Biomedical subjects

Karsten Heekeren

Publications and source records attributed to Karsten Heekeren.

9 recordsLinked to original sources

PubMed2006

An fMRI approach to particularize the frontoparietal network for visuomotor action monitoring: Detection of incongruence between test subjects' actions and resulting perceptions.

Contemporary theories of motor control assume that motor actions underlie a supervisory control system which utilizes reafferent sensory feedbacks of actions for comparison with the original motor programs. The functional network of visuomotor action monitoring is considered to include inferior parietal, lateral and medial prefrontal cortices. To study both sustained monitoring for visuomotor incongruence and the actual detection of incongruence, we used a hybrid fMRI epoch-/event-related design. The basic experimental task was a continuous motor task, comprising a simple racing game. Within certain blocks of this task, incongruence was artificially generated by intermittent takeover of control over the car by the computer. Fifteen male subjects were instructed to monitor for incongruence between their own and the observed actions in order to abstain from their own action whenever the computer took over control. As a result of both sustained monitoring and actual detection of visuomotor incongruence, the rostral inferior parietal lobule displayed a BOLD signal increase. In contrast, the prefrontal cortex (PFC) exhibited two different activation patterns. Dorsolateral (BA 9/46) and medial/cingulate (BA 8, BA 32) areas of the PFC displayed a greater increase of activation in sustained monitoring, while ventrolateral PFC showed greater event-related activation for the actual detection of visuomotor incongruence. Our results suggest that the rostral inferior parietal lobule is specifically involved in the reafferent comparison of the test subjects' own actions and visually perceived actions. Different activation patterns of the PFC may reflect different frontoparietal networks for sustained action monitoring and actual detection of reafferent incongruence.

Adult↗

PubMed2006

Inhibition of return in the human 5HT2A agonist and NMDA antagonist model of psychosis.

Patients with schizophrenia exhibit disturbances of orienting of attention. However, findings have been inconsistent. Pharmacologic challenges with hallucinogens have been used as models for psychosis. The NMDA antagonist state (PCP, ketamine) resembles undifferentiated psychoses with positive and negative symptoms, while the 5-HT(2A) agonist state (LSD, dimethyltryptamine (DMT)) is thought to be an appropriate model for psychoses with prominent positive symptoms. The aim of this study was to investigate orienting of attention in the human NMDA antagonist and 5-HT(2A) agonist models of psychosis. A total of 15 healthy volunteers participated in a randomized, double-blind, crossover study with a low and a high dose of DMT and S-ketamine, which elicited subtle 'prepsychotic' or full-blown psychotic symptoms (low and high dose, respectively). Nine subjects completed both experimental days with the two doses of both drugs. Overall, both hallucinogens slowed down reaction times dose dependently (DMT >S-ketamine) and DMT diminished the general response facilitating (alerting) effect of spatially neutral cues. Inhibition of Return (IOR), that is, the normal reaction time disadvantage for validly cued trials with exogenous cues and long cue target intervals, was blunted after both doses of DMT and the low dose of S-ketamine. IOR reflects an automatic, inhibitory mechanism of attention, which is thought to protect the organism from redundant, distracting sensory information. In conclusion, our data suggest a deficit of IOR in both hallucinogen models of psychosis, with the effect being clearer in the serotonin model. Blunted IOR may underlie or predispose to different psychotic manifestations, but particularly to those with prominent positive symptoms.

Adult↗

PubMed2005

Memory-related hippocampal dysfunction in poly-drug ecstasy (3,4-methylenedioxymethamphetamine) users.

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic in animal studies and its use has been associated with cognitive impairments in humans. OBJECTIVE: To study hippocampal activation during the retrieval from episodic memory in polyvalent users of ecstasy. METHODS: Twelve polyvalent ecstasy users and twelve matched controls were examined by means of functional magnetic resonance imaging (fMRI) while they retrieved face-profession associations from episodic memory. RESULTS: Ecstasy users had a normal structural MRI scan without focal brain lesions or anatomical abnormalities. They exhibited equal retrieval accuracy during memory retrieval to that of the matched controls. Yet, their retrieval-related activity was lower and more spatially restricted in the left anterior hippocampus than that of the controls. CONCLUSIONS: These results provide evidence for abnormal hippocampal functioning in MDMA users even at the presence of normal memory performance. This finding may be linked to MDMA-induced neurotoxicity and suggests that diminished hippocampal activation during memory retrieval might be a more sensitive or earlier index of MDMA-related neurotoxicity than neuropsychological performance.

Adult↗

PubMed2005

Deficient inhibition of return in schizophrenia-further evidence from an independent sample.

Previous studies on spatial orienting of attention in schizophrenia demonstrated a deficit of Inhibition of Return (IOR). However, other studies reported a delay in the manifestation, but an overall normal amount of IOR in patients with schizophrenia. However, the latter studies used a cue-back manipulation which is known to reinstate or speed up IOR. Hence, it is not clear whether even very long cue target intervals would allow IOR to develop in patients with schizophrenia in the absence of a cue-back manipulation. The aim of the present study was to study IOR in patients with schizophrenia using a single cue paradigm and a very long cue target interval of >1 s in order to differentiate between blunted and delayed IOR. We examined 32 inpatients with schizophrenia and 16 healthy controls with a covert orienting of attention task (COVAT) with non-predictive peripheral cues and three stimulus onset asynchronies (SOA: 100 ms, 800 ms and 1050 ms). We found a lack of Inhibition of Return (IOR) in patients with schizophrenia with both long SOAs of 800 and 1050 ms. As in a previous study of our group, the IOR deficit was unrelated to psychopathology, length of illness, number of previous psychotic episodes and type of neuroleptic medication. In summary, our study confirms and extends previous reports of deficient IOR in patients with schizophrenia. IOR seems to be not just delayed, but rather profoundly disturbed in schizophrenia. Deficient IOR in patients with schizophrenia might be viewed as a trait or alternatively as a vulnerability marker of the disorder.

Adult↗

PubMed2004

Neural mechanisms of working memory in ecstasy (MDMA) users who continue or discontinue ecstasy and amphetamine use: evidence from an 18-month longitudinal functional magnetic resonance imaging study.

BACKGROUND: Working memory processing in ecstasy (3,4-methylenedioxymethamphetamine) users is associated with neural alterations as measured by functional magnetic resonance imaging. Here, we examined whether cortical activation patterns change after prolonged periods of continued use or abstinence from ecstasy and amphetamine. METHODS: We used an n-back task and functional magnetic resonance imaging in 17 ecstasy users at baseline (t(1)) and after 18 months (t(2)). Based on the reported drug use at t(2) we separated subjects with continued ecstasy and amphetamine use from subjects reporting abstinence during the follow-up period (n = 9 and n = 8, respectively). RESULTS: At baseline both groups had similar task performance and similar cortical activation patterns. Task performance remained unchanged in both groups. Furthermore, there were no detectable functional magnetic resonance imaging signal changes from t(1) to t(2) in the follow-up abstinent group. However, the continuing users showed a dose-dependent increased parietal activation for the 2-back task after the follow-up period. CONCLUSIONS: Our data suggest that ecstasy use, particularly in high doses, is associated with greater parietal activation during working memory performance. An altered activation pattern might appear before changes in cognitive performance become apparent and, hence, may reflect an early stage of neuronal injury from the neurotoxic drug ecstasy.

Adult↗

PubMed2004

Plasticity of the acoustic startle reflex in currently abstinent ecstasy (MDMA) users.

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is neurotoxic upon central serotonin systems in experimental animals and probably also in humans. Serotonin is involved in the habituation, sensitization and prepulse inhibition (PPI) of the startle reflex. OBJECTIVES: To study the plasticity of startle reflex in currently abstinent MDMA users. METHODS: Electromyographic responses to acoustic startle stimuli (pulse alone and prepulse-pulse trials) were recorded in 23 currently abstinent ecstasy users and 20 matched control subjects. Depending on the extent of their previous drug use ecstasy users were divided into two groups [life-time dose <90 (n=11) and > or =90 pills (n=12), respectively]. RESULTS: There were no significant differences in habituation, sensitization or PPI of the startle reflex between the entire group of ecstasy users and controls. However, sensitization of the startle reflex was stronger in the > or =90 compared with either the <90 MDMA pills or the control group. Correlations between patterns of drug use and startle parameters did not reach the level of significance, although users with a younger age at the onset of MDMA (and other drug) use tended to present with higher sensitization of the startle reflex. CONCLUSIONS: Heavy users of MDMA (and other recreational drugs) present with strong sensitization of the startle reflex. Nevertheless, it is unclear whether this finding is secondary to the use of MDMA and its well-recognized neurotoxic potential. Alternatively, strong sensitization might reflect a pre-existing trait predisposing to drug use. A clearer picture of the impact of ecstasy on startle plasticity may be obtained from longitudinal investigations.

Adult↗

PubMed2004

Blunted inhibition of return in schizophrenia-evidence from a longitudinal study.

Previous cross-sectional studies on covert orienting of visual attention in schizophrenia have been inconsistent. In the present longitudinal study, we examined 40 medicated acutely ill inpatients with a covert orienting of attention task (COVAT) shortly after admission, and again 12-16 weeks after the initial examination, while most patients were in (partial) remission. We administered a COVAT with nonpredictive peripheral cues and two stimulus-onset asynchronies (SOA; 100 and 800 ms). In addition, we examined 34 healthy control subjects twice (2 weeks apart). The most important finding was a lack of inhibition of return (IOR) in patients with schizophrenia, both at the first examination in an acute psychotic state and at the follow-up examination after considerable clinical improvement. The IOR deficit was unrelated to psychopathology, length of illness, number of previous psychotic episodes, and type of neuroleptic (NL) medication. Deficient IOR in patients with schizophrenia appears to be state-independent and might be viewed as a trait or vulnerability marker of the disorder. Subsequent studies with never-medicated populations and with schizotypal or high-risk subjects are needed in order to further analyze the possible role of NL medications and to clarify whether blunted IOR might represent a vulnerability marker of schizophrenia.

Adult↗

PubMed2004

[Notes concerning the uncritical handling of the diagnosis "Kleptomania"].

The diagnosis kleptomania is based on diagnostic criteria which describe a particular distinctive behaviour. Both the DSM-IV and the WHO-ICD10 neglect the different etiologic possibilities. The high co-morbidity of kleptomania with other mental disorders is another problem. The assessment of legal responsibility should not only focus on the analysis of the stealing act, but has to consider potential associated psychopathology. It appears insufficient to describe complex organic disorders (for example a dementia) with the term kleptomania. However, the forensic relevance of kleptomania, which seems to be very rare, is a result of symptom progression, decreasing satisfaction and feelings of shame or distress.

Atrophy↗

PubMed2004

Attentional modulation of prepulse inhibition: a new startle paradigm.

There is increasing evidence for an influence of directed attention on prepulse inhibition (PPI) of the acoustic startle reflex. However, the existing paradigms for the assessment of this effect have methodological problems and pitfalls. In particular, most previous studies used a paradigm which directed the attention of subjects to the prepulse only. In the present study, we used a modified paradigm which directed the attention of the subjects both to the prepulse and the pulse. Twenty healthy male subjects were instructed trial by trial either to relax or to attend to the startle stimulus and decide whether it was a 'simple' (prepulse alone or pulse alone) or a 'composite' trial (pulse plus a prepulse or postpulse). Directed attention enhanced PPI at the lead interval of 240 ms, but not at the lead interval of 100 ms. This finding is in line with the idea that attention contributes to PPI when there is enough time for the attentional mechanisms to exert an influence. This new paradigm offers a valuable tool for the study of attentional modulation of sensorimotor gating in humans.

Acoustic Stimulation↗