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1.  Rearranging the world: Neural networks supporting the processing of temporal connectives 
NeuroImage  2011;59(4):3662-3667.
Summary
Temporal conjunctions ‘before’ and ‘after’ give us freedom to describe a series of events in different orders. Previous studies suggested ‘before’ sentences in which events were expresses in an order inconsistent with their actual order of occurrence need additional computations, i.e. reversing the order of event mention to reach the actual order of event occurrence. This study found the additional computations may be supported by a neural network connecting the caudate nucleus with the medial prefrontal cortex, middle frontal gyrus (MFG), precuneus and occipital cortex. The connectivity in this network was strongly enhanced for ‘before’ than ‘after’ sentences. Meanwhile, another network was observed to support the memory retrieval, connecting the hippocampus with the MFG via the orbital inferior frontal gyrus and temporal pole. The connectivity pattern of this network was not different between conditions. With the common node MFG, these two networks may communicate in working memory to work together.
doi:10.1016/j.neuroimage.2011.11.039
PMCID: PMC4035217  PMID: 22146750
temporal conjunction; caudate nucleus; prefrontal cortex; precuneus; fMRI; functional connectivity
2.  Tracking Functional Brain Changes in Patients with Depression under Psychodynamic Psychotherapy Using Individualized Stimuli 
PLoS ONE  2014;9(10):e109037.
Objective
Neurobiological models of depression posit limbic hyperactivity that should normalize after successful treatment. For psychotherapy, though, brain changes in patients with depression show substantial variability. Two critical issues in relevant studies concern the use of unspecific stimulation experiments and relatively short treatment protocols. Therefore changes in brain reactions to individualized stimuli were studied in patients with depression after eight months of psychodynamic psychotherapy.
Methods
18 unmedicated patients with recurrent major depressive disorder were confronted with individualized and clinically derived content in a functional MRI experiment before (T1) and after eight months (T2) of psychodynamic therapy. A control group of 17 healthy subjects was also tested twice without intervention. The experimental stimuli were sentences describing each participant's dysfunctional interpersonal relationship patterns derived from clinical interviews based on Operationalized Psychodynamic Diagnostics (OPD).
Results
At T1 patients showed enhanced activation compared to controls in several limbic and subcortical regions, including amygdala and basal ganglia, when confronted with OPD sentences. At T2 the differences in brain activity between patients and controls were no longer apparent. Concurrently, patients had improved significantly in depression scores.
Conclusions
Using ecologically valid stimuli, this study supports the model of limbic hyperactivity in depression that normalizes after treatment. Without a control group of untreated patients measured twice, though, changes in patients' brain activity could also be attributed to other factors than psychodynamic therapy.
doi:10.1371/journal.pone.0109037
PMCID: PMC4183537  PMID: 25275317
3.  Preattentive processing of emotional musical tones: a multidimensional scaling and ERP study 
Musical emotion can be conveyed by subtle variations in timbre. Here, we investigated whether the brain is capable to discriminate tones differing in emotional expression by recording event-related potentials (ERPs) in an oddball paradigm under preattentive listening conditions. First, using multidimensional Fechnerian scaling, pairs of violin tones played with a happy or sad intonation were rated same or different by a group of non-musicians. Three happy and three sad tones were selected for the ERP experiment. The Fechnerian distances between tones within an emotion were in the same range as the distances between tones of different emotions. In two conditions, either 3 happy and 1 sad or 3 sad and 1 happy tone were presented in pseudo-random order. A mismatch negativity for the emotional deviant was observed, indicating that in spite of considerable perceptual differences between the three equiprobable tones of the standard emotion, a template was formed based on timbral cues against which the emotional deviant was compared. Based on Juslin's assumption of redundant code usage, we propose that tones were grouped together, because they were identified as belonging to one emotional category based on different emotion-specific cues. These results indicate that the brain forms an emotional memory trace at a preattentive level and thus, extends previous investigations in which emotional deviance was confounded with physical dissimilarity. Differences between sad and happy tones were observed which might be due to the fact that the happy emotion is mostly communicated by suprasegmental features.
doi:10.3389/fpsyg.2013.00656
PMCID: PMC3779798  PMID: 24065950
preattentive processing; musical emotion; timbre; event-related potential; mismatch negativity; multidimensional scaling
4.  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.
doi:10.1371/journal.pone.0101105
PMCID: PMC4076229  PMID: 24977414
5.  Altered resting-state functional connectivity in patients with chronic bilateral vestibular failure 
NeuroImage : Clinical  2014;4:488-499.
Patients with bilateral vestibular failure (BVF) suffer from gait unsteadiness, oscillopsia and impaired spatial orientation. Brain imaging studies applying caloric irrigation to patients with BVF have shown altered neural activity of cortical visual–vestibular interaction: decreased bilateral neural activity in the posterior insula and parietal operculum and decreased deactivations in the visual cortex. It is unknown how this affects functional connectivity in the resting brain and how changes in connectivity are related to vestibular impairment.
We applied a novel data driven approach based on graph theory to investigate altered whole-brain resting-state functional connectivity in BVF patients (n= 22) compared to age- and gender-matched healthy controls (n= 25) using resting-state fMRI. Changes in functional connectivity were related to subjective (vestibular scores) and objective functional parameters of vestibular impairment, specifically, the adaptive changes during active (self-guided) and passive (investigator driven) head impulse test (HIT) which reflects the integrity of the vestibulo-ocular reflex (VOR).
BVF patients showed lower bilateral connectivity in the posterior insula and parietal operculum but higher connectivity in the posterior cerebellum compared to controls. Seed-based analysis revealed stronger connectivity from the right posterior insula to the precuneus, anterior insula, anterior cingulate cortex and the middle frontal gyrus. Excitingly, functional connectivity in the supramarginal gyrus (SMG) of the inferior parietal lobe and posterior cerebellum correlated with the increase of VOR gain during active as compared to passive HIT, i.e., the larger the adaptive VOR changes the larger was the increase in regional functional connectivity.
Using whole brain resting-state connectivity analysis in BVF patients we show that enduring bilateral deficient or missing vestibular input leads to changes in resting-state connectivity of the brain. These changes in the resting brain are robust and task-independent as they were found in the absence of sensory stimulation and without a region-related a priori hypothesis. Therefore they may indicate a fundamental disease-related change in the resting brain. They may account for the patients' persistent deficits in visuo-spatial attention, spatial orientation and unsteadiness. The relation of increasing connectivity in the inferior parietal lobe, specifically SMG, to improvement of VOR during active head movements reflects cortical plasticity in BVF and may play a clinical role in vestibular rehabilitation.
Highlights
•Resting-state connectivity was investigated in bilateral vestibular failure patients.•Patients showed lower connectivity in the posterior insula and parietal operculum.•Connectivity increased with improved VOR gain during self-initiated head movements.•This may indicate adaptive mechanisms in response to bilateral vestibular failure.
doi:10.1016/j.nicl.2014.03.003
PMCID: PMC3984447  PMID: 24818075
Resting-state fMRI; Functional connectivity; Degree; Bilateral vestibular failure; Vestibulo-ocular reflex
6.  Play it again, Sam: brain correlates of emotional music recognition 
Background: Music can elicit strong emotions and can be remembered in connection with these emotions even decades later. Yet, the brain correlates of episodic memory for highly emotional music compared with less emotional music have not been examined. We therefore used fMRI to investigate brain structures activated by emotional processing of short excerpts of film music successfully retrieved from episodic long-term memory.
Methods: Eighteen non-musicians volunteers were exposed to 60 structurally similar pieces of film music of 10 s length with high arousal ratings and either less positive or very positive valence ratings. Two similar sets of 30 pieces were created. Each of these was presented to half of the participants during the encoding session outside of the scanner, while all stimuli were used during the second recognition session inside the MRI-scanner. During fMRI each stimulation period (10 s) was followed by a 20 s resting period during which participants pressed either the “old” or the “new” button to indicate whether they had heard the piece before.
Results: Musical stimuli vs. silence activated the bilateral superior temporal gyrus, right insula, right middle frontal gyrus, bilateral medial frontal gyrus and the left anterior cerebellum. Old pieces led to activation in the left medial dorsal thalamus and left midbrain compared to new pieces. For recognized vs. not recognized old pieces a focused activation in the right inferior frontal gyrus and the left cerebellum was found. Positive pieces activated the left medial frontal gyrus, the left precuneus, the right superior frontal gyrus, the left posterior cingulate, the bilateral middle temporal gyrus, and the left thalamus compared to less positive pieces.
Conclusion: Specific brain networks related to memory retrieval and emotional processing of symphonic film music were identified. The results imply that the valence of a music piece is important for memory performance and is recognized very fast.
doi:10.3389/fpsyg.2014.00114
PMCID: PMC3927073  PMID: 24634661
musical memory; episodic memory; emotions; brain-processing
7.  N1 enhancement in synesthesia during visual and audio–visual perception in semantic cross-modal conflict situations: an ERP study 
Synesthesia entails a special kind of sensory perception, where stimulation in one sensory modality leads to an internally generated perceptual experience of another, not stimulated sensory modality. This phenomenon can be viewed as an abnormal multisensory integration process as here the synesthetic percept is aberrantly fused with the stimulated modality. Indeed, recent synesthesia research has focused on multimodal processing even outside of the specific synesthesia-inducing context and has revealed changed multimodal integration, thus suggesting perceptual alterations at a global level. Here, we focused on audio–visual processing in synesthesia using a semantic classification task in combination with visually or auditory–visually presented animated and in animated objects in an audio–visual congruent and incongruent manner. Fourteen subjects with auditory-visual and/or grapheme-color synesthesia and 14 control subjects participated in the experiment. During presentation of the stimuli, event-related potentials were recorded from 32 electrodes. The analysis of reaction times and error rates revealed no group differences with best performance for audio-visually congruent stimulation indicating the well-known multimodal facilitation effect. We found enhanced amplitude of the N1 component over occipital electrode sites for synesthetes compared to controls. The differences occurred irrespective of the experimental condition and therefore suggest a global influence on early sensory processing in synesthetes.
doi:10.3389/fnhum.2014.00021
PMCID: PMC3906591  PMID: 24523689
synesthesia; multimodal; EEG; N1; integration
8.  Linking motor-related brain potentials and velocity profiles in multi-joint arm reaching movements 
The study of the movement related brain potentials (MRPBs) needs accurate technical approaches to disentangle the specific patterns of bran activity during the preparation and execution of movements. During the last forty years, synchronizing the electromyographic activation (EMG) of the muscle with electrophysiological recordings (EEG) has been commonly ussed for these purposes. However, new clinical approaches in the study of motor diseases and rehabilitation suggest the demand of new paradigms that might go further into the study of the brain activity associated with the kinematics of movements. As a response to this call, we have used a 3-D hand-tracking system with the aim to record continuously the position of an ultrasonic sender attached to the hand during the performance of multi-joint self-paced movements. We synchronized time-series of position and velocity of the sender with the EEG recordings, obtaining specific patterns of brain activity as a function of the fluctuations of the kinematics during natural movement performance. Additionally, the distribution of the brain activity during the preparation and execution phases of movements was similar that reported previously using the EMG, suggesting the validity of our technique. We claim that this paradigm could be usable in patients because of its simplicity and the potential knowledge that can be extracted from clinical protocols.
doi:10.3389/fnhum.2014.00271
PMCID: PMC4010756  PMID: 24808853
motor related brain potentials; 3-D movement analyser; time-series analysis; kinematics; self-paced movement; motor activity
9.  Itch Relief by Mirror Scratching. A Psychophysical Study 
PLoS ONE  2013;8(12):e82756.
Objective
The goal of this study was to test whether central mechanisms of scratching-induced itch attenuation can be activated by scratching the limb contralateral to the itching limb when the participant is made to visually perceive the non-itching limb as the itching limb by means of mirror images.
Methods
Healthy participants were asked to assess the intensity of an experimentally induced itch at their right forearm while they observed externally guided scratch movements either at their right (itching) or left (non-itching) forearm which were either mirrored or not mirrored. In the first experiment, a mirror placed between the participant’s forearms was used to create the visual illusion that the participant’s itching (right) forearm was being scratched while in fact the non-itching (left) forearm was scratched. To control visibility of the left (non-mirrored) forearm, a second experiment was performed in which unflipped and flipped real-time video displays of the participant’s forearms were used to create experimental conditions in which the participant visually perceived scratching either on one forearm only, on both forearms, or no scratching at all.
Results
In both experiments, scratching the non-itching limb attenuated perceived itch intensity significantly and selectively in the mirror condition, i.e., when the non-itching forearm was visually perceived as the itching limb.
Discussion
These data provide evidence that the visual illusion that an itching limb is being scratched while in fact the non-itching limb contralateral to the itching limb is scratched, can lead to significant itch relief. This effect might be due to a transient illusionary intersensory perceptual congruency of visual, tactile and pruriceptive signals. “Mirror scratching” might provide an alternative treatment to reduce itch perception in focal skin diseases with persistent pruritus without causing additional harm to the affected skin and might therefore have significant clinical impact.
doi:10.1371/journal.pone.0082756
PMCID: PMC3873464  PMID: 24386113
10.  An ERP-study of brand and no-name products 
BMC Neuroscience  2013;14:149.
Background
Brands create product personalities that are thought to affect consumer decisions. Here we assessed, using the Go/No-go Association Task (GNAT) from social psychology, whether brands as opposed to no-name products are associated with implicit positive attitudes. Healthy young German participants viewed series of photos of cosmetics and food items (half of them brands) intermixed with positive and negative words. In any given run, one category of goods (e.g., cosmetics) and one kind of words (e.g., positive) had to be responded to, whereas responses had to be withheld for the other categories. Event-related brain potentials were recorded during the task.
Results
Unexpectedly, there were no response-time differences between congruent (brand and positive words) and incongruent (brand and negative words) pairings but ERPs showed differences as a function of congruency in the 600–750 ms time-window hinting at the existence of implicit attitudes towards brand and no-name stimuli. This finding deserves further investigation in future studies. Moreover, the amplitude of the late positive component (LPC) was found to be enhanced for brand as opposed to no-name stimuli.
Conclusions
Congruency effects suggest that ERPs are sensitive to implicit attitudes. Moreover, the results for the LPC imply that pictures of brand products are more arousing than those of no-name products, which may ultimately contribute to consumer decisions.
doi:10.1186/1471-2202-14-149
PMCID: PMC3840626  PMID: 24267403
Go/Nogo; Event-related potentials; Brands; Neuromarketing; Implicit associations; Late positive component; Lateralized readiness potential
11.  Examining the McGurk illusion using high-field 7 Tesla functional MRI 
In natural communication speech perception is profoundly influenced by observable mouth movements. The additional visual information can greatly facilitate intelligibility but incongruent visual information may also lead to novel percepts that neither match the auditory nor the visual information as evidenced by the McGurk effect. Recent models of audiovisual (AV) speech perception accentuate the role of speech motor areas and the integrative brain sites in the vicinity of the superior temporal sulcus (STS) for speech perception. In this event-related 7 Tesla fMRI study we used three naturally spoken syllable pairs with matching AV information and one syllable pair designed to elicit the McGurk illusion. The data analysis focused on brain sites involved in processing and fusing of AV speech and engaged in the analysis of auditory and visual differences within AV presented speech. Successful fusion of AV speech is related to activity within the STS of both hemispheres. Our data supports and extends the audio-visual-motor model of speech perception by dissociating areas involved in perceptual fusion from areas more generally related to the processing of AV incongruence.
doi:10.3389/fnhum.2012.00095
PMCID: PMC3329794  PMID: 22529797
audio-visual integration; McGurk illusion; 7 Tesla; functional magnetic resonance imaging
12.  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.
doi:10.1371/journal.pone.0077336
PMCID: PMC3810472  PMID: 24204812
13.  Extent of cortical involvement in amyotrophic lateral sclerosis – an analysis based on cortical thickness 
BMC Neurology  2013;13:148.
Background
Besides the defining involvement of upper and lower motor neurons, the involvement of extramotor structures has been increasingly acknowledged in amyotrophic lateral sclerosis (ALS).
Methods
Here we investigated a group of 14 mildly to moderately affected ALS patients and 14 age-matched healthy control participants using cortical thickness analysis. Cortical thickness was determined from high resolution 3D T1 magnetic resonance images and involved semiautomatic segmentation in grey and white matter, cortical alignment and determination of thickness using the Laplace method. In addition to a whole-cortex analysis a region of interest approach was applied.
Results
ALS patients showed regions of significant cortical thinning in the pre- and postcentral gyri bilaterally. Further regions of cortical thinning included superior and inferior parietal lobule, angular and supramarginal gyrus, insula, superior frontal, temporal and occipital regions, thus further substantiating extramotor involvement in ALS. A relationship between cortical thickness of the right superior frontal cortex and clinical severity (assessed by the ALS functional rating scale) was also demonstrated.
Conclusions
Cortical thickness is reduced in ALS not only in motor areas but in widespread non-motor cortical areas. Cortical thickness is related to clinical severity.
doi:10.1186/1471-2377-13-148
PMCID: PMC3853794  PMID: 24138960
ALS; Cortical thickness; MRI
14.  Neural Mechanisms of Anaphoric Reference Revealed by fMRI 
Pronouns are bound to their antecedents by matching syntactic and semantic information. The aim of this functional magnetic resonance imaging study was to localize syntactic and semantic information retrieval and integration during pronoun resolution. Especially we investigated their possible interaction with verbal working memory manipulated by distance between antecedent and pronoun. We disentangled biological and syntactic gender information using German sentences about persons (biological/syntactic gender) or things (syntactic gender) followed by congruent or incongruent pronouns. Increasing the distance between pronoun and antecedent resulted in a short and a long distance condition. Analysis revealed a language related network including inferior frontal regions bilaterally (integration), left anterior and posterior temporal regions (lexico-semantics and syntactic retrieval) and the anterior cingulate gyrus (conflict resolution) involved in pronoun resolution. Activities within the inferior frontal region were driven by Congruency (incongruent > congruent) and Distance (long > short). Temporal regions were sensitive to Distance and Congruency (but solely within long distant conditions). Furthermore, anterior temporal regions were sensitive to the antecedent type with an increased activity for person pronouns compared to thing pronouns. We suggest that activity modulations within these areas reflect the integration process of an appropriate antecedent which depends on the type of information that has to be retrieved (lexico-syntactic posterior temporal, lexico-semantics anterior temporal). It also depends on the overall syntactic and semantic complexity of long distant sentences. The results are interpreted in the context of the memory–unification-control model for sentence comprehension as proposed by Vosse and Kempen (2000), Hagoort (2005), and Snijders et al. (2009).
doi:10.3389/fpsyg.2011.00032
PMCID: PMC3110973  PMID: 21713189
language; pronoun; syntax; semantics; memory; unification; MUC; fMRI
15.  Negative affect induced by derogatory verbal feedback modulates the neural signature of error detection 
The present study examines the influence of induced affective state on performance monitoring. The electroencephalogram was recorded while human participants engaged in a speeded choice-reaction time task commonly used to examine performance monitoring processes. Prior to the experiment, participants were randomly allocated to receive either encouraging or derogatory feedback during task execution. Feedback was based on each participant's reaction times. Affective state was assessed prior and after the experiment with a state questionnaire. Although participants of both feedback groups loaded high on items describing tiredness in the state questionnaire, only those with derogatory feedback loaded higher on negative state items and lower on positive state items after completion of the experiment. The error-related negativity (ERN) as an index of performance monitoring was increased after derogatory feedback; this difference was not seen at the beginning of the experiment. Negative state correlated significantly with ERN amplitude. The error positivity, a later component following errors, did not differ between feedback groups. This study provides further evidence that changes in affective state influence how we monitor ongoing behavior.
doi:10.1093/scan/nsp015
PMCID: PMC2728634  PMID: 19454619
event-related brain potentials (ERPs); error-related negativity (ERN); error positivity (Pe); performance monitoring; emotion; feedback
16.  Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation 
PLoS ONE  2013;8(4):e61883.
Background
Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention.
Methods and Results
In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance.
Conclusion
Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.
doi:10.1371/journal.pone.0061883
PMCID: PMC3629163  PMID: 23613966
17.  Observation of sonified movements engages a basal ganglia frontocortical network 
BMC Neuroscience  2013;14:32.
Background
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2202-14-32
PMCID: PMC3602090  PMID: 23496827
18.  Recognition of face-name associations after errorless and errorful learning: an fMRI study 
BMC Neuroscience  2013;14:30.
Background
Errorless learning has advantages over errorful learning. The erroneous items produced during errorful learning compete with correct items at retrieval resulting in decreased memory performance. This interference is associated with an increased demand on executive monitoring processes. Event-related functional magnetic resonance imaging (fMRI) was used to contrast errorless and errorful learning. Learning mode was manipulated by the number of distractors during learning of face-name associations: in errorless learning only the correct name was introduced. During errorful learning either one incorrect name or two incorrect names were additionally introduced in order to modulate the interference in recognition.
Results
The behavioural results showed an enhanced memory performance after errorless learning. The veridicality of recognition of the face-name associations was reflected in a left lateralized fronto-temporal-parietal network. The different learning modes were associated with modulations in left prefrontal and parietal regions.
Conclusions
Errorless learning enhances memory performance as compared to errorful learning and underpins the known advantages for errorless learning. During memory retrieval different networks are engaged for specific purposes: Recognition of face-name associations engaged a lateralized fronto-temporal-parietal network and executive monitoring processes of memory engaged the left prefrontal and parietal regions.
doi:10.1186/1471-2202-14-30
PMCID: PMC3599917  PMID: 23496800
Errorless; Errorful; Executive control; Face-name associations; Recognition; Parietal; Prefrontal
19.  Effects of AKAP5 Pro100Leu Genotype on Working Memory for Emotional Stimuli 
PLoS ONE  2013;8(1):e55613.
Recent investigations addressing the role of the synaptic multiadaptor molecule AKAP5 in human emotion and behavior suggest that the AKAP5 Pro100Leu polymorphism (rs2230491) contributes to individual differences in affective control. Carriers of the less common Leu allele show a higher control of anger as indicated by behavioral measures and dACC brain response on emotional distracters when compared to Pro homozygotes. In the current fMRI study we used an emotional working memory task according to the n-back scheme with neutral and negative emotional faces as target stimuli. Pro homozygotes showed a performance advantage at the behavioral level and exhibited enhanced activation of the amygdala and fusiform face area during working memory for emotional faces. On the other hand, Leu carriers exhibited increased activation of the dACC during performance of the 2-back condition. Our results suggest that AKAP5 Pro100Leu effects on emotion processing might be task-dependent with Pro homozygotes showing lower control of emotional interference, but more efficient processing of task-relevant emotional stimuli.
doi:10.1371/journal.pone.0055613
PMCID: PMC3558499  PMID: 23383244
20.  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.
doi:10.3389/neuro.09.022.2009
PMCID: PMC2741292  PMID: 19750197
local field potentials; intracranial recordings; deep brain stimulation; addiction; reward processing; action monitoring; nucleus accumbens
21.  Oscillatory Brain Activity Related to Control Mechanisms during Laboratory-Induced Reactive Aggression 
Aggressive behavior is a common reaction in humans after an interpersonal provocation, but little is known about the underlying brain mechanisms. The present study analyzed oscillatory brain activity while participants were involved in an aggressive interaction to examine the neural processes subserving the associated decision and evaluation processes. Participants were selected from a larger sample because of their high scores in trait aggressiveness. We used a competitive reaction time task that induces aggressive behavior through provocation. Each trial is separated in a decision phase, during which the punishment for the opponent is set, and an outcome phase, during which the actual punishment is applied or received. We observed provocation-related differences during the decision phase in the theta band which differed depending on participants’ aggressive behavior: high provocation was associated with an increased frontal theta response in participants refraining from retaliation, but with reduced theta power in those who got back to the opponent. Moreover, more aggressive decisions after being punished were associated with a decrease of frontal theta power. Non-aggressive and aggressive participants differed also in their outcome-related response: being punished led to an increased frontal theta power compared to win trials in the latter only, pointing to differences in evaluation processes associated with their different behavioral reactions. The data thus support previous evidence for a role of prefrontal areas in the control of reactive aggression and extend behavioral studies on associations between aggression or violence and impaired prefrontal functions.
doi:10.3389/neuro.08.046.2009
PMCID: PMC2783022  PMID: 19949454
reactive aggression; electroencephalography; wavelet analysis; theta; beta
22.  Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study 
Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.
doi:10.3389/fnhum.2013.00494
PMCID: PMC3759754  PMID: 24027507
stroke; music-supported therapy; music; plasticity; transcranial magnetic stimulation
23.  Functional Connectivity of Reward Processing in the Brain 
Controversial results have been reported concerning the neural mechanisms involved in the processing of rewards and punishments. On the one hand, there is evidence suggesting that monetary gains and losses activate a similar fronto-subcortical network. On the other hand, results of recent studies imply that reward and punishment may engage distinct neural mechanisms. Using functional magnetic resonance imaging (fMRI) we investigated both regional and interregional functional connectivity patterns while participants performed a gambling task featuring unexpectedly high monetary gains and losses. Classical univariate statistical analysis showed that monetary gains and losses activated a similar fronto-striatal-limbic network, in which main activation peaks were observed bilaterally in the ventral striatum. Functional connectivity analysis showed similar responses for gain and loss conditions in the insular cortex, the amygdala, and the hippocampus that correlated with the activity observed in the seed region ventral striatum, with the connectivity to the amygdala appearing more pronounced after losses. Larger functional connectivity was found to the medial orbitofrontal cortex for negative outcomes. The fact that different functional patterns were obtained with both analyses suggests that the brain activations observed in the classical univariate approach identifies the involvement of different functional networks in the current task. These results stress the importance of studying functional connectivity in addition to standard fMRI analysis in reward-related studies.
doi:10.3389/neuro.09.019.2008
PMCID: PMC2647336  PMID: 19242558
reward; nucleus accumbens; connectivity; functional magnetic resonance imaging
24.  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.
doi:10.3389/neuro.09.011.2007
PMCID: PMC2525987  PMID: 18958225
action monitoring; nucleus accumbens; event-related brain potentials; intracranial recordings; neurosurgery
25.  Use of cranial CT to identify a new infarct in patients with a transient ischemic attack 
Brain and Behavior  2012;2(4):377-381.
Research on infarct detection by noncontrast cranial computed tomography (CCT) in patients with transient ischemic attack (TIA) is sparse. However, the aims of this study are to determine the frequency of new infarcts in patients with TIA, to evaluate the independent predictors of infarct detection, and to investigate the association between a new infarct and early short-term risk of stroke during hospitalization. We prospectively evaluated 1533 consecutive patients (mean age, 75.3 ± 11 years; 54% female; mean National Institutes of Health Stroke Scale [NIHSS] score, 1.7 ± 2.9) with TIA who were admitted to hospital within 48 h of symptom onset. A new infarct was detected by CCT in 47 (3.1%) of the 1533 patients. During hospitalization, 17 patients suffered a stroke. Multivariate logistic regression analysis revealed the following independent predictors for infarct detection: NIHSS score ≥10 (odds ratio [OR], 4.8), time to CCT assessment >6 h (OR 2.2), and diabetes (OR 2.3). The evidence of a new infarct was not associated with the risk of stroke after TIA. The frequency of a new infarct in patients with TIA using CCT is low. The use of the CCT tool to predict the stroke risk during hospitalization in patients with TIA is found to be inappropriate. The estimated clinical predictors are easy to use and may help clinicians in the TIA work up.
doi:10.1002/brb3.59
PMCID: PMC3432960  PMID: 22950041
CCT; epidemiology; infarct; prognosis; stroke; TIA

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