Biomedical subjects

John G Csernansky

Publications and source records attributed to John G Csernansky.

At least 19 recordsLinked to original sources

PubMed2005

Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type.

To better define the pattern of hippocampal deformity early in the course of Alzheimer's disease, we compared the pattern of hippocampal surface variation in subjects with very mild dementia of the Alzheimer type (DAT) and nondemented subjects. The surface of the hippocampus was divided a priori on a neuroanatomical template into three zones approximating the locations of underlying subfields [Csernansky, J.G., Wang, L., Swank, J., Miller, J.P., Gado, M., McKeel, D., Miller, M.I., Morris, J.C., 2005. Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly. NeuroImage 25, 783--792]; i.e., a lateral zone (LZ) approximating the CA1 subfield, a superior zone (SZ) approximating the combined CA2, CA3, CA4 subfields and the gyrus dentatus (GD), and an inferior-medial zone (IMZ) approximating the subiculum. Large-deformation high-dimensional brain mapping (HDBM-LD) was used to generate the hippocampal surfaces of all subjects and to register the surface zones across subjects. Average variations within each zone were calculated for the subjects with very mild DAT as compared to the average of the nondemented subjects. After correcting for multiple comparisons, the very mild DAT subjects showed significant inward variation in the left and right LZ, the left and right IMZ, but not in the left and right SZ as compared to nondemented subjects. In logistic regression analyses, inward variation of the left and right LZ or IMZ by 0.1 mm relative to the average of the nondemented subjects increased the odds of the subject being a very mild DAT subject (range-1.18 to 1.57) rather than being a nondemented subject. The odds ratios for the left and right SZ were not significant. These results represent a replication of our previous findings [Csernansky, J.G., Wang, L., Joshi, S., Miller, J.P., Gado, M., Kido, D., McKeel, D., Morris, J.C., Miller, M.I., 2000. Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Neurology 55, 1636--1643.] and suggest that inward deformities of the hippocampal surface in proximity to the CA1 subfield and subiculum can be used to distinguish subjects with very mild DAT from nondemented subjects.

Activities of Daily Living↗

PubMed2005

Acetylcholinesterase inhibitors ameliorate behavioral deficits in the Tg2576 mouse model of Alzheimer's disease.

RATIONALE: Acetylcholinesterase inhibitors are widely used for the treatment of patients with Alzheimer's disease (AD). However, the relationship between the capacity of such drugs to ameliorate the symptoms of AD and their ability to alter the underlying disease process is not well understood. Transgenic mice that overexpress the human form of amyloid precursor protein and develop deposits of beta-amyloid (Abeta) and behavioral deficits during adulthood are useful for investigating this question. OBJECTIVES: The effects of administration of two acetylcholinesterase inhibitors, physostigmine and donepezil, on Abeta plaque formation and memory-related behaviors were investigated in the Tg2576-transgenic mouse model of AD. At 9-10 months of age, Tg2576-transgenic [Tg(+)] mice develop Abeta plaques and impairments on paradigms related to learning and memory as compared to transgene-negative [Tg(-)] mice. METHODS: Beginning at 9 months of age, increasing doses of physostigmine (0.03, 0.1, and 0.3 mg/kg), donepezil (0.1, 0.3, and 1.0 mg/kg), or saline were administered over 6 weeks to cohorts of Tg(+) and Tg(-) mice. Performance on tests of spatial reversal learning and fear conditioning was evaluated at each drug dose throughout the period of drug administration. After drug administration was completed, the animals were sacrificed and Abeta plaque number was quantified. RESULTS: Administration of physostigmine and donepezil improved deficits in contextual and cued memory in Tg(+) mice so that their behaviors became more similar to Tg(-) mice. However, administration of physostigmine and donepezil tended to improve cued memory and deficits in spatial learning in both Tg(+) and Tg(-) mice. Physostigmine administration demonstrated more prominent effects in improving contextual memory than donepezil, while donepezil was more effective than physostigmine in improving deficits in the acquisition of the spatial memory paradigm. Administration of neither drug altered the deposition of Abeta plaques. CONCLUSIONS: These studies suggest that acetylcholinesterase inhibitors can ameliorate memory deficits in Tg(+) mice without necessarily altering the deposition of Abeta plaques. Tg2576 mice may be useful as an animal model to further investigate the mechanisms by which aceytlcholinesterase inhibitors improve cognitive deficits in patients with AD.

Alzheimer Disease↗

PubMed2005

Low dose quetiapine reverses deficits in contextual and cued fear conditioning in rats with excitotoxin-induced hippocampal neuropathy.

Previous studies have demonstrated that adult rats with excitotoxic lesions of the hippocampus display deficits in memory-related behaviors similar to the memory deficits associated with schizophrenia. In this study, we assessed the sub-chronic effects of quetiapine, risperidone and haloperidol on performance deficits after intracerebroventricular administration of the excitotoxin, kainic acid, using paradigms for contextual and cued fear conditioning and spatial reversal learning in rats. The effects of three doses of quetiapine (5, 10 and 20 mg/kg) and single doses of risperidone (0.5 mg/kg) and haloperidol (0.15 mg/kg) were compared. Quetiapine administration at the lowest dose (5 mg/kg) reversed deficits in contextual and cued fear conditioning, but not deficits in spatial reversal learning, in kainic acid-treated animals. However, the two higher doses of quetiapine, and the single doses of risperidone and haloperidol, did not reverse any of the kainic acid-induced behavioral deficits. These results may be relevant to the effects of quetiapine and other antipsychotic drugs on memory deficits in patients with schizophrenia.

Animals↗

PubMed2005

The influence of encoding strategy on episodic memory and cortical activity in schizophrenia.

BACKGROUND: Recent work suggests that episodic memory deficits in schizophrenia may be related to disturbances of encoding or retrieval. Schizophrenia patients appear to benefit from instruction in episodic memory strategies. We tested the hypothesis that providing effective encoding strategies to schizophrenia patients enhances encoding-related brain activity and recognition performance. METHODS: Seventeen schizophrenia patients and 26 healthy comparison subjects underwent functional magnetic resonance imaging scans while performing incidental encoding tasks of words and faces. Subjects were required to make either deep (abstract/concrete) or shallow (alphabetization) judgments for words and deep (gender) judgments for faces, followed by subsequent recognition tests. RESULTS: Schizophrenia and comparison subjects recognized significantly more words encoded deeply than shallowly, activated regions in inferior frontal cortex (Brodmann area 45/47) typically associated with deep and successful encoding of words, and showed greater left frontal activation for the processing of words compared with faces. However, during deep encoding and material-specific processing (words vs. faces), participants with schizophrenia activated regions not activated by control subjects, including several in prefrontal cortex. CONCLUSIONS: Our findings suggest that a deficit in use of effective strategies influences episodic memory performance in schizophrenia and that abnormalities in functional brain activation persist even when such strategies are applied.

Adult↗

PubMed2005

Direct and indirect effects of fetal irradiation on cortical gray and white matter volume in the macaque.

BACKGROUND: Schizophrenia is associated with reductions in thalamic neuronal number and cortical gray matter volume. Exposure of nonhuman primates to x-irradiation in early gestation has previously been shown to decrease thalamic volume and neuronal number. Here we examine whether early gestational irradiation also results in cortical volume reduction. METHODS: High-resolution, T1-weighted magnetic resonance scans were collected in adult monkeys 1) exposed to irradiation during the early gestational period (E33-E42) corresponding to thalamic neurogenesis, 2) irradiated in midgestation (E70-81) during neocortical neurogenesis, and 3) not exposed to irradiation. Cortical gray matter and white matter volumes were derived via manual segmentation; frontal and nonfrontal volumes were distinguished via sulcal landmarks. RESULTS: Monkeys irradiated in early gestation exhibited a trend reduction in nonfrontal gray matter volume (17%) and significant reductions in white matter volume in frontal (26%) and nonfrontal (36%) lobes. Monkeys irradiated in midgestation had smaller gray (frontal: 28%; nonfrontal: 22%) and white matter (frontal: 29%; nonfrontal: 38%) volumes. CONCLUSIONS: The cortical deficits observed in midgestationally irradiated monkeys are consistent with a reduction in cortical neuronal number. Cortical volume reductions following early gestational irradiation may be secondary to reduced thalamic neuronal number and therefore model the thalamocortical pathology of schizophrenia.

Age Factors↗

PubMed2005

Neuroanatomical predictors of response to donepezil therapy in patients with dementia.

BACKGROUND: Patients with dementia of the Alzheimer type (DAT) respond variably to treatment with acetylcholinesterase inhibitors. OBJECTIVE: To determine whether measures of hippocampal volume and shape predict the response to donepezil in patients with DAT. DESIGN: T1-weighted, magnetic resonance images were obtained from patients with DAT, who subsequently underwent treatment with donepezil. Brain-mapping algorithms were used to quantify hippocampal volume and shape, and growth curves were used to estimate clinical outcome. SETTING: A referral outpatient center specializing in treatment of dementia. PATIENTS: Thirty-seven patients with very mild or mild DAT received donepezil therapy for up to 4 weeks before magnetic resonance imaging and for 24 to 96 weeks after magnetic resonance imaging. INTERVENTION: Donepezil, 10 mg/d. MAIN OUTCOME MEASURE: Rate of change in the cognitive portion of the Alzheimer's Disease Assessment Scale total scores. RESULTS: Smaller hippocampal volume and inward variation of the lateral and inferomedial portions of the hippocampal surface were correlated with a poorer response to donepezil therapy. CONCLUSIONS: Measures of hippocampal volume and surface variation can be used to predict the response of patients with DAT to the acetylcholinesterase inhibitor donepezil.

Alzheimer Disease↗

PubMed2005

Easier tasks can have better discriminating power: the case of verbal fluency.

Loren and Jean Chapman highlighted the importance that the psychometric characteristics of a task may have when comparing different populations (L. J. Chapman & J. P. Chapman, 1973, 1978). Specifically, they pointed out that when comparing 2 tasks measuring different constructs, there is a greater likelihood of finding larger deficits on a task with higher discriminating power, irrespective of what the task measures. While researchers have addressed this issue, they typically have assumed that more difficult tasks have greater discriminating power, often without actually measuring discriminating power. In this article, the authors present data from 2 studies using phonologic and category fluency tasks to demonstrate that the critical factor for task selection and matching is discriminating power, not task difficulty.

Adult↗

PubMed2005

Cholinesterase inhibitors ameliorate behavioral deficits induced by MK-801 in mice.

Enhancing cholinergic function has been suggested as a possible strategy for ameliorating the cognitive deficits of schizophrenia. The purpose of this study was to examine the effects of acetylcholinesterase (AChE) inhibitors in mice treated with the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, which has been suggested as an animal model of the cognitive deficits of schizophrenia. Three separate experiments were conducted to test the effects of physostigmine, donepezil, or galantamine on deficits in learning and memory induced by MK-801. In each experiment, MK-801 (0.05 or 0.10 mg/kg) or saline was administered i.p. 20 min prior to behavioral testing over a total of 12 days. At 30 min prior to administration of MK-801 or saline, one of three doses of the AChE inhibitor (ie physostigmine-0.03, 0.10, or 0.30 mg/kg; donepezil-0.10, 0.30, or 1.00 mg/kg; or galantamine-0.25, 0.50, or 1.00 mg/kg) or saline was administered s.c. Behavioral testing was performed in all experimental animals using the following sequence: (1) spatial reversal learning, (2) locomotion, (3) fear conditioning, and (4) shock sensitivity. Both doses of MK-801 produced impairments in spatial reversal learning and in contextual and cued memory, as well as hyperlocomotion. Physostigmine and donepezil, but not galantamine, ameliorated MK-801-induced deficits in spatial reversal learning and in contextual and cued memory in a dose-dependent manner. Also, physostigmine, but not donepezil or galantamine, reversed MK-801-induced hyperlocomotion. Galantamine, but not physostigmine or donepezil, altered shock sensitivity. These results suggest that AChE inhibitors may differ in their capacity to ameliorate learning and memory deficits produced by MK-801 in mice, which may have relevance for the cognitive effects of cholinomimetic drugs in patients with schizophrenia.

Animals↗

PubMed2004

Validation of semiautomated methods for quantifying cingulate cortical metrics in schizophrenia.

This paper validates semiautomated methods for reconstructing cortical surfaces of the cingulate gyrus from high-resolution magnetic resonance (MR) images. Bayesian segmentation was used to delineate the image voxels into five tissue types: cerebrospinal fluid (CSF), gray matter (GM), white matter (WM), and partial volumes of CSF/GM and GM/WM; the tissues were then recalibrated as CSF, GM, and WM via the Neyman-Pearson Likelihood Ratio Test. To generate cortical surfaces at the interface of GM and WM, the thresholds between the tissue types were first used to reassign partial volume voxels to CSF, GM, and WM with minimum error (that varied from 0.06 to 0.15 for the 10 subjects). Next, topology-correct cortical surfaces were generated and validated with almost all surface vertices lying within one voxel (0.5 mm) of hand contours. Dynamic programming was used to delineate and extract the cingulate gyrus from the cortical surfaces based on its gyral and sulcal boundaries. The intraclass correlation coefficient for surface area obtained by two raters for all 10 surfaces was 0.82. In addition, by repeating the entire procedure three times in one subject, we obtained a coefficient of variation of 0.0438 for surface area.

Adult↗

PubMed2004

MRI-based high-dimensional hippocampal mapping in mesial temporal lobe epilepsy.

MRI-based evaluation of the hippocampus is important in the assessment and treatment of patients with mesial temporal lobe epilepsy (MTLE). Using MRI-based large-deformation high-dimensional mapping (HDM-LD), which allows structural evaluation of regions of the hippocampus, we document the HDM-LD-defined pattern of hippocampal deformation in MTLE patients compared with matched controls. In 30 subjects with MTLE and confirmed medial temporal lobe sclerosis (MTS), we performed measurements of intracranial area, brain parenchymal volume and deformation-based hippocampal segmentations, and then grouped patients into right and left MTS groups (resulting in 15 subjects in each group). Using HDM-LD techniques, we compared the right and left MTS groups with a group of 15 matched controls. Analysis included both the MTS and contralateral hippocampi, and covariance for changes in brain parenchymal volume. Final results were interpreted using a segmentation showing normal hippocampal surface subfield anatomy. Comparing the MTS groups with controls, after covarying with brain parenchymal volume, the MTS hippocampi showed significant volume loss (P < 0.0001), contralateral hippocampi showed no significant volume loss. HDM-LD techniques showed significant shape changes, with marked inward deviation in the Sommer sector of the MTS hippocampi. In the contralateral hippocampi, the inferior surface of the hippocampal body showed inward deformation in the medial aspect of the subiculum, with minimal involvement of the Sommer sector. HDM-LD shows involvement of subregions of the hippocampus which are consistent with MTS histopathology. Contralateral hippocampi show different HDM-LD changes, suggesting that the underlying disease process in the contralateral hippocampi is different from MTS.

Adult↗

PubMed2004

Correlates of cognitive deficits in first episode schizophrenia.

OBJECTIVE: The presence of cognitive dysfunction in schizophrenia has been well documented, but questions remain about whether there are relationships between this dysfunction and clinical symptomatology. If present, such relationships should be most clearly observable in patients with first episode schizophrenia; that is, before the effects of chronic illness, institutionalization, or treatment might confound them. METHOD: 307 schizophrenia subjects in their first episode of illness were recruited to participate in a clinical trial comparing the long-term efficacy of haloperidol and risperidone. The psychopathology, cognitive functioning, early treatment history, and duration of untreated psychosis of these subjects were assessed prior to their assignment to randomized, double-blind treatment. Approximately two-thirds of the subjects were receiving antipsychotic treatment at the time of assessment; however, the duration of treatment was limited to 12 weeks or less. RESULTS: The severity of negative symptoms at the time of assessment was associated with deficits in memory, verbal fluency, psychomotor speed and executive function. Positive symptoms were not associated with cognitive deficits. Also, the duration of untreated illness (DUI) prior to assessment was not significantly associated with cognitive impairment. CONCLUSIONS: The results of this study of first episode schizophrenia patients suggest that a relationship exists between negative symptoms and cognitive dysfunction. However, that relationship accounts for only a minor portion of the variance (i.e., 10-15%) in the severity of cognitive dysfunction after controlling for a number of potentially confounding factors. This finding provides support for the theory that the neurobiological processes that give rise to symptomatology and cognitive dysfunction in schizophrenia are partially overlapping.

Adolescent↗

PubMed2004

Platelet serotonin content correlates inversely with life history of aggression in personality-disordered subjects.

The objective of this study was to test the hypothesis that platelet serotonin (5-hydroxytryptamine, 5-HT) content is correlated with measures of aggression in healthy human subjects. Platelet 5-HT content (ng/mg protein) was measured in personality-disordered (PD) and normal control (NC) subjects. Aggression was assessed with the Life History of Aggression (LHA), the Buss-Durkee Hostility Inventory (BDHI), and the Motor Aggression and Research Criteria for Intermittent Explosive Disorder (IED-IR); impulsivity was assessed with the Eysenck Personality Questionnaire II (EPQII) and the Barratt Impulsiveness Scale (BIS-11). LHA Aggression, but not impulsivity, scores showed significant inverse correlations with platelet 5-HT content in all subjects or in PD subjects alone. The findings in PD subjects remained significant after co-varying for race. PD subjects with IED-IR had lower platelet 5-HT content compared with PD subjects who did not have IED-IR, although this finding only approached significance after controlling for race. This study demonstrates an association between reduced platelet 5-HT content and aggression in PD subjects. Similar to other studies of platelet 5-HT markers, these data suggest that platelet 5-HT content may also reflect central 5-HT alterations and may be used as a biological marker in appropriate patient samples.

Aggression↗

PubMed2004

Computational anatomy and neuropsychiatric disease: probabilistic assessment of variation and statistical inference of group difference, hemispheric asymmetry, and time-dependent change.

Three components of computational anatomy (CA) are reviewed in this paper: (i) the computation of large-deformation maps, that is, for any given coordinate system representations of two anatomies, computing the diffeomorphic transformation from one to the other; (ii) the computation of empirical probability laws of anatomical variation between anatomies; and (iii) the construction of inferences regarding neuropsychiatric disease states. CA utilizes spatial-temporal vector field information obtained from large-deformation maps to assess anatomical variabilities and facilitate the detection and quantification of abnormalities of brain structure in subjects with neuropsychiatric disorders. Neuroanatomical structures are divided into two types: subcortical structures-gray matter (GM) volumes enclosed by a single surface-and cortical mantle structures-anatomically distinct portions of the cerebral cortical mantle layered between the white matter (WM) and cerebrospinal fluid (CSF). Because of fundamental differences in the geometry of these two types of structures, image-based large-deformation high-dimensional brain mapping (HDBM-LD) and large-deformation diffeomorphic metric matching (LDDMM) were developed for the study of subcortical structures and labeled cortical mantle distance mapping (LCMDM) was developed for the study of cortical mantle structures. Studies of neuropsychiatric disorders using CA usually require the testing of hypothesized group differences with relatively small numbers of subjects per group. Approaches that increase the power for testing such hypotheses include methods to quantify the shapes of individual structures, relationships between the shapes of related structures (e.g., asymmetry), and changes of shapes over time. Promising preliminary studies employing these approaches to studies of subjects with schizophrenia and very mild to mild Alzheimer's disease (AD) are presented.

Algorithms↗

PubMed2004

Abnormalities of thalamic volume and shape in schizophrenia.

OBJECTIVE: Postmortem and neuroimaging studies of schizophrenia have reported deficits in the volume of the thalamus and its component nuclei. However, the pattern of shape change associated with such volume loss has not been investigated. In this study, alterations in thalamic volume, shape, and symmetry were compared in subjects with and without schizophrenia. METHOD: T(1)-weighted magnetic resonance scans were collected in 52 schizophrenia and 65 comparison subjects matched for age, gender, race, and parental socioeconomic status. High-dimensional (large-deformation) brain mapping was used to assess thalamic morphology. RESULTS: Significant differences in thalamic volume, deformities of thalamic shape at the anterior and posterior extremes of the structure, and a significant exaggeration of thalamic asymmetry (i.e., left smaller than right) were found in the schizophrenia subjects. After covarying for total cerebral volume, the difference in thalamic volume became insignificant. When information about thalamic shape was combined with previously collected information about hippocampal shape, the discrimination between schizophrenia patients and comparison subjects was improved. CONCLUSIONS: Thalamic volume was smaller than normal in schizophrenia patients, but only proportionate to reductions in reduced total cerebral volume. The presence of changes in thalamic shape and asymmetry suggest greater pathologic involvement of individual nuclei at its anterior and posterior extremes of the thalamic complex.

Adult↗

PubMed2003

Hippocampal deformities in the unaffected siblings of schizophrenia subjects.

BACKGROUND: Neuroanatomical abnormalities have been reported in schizophrenia subjects and their relatives and may be related to genetic vulnerability. The objective of this study was to further elucidate hippocampal deformities as a marker of genetic vulnerability for schizophrenia. METHODS: Magnetic resonance scans were collected in 13 pairs of schizophrenics and their unaffected siblings from families with multiple affected members, in 12 schizophrenics from families without another affected member, and in 10 healthy controls. Hippocampal volume and shape were compared using large-deformation high-dimensional brain mapping. RESULTS: Decreases in hippocampal volume, covaried for total cerebral volume, were observed in the schizophrenia subjects from families with multiple affected members, as well as in their unaffected siblings. Shape analysis demonstrated that both groups of schizophrenia subjects, as well as the unaffected siblings, could be distinguished from the controls; however, no significant difference in hippocampal shape was found between the schizophrenia subjects and their unaffected siblings. Visualization of the pattern of hippocampal shape deformity in both groups of schizophrenia subjects and in the unaffected siblings showed inward deformities of the head of the hippocampus. CONCLUSIONS: Deformations of hippocampal anatomy may be related to the genetic vulnerability of acquiring schizophrenia.

Adult↗

PubMed2003

Intracerebroventricular kainic acid administration to neonatal rats alters interneuron development in the hippocampus.

The effects of neonatal exposure to excitotoxins on the development of interneurons have not been well characterized, but may be relevant to the pathogenesis of neuropsychiatric disorders. In this study, the excitotoxin, kainic acid (KA) was administered to rats at postnatal day 7 (P7) by intracerebroventricular (i.c.v.) infusion. At P14, P25, P40 and P60, Nissl staining and immunohistochemical studies with the interneuron markers, glutamic acid decarboxylase (GAD-67), calbindin-D28k (CB) and parvalbumin (PV) were performed in the hippocampus. In control animals, the total number of interneurons, as well as the number of interneurons stained with GAD-67, CB and PV, was nearly constant from P14 through P60. In KA-treated rats, Nissl staining, GAD-67 staining, and CB staining revealed a progressive decline in the overall number of interneurons in the CA1 and CA3 subfields from P14 to P60. In contrast, PV staining in KA-treated rats showed initial decreases in the number of interneurons in the CA1 and CA3 subfields at P14 followed by increases that approached control levels by P60. These results suggest that, in general, early exposure to the excitotoxin KA decreases the number of hippocampal interneurons, but has a more variable effect on the specific population of interneurons labeled by PV. The functional impact of these changes may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia.

Aging↗

PubMed2003

NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice.

The interpretation of learning and memory deficits in transgenic mice has largely involved theories of NMDA receptor and/or hippocampal function. However, there is little empirical data that describes what NMDA receptors or the hippocampus do in mice. This research assessed the effects of different doses of the NMDA receptor antagonist, MK-801, or different-sized hippocampal lesions on several behavioral parameters in adult male C57Bl/6 mice. In the first set of experiments, different doses of MK-801 (0.05-0.3mg/kg, s.c.) were assayed in fear conditioning, shock sensitivity, locomotion, anxiety, and position habit reversal tests. Contextual and cued fear conditioning, and position habit reversal were impaired in a dose-dependent manner. Locomotor activity was increased immediately after injection of the highest dose of MK-801. A second set of experiments determined the behavioral effects of a moderate and large excitotoxic hippocampal lesion. Both lesions impaired contextual conditioning, while the larger lesion interfered with cued conditioning. Reversal learning was significantly diminished by the large lesion, while the moderate lesion had a detrimental effect at a trend level (P<0.10). These results provide important reference data for studies involving genetic manipulations of NMDA receptor or hippocampal function in mice. Furthermore, they serve as a basis for a non-transgenic mouse model of the NMDA receptor or hippocampal dysfunction hypothesized to occur in human cognitive disorders.

Animals↗

PubMed2003

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.

Adult↗