Biomedical subjects

Andreas Meyer-Lindenberg

Publications and source records attributed to Andreas Meyer-Lindenberg.

25 records · Page 2Linked to original sources

PubMed2005

Executive function and cognitive subprocesses in first-episode, drug-naive schizophrenia: an analysis of N-back performance.

OBJECTIVE: This study investigated changes in the cognitive architecture of N-back performance in schizophrenia. METHOD: N-back performance of 12 patients with first-episode, drug-naive schizophrenia and matched healthy comparison subjects was studied in a reaction-time decomposition paradigm. RESULTS: Imposition of a working memory load led to a significant drop in response accuracy in patients. Reaction-time decomposition suggested slowing of visuomotor and choice reaction processing as well as an inability of parallel processing directed by working memory. DISCUSSION: Although N-back tasks validly access working memory function as a neurocognitive trait in the illness, several additional subprocesses and the ability for cognitive parallel processing are altered and require further study in schizophrenia.

Adult↗

PubMed2004

The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology.

A variation in the BDNF gene (val66met) affects the function of BDNF in neurons, predicts variation in human memory, and is associated with several neurological and psychiatric disorders. Here, we show that, in magnetic resonance imaging scans of a large sample of normal individuals, this polymorphism affects the anatomy of the hippocampus and prefrontal cortex, identifying a genetic mechanism of variation in brain morphology related to learning and memory.

Adolescent↗

PubMed2004

Neural basis of genetically determined visuospatial construction deficit in Williams syndrome.

A unique opportunity to understand genetic determinants of cognition is offered by Williams syndrome (WS), a well-characterized hemideletion on chromosome 7q11.23 that causes extreme, specific weakness in visuospatial construction (the ability to visualize an object as a set of parts or construct a replica). Using multimodal neuroimaging, we identified a neural mechanism underlying the WS visuoconstructive deficit. Hierarchical assessment of visual processing with fMRI showed isolated hypoactivation in WS in the parietal portion of the dorsal stream. In the immediately adjacent parietooccipital/intraparietal sulcus, structural neuroimaging showed a gray matter volume reduction in participants with WS. Path analysis demonstrated that the functional abnormalities could be attributed to impaired input from this structurally altered region. Our observations confirm a longstanding hypothesis about dorsal stream dysfunction in WS, demonstrate effects of a localized abnormality on visual information processing in humans, and define a systems-level phenotype for mapping genetic determinants of visuoconstructive function.

Adult↗

PubMed2004

Shared and distinct neurophysiological components of the digits forward and backward tasks as revealed by functional neuroimaging.

The digits forward (DF) and backward (DB) tasks are widely used neuropsychological measures believed to tap overlapping systems of phonological processing and working memory. Studies of focal brain lesions have partially elucidated the brain regions essential for these tasks; however relatively little information exists on the underlying functional neuroanatomy in the intact brain. We therefore examined the shared and separate neural systems of these tasks in two positron emission tomography (PET) experiments. In Experiment 1, eight healthy participants performed verbal DF, DB, and a sensorimotor control task during measurement of regional cerebral blood flow (rCBF). DF and DB each activated frontal, parietal, and cerebellar regions as well as prominently activating medial occipital cortex. To eliminate possible visuospatial confounds, Experiment 2 replicated the first experiment in six additional healthy participants who were blindfolded during the study. No differences in activation were found between the two experimental groups. Combined data from both experiments demonstrate that DF and DB rely upon a largely overlapping functional neural system associated with working memory, most notably right dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL) as well as the anterior cingulate, a region associated with attentional effort. The degree of activation increased linearly with increasing task difficulty in DF. DB additionally recruited bilateral DLPFC, left IPL, and Broca's area. Medial occipital cortex (including higher and lower visual processing areas) was robustly activated in both DF and DB and could not be attributed to visual processing per se, suggesting a possible visual imagery strategy for these aural-verbal tasks.

Adolescent↗

PubMed2003

Interindividual differences in functional interactions among prefrontal, parietal and parahippocampal regions during working memory.

To clarify the neural systems deployed by individual subjects during working memory (WM), we collected functional neuroimaging data from healthy subjects, and constructed a model of 2-back WM using structural equation modeling (SEM). A group model was constructed, and models for each subject were validated against it. The group model consisted principally of regions in the prefrontal and parietal cortex, with considerable interindividual variance in the single-subject models. To explore this variance, subjects were split into two groups based on performance. Performance level and self-reported strategy scores were used in a correlation analysis against path weights between nodes of individual models. High performers utilized a left hemisphere sub-network involving inferior parietal lobule and Broca's area, whereas lower performers utilized a right hemisphere sub-network with interactions between inferior parietal lobule and dorsolateral prefrontal cortex. Further, we observed an interaction between the parahippocampal formation and the inferior parietal lobule that was related to the different strategies used by the individuals to perform the task. Strategy and performance level appear to be intricately related in this task, with neural systems supporting verbal processing producing better performance than those associated with spatial processing. These results demonstrate that individual behavioral characteristics are reflected in specific neurofunctional patterns at the system level and that these can be captured by analytical techniques such as SEM.

Adult↗

PubMed2002

Transitions between dynamical states of differing stability in the human brain.

What mechanisms underlie the flexible formation, adaptation, synchronization, and dissolution of large-scale neural assemblies from the 10(10) densely interconnected, continuously active neurons of the human brain? Nonlinear dynamics provides a unifying perspective on self-organization. It shows that the emergence of patterns in open, nonequilibrium systems is governed by their stability in response to small disturbances and predicts macroscopic transitions between patterns of differing stability. Here, we directly demonstrate that such transitions can be elicited in the human brain by interference at the neural level. As a probe, we used a classic motor coordination paradigm exhibiting well described movement states of differing stability. Functional neuroimaging identified premotor (PMA) and supplementary motor (SMA) cortices as having neural activity linked to the degree of behavioral instability. These regions then were transiently disturbed with graded transcranial magnetic stimulation, which caused sustained and macroscopic behavioral transitions from the less stable out-of-phase to the stable in-phase movement, whereas the stable pattern could not be affected. Moreover, the strength of the disturbance needed (a measure of neural stability) was linked to the degree of behavioral stability, demonstrating the applicability of nonlinear system theory as a powerful predictor of the dynamical repertoire of the human brain.

Adult↗

PubMed2002

Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia.

Both dopaminergic neurotransmission and prefrontal cortex (PFC) function are known to be abnormal in schizophrenia. To test the hypothesis that these phenomena are related, we measured presynaptic dopaminergic function simultaneously with regional cerebral blood flow during the Wisconsin Card Sorting Test (WCST) and a control task in unmedicated schizophrenic subjects and matched controls. We show that the dopaminergic uptake constant Ki in the striatum was significantly higher for patients than for controls. Patients had significantly less WCST-related activation in PFC. The two parameters were strongly linked in patients, but not controls. The tight within-patient coupling of these values, with decreased PFC activation predicting exaggerated striatal 6-fluorodopa uptake, supports the hypothesis that prefrontal cortex dysfunction may lead to dopaminergic transmission abnormalities.

Cerebrovascular Circulation↗