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1.  Trait Aggressiveness Is Not Related to Structural Connectivity between Orbitofrontal Cortex and Amygdala 
PLoS ONE  2014;9(6):e101105.
Studies in both pathological and healthy samples have suggested altered functional connectivity between orbitofrontal cortex (OFC) and amygdala as a possible cause of anger and aggression. In patient populations presenting with pathological aggression, there is also evidence for changes in structural connectivity between OFC and amygdala. In healthy samples, however, the relationship between white matter integrity and aggression has not been studied to date. Here, we investigated the relationship between trait aggressiveness and structural OFC-amygdala connectivity in a large sample (n = 93) of healthy young men. Using diffusion tensor imaging, we measured the distribution of fractional anisotropy and mean diffusivity along the uncinate fascicle bilaterally. We found no differences in either measure between participants high and low in physical aggressiveness, or between those high and low in trait anger. Our results therefore argue against a direct relationship between structural OFC-amygdala connectivity and normal-range trait aggressiveness.
PMCID: PMC4076229  PMID: 24977414
2.  Altered Resting State Brain Networks in Parkinson’s Disease 
PLoS ONE  2013;8(10):e77336.
Parkinson’s disease (PD) is a neurodegenerative disorder affecting dopaminergic neurons in the substantia nigra leading to dysfunctional cortico-striato-thalamic-cortical loops. In addition to the characteristic motor symptoms, PD patients often show cognitive impairments, affective changes and other non-motor symptoms, suggesting system-wide effects on brain function. Here, we used functional magnetic resonance imaging and graph-theory based analysis methods to investigate altered whole-brain intrinsic functional connectivity in PD patients (n = 37) compared to healthy controls (n = 20). Global network properties indicated less efficient processing in PD. Analysis of brain network modules pointed to increased connectivity within the sensorimotor network, but decreased interaction of the visual network with other brain modules. We found lower connectivity mainly between the cuneus and the ventral caudate, medial orbitofrontal cortex and the temporal lobe. To identify regions of altered connectivity, we mapped the degree of intrinsic functional connectivity both on ROI- and on voxel-level across the brain. Compared to healthy controls, PD patients showed lower connectedness in the medial and middle orbitofrontal cortex. The degree of connectivity was also decreased in the occipital lobe (cuneus and calcarine), but increased in the superior parietal cortex, posterior cingulate gyrus, supramarginal gyrus and supplementary motor area. Our results on global network and module properties indicated that PD manifests as a disconnection syndrome. This was most apparent in the visual network module. The higher connectedness within the sensorimotor module in PD patients may be related to compensation mechanism in order to overcome the functional deficit of the striato-cortical motor loops or to loss of mutual inhibition between brain networks. Abnormal connectivity in the visual network may be related to adaptation and compensation processes as a consequence of altered motor function. Our analysis approach proved sensitive for detecting disease-related localized effects as well as changes in network functions on intermediate and global scale.
PMCID: PMC3810472  PMID: 24204812
3.  Observation of sonified movements engages a basal ganglia frontocortical network 
BMC Neuroscience  2013;14:32.
Producing sounds by a musical instrument can lead to audiomotor coupling, i.e. the joint activation of the auditory and motor system, even when only one modality is probed. The sonification of otherwise mute movements by sounds based on kinematic parameters of the movement has been shown to improve motor performance and perception of movements.
Here we demonstrate in a group of healthy young non-athletes that congruently (sounds match visual movement kinematics) vs. incongruently (no match) sonified breaststroke movements of a human avatar lead to better perceptual judgement of small differences in movement velocity. Moreover, functional magnetic resonance imaging revealed enhanced activity in superior and medial posterior temporal regions including the superior temporal sulcus, known as an important multisensory integration site, as well as the insula bilaterally and the precentral gyrus on the right side. Functional connectivity analysis revealed pronounced connectivity of the STS with the basal ganglia and thalamus as well as frontal motor regions for the congruent stimuli. This was not seen to the same extent for the incongruent stimuli.
We conclude that sonification of movements amplifies the activity of the human action observation system including subcortical structures of the motor loop. Sonification may thus be an important method to enhance training and therapy effects in sports science and neurological rehabilitation.
PMCID: PMC3602090  PMID: 23496827
4.  Deep Brain Stimulation of Nucleus Accumbens Region in Alcoholism Affects Reward Processing 
PLoS ONE  2012;7(5):e36572.
The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H2[15O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control.
PMCID: PMC3358316  PMID: 22629317
5.  Brain Potentials of Conflict and Error-Likelihood Following Errorful and Errorless Learning in Obsessive-Compulsive Disorder 
PLoS ONE  2009;4(8):e6553.
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.
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.
PMCID: PMC2720456  PMID: 19672309
6.  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.
PMCID: PMC2741292  PMID: 19750197
local field potentials; intracranial recordings; deep brain stimulation; addiction; reward processing; action monitoring; nucleus accumbens
7.  Different Methods to Define Utility Functions Yield Similar Results but Engage Different Neural Processes 
Although the concept of utility is fundamental to many economic theories, up to now a generally accepted method determining a subject's utility function is not available. We investigated two methods that are used in economic sciences for describing utility functions by using response-locked event-related potentials in order to assess their neural underpinnings. For determining the certainty equivalent, we used a lottery game with probabilities to win p = 0.5, for identifying the subjects’ utility functions directly a standard bisection task was applied. Although the lottery tasks’ payoffs were only hypothetical, a pronounced negativity was observed resembling the error related negativity (ERN) previously described in action monitoring research, but this occurred only for choices far away from the indifference point between money and lottery. By contrast, the bisection task failed to evoke an remarkable ERN irrespective of the responses’ correctness. Based on these findings we are reasoning that only decisions made in the lottery task achieved a level of subjective relevance that activates cognitive-emotional monitoring. In terms of economic sciences, our findings support the view that the bisection method is unaffected by any kind of probability valuation or other parameters related to risk and in combination with the lottery task can, therefore, be used to differentiate between payoff and probability valuation.
PMCID: PMC2773176  PMID: 19893764
utility function; neuroeconomics; error-related negativity; executive functions; cognitive electrophysiology; lottery; bisection
8.  Contribution of Subcortical Structures to Cognition Assessed with Invasive Electrophysiology in Humans 
Frontiers in Neuroscience  2008;2(1):72-78.
Implantation of deep brain stimulation (DBS) electrodes via stereotactic neurosurgery has become a standard procedure for the treatment of Parkinson's 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, Tourette's 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.
PMCID: PMC2570064  PMID: 18982109
deep brain stimulation; action monitoring; motivation; subcortical nuclei; memory; nucleus accumbens; nucleus subthalamicus; electrophysiology
9.  Dopamine Agonist Increases Risk Taking but Blunts Reward-Related Brain Activity 
PLoS ONE  2008;3(6):e2479.
The use of D2/D3 dopaminergic agonists in Parkinson's 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.
PMCID: PMC2423613  PMID: 18575579
10.  Internal and external information in error processing 
BMC Neuroscience  2008;9:33.
The 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.
When 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.
The described pattern of results indicates a functional interrelationship of response and feedback related negativities in performance monitoring.
PMCID: PMC2291472  PMID: 18366727
11.  Nucleus Accumbens is Involved in Human Action Monitoring: Evidence from Invasive Electrophysiological Recordings 
The Nucleus accumbens (Nacc) has been proposed to act as a limbic-motor interface. Here, using invasive intraoperative recordings in an awake patient suffering from obsessive-compulsive disease (OCD), we demonstrate that its activity is modulated by the quality of performance of the subject in a choice reaction time task designed to tap action monitoring processes. Action monitoring, that is, error detection and correction, is thought to be supported by a system involving the dopaminergic midbrain, the basal ganglia, and the medial prefrontal cortex. In surface electrophysiological recordings, action monitoring is indexed by an error-related negativity (ERN) appearing time-locked to the erroneous responses and emanating from the medial frontal cortex. In preoperative scalp recordings the patient's ERN was found to be significantly increased compared to a large (n = 83) normal sample, suggesting enhanced action monitoring processes. Intraoperatively, error-related modulations were obtained from the Nacc but not from a site 5 mm above. Importantly, cross-correlation analysis showed that error-related activity in the Nacc preceded surface activity by 40 ms. We propose that the Nacc is involved in action monitoring, possibly by using error signals from the dopaminergic midbrain to adjust the relative impact of limbic and prefrontal inputs on frontal control systems in order to optimize goal-directed behavior.
PMCID: PMC2525987  PMID: 18958225
action monitoring; nucleus accumbens; event-related brain potentials; intracranial recordings; neurosurgery

Results 1-11 (11)