Marcus Heldmann

Dopamine Agonist Increases Risk Taking but Blunts Reward-Related Brain Activity

The use of D2/D3 dopaminergic agonists in Parkinsons disease (PD) may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system.

Disentangling Sequential Effects of Stimulus- and Response-related Conflict and Stimulus-Response Repetition using Brain Potentials

Conflict monitoring theory holds that detection of conflicts in information processing by the anterior cingulate cortex (ACC) results in processing adaptation that minimizes subsequent conflict. Applying an Eriksen f lanker task with four stimuli mapped onto two responses, we investigated whether such modulation occurs only after response-related or also after stimulus-related conflict, focusing on the N2 component of the event-related potential. Contrasting with previous findings, both stimulus- and response-related conflict elicited enhancement of the N2, suggesting that the ACC is sensitive to conflict at both the stimulus and the response level. However, neither type of conflict resulted in reduced conflict effects on the following trial when stimulus-response (S-R) sequence effects were controlled by excluding identical S-R repetition trials. Identical S-R repetitions were associated with facilitated processing, thus demonstrating that inclusion of these trials in the analysis may mimic results predicted by the conflict adaptation hypothesis.

Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects.

The ventral striatum/nucleus accumbens (NAcc) has been implicated in the craving for drugs and alcohol which is a major reason for relapse of addicted people. Craving might be induced by drug-related cues. This suggests that disruption of craving-related neural activity in the NAcc may significantly reduce craving in alcohol-dependent patients. Here we report on preliminary clinical and neurophysiological evidence in three male patients who were treated with high frequency deep brain stimulation of the NAcc bilaterally. All three had been alcohol-dependent for many years, unable to abstain from drinking, and had experienced repeated relapses prior to the stimulation. After the operation, craving was greatly reduced and all three patients were able to abstain from drinking for extended periods of time. Immediately after the operation but prior to connection of the stimulation electrodes to the stimulator, local field potentials were obtained from the externalized cables in two patients while they performed cognitive tasks addressing action monitoring and incentive salience of drug-related cues. LFPs in the action monitoring task provided further evidence for a role of the NAcc in goal-directed behaviors. Importantly, alcohol-related cue stimuli in the incentive salience task modulated LFPs even though these cues were presented outside of the attentional focus. This implies that cue-related craving involves the NAcc and is highly automatic.

Internal and external information in error processing

BackgroundThe use of self-generated and externally provided information in performance monitoring is reflected by the appearance of error-related and feedback-related negativities (ERN and FRN), respectively. Several authors proposed that ERN and FRN are supported by similar neural mechanisms residing in the anterior cingulate cortex (ACC) and the mesolimbic dopaminergic system. The present study is aimed to test the functional relationship between ERN and FRN. Using an Eriksen-Flanker task with a moving response deadline we tested 17 young healthy subjects. Subjects received feedback with respect to their response accuracy and response speed. To fulfill both requirements of the task, they had to press the correct button and had to respond in time to give a valid response.ResultsWhen performance monitoring based on self-generated information was sufficient to detect a criterion violation an ERN was released, while the subsequent feedback became redundant and therefore failed to trigger an FRN. In contrast, an FRN was released if the feedback contained information which was not available before and action monitoring processes based on self-generated information failed to detect an error.ConclusionThe described pattern of results indicates a functional interrelationship of response and feedback related negativities in performance monitoring.

Contribution of subcortical structures to cognition assessed with invasive electrophysiology in humans

Implantation of deep brain stimulation (DBS) electrodes via stereotactic neurosurgery has become a standard procedure for the treatment of Parkinsons disease. More recently, the range of neuropsychiatric conditions and the possible target structures suitable for DBS have greatly increased. The former include obsessive compulsive disease, depression, obesity, tremor, dystonia, Tourettes syndrome and cluster-headache. In this article we argue that several of the target structures for DBS (nucleus accumbens, posterior inferior hypothalamus, nucleus subthalamicus, nuclei in the thalamus, globus pallidus internus, nucleus pedunculopontinus) are located at strategic positions within brain circuits related to motivational behaviors, learning, and motor regulation. Recording from DBS electrodes either during the operation or post-operatively from externalized leads while the patient is performing cognitive tasks tapping the functions of the respective circuits provides a new window on the brain mechanisms underlying these functions. This is exemplified by a study of a patient suffering from obsessive-compulsive disease from whom we recorded in a flanker task designed to assess action monitoring processes while he received a DBS electrode in the right nucleus accumbens. Clear error-related modulations were obtained from the target structure, demonstrating a role of the nucleus accumbens in action monitoring. Based on recent conceptualizations of several different functional loops and on neuroimaging results we suggest further lines of research using this new window on brain functions.

Syllable congruency and word frequency effects on brain activation.

This article investigates the neural representation of the processes involved in recognizing multisyllabic words in Spanish asking whether lexical and sublexical processes are reflected in a different neuronal activation pattern. High and low frequency words were presented for lexical decision in two different colors. In the congruent condition the color boundaries matched the limit of the first syllable, whereas in the incongruent condition color boundaries and syllable boundaries did not match. The results revealed robust and dissociable brain activations for lexical frequency and syllable‐color congruency, but no interaction between the two. We interpreted the greater activation for low relative to high frequency words in the left pre/SMA region, and in the insula/inferior frontal cortex bilaterally to reflect a differential recruitment of lexico‐phonological and/or semantic processes. In contrast, we considered two interpretations for the greater deactivation in the precuneus for both lexical frequency and syllable‐color congruency words, and in the thalami and a frontal area for syllable‐color congruency words only. The deactivations may reflect the differential engagement of semantic processing or may result from the differential allocation of attentional resources. Importantly, while a differential deactivation pattern was observed in the precuneus region for lexicality and syllable‐color congruency, BOLD deconvolution revealed a remarkable difference in timing of the two effects with a much earlier deactivation peak for the syllable‐color congruency factor. Thus, effects of lexical frequency and syllable‐color congruency on brain activation show an important dissociation between lexical and sublexical processes during visual word recognition of multisyllabic words. Hum Brain Mapp 2009.

Brain Potentials of Conflict and Error-Likelihood Following Errorful and Errorless Learning in Obsessive-Compulsive Disorder

Background The anterior cingulate cortex (ACC) is thought to be overacting in patients with Obsessive Compulsive Disorder (OCD) reflecting an enhanced action monitoring system. However, influences of conflict and error-likelihood have not been explored. Here, the error-related negativity (ERN) originating in ACC served as a measure of conflict and error-likelihood during memory recognition following different learning modes. Errorless learning prevents the generation of false memory candidates and has been shown to be superior to trial-and-error-learning. The latter, errorful learning, introduces false memory candidates which interfere with correct information in later recognition leading to enhanced conflict processing. Methodology/Principal Findings Sixteen OCD patients according to DSM-IV criteria and 16 closely matched healthy controls participated voluntarily in the event-related potential study. Both, OCD- and control group showed enhanced memory performance following errorless compared to errorful learning. Nevertheless, response-locked data showed clear modulations of the ERN amplitude. OCD patients compared to controls showed an increased error-likelihood effect after errorless learning. However, with increased conflict after errorful learning, OCD patients showed a reduced error-likelihood effect in contrast to controls who showed an increase. Conclusion/Significance The increase of the errorlikelihood effect for OCD patients within low conflict situations (recognition after errorless learning) might be conceptualized as a hyperactive monitoring system. However, within high conflict situations (recognition after EF-learning) the opposite effect was observed: whereas the control group showed an increased error-likelihood effect, the OCD group showed a reduction of the error-likelihood effect based on altered ACC learning rates in response to errors. These findings support theoretical frameworks explaining differences in ACC activity on the basis of conflict and perceived error-likelihood as influenced by individual error learning rate.

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction – Safety and Clinical Long-term Results of a Pilot Trial

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.

Brain potentials reveal the role of conflict in human errorful and errorless learning

The avoidance of errors during learning, so-called errorless learning, results in increased memory performance. In the present study subjects had to learn items in an errorful and an errorless manner. After each learning session learned items were presented again, but now intermixed with items not learned before. Response-locked event-related potentials were used to investigate the neural underpinnings of cognitive control mechanisms during recognition of items learned under errorless and errorful conditions. Irrespective of the responses correctness a typical error-related negativity (ERN) was observed for items classified as learned before. In contrast to the apparent difference in memory performance between learning modes, ERN amplitudes to hits and false alarms were not different. The present pattern of results can be explained neither in terms of error detection nor the conflict monitoring account. Instead we are trying to argue that the findings add support to a theoretical proposal which posits that variations of the ERN amplitude can be best explained by the subjects perceived likelihood of making an error.

Event-Related Potentials in a Decision-Making Task with Delayed and Immediate Reward Conditions

Abstract: We investigated performance monitoring of a group of healthy normal subjects in a delay of gratification paradigm. Focusing on response-locked event-related brain potentials we observed an Ne-Pe-like complex in all conditions. While there was no modulation of the Ne-like component, the subsequent Pe-like positivity was largest in conditions in which subjects went for the largest immediate reward, regardless of whether this was disadvantageous (i.e., foreclosed a larger delayed reward) or not. We interpreted the positivity as mainly reflecting the size of the immediate reward.