Biomedical subjects

Anthony P Weiss

Publications and source records attributed to Anthony P Weiss.

17 recordsLinked to original sources

PubMed2006

Fronto-hippocampal function during temporal context monitoring in schizophrenia.

BACKGROUND: Patients with schizophrenia have difficulty using contextual information to recall the source of information. Given the importance of the hippocampus and prefrontal cortex (PFC) in this type of memory, we hypothesized that this cognitive deficit stemmed from aberrant fronto-hippocampal activation during memory retrieval. METHODS: Patients with schizophrenia (n = 16) and age-matched comparison subjects (n = 16) underwent functional magnetic resonance imaging while performing a verbal memory task that requires intact use of temporal context. Blood oxygen-level dependent (BOLD) signal during correct memory decisions was compared between the two groups with statistical parametric mapping. RESULTS: Contrary to our hypotheses, patients with schizophrenia demonstrated nearly identical memory performance to that of the comparison subjects. Despite this, there were significant between-group BOLD signal differences, including a pattern of task-dependent hypofrontality or hyperfrontality. In addition, whereas the highest-performing subset of the comparison group demonstrated robust modulation of hippocampal activity, this pattern was not seen in the highest-performing patients with schizophrenia. CONCLUSIONS: Despite memory performance similar to that of comparison subjects, patients with schizophrenia activated different neural pathways to achieve this success. This might reflect underlying neuropathology in fronto-hippocampal circuitry, the use of an alternate cognitive strategy to accomplish task performance, or both.

Adult↗

PubMed2006

Treatment of cardiac risk factors among patients with schizophrenia and diabetes.

OBJECTIVE: The appropriateness and effectiveness of the outpatient medical management of cardiac risk factors for patients with diabetes who had a diagnosis of schizophrenia or a related psychotic syndrome were examined. METHODS: In a cross-sectional analysis of 4,236 patients with diabetes, ICD-9 billing codes were used to identify 214 patients with schizophrenia or a schizophrenia-related syndrome. Measures of treatment appropriateness and effectiveness for the management of cardiac risk factors (control of blood sugar, blood pressure, and lipids) were assessed for this group and compared with measures from patients with diabetes but no severe mental illness (N = 3,594). Odds ratios were adjusted for between-group differences in gender, race, age, and clinic setting. RESULTS: There were no statistically significant between-group differences on any of the five measures of treatment appropriateness, indicating that patients with schizophrenia received a similar regimen of medical treatment for cardiac factors. However, two of the seven measures of treatment effectiveness indicated significant deficiencies, with fewer patients with schizophrenia meeting the clinical quality benchmarks for cholesterol and low-density lipoprotein control. This disparity may have been caused by factors other than the measured treatment appropriateness variables, including the prescription of older lipid-lowering agents and a higher rate of missed appointments in the group with schizophrenia. CONCLUSIONS: Effective lipid control may be more difficult to attain for at least some patients with schizophrenia. Given that population's high rates of cardiovascular mortality, additional research to clarify the barriers to effective lipid management is essential.

Aged↗

PubMed2005

Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia.

INTRODUCTION: Patients with schizophrenia show deficits in facial affect and facial identity recognition and exhibit structural and neurophysiological abnormalities in brain regions known to mediate these processes. Functional neuroimaging studies of neural responses to emotional facial expressions in schizophrenia have reported both increases and decreases in medial temporal lobe (MTL) activity in schizophrenia. Some of this variability may be related to the tasks performed and the baseline conditions used. Here we tested whether MTL responses to human faces in schizophrenia are abnormal when unconstrained by a cognitive task and measured relative to a low-level baseline (fixation) condition. METHODS: 15 patients with schizophrenia and 16 healthy control subjects underwent functional magnetic resonance imaging (fMRI) while passively viewing human faces displaying fearful, happy, and neutral emotional expressions. RESULTS: Relative to control subjects, the patients demonstrated (1) significantly greater activation of the left hippocampus while viewing all three facial expressions and (2) increased right amygdala activation during the initial presentation of fearful and neutral facial expressions. CONCLUSIONS: In schizophrenia, hippocampal and amygdala activity is elevated during the passive viewing of human faces.

Adult↗

PubMed2005

Hippocampal and parahippocampal volumes in schizophrenia: a structural MRI study.

Smaller medial temporal lobe volume is a frequent finding in studies of patients with schizophrenia, but the relative contributions of the hippocampus and three surrounding cortical regions (entorhinal cortex, perirhinal cortex, and parahippocampal cortex) are poorly understood. We tested the hypothesis that the volumes of medial temporal lobe regions are selectively changed in schizophrenia. We studied 19 male patients with schizophrenia and 19 age-matched male control subjects. Hippocampal and cortical volumes were estimated using a three-dimensional morphometric protocol for the analysis of high-resolution structural magnetic resonance images, and repeated measures ANOVA was used to test for region-specific differences. Patients had smaller overall medial temporal lobe volumes compared to controls. The volume difference was not specific for either region or hemisphere. The finding of smaller medial temporal lobe volumes in the absence of regional specificity has important implications for studying the functional role of the hippocampus and surrounding cortical regions in schizophrenia.

Adult↗

PubMed2005

Hippocampal activation during processing of previously seen visual stimulus pairs.

Activity in the hippocampus is modulated by novelty detection, and by the processing of conjunctions between two stimuli. We investigated whether the hippocampus is activated by discrimination of stimulus-stimulus relationships in novel versus familiar pairs of visual stimuli in 15 healthy subjects using functional magnetic resonance imaging. Subjects were asked to recognize the previously rewarded stimulus in each case. We found significantly greater activation of the right hippocampus when discriminating previously seen compared with novel pairs of visual stimuli. This activation was evident in individual subjects and was not related to stimulus novelty, reward contingency, or task instruction. Right hippocampal activation during discrimination of previously seen pairs of objects was correlated with activity in the anteromedial thalamus, cingulate cortex, and contralateral hippocampus.

Adult↗

PubMed2005

Sustained activation of the hippocampus in response to fearful faces in schizophrenia.

BACKGROUND: In healthy individuals, the activity of the medial temporal lobe habituates rapidly with the repeated presentation of a stimulus. Using functional magnetic resonance imaging (fMRI), we tested the hypothesis that habituation of the medial temporal lobe is reduced in schizophrenia. METHODS: During fMRI scanning, fearful and happy faces were presented repeatedly to healthy control subjects (n =16) and patients with schizophrenia (n =18). Habituation of medial temporal lobe structures was measured by comparing the hemodynamic response occurring during the early and late portions of the presentation of each face. RESULTS: Control subjects demonstrated significant medial temporal lobe habituation to fearful but not to happy faces. In contrast, patients with schizophrenia did not demonstrate medial temporal lobe habituation in response to fearful or happy faces. In a direct, between-group comparison, right hippocampal habituation to fearful faces was significantly greater in control subjects than in the schizophrenia patients. Also, there were no significant differences between the patients and control subjects in the early medial temporal lobe response to fearful faces, suggesting that attenuated hippocampal habituation in schizophrenia is not associated with a reduction in initial activation. CONCLUSIONS: These findings suggest that there is abnormal modulation of hippocampal responses to fearful faces in schizophrenia.

Adult↗

PubMed2005

Anterior and posterior hippocampal volumes in schizophrenia.

BACKGROUND: While the evidence for hippocampal structural abnormalities in schizophrenia is now well accepted, whether there is differentially greater volume loss within specific subregions of the hippocampus remains a matter of some debate. Here we present volume estimates of anterior and posterior hippocampal volumes using a novel morphometric protocol. METHODS: We studied 25 male patients with schizophrenia and 25 age-matched male control subjects. Hippocampal volumes were estimated using a three-dimensional morphometric protocol for the analysis of high-resolution structural magnetic resonance images (MRI). Anterior hippocampal volumes were differentiated from posterior hippocampal volumes by the presence of the uncus in coronal slices. RESULTS: While the patients with schizophrenia had significantly smaller overall hippocampal volumes relative to the control group, there was no evidence for a topographically specific pattern of volume loss along the anterior-posterior hippocampal axis. CONCLUSIONS: These results confirm the presence of overall hippocampal volume decreases in patients with schizophrenia, but do not confirm a topographically specific localization of this effect. It appears that the hippocampal volume deficit in schizophrenia is diffuse, a finding that has important consequences for understanding the underlying pathophysiologic mechanisms in schizophrenia.

Adult↗

PubMed2004

Impaired hippocampal function during the detection of novel words in schizophrenia.

BACKGROUND: Patients with schizophrenia have smaller hippocampal volumes and perform abnormally on most declarative memory tasks. Although these findings are likely related, the impact of hippocampal pathology on cognitive performance in schizophrenia remains unclear. This study examined this relationship by measuring the volume of the hippocampus and its activation during memory task performance. METHODS: Participants included 15 patients with schizophrenia and 16 age-matched control subjects. Hippocampal volume was determined via three-dimensional volumetric analysis of high-resolution magnetic resonance images. Hippocampal activity was assessed by measuring changes in blood oxygen level-dependent signal during a recognition memory task. RESULTS: Patients with schizophrenia had smaller hippocampal volumes bilaterally and demonstrated poorer performance on the recognition memory task, largely because of a heightened rate of false alarms to novel stimuli. Both groups showed robust hippocampal activity to old and new items when compared with a low-level baseline task; however, direct comparison of hippocampal activity during recognition task performance revealed that healthy control, but not the schizophrenia, subjects showed significant right anterior hippocampal activation during the evaluation of novel items. CONCLUSIONS: The impaired ability to classify new items as previously not experienced is associated with decreased recruitment and smaller volume of the hippocampus in schizophrenia.

Adult↗

PubMed2004

Hippocampal activation during transitive inference in humans.

Studies in rodents have demonstrated that the integration and flexible expression of memories, necessary for transitive inference, depend on an intact hippocampus. To test this hypothesis in humans, we studied brain activation during the discrimination of a series of overlapping and non-overlapping arbitrary visual stimulus pairs. We report that transitive inference about overlapping pairs is associated with right anterior hippocampal activation, whereas recognition of non-overlapping stimulus pairs is associated with bilateral medial temporal lobe activation centered in the anterior parahippocampal gyrus. We conclude that immediate access to simple stimulus-stimulus relationships is mediated via the parahippocampal gyrus, whereas the flexible representation of memory requires the recruitment of the hippocampus.

Adult↗

PubMed2004

Anterior cingulate cortex activation during cognitive interference in schizophrenia.

BACKGROUND: Previous studies have reported evidence of structural and functional abnormalities in the anterior cingulate cortex of patients with schizophrenia. METHOD: The authors studied 19 male patients with chronic schizophrenia and 15 healthy male comparison subjects with functional magnetic resonance imaging and the novel Multi-Source Interference Task, a task designed to elicit robust dorsal anterior cingulate cortex activation in individual subjects. Group averaged and individual (region-of-interest-based) brain activation patterns were compared during the performance of control and interference trials. RESULTS: Performance (reaction times and accuracy) did not differ between healthy subjects and patients with schizophrenia. Comparison of interference and neutral blocks revealed activation in the medial wall of the prefrontal cortex in 93% (N=14) of the healthy subjects and 84% (N=16) of the subjects with schizophrenia. Sixty-seven percent (N=10) of the healthy subjects but only 16% (N=3) of the subjects with schizophrenia displayed maximum medial wall activation within the dorsal anterior cingulate cortex. CONCLUSIONS: The Multi-Source Interference Task produced robust activation in the medial wall of the prefrontal cortex during cognitive interference. Analysis of individual activation patterns revealed medial wall abnormalities in schizophrenia patients.

Cognition Disorders↗

PubMed2003

Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia.

BACKGROUND: Patients with schizophrenia demonstrate poor verbal memory, ascribed to impaired prefrontal and hippocampal function. Healthy adults can increase recall accuracy following encoding interventions, such as item repetition and the formation of semantic associations. We examined the effects of these interventions on both memory performance and retrieval-related hippocampal activity in healthy adults and patients with schizophrenia. METHODS: Twelve patients with schizophrenia and twelve healthy control subjects participated. During study, subjects counted either the number of meanings or T-junctions in words seen only once or repeated four times. At test, O15-positron emission tomography scans were acquired while subjects completed word-stems with previously studied items. RESULTS: Control subjects recalled more words overall, but both groups demonstrated similar performance benefits following deeper encoding. Both item repetition and the use of a semantic encoding task were associated with memory retrieval-related hippocampal recruitment in control but not schizophrenic participants. Patients with schizophrenia demonstrated greater activation of prefrontal cortical areas during word retrieval. CONCLUSIONS: Despite a lack of hippocampal recruitment, patients with schizophrenia showed intact modulation of memory performance following both encoding interventions. Impaired hippocampal recruitment, in concert with greater prefrontal activation, may reflect a specific deficit in conscious recollection in schizophrenia.

Hippocampus↗

PubMed2003

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression.

OBJECT: Neurosurgical procedures are a viable intervention for severe, treatment-refractory major depression, although they have been associated with only modest rates of efficacy. The purpose of this study was to identify possible neuroimaging predictors of treatment response to anterior cingulotomy in patients with major depression. METHODS: Thirteen patients underwent stereotactic anterior cingulotomy for treatment-refractory major depression. Symptom severity was measured using the Beck Depression Inventory (BDI) both before and approximately 12 months after surgery. The authors performed [18F]fluorodeoxyglucose-positron emission tomography (PET) studies in all patients preoperatively. Statistical parametric mapping methods were used to test for loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in BDI scores. The mean (+/- standard deviation) change in the BDI score from the preoperative period (43.7 +/- 7.8) to the postoperative period (30.5 +/- 21.3) was 33.1 +/- 45.4%. Two loci--the left subgenual prefrontal cortex and left thalamus--were identified as sites at which preoperative metabolism was significantly correlated with subsequent improvement in depressive symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at these loci were associated with better postoperative results. CONCLUSIONS: Possible PET scanning predictors of treatment response were identified in patients with major depression who had undergone anterior cingulotomy. Further research will be necessary to determine the reproducibility of this finding. If confirmed, the availability of an index for noninvasively predicting a patient's response to cingulotomy for the treatment of major depression would be of great clinical value.

Adult↗

PubMed2002

Reversed hemispheric asymmetry during simple visual perception in schizophrenia.

Processing of sensory information in the human brain progresses from primary areas, dedicated to a single sensory feature, to multimodal areas, which integrate many features across sensory modalities. For some of these processes hemispheric dominance has developed. Here we report the results of a passive viewing task using positron emission tomography. Subjects were scanned twice while staring at a stationary visual noise pattern. Normal subjects showed a significant reduction of regional cerebral blood flow (rCBF) in a distributed right hemisphere network of brain regions during the second visual task. Schizophrenic subjects, however, showed significant increases of right hemisphere rCBF during the second visual task and showed significant decreases only in the left hemisphere. These results are consistent with the notion of reversed hemispheric asymmetry during the processing of sensory information in schizophrenia.

Adult↗

PubMed2002

Hippocampal and brain stem activation during word retrieval after repeated and semantic encoding.

Repeated word presentation during learning and the use of a semantic encoding task both increase the accuracy of subsequent word retrieval. Previous neuroimaging studies have shown that successful word retrieval depends on the recruitment of the hippocampus, whereas the effort of retrieval is linked to activation of prefrontal cortex modules. We studied the effects of repetition (4x versus 1x presentation) and encoding task (semantic versus perceptual) on hippocampal and prefrontal cortex activation during word-stem cued recall using positron emission tomography. Repeated and semantic encoding resulted in increased recall accuracy, with word repetition showing a greater effect when using a semantic encoding task. The more successful retrieval of words presented repeatedly compared with words presented once was associated with activation of the left anterior hippocampus. The more successful retrieval of words encoded using a semantic compared with a perceptual task was associated with activation of the right posterior and, less significantly, the left anterior hippocampus. The greater benefit of repeated learning when using the semantic task was linked to activation of the right brainstem, in the region of the ventral tegmentum. Our results suggest that word repetition and semantic encoding increase recall accuracy during subsequent word retrieval via distinct hippocampal mechanisms and that ventral tegmentum activation is relevant for word retrieval after semantic encoding. These findings confirm the importance of hippocampal recruitment during word retrieval and provide novel evidence for a role of brainstem neurons in word retrieval after semantic encoding.

Adult↗

PubMed2002

Magnetic resonance imaging-guided stereotactic limbic leukotomy for treatment of intractable psychiatric disease.

OBJECTIVE: To assess the efficacy and complication rates of magnetic resonance imaging-guided stereotactic limbic leukotomy for the treatment of intractable major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). METHODS: We conducted preoperative evaluations and postoperative follow-up assessments of efficacy and complications for 21 patients who underwent limbic leukotomy. Efficacy was based on physician- and patient-rated global assessments of functioning, as well as evaluations using disease-specific rating scales commonly used in studies of MDD and OCD. RESULTS: The mean time from limbic leukotomy to follow-up assessment was 26 months. On the basis of standard outcome measures, 36 to 50% of patients were considered to be treatment responders. Although permanent surgical morbidity was rare, there were reports of postoperative sequelae, including apathy, urinary incontinence, and memory complaints, which occurred in a substantial minority of cases. CONCLUSION: For this cohort of 21 patients with chronic severe MDD or OCD, who had experienced failure with an exhaustive array of previous treatments, limbic leukotomy was associated with substantial benefit for 36 to 50%. This rate is comparable to those of previous studies of limbic system surgery and indicates that limbic leukotomy is a feasible treatment option for severe, treatment-refractory MDD or OCD. Adverse consequences associated with the procedure included affective, cognitive, and visceromotor sequelae, which were generally transient.

Adult↗

PubMed2002

Intact suppression of increased false recognition in schizophrenia.

OBJECTIVE: Recognition memory is impaired in patients with schizophrenia, as they rely largely on item familiarity, rather than conscious recollection, to make mnemonic decisions. False recognition of novel items (foils) is increased in schizophrenia and may relate to this deficit in conscious recollection. By studying pictures of the target word during encoding, healthy adults can suppress false recognition. This study examined the effect of pictorial encoding on subsequent recognition of repeated foils in patients with schizophrenia. METHOD: The study included 40 patients with schizophrenia and 32 healthy comparison subjects. After incidental encoding of 60 words or pictures, subjects were tested for recognition of target items intermixed with 60 new foils. These new foils were subsequently repeated following either a two- or 24-word delay. Subjects were instructed to label these repeated foils as new and not to mistake them for old target words. RESULTS: Schizophrenic patients showed greater overall false recognition of repeated foils. The rate of false recognition of repeated foils was lower after picture encoding than after word encoding. Despite higher levels of false recognition of repeated new items, patients and comparison subjects demonstrated a similar degree of false recognition suppression after picture, as compared to word, encoding. CONCLUSIONS: Patients with schizophrenia displayed greater false recognition of repeated foils than comparison subjects, suggesting both a decrement of item- (or source-) specific recollection and a consequent reliance on familiarity in schizophrenia. Despite these deficits, presenting pictorial information at encoding allowed schizophrenic subjects to suppress false recognition to a similar degree as the comparison group, implying the intact use of a high-level cognitive strategy in this population.

Adult↗

PubMedDate not supplied

Neuroimaging-genetic paradigms: a new approach to investigate the pathophysiology and treatment of cognitive deficits in schizophrenia.

Cognitive impairment is a prominent and debilitating feature of schizophrenia. Genetic predisposition likely accounts for a large proportion of these cognitive deficits. Direct associations between candidate genes and cognitive dysfunction have been difficult to establish, however, largely due to the subtle effects of these genes on observable behavior. Neuroimaging techniques can provide a sensitive means to bridge the neurobiology of genes and behavior. Here we illustrate the use of neuroimaging-genetics paradigms to elaborate the relationship between genes and cognitive dysfunction in schizophrenia. After reviewing principles important for the selection of genes, neuroimaging techniques, and subjects, we describe how imaging-genetics investigations have helped clarify the contribution of five candidate genes (COMT, GRM3, G72, DISC1, and BDNF) to cognitive deficits in schizophrenia. The potential of this approach for improving patient care will depend on its ability to predict outcomes with greater accuracy and sensitivity than current clinical measures.

Brain↗