shape; they were observed predominantly in parietal lobes. CONCLUSION: This quantitative MR study of adult rubella patients disclosed abnormal white matter lesions that may correspond to neurovascular lesions known neuropathologically. They do not appear to be directly related to schizophrenialike symptoms.

Adult↗

Brain dysmorphology in adults with congenital rubella plus schizophrenialike symptoms.

Brain morphology was quantified with magnetic resonance imaging (MRI) in adult patients with congenital rubella who also had schizophrenialike symptoms. MRIs were compared with those of adult early-onset schizophrenic patients without congenital rubella and age-matched healthy control subjects. The rubella patients had significantly smaller intracranial volumes and shorter stature than the schizophrenic patients or the controls; however, both patient groups had smaller cortical gray matter, but not white matter, volumes than the control group, even when the MRI volumes were corrected for head size and age. In addition, both patient groups showed significant enlargement of the lateral ventricles but not cortical sulci when compared with expected values of normal adults of the same age and head size. Overall, the pattern of dysmorphology was identical in the rubella and the schizophrenic groups. The observations in the rubella group are consistent with a developmental lesion that limits full brain growth, with the small intracranial volume due at least in part to a severe cortical gray matter volume deficit. Thus, the brain dysmorphology of congenital rubella may provide an instance of prenatal viral infection that models the schizophrenic pattern and provides indirect support for a developmental hypothesis of the neuropathogenesis of schizophrenia.

Adult↗

Longitudinal volumetric computed tomographic analysis of regional brain changes in normal aging and Alzheimer's disease.

OBJECTIVE: This study used a semiautomated image analysis technique to quantify the rate and regional pattern of cerebrospinal fluid (CSF) volume changes in the computed tomographic brain examinations of healthy adults and patients with Alzheimer's disease (AD). DESIGN: Longitudinal, within-subject design, with statistical correction for longitudinal method error (eg, head repositioning effects). SETTING: Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS: The 41 patients with AD were recruited from the Geriatric Psychiatry Research Unit and the National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 35 healthy control subjects were recruited from the local community. MAIN OUTCOME MEASURES: Cerebrospinal fluid volumes estimated from computed tomographic scans. RESULTS: Even after accounting for an estimate of method error (eg, head positioning effects) across computed tomographic examinations, the patients with AD showed greater annual CSF volume increases than did the control group. This CSF volume enlargement was not uniform across brain regions of interest; rather, the patients with AD showed disproportionate volume increases in the ventricular system and the sylvian fissures. Greater CSF volume changes in the patients with AD were significantly associated with greater cognitive decline on the Mini-Mental State Examination. Furthermore, younger patients with AD showed more rapid progression on computed tomographic scans than did older patients. CONCLUSIONS: The rate of CSF volume enlargement is region specific, with the most marked annual rate of change occurring in the ventricular system and the sylvian fissures. In addition, younger patients show more rapid progression in the ventricular and frontal sulcal brain regions of interest than do older patients.

Aged↗

Elderly men and women are less responsive to startling noises: N1, P3 and blink evidence.

Previously we observed that the P3 component of the event-related brain potential (ERP) elicited by startling noises, and to a lesser extent P3 to target tones, is reduced in the elderly (Ford & Pfefferbaum, 1991). In the current experiment, we tried to eliminate possible effects of age-related hearing deficits on the responses to noises by filtering them to include only frequencies heard best by the elderly (0-1000 Hz) and by setting noise intensity relative to each subject's threshold (sensation level, SL). Twelve younger (mean 22 years) and 12 older (mean 69 years) men and women listened to three sequences of tones (80%, 500 Hz, 70 dB SPL) and noises (20%). One type of noise occurred in each sequence (wide band noise set to 107 dB SPL, narrow band noise set to 107 dB SPL, or narrow band noise set to approximately 65 dB SL). The order of the three sequences was counterbalanced across age and sex. Younger subjects blinked to the noise 4-5 times more often than older subjects and had N1 and P3 amplitudes that were 2-3 times larger, regardless of the noise type. N1 amplitude to the background frequent tones and non-startle blinks did not differ between groups. Thus, even when noises were narrow band and set relative to each subject's threshold, older subjects were less responsive to startling auditory stimuli than were younger.

Acoustic Stimulation↗

Anterior hippocampal volume deficits in nonamnesic, aging chronic alcoholics.

Magnetic resonance imaging was used to quantify the volume of the hippocampus in 47 men with chronic alcoholism and 72 healthy male control subjects. The subjects ranged in age from 21 to 70 years, thus permitting a test of whether older alcoholics suffer greater brain tissue volume reduction than do younger ones. Comparison brain regions included temporal lobe gray matter, white matter, and cerebrospinal fluid, as well as measures of the lateral ventricles, third ventricle, and temporal horns. The results of this cross-sectional study showed that the anterior, but not the posterior, portions of the hippocampus in both hemispheres were significantly smaller in the alcoholic than the healthy control group. Furthermore, the bilateral anterior hippocampal volume loss was greater in older than younger alcoholics. Despite the hippocampal volume deficit, these alcoholics did not demonstrate an explicit memory impairment; furthermore, memory test scores did not correlate significantly with hippocampal volumes. In the alcoholics, the age-related volume loss, which was over and above that expected in normal aging, was also evident in the temporal cortex and white matter. Likewise, alcoholic ventricular enlargement was age-related. Analysis of covariance revealed that the anterior hippocampal deficit persisted after accounting for the temporal lobe gray matter volume deficit. Multiple regression analysis revealed that the age-related brain volume abnormalities observed in the alcoholics could not be attributed to duration of alcoholism or total lifetime consumption of alcohol.

Adult↗

Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics.

Chronic alcoholism is associated with smaller volumes of cortical gray matter and white matter and a complementary increase in brain cerebrospinal fluid (CSF) volumes, relative to age norms. This longitudinal study quantified the extent of brain volume changes associated with abstinence and drinking at three time points in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58 alcoholic men after an average of 12 days (MRI-1) and 32 days (MRI-2) of sobriety. In addition, 58 healthy control subjects were scanned at a comparable interval. At MRI-3, 11 controls and 39 alcoholics were rescanned, 2-12 months after MRI-2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI slices were segmented into cortical gray matter, white matter, and CSF and summed over seven slices; lateral and third ventricular volumes were also estimated. MRI volume changes were corrected using an estimate of interscan measurement error caused by head positioning differences, and then divided by the interval to yield rates of change (slopes). From MRI-1 to MRI-2, the alcoholic group showed declines in CSF volumes of the lateral ventricles and posterior cortical sulci, and a trend toward an increase in anterior cortical gray matter volume relative to the control group. From MRI-2 to MRI-3, third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers, lifetime consumption of alcohol (as of MRI-1) predicted later vulnerability to white matter volume decline and third ventricular enlargement with resumption of drinking. These data suggest that improvement in cortical gray matter, sulcal, and lateral ventricular volumes occur early in the course of abstinence, and that improvement in third ventricular volume appears later with continued abstinence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗