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Stephan Heckers

Publications and source records attributed to Stephan Heckers.

30 records · Page 2Linked to original sources
PubMed2004

Hemispheric specialization of the lateral prefrontal cortex for strategic processing during spatial and shape working memory.

OBJECTIVE: We investigated whether spatial working memory (WM) is associated with functional specialization of the right prefrontal cortex (PFC) relative to WM for shapes. We designed spatial and shape WM tasks that are relatively easy to perform and that minimize both task-switching and manipulation demands. The tasks use identical stimuli and require the same motor response. METHODS: We presented 12 subjects with target shapes that appeared in particular locations. Subjects maintained either the location or the shape of the targets in WM and responded to each probe by indicating whether it was a target. During a non-WM control task, subjects indicated whether the probe appeared on the right or left side of the screen. Subjects were scanned with a 3.0 T Siemens scanner and data were analyzed using SPM99. The WM tasks were compared to identify PFC activation that was different for spatial versus shape WM. Each WM task was also compared to the control task. RESULTS: compared with shape WM, spatial WM performance was faster and more accurate and was associated with increased right ventrolateral and frontopolar PFC activation. In contrast, compared to spatial WM, shape WM was associated with increased left ventrolateral PFC activity. CONCLUSIONS: These findings demonstrate hemispheric specialization for spatial versus shape WM in the ventrolateral PFC. The increased activity in the right PFC for spatial WM cannot be attributed to increased task difficulty, the stimuli used, or the response requirements. Rather, we propose that differences in performance and activation reflect the use of configural processing strategies for spatial WM.

Adult↗
PubMed2004

Antipsychotic polypharmacy in patients with schizophrenia: a multicentre comparative study in East Asia.

AIMS: Previous studies of the prescription patterns of psychotropic medications in patients with schizophrenia have highlighted a high rate of antipsychotic polypharmacy, but data in Asia are sparse. This study seeks to examine the prevalence of antipsychotic polypharmacy in patients with schizophrenia and compare the differences between patients receiving one vs. those receiving more than one antipsychotic. METHODS: Antipsychotic prescription for a sample of 2399 patients with schizophrenia from six countries and territories was evaluated. Daily doses of antipsychotic medications were converted to standard chlorpromazine equivalents (CPZ). RESULTS: Antipsychotic polypharmacy was found in 45.7% (n = 1097) of the patients with wide intercountry variations. Polypharmacy was associated with male gender [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.06, 1.46, P < 0.01], advanced age (t = -7.81, d.f. = 2396, P < 0.001), psychiatric hospital setting (OR 1.34, 95% CI 1.11, 1.62) as well as higher daily CPZeq doses (411.47 vs. 983.10 CPZeq day(-1), z = -25.94, P < 0.001), anticholinergic use (OR 3.17, 95% CI 2.65, 3.79, P < 0.001) and less use of an atypical antipsychotic drug (OR 0.83, 95% CI 0.71, 0.98, P < 0.05). On multivariate analysis, country, age and duration of illness were significantly associated with antipsychotic polypharmacy. CONCLUSION: This study highlighted the wide intercountry variations of antipsychotic polypharmacy which are likely to be influenced by a complex combination of clinical, setting, cultural and personal practice factors, requiring more research.

Antipsychotic Agents↗
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

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment.

The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.

Antipsychotic Agents↗
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

Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia.

BACKGROUND: Expression of messenger RNA (mRNA) for the gamma-aminobutyric acid (GABA)-synthesizing enzyme, glutamic acid decarboxylase (GAD), in the prefrontal cortex and the number of GABAergic neurons in the hippocampus are reduced in schizophrenia and bipolar disorder. We tested the hypothesis that the expression of the 2 isoforms, one 65 kd (GAD(65)) and the other 67 kd (GAD(67)), is differentially affected in the hippocampus in schizophrenia and bipolar disorder. METHODS: Hippocampal sections from 15 subjects in 3 groups (control subjects and subjects with schizophrenia and bipolar disorder) were studied using an in situ hybridization protocol with sulfur 35-labeled complementary riboprobes for GAD(65) and GAD(67) mRNA. Emulsion-dipped slides were analyzed for the density of GAD mRNA-positive neurons in 4 sectors of the hippocampus and for the cellular expression level of both GAD mRNAs. RESULTS: The density of GAD(65) and GAD(67) mRNA-positive neurons was decreased by 45% and 43%, respectively, in subjects with bipolar disorder, but only 14% and 4%, respectively, in subjects with schizophrenia. The decreased density of GAD(65) mRNA-positive neurons in subjects with bipolar disorder was significant in sectors CA2/3 and dentate gyrus, and that of GAD(67) mRNA-positive neurons was significant in CA4, but not other hippocampal sectors. Cellular GAD(65) mRNA expression was significantly decreased in subjects with bipolar disorder, particularly in CA4, but not in schizophrenic subjects. Cellular GAD(67) mRNA expression was normal in both groups. CONCLUSION: We have found a region-specific deficit of GAD(65) and GAD(67) mRNA expression in bipolar disorder.

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

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

A role for glia in the action of electroconvulsive therapy.

In this article, we consider possible mechanisms of action for electroconvulsive therapy (ECT) based on evidence regarding cellular changes in affective and psychotic illnesses. Postmortem investigations of major depression and schizophrenia have revealed abnormalities in the number of neuronal and glial cells. Such cellular changes could indicate a perturbed balance between neurogenesis and neuronal death in the adult brain. Psychotropic drugs and ECT have been shown to stimulate neurogenesis, giving rise to the hypothesis that this generation of new cells mediates some of their therapeutic effect. A possible trophic effect on glial cells has not been examined. Since glial cells are essential for proper neuronal function, treatments that alter glial function would have significant effects on brain function. We suggest that the effectiveness of ECT is, in part, related to its effect on glial cells. This testable hypothesis may advance our understanding and treatment of psychiatric disorders.

Bipolar Disorder↗