Abnormalities of the left temporal lobe in schizophrenia.
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Biomedical subjects
Publications and source records attributed to A Pfefferbaum.
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The Rey-Osterrieth complex figure was used to assess the separate influences of the constructional accuracy and the organizational strategy employed while copying the figure on the later, incidental recall of the figure. We tested a model, which hypothesized that subjects who copied the main framework of the figure holistically would be more likely to achieve good copy accuracy scores and to reproduce the figure more accurately at recall than subjects who used a piecemeal approach during copy. Subjects included 68 detoxified, chronic alcoholics (ALC), 28 patients with schizophrenia (SZ), and 69 normal control subjects (NCS). The results showed that the ALC and the SZ groups, on average, had lower accuracy and strategy scores at copy than did the NCS group, and furthermore, that the combined contributions of copy accuracy and copy strategy accounted for group differences at recall. A path analysis revealed that, for all three groups, copy strategy had a significant direct effect on copy accuracy. Moreover, copy accuracy and copy strategy made independent contributions to recall accuracy within the ALC and NCS groups; by contrast, within the SZ group, copy strategy made an independent contribution to recall performance but copy accuracy did not. These results suggest that (1) organizational strategy can influence constructional accuracy at both copy and recall; (2) copy accuracy and strategy have the potential to influence recall independently; and (3) the recall deficit in ALC could be attributed to abnormalities in both accuracy and strategy at copy, whereas in SZ it could be attributed only to strategy abnormalities. The deficits observed on the complex figure test in the ALC and SZ were primarily nonmnemonic and were related to ability in figure construction and organizational strategy.
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Magnetic resonance imaging was used to investigate whether the structural brain differences commonly observed in patients with schizophrenia as compared with normal control subjects are specific to gray or white matter, and furthermore whether such abnormalities are localizable to circumscribed cortical regions. Accordingly, 22 patients meeting DSM-III-R criteria for schizophrenia and 20 healthy community volunteers, all 23 to 45 years old, received magnetic resonance imaging scans. Seven axial magnetic resonance imaging sections of 5-mm thickness were segmented into cerebrospinal fluid, gray matter, and white matter compartments and used for volumetric quantification. For the healthy control subjects, age correlated significantly with the percentage of all magnetic resonance imaging sections taken up by gray matter but not white matter. After correcting for the normal effect of age, the schizophrenic group was found to have significantly less gray matter than the control group but no difference in white matter; ventricular volume was 34% greater in the schizophrenic group. The schizophrenic group had less gray matter in all six cortical subregions analyzed; these differences attained statistical significance for all but the parietal measure. These findings have implications for studies of localized gray matter abnormalities and suggest that regional brain volume measurements need to be expressed in the context of possible widespread gray matter volume deficits in schizophrenia.
Using in vivo magnetic resonance (MR) images, the percentages of gray matter, white matter, and cerebrospinal fluid (CSF) in the brains of 8 young and 6 elderly normal male community volunteers were quantified. Compared with the young men, the elderly men had a significantly lower percentage of gray matter (p less than .01) and higher percentage of CSF (p less than .01). The percentage of white matter was not significantly different between the two groups. This finding suggests that the age-related decrease in brain tissue is chiefly due to loss of gray matter.
Magnetic resonance imaging (MRI) was used to study in vivo the brains of 49 patients with chronic alcoholism, 3 to 4 weeks post-withdrawal, and 43 normal healthy controls, all right-handed male veterans between the ages of 23 and 70 years. MRI scans were analyzed using a semi-automated procedure, which allowed the subcortical regions to be segmented into cerebrospinal fluid (CSF) and brain tissue and the cortical regions to be segmented into CSF, gray matter, and white matter. An age regression model was used to examine the effects of alcohol on brain structure, over and above that expected from the normal aging process. The alcoholics exhibited decreased tissue and increased CSF after correcting for aging. In the cortex, there was significant loss of both gray matter and white matter volume. In this sample of alcoholics, no particular cortical region was preferentially affected or spared. Furthermore, brain tissue volume loss increased with advanced age in the alcoholics. In this group of alcoholics there was no relationship between length of illness and age, i.e., the younger alcoholics had as heavy alcohol use histories as did the older alcoholics. Thus, the increased brain tissue loss with advanced age is interpreted as evidence for age-related increase in brain vulnerability to chronic alcohol abuse.
Event-related potentials (ERPs) and electrodermal activity were studied in 14 medicated schizophrenics, 17 unmedicated schizophrenics, and 23 age- and education-matched controls. Subjects were run in three auditory stimulus paradigms differing from the usual ERP paradigms in having interstimulus intervals greater than 12 sec to permit measurement of the longer latency skin conductance response (SCR). In every paradigm medicated but not unmedicated schizophrenics had smaller N120 amplitudes and fewer SCRs than controls. In addition, medicated schizophrenics showed reduced P200 amplitude and latency, longer P320 latency, and reduced skin conductance levels in certain paradigms. These effects cannot easily be attributed to different mental states of medicated and unmedicated patients, since their Brief Psychiatric Rating Scale scores were almost the same. It is more probable that antipsychotic and antiparkinsonian drugs reduced electrodermal activity through anticholinergic mechanisms and that the antipsychotic drugs attenuated N120 through other biological mechanisms.
Seventeen young (mean age = 20.2 years old) and 16 elderly (mean age = 72.6 years old) women were tested with event-related potential (ERP) paradigms designed to elicit responses in reaction time tasks and to a startling noise burst. EEG was analyzed from 17 standard 10-20 electrode sites. Reaction time and performance data suggested that the elderly did not perform worse than the young. Nevertheless, the physiological responses of the elderly differed significantly from those of the young. While the task-dependent P3s at Pz were smaller in the elderly than in the young, the automatic P3 was smaller yet. The distribution of both types of P3 across the scalp was more uniform in the elderly than in the young. Single-trial analyses revealed that the P3 amplitude differences at Pz were not due to latency dispersal of single trials. Single-trial startle eye blink responses to intense noise bursts during the automatic paradigm were considerably less frequent in the elderly, although their individual startle blinks were actually larger. The data demonstrate that the electrophysiological responses of the elderly are different from the young both in tasks eliciting automatic responses and in tasks requiring controlled processing.
This study presents a structural and functional description of a case of striatonigral degeneration (SND) and emphasizes neuropsychological findings. The patient, a 55-year-old woman with progressive and relatively intractable rigidity and bradykinesia, particularly of the right side, was studied with brain MR scans and with a wide variety of sensory, motor, and cognitive tests known to be subserved by specific brain regions. T2-weighted MR images revealed curvilinear areas of high signal in the lateral putamen at low magnetic field strength (0.3T) and adjacent regions of marked low signal in the posterior-lateral putamen at high magnetic field (1.5T). High signal changes in the insular cortex were also noted on the high field images. Letter fluency and short-term memory as well as motor speed, strength, and sequencing were selectively impaired. Taken together, the data of this case suggest that structural involvement of the putamen resulted in dysfunctions usually associated with the primary motor cortex and orbitofrontal cortex, while sparing functions of other frontal regions as well as temporal and parietal cortices.
Multilead event-related potentials (ERPs), elicited by auditory and visual stimuli requiring a button press response and by a startling noise requiring no response, were recorded from male alcoholics and age-matched male controls (26-60 years old). Single-trial analyses of blink responses to the startling stimuli indicated that alcoholics startle less frequently but with equivalent amplitude as the controls. In contrast, single-trial analyses of P3 indicated that alcoholics generate a P3 as often as controls, but that their individual P3s are smaller. Alcoholics who reported a positive family history of problem drinking had larger startle blink amplitudes and smaller auditory and visual P3s than did alcoholics who reported a negative family history. Hierarchical regression analysis was used to demonstrate that smaller P3s in family history positive alcoholics were independent of lifetime alcohol consumption.
The first human MR imaging results for the hepatobiliary contrast agent manganese(II)N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (MnDPDP) are reported. MnDPDP is a paramagnetic contrast agent specific for hepatobiliary imaging. An imaging study was performed to investigate the presence of contrast enhancement or facilitated visualization of normal structures. Twelve healthy subjects receiving MnDPDP at doses of 3, 10, or 15 mumol/kg were imaged after injection for approximately 30 minutes at 1-5-minute intervals. Transaxial abdominal images were obtained at 1.5 T in a single breath-hold interval of 21 seconds with use of a spin-echo pulse sequence (repetition time = 150 msec, echo time = 20 msec). Liver parenchyma enhancement was observed 1 minute after injection and persisted for at least 30 minutes. Clearance into the gallbladder was visualized within 15 minutes. Enhancement was dose-dependent; a dose of 10 mumol/kg produced a 75%-100% signal enhancement of the liver at 10 minutes after injection.
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Limbic system structures are of central interest in many neuropsychiatric disorders. Magnetic resonance imaging (MRI) has a unique potential for imaging limbic system structures in vivo, but methodological constraints can limit the usefulness and interpretation of the collected image data. In this article, we present approaches for the acquisition and quantification of high resolution MR images of the limbic system. We used a long TR, cardiac gated, flow compensated, spin echo sequence to collect 22, 3-mm thick contiguous sections encompassing the limbic system. The sections were oriented relative to standard internal neuroanatomical landmarks. The sequence provided good gray matter/white matter/cerebrospinal fluid (CSF) and CSF/bone contrast; the latter is necessary for quantifying intracranial size and total CSF volume. Using operationalized criteria, we achieved high interrater reliability in volumetric measurement of temporal horn and hippocampus. This technique was then used to examine the effect of normal aging by comparing eight young (mean = 24 years) and seven old (mean = 73 years) healthy community members. We were able to demonstrate a significant age-related increase in temporal horn volume and a trend toward an age-related decrease in hippocampal volume.
The advent of computed tomography (CT) of the brain has facilitated the study of brain asymmetries in normal individuals and in patients with various diseases. A computerized volumetric approach to quantifying CT scan data is used to demonstrate that imperfect alignment of the subject's head in the CT scanner can be a major source of artifact in the assessment of cerebral asymmetry. An approach for estimating the extent of misalignment of the head in the scanner is described. This approach can be used to take variations in head alignment into account when studying cerebral asymmetries. When volumetric measures were used, left-handed subjects (n = 5) were found to have a significantly lower left/right ratio of total cerebral hemispheric tissue than right-handed subjects (n = 41). The amount of asymmetry in the lateral ventricles was found to depend on their total size. A method for controlling for the effect of size when measuring asymmetry of the lateral ventricles is described. In both right- and left-handed subjects, the left lateral ventricles were significantly larger than the right. A magnetic resonance (MR) scan was performed with standard alignment and with a deliberate 10 degrees misalignment, using a volunteer subject. These data are presented to demonstrate how artifactual cerebral asymmetries can be generated by head tilt and to test the quantification procedures developed.
Patients with presumptive Alzheimer's disease (AD) and healthy community volunteers received computed tomographic (CT) brain scans and cognitive tests. The CT scans were quantitatively analyzed with a semiautomated thresholding technique to derive volumetric measures of cerebrospinal fluid (CSF)-to-tissue ratios in six regions of interest (ROIs): lateral ventricles; vertex sulci, frontal sulci, Sylvian fissures, parieto-occipital sulci, and third ventricle. Regression analysis was performed on CT data from 85 older volunteers (ages 51-82) to generate age norms for each ROI. Within this group, tissue loss, as measured by the % CSF in each ROI, was highly correlated with age, although each ROI showed different rates of change over age. For all ROIs, the AD group had significantly more tissue loss than expected in normal aging. In addition, AD patients with a presenescent onset (before age 65) tended to have greater vertex sulcal and frontal sulcal tissue reduction than AD patients with a senescent onset (age 65 or after). When regional tissue reduction, corrected for age, was correlated with cognitive test scores, two sets of double dissociations emerged within the AD group: large CT z scores (i.e., decreased tissue and increased CSF) of frontal sulci, but not of the third ventricle, correlated with low Comprehension and Boston Naming Test scores, whereas large CT z scores of the third ventricle, but not of the frontal sulci, correlated with low scores on Digit Symbol and Picture Arrangement. These results suggest that heterogeneity of structural and functional integrity exists among patients with AD.
Magnetic resonance imaging (MRI) offers the potential for identifying, in vivo, specific brain abnormalities associated with schizophrenia. The detection of small morphological differences in areas such as the prefrontal cortex, limbic structures, and basal ganglia requires attention to a number of technical and methodological details. The effects of age, height, sex, head size, and overall tissue loss are of particular concern and are discussed. MRI acquisition and processing techniques for improving gray/white tissue contrast and image resolution are described, as are techniques for quantitative, volumetric measurement of localized regions of interest and specific brain structures as well as of the brain as a whole. Techniques for evaluating frontal lobes, temporal lobes, and basal ganglia integrity are reviewed, and recent observations on these brain regions in patients with schizophrenia are described.