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Biomedical subjects

T L Jernigan

Publications and source records attributed to T L Jernigan.

At least 19 recordsLinked to original sources
PubMed2004

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Adult↗
PubMed2001

Mapping callosal morphology and cognitive correlates: effects of heavy prenatal alcohol exposure.

BACKGROUND: Abnormalities of the corpus callosum (CC) have been documented in fetal alcohol syndrome (FAS), ranging from subtle decrements in its size to partial and even complete agenesis. Prenatal exposure to alcohol is also known to result in neurocognitive deficits. OBJECTIVE: To 1) investigate abnormalities in size, shape, and location of the CC within the brain in individuals with FAS and in those exposed to high amounts of alcohol prenatally but without FAS (PEA group); and 2) determine if there is a relationship between callosal dysmorphology and cognitive test performance. METHODS: MRI and novel surface-based image analytic methods were used. Twenty alcohol-exposed subjects (8 to 22 years) along with 21 normal controls (8 to 25 years) were studied with high-resolution MRI and measures of verbal learning and visuospatial abilities. RESULTS: In addition to callosal area reductions, most severe in the splenium, the CC is significantly displaced in patients exposed to alcohol prenatally. In the alcohol-exposed group, this structure lies more anterior and inferior in posterior regions with relatively normal localization of anterior regions. These findings are significant in the FAS group, and a similar but less severe pattern is observed in the PEA patients. The authors show that the amount of CC displacement is correlated with impairment in verbal learning ability and that CC displacement is a better predictor of verbal learning than regional CC area. The brain-behavior relationship is only significant within the alcohol-exposed group, and the effect is not solely mediated by overall impaired verbal intellectual functioning. CONCLUSIONS: These results further emphasize the vulnerability of midline brain structures to prenatal alcohol exposure.

Adolescent↗
PubMed2001

Voxel-based morphometric analyses of the brain in children and adolescents prenatally exposed to alcohol.

Children of mothers who abuse alcohol during pregnancy can suffer varying degrees of neurological abnormality, cognitive impairment, and behavioral problems, and in the worst case, are diagnosed with fetal alcohol syndrome (FAS). The purpose of the present study was to localize brain abnormalities in a group of children and adolescents prenatally exposed to alcohol using high resolution, 3D structural MRI data and whole-brain voxel-based morphometry (VBM). Data were collected for 21 children and adolescents with histories of prenatal alcohol exposure (ALC) and 21 normally developing individuals. Statistical parametric maps revealed abnormalities most prominent in the left hemisphere perisylvian cortices of the temporal and parietal lobes where the ALC patients tended to have too much gray matter and not enough white matter. These results provide further support for dysmorphology in temporo-parietal cortices above and beyond the overall microcephaly that results from severe prenatal alcohol exposure.

Adolescent↗
PubMed2001

Mesial temporal, diencephalic, and striatal contributions to deficits in single word reading, word priming, and recognition memory.

Fifty-three volunteer participants were studied with the fade-in task (Ostergaard, 1998) to measure naming latency, word priming, and recognition-memory performance. and with morphometric magnetic resonance imaging (MRI) techniques to measure volumes of mesial temporal lobe, diencephalic, striatal, and neocortical structures. The relationship between measures of cerebral volume loss and performance deficits was modeled using simultaneous regression analyses in which the behavioral measures were dependent variables. The results suggested that damage in both hippocampal and amygdala/entorhinal areas as well as damage in the diencephalon and the nucleus accumbens all contributed independently to the severity of recognition-memory deficits. Both caudate nucleus damage and hippocampal damage contributed independently to increased naming latency (slowed single-word reading). Finally, only damage in the hippocampus appeared to result in decreased word priming. These results provide further evidence against the assertion that word priming represents a form of memory unaffected by damage to the mesial temporal lobes.

Adult↗
PubMed2001

Improved memory functioning and frontal lobe maturation between childhood and adolescence: a structural MRI study.

Previous studies conducted by our group have provided evidence for age-related reductions in cortical thickness in dorsal frontal and parietal regions between childhood and adulthood, and gray matter volume increases of mesial temporal and anterior diencephalic structures. The purpose of this study was to describe neurobehavioral correlates of these brain maturational changes using morphometric analyses of brain magnetic resonance images (MRI) and two tests of cognitive abilities. Participants were 35 normal children roughly stratified by age (7 to 16 years) and sex (20 boys and 15 girls) and frontal and mesial temporal regions were anatomically defined in each subjects' MRI data. The California Verbal Learning Test-Children's Version and the Rey-Osterrieth Complex Figure test were used as measures of verbal and visuospatial memory and organizational abilities. Analyses designed to show regionally specific relationships between the brain and behavioral measures revealed interesting results. Specifically, frontal lobe gray matter thinning was more strongly predictive of delayed verbal memory functioning than was the mesial temporal lobe gray matter volume, and this relationship did not appear to be mediated by factors indexed in chronological age. Similar, but less regionally specific relationships were observed for measures of visuospatial memory abilities and frontal lobe maturation. Functional imaging studies in the literature consistently report activation in frontal regions in adults during retrieval tasks. The relationship between frontal lobe maturation and delayed recall observed here may be reflective of the children's development towards the more adult-like frontal lobe function revealed in the functional imaging studies.

Adolescent↗
PubMed2001

Elevated cerebrospinal fluid quinolinic acid levels are associated with region-specific cerebral volume loss in HIV infection.

Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release quinolinic acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. In the present cross-sectional study of 94 HIV-1-infected patients, elevated CSF quinolinic acid concentrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) but not in regions relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white matter). Increased CSF quinolinic acid concentrations also correlated with higher CSF HIV-1 RNA levels. In support of the specificity of these associations, blood levels of quinolinic acid were unrelated to striatal and limbic volumes, and CSF levels of beta(2)-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that quinolinic acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local quinolinic acid biosynthesis.

Adult↗
PubMed2001

Brain dysmorphology in individuals with severe prenatal alcohol exposure.

Our previous studies revealed abnormalities on structural MRI (sMRI) in small groups of children exposed to alcohol prenatally. Microcephaly, disproportionately reduced basal ganglia volume, and abnormalities of the cerebellar vermis and corpus callosum were demonstrated. The present study used sMRI to examine in detail the regional pattern of brain hypoplasia resulting from prenatal exposure to alcohol using a higher resolution imaging protocol and larger sample sizes than reported previously. Fourteen participants (mean 11.4 years; eight females, six males) with fetal alcohol syndrome (FAS) and 12 participants (mean 14.8 years; four females, eight males) with prenatal exposure to alcohol (PEA) but without the facial features of FAS were compared to a group of 41 control participants (mean 12.8 years, 20 females, 21 males). Findings of significant microcephaly and disproportionately reduced basal ganglia volumes in the FAS group were confirmed. Novel findings were that in FAS participants, white matter volumes were more affected than gray matter volumes in the cerebrum, and parietal lobes were more affected than temporal and occipital lobes. Among subcortical structures, in contrast to the disproportionate effects on caudate nucleus, the hippocampus was relatively preserved in FAS participants. Differences between the PEA group and controls were generally non-significant; however, among a few of the structures most affected in FAS participants, there was some evidence for volume reduction in PEA participants as well, specifically in basal ganglia and the parietal lobe. There were no group differences in cerebral volume asymmetries. Severe prenatal alcohol exposure appears to produce a specific pattern of brain hypoplasia.

Adolescent↗
PubMed1999

Localizing age-related changes in brain structure between childhood and adolescence using statistical parametric mapping.

Volumetric studies have consistently shown reductions in cerebral gray matter volume between childhood and adolescence, with the most dramatic changes occurring in the more dorsal cortices of the frontal and parietal lobes. The purpose of this study was to examine the spatial location of these changes employing methods typical of functional imaging studies. T1-weighted structural MRI data (1.2 mm) were analyzed for nine normally developing children and nine normal adolescents. Validity and reliability of the tissue segmentation protocol were assessed as part of several preprocessing analyses prior to statistical parametric mapping (SPM). Using SPM96, a simple contrast of average gray matter differences between the two age groups revealed 57 significant clusters (SPM[Z] height threshold, P<0.001, extent threshold 50, uncorrected). The pattern and distribution of differences were consistent with earlier findings from the volumetric assessment of the same subjects. Specifically, more differences were observed in dorsal frontal and parietal regions with relatively few differences observed in cortices of the temporal and occipital lobes. Permutation tests were conducted to assess the overall significance of the gray matter differences and validity of the parametric maps. Twenty SPMs were created with subjects randomly assigned to groups. None of the random SPMs approached the number of significant clusters observed in the age difference SPM (mean number of significant clusters = 5.8). The age effects observed appear to result from regions that consistently segment as gray matter in the younger group and consistently segment as white matter in the older group. The utility of these methods for localizing relatively subtle structural changes that occur between childhood and adolescence has not previously been examined.

Adolescent↗
PubMed1999

Regional cerebral volume loss associated with verbal learning and memory in dementia of the Alzheimer type.

Twenty-seven research participants with dementia of the Alzheimer type were studied with the California Verbal Learning Test (D. C. Delis, J. H. Kramer, E. Kaplan, & B. A. Ober, 1987) and standardized volume measures of the mesial temporal cortical gray matter, neocortical gray matter, thalamus, and caudate nuclei, from magnetic resonance imaging. A pattern of atrophic brain changes in the mesial temporal lobes (MTL) and the thalamus, with relatively less severe atrophy in the neocortical gray matter, was associated with poorer learning of the word list. Similar patterns of brain atrophy were observed for measures of delayed recall and recognition hits. However, for delayed recall, neither contribution was statistically significant, and for recognition hits, MTL was only at the trend level for significance. These results provide evidence that the verbal memory deficit of Alzheimer's disease (AD) is associated not only with the mesial temporal limbic cortex, thought to be the site of earliest and most severe pathology in AD, but also with damage in the thalamus.

Aged↗
PubMed1999

Does an increase in sulcal or ventricular fluid predict where brain tissue is lost?

Quantitative volumes of cerebrospinal fluid (CSF) and brain tissue were measured on magnetic resonance images (MRIs) of 287 individuals from 5 diagnostic groups: Alzheimer's disease (AD), chronic alcoholics (ALC), individuals positive for human immunodeficiency virus (HIV), schizophrenia subjects (SZ), and normal comparison subjects (NC) older than 50 years of age. Within each group, mean volumes were calculated for ventricular CSF, cortical (sulcal) CSF, cortical gray matter, total white matter, basal ganglia gray matter, and thalamic gray matter. Correlations of CSF measures with brain tissue measures were determined, and multiple regression analyses were performed to try and predict volume of gray matter or white matter region from volume of CSF compartment. Results indicated the following: 1. Enlarged cortical fluid volume significantly predicts cortical gray matter deficits for subjects with AD and those who are ALC and SZ but not for subjects with HIV or NC. 2. Enlarged cortical fluid volume also significantly predicts white matter deficits in all five groups. 3. Enlarged ventricular fluid volume significantly predicts basal ganglia deficits in AD, HIV, and NC but not in SZ or ALC. 4. Enlarged ventricular volume has no predictive value for thalamic volume for any of the groups. This study supports the clinical practice of predicting brain tissue volume loss from CSF enlargement but not for all brain regions in all diagnoses.

Adult↗
PubMed1998

Progressive cerebral volume loss in human immunodeficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. HIV Neurobehavioral Research Center Group.

OBJECTIVE: To compare rates and anatomical patterns of brain atrophy during 3 stages of human immunodeficiency virus (HIV) disease. DESIGN: Comparisons of multiple serial brain magnetic resonance images in men without HIV infection and HIV-infected men in Centers for Disease Control and Prevention (CDC, Atlanta, Ga) stages A, B, and C. SETTING: Longitudinal cohort study of the San Diego HIV Neurobehavioral Research Center, San Diego, Calif. PARTICIPANTS: Eighty-six HIV-1-positive (HIV-positive) and 23 HIV-negative men who were similar in age and risk group. The number of HIV-positive men in each CDC stage was as follows: A, 33; B, 19; C, 34. All HIV-positive men were free of clinically detectable opportunistic neurologic illness. MAIN OUTCOME MEASURES: Regional volumes of serial magnetic resonance images converted to standardized slope estimates of change in regional volumes of interest. RESULTS: Medically asymptomatic men (CDC stage A) and medically symptomatic men (CDC stage C) had more rapid loss of cortical tissues than did HIV-negative men as manifested by higher slopes (Tukey honestly significant difference test, P=.02 and P=.001, respectively) for cortical fluid volume. Accelerated ventricular volume enlargement occurred only in men with CDC stage C disease. Reduction in the volume of white matter was accelerated in participants with CDC stage C disease compared with participants with CDC stage A disease. Of the gray matter regions, only the caudate nucleus sustained accelerated volume loss during CDC stage C disease. Participants whose systemic disease progressed to a higher CDC stage had significantly accelerated ventricular volume increases and caudate atrophy. Rates of cortical and subcortical fluid volume increases and reductions in the volumes of white matter and the caudate nucleus were significantly related to the rate of decline in the CD4+ lymphocyte count. CONCLUSIONS: In the absence of cerebral opportunistic disease, HIV infection causes progressive atrophy within the gray and white matter in the brain. These changes were most severe in the most advanced stage of disease but were evident even in medically asymptomatic HIV-positive persons. Within the gray matter, the caudate nucleus exhibited progressive volume loss linked to disease stage and the rate of decline of the CD4+ cell count. Structural brain changes can begin in the early stages of HIV infection and accelerate during advanced illness.

Adult↗
PubMed1998

Brain activation during word identification and word recognition.

Previous memory research has suggested that the effects of prior study observed in priming tasks are functionally, and neurobiologically, distinct phenomena from the kind of memory expressed in conventional (explicit) memory tests. Evidence for this position comes from observed dissociations between memory scores obtained with the two kinds of tasks. However, there is continuing controversy about the meaning of these dissociations. In recent studies, Ostergaard (1998a, Memory Cognit, 26:40-60; 1998b, J. Int. Neuropsychol. Soc., in press) showed that simply degrading visual word stimuli can dramatically alter the degree to which word priming shows a dissociation from word recognition; i.e., effects of a number of factors on priming paralleled their effects on recognition memory tests when the words were degraded at test. In the present study, cerebral blood flow changes were measured while subjects performed the word identification (reading) and recognition memory tasks used previously by Ostergaard. The results are the direct comparisons of the two tasks and the effects of stimulus degradation on blood flow patterns during the tasks. Clear differences between word identification and word recognition were observed: the latter task evoked considerably more prefrontal activity and stronger cerebellar activation. Stimulus degradation was associated with focal increases in bilateral fusiform regions within the occipital lobe. No task, degradation, or item repetition effects were demonstrated in mesial temporal regions, no repetition effects were observed in any region, and there was no evidence for different effects of stimulus degradation in the priming and recognition memory conditions. Power limitations may have contributed to the null effects.

Adult↗
PubMed1998

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia.

Age of onset of schizophrenia (AOS) may be largely determined by neurobiological factors. We examined in a diverse sample of schizophrenia out-patients the relationships of AOS with neuropsychological abilities and structural brain abnormalities as measured on cerebral magnetic resonance imaging (MRI). A total of 82 out-patients meeting DSM-III-R criteria for schizophrenia were evaluated with a comprehensive neuropsychological battery and semi-automated quantitatively analysed cerebral MRI. Earlier AOS correlated with poorer performance in learning and abstraction/cognitive flexibility, and with larger volumes of caudate and lenticular nuclei, and smaller volume of thalamus on MRI. A model for predicting AOS consisting of abstraction and thalamic and caudate volumes remained significant after controlling for duration of illness, current age and daily neuroleptic dose. In conclusion, AOS may be related to specific rather than general measures of cognitive performance and structural brain abnormalities.

Adult↗
PubMed1997

Lack of clinically significant gross structural abnormalities in MRIs of older patients with schizophrenia and related psychoses.

The authors examined the reports of MRI brain studies of 69 patients with DSM-III-R-diagnosed psychotic disorders (30 early-onset and 24 late-onset schizophrenia patients and 15 with other psychoses) and 41 normal comparison subjects. Participants' ages ranged from 45 to 87 years. A qualitative rating scheme determined type and severity of clinically detectable abnormalities, including volume loss, infarcts, lacunae, and white matter hyperintensities. In this clinically well-characterized sample, the vast majority of the MRIs were within normal limits. There were no significant differences between psychosis patients and normal comparison subjects or between early-onset and late-onset schizophrenia patients in frequency, type, or severity of gross structural abnormalities. The results indicate that late-onset schizophrenia and related disorders can exist without clinically significant gross structural abnormalities in the brain.

Age of Onset↗
PubMed1996

Association of dementia severity with cortical gray matter and abnormal white matter volumes in dementia of the Alzheimer type.

OBJECTIVE: To examine associations between dementia severity and quantitative magnetic resonance imaging measures of cortical gray matter volume and abnormal white matter volume in 52 patients diagnosed with probable Alzheimer disease. DESIGN: Analysis of the relationship between magnetic resonance imaging volume measures and dementia severity using multiple regression and Pearson correlations. SETTING: Alzheimer's Disease Research Center, University of California, San Diego. PARTICIPANTS: Twenty-three men and 29 women with probable Alzheimer disease (average age, 71.7 years; average education, 13.3 years). MAIN OUTCOME MEASURES: The Mattis Dementia Rating Scale (MDRS) and the Mini-Mental State Examination. RESULTS: Using simultaneous multiple regression, magnetic resonance imaging volumetric measures of cortical gray matter and abnormal white matter were independently associated with dementia severity measured by either the MDRS or the Mini-Mental State Examination. Cortical gray matter volume and abnormal white matter volume also made independent contributions to performance in 4 of 5 cognitive domains assessed by the MDRS. Regional analysis indicated that limbic cortical gray matter volume and nonlimbic cortical gray matter volume were also correlated with the MDRS score; however, in the regression analysis the individual gray matter measures were not independently associated with MDRS performance. A similar analysis revealed statistically independent relationships of limbic gray matter volume and abnormal white matter volume, but not nonlimbic cortical gray matter volume, to Mini-Mental State Examination performance. CONCLUSIONS: Quantitative magnetic resonance methods provided strong evidence that cortical gray matter volume, which may reflect atrophy, and abnormal white matter volume are independently related to dementia severity in probable Alzheimer disease: lower gray matter and higher abnormal white matter volumes are associated with more severe dementia.

Aged↗
PubMed1996

Abnormal development of the cerebellar vermis in children prenatally exposed to alcohol: size reduction in lobules I-V.

Abnormalities of the cerebellar vermis have been well documented in animal models of fetal alcohol syndrome. At this point, it is not known if the same brain region is affected in humans prenatally exposed to alcohol. In this study, the area of the cerebellar vermis was measured from brain magnetic resonance images of 9 children and young adults with prenatal alcohol exposure and 24 control subjects in the same age range. Six of the exposed children met standard criteria for fetal alcohol syndrome. The remaining three subjects had significant histories of prenatal exposure to alcohol, but did not have enough of the classic facial features for the diagnosis. For each subject with a suitable midsagittal section, three vermal areas were circumscribed: anterior vermis (vermal lobules I-V), posterior vermis (vermal lobules VI and VII), and the remaining vermal area (including lobules VIII-X). Statistical analyses revealed that the anterior region of the vermis was significantly smaller in subjects with prenatal alcohol exposure, whereas the posterior region and the remaining vermal area did not differ between groups. Previous findings from an animal model of neonatal alcohol exposure have documented Purkinje cell loss in vermal lobules I-V and IX-X, with notable sparing in lobules VI-VII. Thus, the results of both studies indicate similar patterns of abnormal brain development in the anterior vermal region, with apparent sparing in the posterior vermal region. Our findings, for the first time, suggest that regionally specific Purkinje cell death may also occur in humans prenatally exposed to alcohol.

Adolescent↗