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Biomedical subjects

G D Pearlson

Publications and source records attributed to G D Pearlson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Elucidating the contributions of processing speed, executive ability, and frontal lobe volume to normal age-related differences in fluid intelligence.

One theory of normal cognitive aging asserts that decreases in simple processing speed mediate the age-related decline of fluid intelligence. Another possibility is that age-related atrophic changes in frontal brain structures undermine the functioning of executive abilities, thereby producing the same decline. In this study, we used principal components analysis to derive a measure of fluid-spatial intelligence in 197 normal adults between 20 and 92 years of age. Measures of perceptual comparison speed, working memory, and executive ability, as well as regional brain volumes based on high resolution magnetic resonance imaging were obtained from a subsample of 112 participants. We then conducted a series of hierarchical multiple regression analyses to test whether (1) the processing speed theory, (2) frontal-executive theory, or (3) some combination of these best accounted for age-related variation in fluid intelligence. The results showed that perceptual comparison speed, executive ability, and frontal lobe volume each made significant contributions to a regression equation that explained 57% of the variance in fluid intelligence. These findings suggest that both the processing speed and frontal-executive theory of cognitive aging are partially correct and complement one another.

Adult↗
PubMed2000

Neurobiology of schizophrenia.

Schizophrenia is a common chronic and disabling brain disease of unknown etiology, pathogenesis, and mechanism. Whether schizophrenia represents a single disorder of markedly variable expression or a family of clinically related disorders is unclear. Genetic factors, most likely multiple genes of modest effect, play a major role in its etiology, but an environmental "second hit" may be necessary for clinical expression. The inherited biological susceptibility to schizophrenia is probably expressed clinically as nonpsychotic abnormal personality traits, plus numerous biological markers (cognitive, anatomical, and psychophysiological) that are all found significantly more commonly in the population than is schizophrenia. Neuropathological studies suggest that schizophrenia may be a neurodevelopmental disorder, characterized by reduced neuropil, with no evidence for ongoing cell death. A hypothesized mechanism for these changes involves cell migrational abnormalities occurring in the fetal brain. Schizophrenia is also distinguished by biochemical abnormalities involving the dopamine, GABA, and glutamate systems, and NMDA and nicotinic receptors. Structural and functional brain imaging studies suggest both global and regional abnormalities as well as "disconnections" of specific cerebral circuits. Despite the lack of knowledge regarding pathophysiology, there are reasonably effective treatments for schizophrenia. As the neurobiology of the disorder is unraveled, more effective, targeted treatments will become available.

Humans↗
PubMed1999

MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults.

OBJECTIVE: To determine whether volumes of hippocampus and amygdala are abnormal in people with autism. BACKGROUND: Neuropathologic studies of the limbic system in autism have found decreased neuronal size, increased neuronal packing density, and decreased complexity of dendritic arbors in hippocampus, amygdala, and other limbic structures. These findings are suggestive of a developmental curtailment in the maturation of the neurons and neuropil. METHODS: Measurement of hippocampus, amygdala, and total brain volumes from 1.5-mm coronal, spoiled gradient-recalled echo MRI scans in 14 non-mentally retarded autistic male adolescents and young adults and 14 individually matched, healthy community volunteers. RESULTS: Amygdala volume was significantly smaller in the autistic subjects, both with (p = 0.006) and without (p = 0.01) correcting for total brain volume. Total brain volume and absolute hippocampal volume did not differ significantly between groups, but hippocampal volume, when corrected for total brain volume, was significantly reduced (p = 0.04) in the autistic subjects. CONCLUSIONS: There is a reduction in the volume of amygdala and hippocampus in people with autism, particularly in relation to total brain volume. The histopathology of autism suggests that these volume reductions are related to a reduction in dendritic tree and neuropil development, and likely reflect the underdevelopment of the neural connections of limbic structures with other parts of the brain, particularly cerebral cortex.

Adolescent↗
PubMed1999

Structural and functional brain changes in bipolar disorder: a selective review.

The purpose of this paper is to provide a concise, selective review of the major issues and findings germane to structural and functional neuroimaging studies of bipolar affective disorder (BPD). In attempting to identify the brain changes associated with BPD, investigators have used neuroimaging techniques to focus on several interrelated questions. These are: What are the changes and where do they occur? Do their nature and location suggest a particular etiopathologic basis or have notable clinical correlates? With regard to specificity, are the changes unique to BPD, or do they overlap with those reported in other neuropsychiatric illnesses, especially schizophrenia? Do they occur in brain systems that normally play a role in modulating mood? Finally, how do the brain changes integrate with neurocognitive, neurogenetic, and neuropathologic data in the same patients? To date, these questions have been addressed only preliminarily. We outline some of the strategies used to pursue answers to these questions and review conclusions to date.

Affective Symptoms↗
PubMed1999

Structural brain imaging in schizophrenia: a selective review.

Structural neuroimaging studies have provided some of the most consistent evidence for brain abnormalities in schizophrenia. Since the initial computed tomography study by Johnstone and co-workers, which reported lateral ventricular enlargement in schizophrenia, advances in brain imaging technology have enabled further and more refined characterization of abnormal brain structure in schizophrenia in vivo. This selective review discusses the major issues and findings in structural neuroimaging studies of schizophrenia. Among these are evidence for generalized and regional brain volume abnormalities, the specificity of anatomic findings to schizophrenia and to men versus women with schizophrenia, the contribution of genetic influences, and the timing of neuroanatomic pathology in schizophrenia. The second section reviews new approaches for examining brain structure in schizophrenia and their applications to studies on the pathophysiology of schizophrenia.

Brain↗
PubMed1999

New insights on the neuroanatomy of schizophrenia.

Recent ideas and research evidence about the neuroanatomy of schizophrenia come to us from diverse sources. These include 1) conventional (magnetic resonance imaging morphometry); 2) novel (diffusion tensor imaging) structural anatomic techniques; 3) information on patterns of anatomic changes from longitudinal anatomic studies; 4) illumination of functional connectivity and pathway anomalies associated with the disorder; 5) family studies on the distribution of anatomic abnormalities within affected and unaffected family members; and 6) anatomic distributions of neurotransmitters and their receptors, as well as their response to drugs used to treat the disorder. Taken together, these new data provide an exciting look at the direction in which the field is headed.

Anthropometry↗
PubMed1999

MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia.

OBJECTIVE: This study sought to determine whether volumes of the hippocampus and amygdala are disproportionately smaller in subjects with Down's syndrome than in normal comparison subjects and whether volume reduction is greater in Down's syndrome subjects with dementia. METHOD: The subjects were 25 adults with Down's syndrome (eight with dementia) and 25 cognitively normal adults who were individually matched on age, sex, and race. Magnetic resonance imaging measures included volumes of the hippocampus, amygdala, and total brain. Nineteen of the Down's syndrome subjects had follow-up scans (interscan interval = 9-41 months). RESULTS: Nondemented Down's syndrome subjects had significantly smaller volumes of the hippocampus, but not the amygdala, than their comparison subjects, even when total brain volume was controlled for. Volumes of both the hippocampus and the amygdala were smaller in the demented Down's syndrome subjects than in their comparison subjects, even when total brain volume was controlled for. Age was not correlated with volume of the hippocampus or amygdala among the nondemented Down's syndrome subjects and the comparison subjects; age was correlated with volume of the amygdala, but not the hippocampus, among the Down's syndrome subjects with dementia. Changes in volume over time were not statistically significant for either the demented or the nondemented subjects. CONCLUSIONS: Hippocampal volume, while disproportionately small for brain size in individuals with Down's syndrome, remains fairly constant through the fifth decade of life in those without dementia. All subjects over age 50 who had Down's syndrome demonstrated volume reduction in the hippocampus as well as clinical signs of dementia. Dementia was also associated with volume reductions in the amygdala that exceeded reductions in total brain volume.

Adult↗
PubMed1998

Mesial temporal lobe measurements on magnetic resonance imaging scans.

Changes in the mesial temporal lobe, particularly in the hippocampus, amygdala, and entorhinal cortex, are reported to occur in several neuropsychiatric conditions. Neuroimaging provides a non-invasive means of studying these changes. We present a method for reliably measuring the hippocampus, amygdala, and entorhinal cortex on MRI. The advantages of our method include high reliability, the use of orthogonal views in delineating boundaries and circumscription of measurement such that no tissue of any one anatomic structure is included in the measurement of another structure.

Amygdala↗
PubMed1998

SPECT brain blood flow changes with continuous ligand infusion during previously learned WCST performance.

Performance of the Wisconsin Card Sorting Test (WCST) and related brain-activation patterns reflect both task learning and execution. Normal subjects learned the WCST prior to performance during slow SPECT ligand infusion. Blood flow increased in bilateral inferior frontal, right middle and inferior parietal cortices. Activity decreased in hippocampi, temporal cortex, anterior cingulate and caudate.

Adult↗
PubMed1998

Site of opioid action in the human brain: mu and kappa agonists' subjective and cerebral blood flow effects.

OBJECTIVE: Humans experience the subjective effects of mu and kappa opioid agonists differently: mu agonists produce mainly euphoria, while kappa agonists are more likely to produce dysphoria. This study tested the hypothesis that these subjective effects would be associated with anatomically distinct changes in regional cerebral blood flow (CBF) relative to baseline as assessed with single photon emission computed tomography (SPECT). METHOD: Nine nondependent opioid abusers participated in the study. In the first phase of the study, the participants were acclimated to effects of the study drugs. In the second phase they underwent repeat challenges with the study drugs followed by an assessment of CBF with use of the SPECT tracer [99mTc]HMPAO. Medications tested were the prototypic mu agonist hydromorphone, the mixed agonist/antagonist butorphanol (which has a kappa agonist component of activity), and saline placebo. RESULTS: Subjective effects of the drugs were distinctly different. Hydromorphone produced increased ratings of "good effects," while butorphanol led to more "bad effects." Hydromorphone significantly increased regional CBF in the anterior cingulate cortex, both amygdalae, and the thalamus--all structures belonging to the limbic system. Butorphanol caused a less distinct picture of regional CBF increases, mainly in the area of both temporal lobes. CONCLUSIONS: This study demonstrates that opioids with different subjective effects also produce statistically significant patterns of change in regional CBF from baseline, and the regions of statistical significance appear in different brain regions. In addition, these results demonstrate the applicability of SPECT functional neuroimaging in the study of medications with potential abuse liability.

Amygdala↗
PubMed1998

Structural evaluation of the prefrontal cortex in schizophrenia.

OBJECTIVE: Altered prefrontal cortical function has been repeatedly implicated in the pathophysiology of schizophrenia. Attempts to determine whether this altered function is associated with structural changes in the prefrontal cortex have been hampered by the failure to examine more anatomically and functionally homogeneous regions. The authors have developed a reliable set of anatomical landmarks for subdividing the prefrontal cortex into superior, middle, inferior, and orbital regions, in order to determine whether patients with schizophrenia exhibit selective morphological abnormalities of the prefrontal cortex. METHOD: Magnetic resonance imaging (MRI) studies were obtained in 24 normal control subjects (14 men and 10 women) and 18 patients with schizophrenia (12 men and six women) by using a high-resolution thin spoiled-gradient recall acquisition in the steady-state protocol. The MRI images were used to determine prefrontal gray matter volumes for the four prefrontal regions and prefrontal total gray and white volumes. RESULTS: Patients with schizophrenia exhibited selective gray matter volume reductions in the right and left inferior prefrontal cortex. There were no significant group differences in the other prefrontal regions. Patients with schizophrenia also exhibited decreased prefrontal total white matter and total volumes; there was no significant difference in prefrontal total gray matter volume. CONCLUSIONS: Patients with schizophrenia are characterized by relatively selective reductions in inferior prefrontal cortex gray matter volumes.

Adult↗
PubMed1998

Frontal lobe volume in patients with Huntington's disease.

Neuropathologic and neuroimaging studies have suggested that frontal lobes are affected in Huntington's disease (HD), and that atrophy in this region may be associated with some of the cognitive impairment and clinical decline observed in patients with HD. We measured gray and white matter volumes within the frontal lobes on MRI for 20 patients with HD (10 mildly affected and 10 moderately affected) and 20 age- and sex-matched control subjects. We also correlated frontal lobe measurements with measures of symptom severity and cognitive function. Patients who were mildly affected had frontal lobe volumes (both gray and white matter) essentially identical to those of control subjects, despite clearly abnormal basal ganglia. Patients who were moderately affected demonstrated significant reductions in total frontal lobe volume (17%) and frontal white matter volume (28%). Frontal lobe white matter volume reductions, but not total frontal lobe volume reductions, were disproportionately greater than overall brain volume reductions (17%). Frontal lobe volume correlated with symptom severity and general cognitive function, but these correlations did not remain significant after taking into account total brain volume. We conclude that cognitive impairment and symptom severity are associated with frontal lobe atrophy, but this association is not specific to the frontal lobes. Frontal lobe atrophy (like total brain atrophy) occurs in later stages of increasing HD symptom severity and this atrophy primarily involves white matter.

Adult↗
PubMed1998

MRI brain changes in subjects with Down syndrome with and without dementia.

Individuals with Down syndrome (DS), a disorder of known genetic etiology (trisomy of chromosome 21), exhibit several types of structural brain abnormalities that are detectable pathologically and by MRI. In addition, in middle age, individuals with DS develop histological and, in some cases, clinical features of Alzheimer's disease (AD). Abnormalities in MRI scans of 50 adults with DS, 11 of whom had clinical dementia, are described and compared with those of 23 cognitively normal, healthy subjects who were matched for age, sex, and race. Qualitative visual analogue scale (VAS) ratings on MRI hard copies for all subjects and computer-aided volume measures for a subsample of subjects were carried out. On VAS, subjects with DS had larger lateral ventricles, a higher frequency of posterior fossa arachnoid cysts/megacisterna magna and fewer scans rated as normal compared with controls. Quantitatively, total brain and gray-matter volumes were reduced in DS, as were the volumes of the left hippocampus and amygdala; ventricle volumes were larger. Post hoc comparisons of subjects with DS with and without dementia revealed that on VAS the former had more generalized atrophy for age, mesial temporal shrinkage, and third ventricular enlargement. Similarly, total brain, left hippocampus, and left amygdala volumes were reduced quantitatively in subjects with DS with dementia, while ventricular volumes were increased.

Adult↗
PubMed1997

Measurement of frontal lobe volume on magnetic resonance imaging scans.

This article describes rules for measurement of the frontal lobe on thin SPGR (spoiled gradient recalled echo in steady state) MRI (magnetic resonance imaging) scans. Measurements were performed using a locally-developed software program that allows 3-dimensional reconstruction of images, 'painting' of landmarks on the surface of the brain, and reconstruction of 2-dimensional images in any plane with landmark 'paint' remaining on the surface of the brain. Excellent inter-rater reliability has been achieved for this method. The approach may be particularly useful for studies involving groups of patients whose brains are known to be dysmorphic and who may not, therefore, be appropriate for measurement methods that involve image warping or dependence on arbitrary landmarks for defining the posterior boundary of the frontal lobe.

Adult↗
PubMed1997

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls.

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups had smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.

Age of Onset↗
PubMed1997

Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder.

Prior magnetic resonance imaging (MRI) studies report both medial and lateral cortical temporal changes and disturbed temporal lobe asymmetries in schizophrenic patients compared with healthy controls. The specificity of temporal lobe (TL) changes in schizophrenia is unknown. We determined the occurrence and specificity of these TL changes. Forty-six schizophrenic patients were compared to 60 normal controls and 27 bipolar subjects on MRI measures of bilateral volumes of anterior and posterior superior temporal gyrus (STG), amygdala, entorhinal cortex, and multiple medial temporal structures, as well as global brain measures. Several regional comparisons distinguished schizophrenia from bipolar disorder. Entorhinal cortex, not previously assessed using MRI in schizophrenia, was bilaterally smaller than normal in schizophrenia but not in bipolar disorder. Schizophrenic but not bipolar patients had an alteration of normal posterior STG asymmetry. Additionally, left anterior STG and right amygdala were smaller than predicted in schizophrenia but not bipolar disorder. Left amygdala was smaller and right anterior STG larger in bipolar disorder but not schizophrenia.

Adolescent↗
PubMed1997

Cerebellar volume in adults with Down syndrome.

OBJECTIVES: To determine the effects of aging on cerebellar volume in individuals with Down syndrome (DS). To determine whether volume of cerebellum is associated with dementia or with age-related decline in fine-motor control. DESIGN: Case-control study involving comparison of cerebellar volumes in adults with DS and matched control subjects; survey study involving correlations between cerebellar volume and subjects' age and performance on a test of fine motor control; and longitudinal study assessing change in cerebellar volume in adults with DS. SETTING: The Johns Hopkins University School of Medicine, Baltimore, Md. PATIENTS AND OTHER PARTICIPANTS: Subjects included 40 adults with DS. Thirty of them were matched on age, sex, and race with cognitively normal subjects. A diagnosis of probable dementia was made for 5 of the subjects with DS. Longitudinal data were available for 23 of the 40 subjects with DS, with a mean interscan interval of 2 years. MAIN OUTCOME MEASURES: Volumes of cerebellum, total brain, and intracranial region were measured on magnetic resonance imaging scans. The Purdue Pegboard, a test of fine-motor control, was administered to 38 of the subjects with DS. RESULTS: Subjects with DS had significantly smaller cerebellar volumes than matched controls, even after adjusting for total brain volume or total intracranial volume. Volume of cerebellum did not correlate significantly with age for either the subjects with DS or controls. Longitudinal change in cerebellar volume in subjects with DS was not significant. Volume of total brain, but not cerebellum, correlated significantly with performance on the Purdue Pegboard. CONCLUSIONS: Although cerebellar volumes are disproportionately small in individuals with DS, they do not diminish significantly with age and do not undergo age-related atrophy that is different from that of normal controls. Volume reduction in the cerebellum does not appear to be specifically responsible for the age-related decline in fine-motor control that is observed in adults with DS.

Adult↗