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Biomedical subjects

Georg Grön

Publications and source records attributed to Georg Grön.

At least 19 recordsLinked to original sources
PubMed2006

Electroconvulsive therapy in the treatment of depression in a former ecstasy user.

Depression in former ecstasy users may not respond to selective serotonin reuptake inhibitors (SSRIs) possibly due to damaged serotonergic synapses following long-term heavy ecstasy use. We report findings in a patient suffering from MDMA-induced depression which was refractory to several antidepressive medications including selective noradrenergic reuptake inhibitor (SNRI) and SSRI. An add-on repeated bilateral electroconvulsive therapy (ECT) was able to achieve a stable remission of affective and cognitive symptoms with a follow-up of more than 1.5 years. Add-on ECT could be a treatment option in former ecstasy users with severe depressive disorders that fail to respond to SSRI and/or SNRI. Clinical trials are needed to evaluate further the usefulness of ECT in this patient group.

Adrenergic Uptake Inhibitors↗
PubMed2006

Error processing in major depressive disorder: evidence from event-related potentials.

In a previous study we showed that errors following errors activate a strategic (prefrontal) mechanism. In an error trial (trial n) following an erroneous previous trial (trial n - 1) healthy control subjects were found to have enlarged (more negative) amplitudes of the error related negativity (ERN)/error negativity (Ne), an electrophysiological correlate of response monitoring, in response to a negative feedback signal. Contrary to that, patients with major depressive disorder showed smaller (less negative) ERN/Ne amplitudes. It has been discussed controversially whether errors of choice (e.g., pressing an incorrect response button in an Eriksen flanker task) and errors of commission (e.g., pressing a button when one is not supposed to in a Go/Nogo task) are related to different ERN/Ne mechanisms. In the present study, we examined whether our previous result only holds for errors of choice in an Eriksen flankers task or extends to errors of commission in a Go/Nogo task, as well. Ten patients with DSM-IV major depressive disorder and 10 matched controls participated in a Go/Nogo task with performance feedback which signaled monetary reward. Patients with major depressive disorder again showed a less negative ERN/Ne amplitude in error trials following error trials. This result might reflect impaired response monitoring processes in major depressive disorder resulting from an impaired activation of a central reward pathway and/or a deficit in strategic reasoning.

Adult↗
PubMed2005

Electrophysiological correlates of error processing in borderline personality disorder.

The electrophysiological correlates of error processing were investigated in patients with borderline personality disorder (BPD) using event-related potentials (ERP). Twelve patients with BPD and 12 healthy controls were additionally rated with the Barratt impulsiveness scale (BIS-10). Participants performed a Go/Nogo task while a 64 channel EEG was recorded. Three ERP components were of special interest: error-related negativity (ERN)/error negativity (Ne), early error positivity (early Pe) reflecting automatic error processing, and the late Pe component which is thought to mirror the awareness of erroneous responses. We found smaller amplitudes of the ERN/Ne in patients with BPD compared to controls. Moreover, significant correlations with the BIS-10 non-planning sub-score could be demonstrated for both the entire group and the patient group. No between-group differences were observed for the early and late Pe components. ERP measures appear to be a suitable tool to study clinical time courses in BPD.

Adult↗
PubMed2005

Cholinergic enhancement of episodic memory in healthy young adults.

RATIONALE: Acetylcholine esterase (AchE) inhibitors are known to remediate symptoms of Alzheimer's disease. However, only few systematic data exist on the effects of cholinergic treatment on cognitive functions in normal subjects. OBJECTIVE: This study evaluated the effects of donepezil, an inhibitor of AchE, on cognitive performance in young and healthy subjects. METHODS: We used a randomised double-blind parallel group placebo-controlled repeated measures design to investigate changes of cognitive functions in a group of 30 young healthy male subjects (mean age 23.9 years+/-2.24 SD) upon application of donepezil or placebo for 30 days. Attentional and executive functions, visual and verbal short-term and working memory, semantic memory, as well as verbal and visual episodic memory were investigated using an extensive neuropsychological test battery. RESULTS: Time-by-group interactions demonstrated significant drug effects that were specific to episodic memory in both the verbal and visual domain. Additionally, donezepil significantly improved long-term visual episodic recall. In none of the other functions under investigation any significant treatment effects were observed. CONCLUSION: Given this specific drug effect and the well-known relevance of the hippocampal region for episodic memory, we conclude that this region appears to be the major target of cholinergic enhancement in healthy subjects due to long-term inhibition of AchE.

Adult↗
PubMed2005

Functional principal component analysis of fMRI data.

We describe a principal component analysis (PCA) method for functional magnetic resonance imaging (fMRI) data based on functional data analysis, an advanced nonparametric approach. The data delivered by the fMRI scans are viewed as continuous functions of time sampled at the interscan interval and subject to observational noise, and are used accordingly to estimate an image in which smooth functions replace the voxels. The techniques of functional data analysis are used to carry out PCA directly on these functions. We show that functional PCA is more effective than is its ordinary counterpart in recovering the signal of interest, even if limited or no prior knowledge of the form of hemodynamic function or the structure of the experimental design is specified. We discuss the rationale and advantages of the proposed approach relative to other exploratory methods, such as clustering or independent component analysis, as well as the differences from methods based on expanded design matrices.

Adult↗
PubMed2005

Error processing and impulsiveness in normals: evidence from event-related potentials.

Electrophysiological correlates of impulsiveness were investigated in thirty-two healthy subjects using event-related potentials (ERP). Impulsiveness was determined by calculating individual reaction times (as a function of general response speed) in order to split the entire group into two subgroups with a more controlled (n = 16) and less controlled (n = 16) response style. Participants performed a Go/Nogo task while a 64 channel EEG was recorded. Artifact-free EEG segments were used to compute ERPs on correct Go trials and incorrect Nogo trials, separately. Three ERP components were of special interest: the error-related negativity (ERN)/error negativity (Ne) and the "early" error positivity (Pe) reflecting automatic error processing and the "late" error positivity (Pe) which is thought to mirror the awareness of erroneous responses. Subjects with higher impulsiveness showed smaller amplitudes than subjects with lower impulsiveness for the ERN/Ne component and the "early" Pe component. With regard to the "late" Pe groups did not differ. Hence, ERP measures appear suitable for detailed analyses of impulsiveness in healthy participants. Moreover, present results argue for the necessity of careful control of impulsiveness when including normal comparison groups in the context of clinical studies.

Adult↗
PubMed2005

Enhancing gray-to-white matter contrast in 3T T1 spin-echo brain scans by optimizing flip angle.

BACKGROUND AND PURPOSE: Compared with MR imaging at 1.5T T1-weighted spin-echo imaging at 3T shows up with reduced gray-to-white matter contrast. The purpose of the present study was to show the effects of alterations of different flip angles as an easily accessible parameter to increase gray-to-white matter contrast. METHODS: Spin-echo T1 sequences of 6 healthy volunteers were acquired in a 3T head scanner with 5 different flip angles. Observer-independent contrast-to-noise ratios for gray versus white matter from different flip angles, as well as subjective ratings of image quality from 2 blinded neuroradiologists, were compared statistically. RESULTS: Gray-to-white matter contrast increased significantly with decreasing flip angle. No artifacts were introduced by decreasing flip angles, and T1 contrast characteristics were robust and stable at lowered flip angles. Also, specific absorption ratios significantly decreased with decreasing flip angles. CONCLUSION: Using a flip angle of 50 degrees significantly increases gray-to-white matter contrast in T1 spin-echo brain scans at 3T B0 field strength.

Adult↗
PubMed2004

Stereotaxic rTMS for the treatment of auditory hallucinations in schizophrenia.

Auditory verbal hallucinations in schizophrenia may be due to dysfunctional inner speech-related cortical areas. Repetitive transcranial magnetic stimulation (rTMS) has been reported to be an effective treatment of hallucinations. In a cross-over sham controlled study, we guided rTMS stereotactically to inner speech-related cortical areas in hallucinating patients. These areas were identified individually prior to rTMS using fMRI in a subgroup of our patients. Active stimulation was applied over Broca's area and over the superior temporal gyrus as determined by fMRI, or according to structural images in the remaining patients. rTMS did not lead to a significant reduction of hallucination severity. Conclusively, rTMS has to be regarded critically as a possible novel tool for the treatment of hallucinations.

Adult↗
PubMed2004

Monocular visual activation patterns in albinism as revealed by functional magnetic resonance imaging.

Human albinism is characterized by a disturbance of the chiasmatic projection system leading to predominant representation of just one eye in the contralateral hemisphere. Patients show congenital nystagmus without perceiving oscillopsia. The purpose of the present study was to demonstrate the consequences of atypical chiasmatic crossing with monocular visual stimulation using functional magnetic resonance imaging (fMRI). Sixteen patients with albinism and fifteen normally pigmented controls were stimulated with a monocular visual activation paradigm using flickering checkerboards. In patients, we observed contralaterally dominated activation of visual cortices correlating to clinical albinism parameters. This confirms albinism as a continuous range of hypopigmentation disorders. Additionally, albinos showed activation of the superior colliculus and of visual motion areas although the stimulus was stationary. Activation of visual motion areas is due probably to congenital nystagmus without a conscious correlate like oscillopsia.

Adult↗
PubMed2004

The effect of erroneous responses on response monitoring in patients with major depressive disorder: a study with event-related potentials.

Perceived failure is reported to have detrimental effects on subsequent performance in patients with major depressive disorder. We investigated the error-related negativity (ERN)/error negativity (Ne), an electrophysiological correlate of response monitoring, using a 64-channel EEG. Sixteen patients with DSM-IV major depressive disorder and 16 matched controls participated in an Eriksen flanker task with continuous performance feedback that signaled monetary reward. Compared to controls, patients with major depressive disorder showed a less negative ERN/Ne in error trials following error trials. This result might reflect impaired response monitoring processes in major depressive disorder resulting from an underactivity in a central reward pathway and/or a deficit in strategic reasoning.

Adult↗
PubMed2003

Enantioselective quantitation of the ecstasy compound (R)- and (S)-N-ethyl-3,4-methylenedioxyamphetamine and its major metabolites in human plasma and urine.

An enantioselective HPLC method has been developed and validated for the stereospecific analysis of N-ethyl-3,4-methylenedioxyamphetamine (MDE) and its major metabolites N-ethyl-4-hydroxy-3-methoxyamphetamine (HME) and 3,4-methylenedioxyamphetamine (MDA). These compounds have been analyzed both from human plasma and urine after administration of 70 mg pure MDE-hydrochloride enantiomers to four subjects. The samples were prepared by hydrolysis of the o-glucuronate and sulfate conjugates using beta-glucuronidase/arylsulfatase and solid-phase extraction with a cation-exchange phase. A chiral stationary protein phase (chiral-CBH) was used for the stereoselective determination of MDE, HME and MDA in a single HPLC run using sodium dihydrogenphosphate, ethylendiaminetetraacetic acid disodium salt and isopropanol as the mobile phase (pH 6.44) and fluorimetric detection (lambda(ex) 286 nm, lambda(em) 322 nm). Moreover, a suitable internal standard (N-ethyl-3,4-methylenedioxybenzylamine) was synthesized and qualified for quantitation purposes. The method showed high recovery rates (>95%) and limits of quantitation for MDE and MDA of 5 ng/ml and for HME of 10 ng/ml. The RSDs for all working ranges of MDE, MDA and HME in plasma and urine, respectively, were less than 1.5%. After validation of the analytical methods in plasma and urine samples pharmacokinetic parameters were calculated. The plasma concentrations of (R)-MDE exceeded those of the S-enantiomer (ratio R:S of the area under the curve, 3.1) and the plasma half time of (R)-MDE was longer than that of (S)-MDE (7.9 vs. 4.0 h). In contrast, the stereochemical disposition of the MDE metabolites HME and MDA was reversed. Concentrations of the (S)-metabolites in plasma of volunteers were much higher than those of the (R)-enantiomers.

3,4-Methylenedioxyamphetamine↗
PubMed2003

No hypofrontality, but absence of prefrontal lateralization comparing verbal and spatial working memory in schizophrenia.

Hypofrontality and decreased lateralization have been two major, albeit controversial, results from functional neuroimaging studies of schizophrenia. We used fMRI to study cortical activation during a verbal and spatial working memory (WM) task (2-back) in 15 inpatients acutely ill with schizophrenia and 15 matched control subjects. We hypothesized (i) hypofrontality in patients in both tasks and (ii) decreased lateralization of prefrontal activation in patients under the assumption that, in controls, left prefrontal cortex (PFC) is engaged preferentially in the verbal task (verbal domain dominance) and the right prefrontal cortex is engaged preferentially in the spatial task (spatial domain dominance). Our results showed no significant differences in frontal activation between controls and patients, i.e. no hypofrontality in patients, even at a very liberal threshold (p<0.01). This may be explained by the fact that nearly all patients studied received atypical neuroleptics. Nonetheless, we found evidence for more subtle, domain-related prefrontal dysfunction. Whereas controls showed verbal WM domain dominance in left inferior frontal cortex and spatial WM domain dominance in right prefrontal cortex, these domain dominance effects were absent in the patient group, i.e. there were no lateralization effects. Finally, only patients showed an inverse correlation between performance and right prefrontal activation in verbal WM. We conclude that the finding of hypofrontality may depend on the medication of the patients and that there is prefrontal dysfunction even in the absence of hypofrontality.

Adult↗
PubMed2003

Alike performance during nonverbal episodic learning from diversely imprinted neural networks.

Performance on neuropsychological testing permits inferences to be made regarding neural networks required to solve the task. In healthy young human subjects it is common sense that differential performance in cognitive tasks results from recruitment of different neural networks and that alike performance results from recruitment of alike neural networks. It was the goal of the present study to investigate whether these assumptions are also valid in cross-cultural studies. To address this, we used functional MRI during a nonverbal episodic memory task with repeated learning of abstract geometric patterns. Behavioural performance in this task was alike over repeated trials in native Chinese and Caucasian subjects. Given this equivalent performance, the distinct pattern of neuronal activation observed is interpreted as the outcome of different culturally imprinted processing routines. In the 'what' and 'where' framework of visuo-spatial processing initial learning in Chinese subjects activated the dorsal stream for analysis of spatial features whereas Caucasians recruited the ventral stream for object identification. With repeated learning Chinese subjects integrated visuo-spatial processing to object coding and vice versa. Thus, imprints of culture result in activation of distinct neural networks and mandate monitoring of both behavioural performance and neural recruitment in cross-cultural studies of cognition.

Adult↗
PubMed2003

Aerobic endurance exercise improves executive functions in depressed patients.

BACKGROUND: Aerobic endurance exercise has been shown to improve higher cognitive functions such as executive control in healthy subjects. We tested the hypothesis that a 30-minute individually customized endurance exercise program has the potential to enhance executive functions in patients with major depressive disorder. METHOD: In a randomized within-subject study design, 24 patients with DSM-IV major depressive disorder and 10 healthy control subjects performed 30 minutes of aerobic endurance exercise at 2 different workload levels of 40% and 60% of their predetermined individual 4-mmol/L lactic acid exercise capacity. They were then tested with 4 standardized computerized neuropsychological paradigms measuring executive control functions: the task switch paradigm, flanker task, Stroop task, and GoNogo task. Performance was measured by reaction time. Data were gathered between fall 2000 and spring 2002. RESULTS: While there were no significant exercise-dependent alterations in reaction time in the control group, for depressive patients we observed a significant decrease in mean reaction time for the congruent Stroop task condition at the 60% energy level (p = .016), for the incongruent Stroop task condition at the 40% energy level (p = .02), and for the GoNogo task at both energy levels (40%, p = .025; 60%, p = .048). The exercise procedures had no significant effect on reaction time in the task switch paradigm or the flanker task. CONCLUSION: A single 30-minute aerobic endurance exercise program performed by depressed patients has positive effects on executive control processes that appear to be specifically subserved by the anterior cingulate.

Adult↗
PubMed2002

Subjective memory complaints: objective neural markers in patients with Alzheimer's disease and major depressive disorder.

Patients with probable Alzheimer's disease and depressive patients frequently present with subjective memory complaints. Objective distinction of underlying neuronal substrate malfunction and early cross-sectional differential diagnosis have been elusive thus far. We used repetitive learning and free recall of abstract geometric patterns during functional magnetic resonance imaging to assess episodic memory in older subjects (ages 56-64 years) who sought first-time medical attention with subjective memory complaints and were diagnosed with probable Alzheimer's disease (NINCDS-ADRDA criteria; ages 51-67 years) or major depressive disorder (DSM-IV; ages 50-65 years). Contrasting healthy seniors or depressive patients with Alzheimer's disease patients revealed superiority of hippocampal activation. Contrasting Alzheimer's disease patients with seniors showed bilateral prefrontal activity as a correlate of futile compensation of episodic memory failure. Contrasting patients who had major depressive disorder with seniors or patients who had Alzheimer's disease showed bilateral activation of the orbitofrontal cortex and the anterior cingulate. Subjective memory complaints may be classified objectively and very early with functional magnetic resonance imaging of episodic memory in groups of patients with Alzheimer's disease and depressive syndrome. This may facilitate drug trials with evaluation of specific treatments, but further studies will be needed to establish the differential diagnosis for the individual patient.

Aged↗
PubMed2002

Dissociating a common working memory network from different neural substrates of phonological and spatial stimulus processing.

Positron emission tomography was used to investigate common versus specific cortical regions for the maintenance of spatial versus phonological information in working memory (WM). Group and single-subject analyses of regional cerebral blood flow during a new 2 x 2 factorial n-back task were performed. Eight subjects had to memorize either phonological features or the location of serially presented syllables. Brain activation during phonological judgment and spatial judgment (0-back) was compared with that during two corresponding WM conditions (2-back). We observed a common network associated with the requirement of maintaining and sequencing items in WM. Seven or more subjects activated (posterior) superior frontal sulcus (pSFS, BA 6/8, global maximum) and/or adjacent gyri, posterior parietal cortex, and precuneus (BA 7). Less consistently, bilateral middle frontal gyrus (BA 9/46) was involved. Bilateral anterior (BA 39/40) and posterior (BA 7) intraparietal sulcus, as well as right pSFS, exhibited dominance for spatial WM. Although underlying stimulus processing pathways for both types of information were different, no region specific for phonological WM was found. Robust activation within the left inferior frontal gyrus (BA 44 and 45) was present, during both phonological WM and phonological judgment. We conclude that the controversial left prefrontal lateralization for verbal WM reflects more general phonological processing strategies, not necessarily required by tasks using letters. We propose a stimulus-independent role for the bilateral pSFS and its vicinity for maintenance and manipulation of different context-dependent information within working memory.

Adult↗
PubMedDate not supplied

Evidence for quantitative domain dominance for verbal and spatial working memory in frontal and parietal cortex.

Neuroimaging studies in humans have shown that different working memory (WM) tasks recruit a common bilateral fronto-parietal cortical network. Animal studies as well as neuroimaging studies in humans have suggested that this network, in particular the prefrontal cortex, is preferentially recruited when material from different domains (e.g. spatial information or verbal/object information) has to be memorized. Early imaging studies have suggested qualitative dissociations in the prefrontal cortex for spatial and object/verbal WM, either in a left-right or a ventral-dorsal dimension. However, results from different studies are inconsistent. Moreover, recent fMRI studies have failed to find evidence for domain dependent dissociations of WM-related activity in prefrontal cortex. Here we present evidence from two independent fMRI studies using physically identical stimuli in a verbal and spatial WM task showing that domain dominance for WM does indeed exist, although only in the form of quantitative differences in activation and not in the form of a dissociation with different prefrontal regions showing mutually exclusive activation in different domains. Our results support a mixed dimension model of domain dominance for WM within the prefrontal cortex, with left ventral prefrontal cortex (PFC) supporting preferentially verbal WM and right dorsal PFC supporting preferentially spatial WM. The concept of domain dominance is discussed in the light of recent theories of prefrontal cortex function.

Adult↗