Showing papers by "Gereon R. Fink published in 2010"
TL;DR: Results demonstrate that following someone else's gaze to engage in joint attention resulted in activation of anterior portion of medial prefrontal cortex known to be involved in the supramodal coordination of perceptual and cognitive processes, and support the idea that other-initiated joint attention relies upon recruitment of MPFC previously related to the “meeting of minds.”
Abstract: The ability and motivation to share attention is a unique aspect of human cognition. Despite its significance, the neural basis remains elusive. To investigate the neural correlates of joint attention, we developed a novel, interactive research paradigm in which participants' gaze behavior-as measured by an eye tracking device-was used to contingently control the gaze of a computer-animated character. Instructed that the character on screen was controlled by a real person outside the scanner, 21 participants interacted with the virtual other while undergoing fMRI. Experimental variations focused on leading versus following the gaze of the character when fixating one of three objects also shown on the screen. In concordance with our hypotheses, results demonstrate, firstly, that following someone else's gaze to engage in joint attention resulted in activation of anterior portion of medial prefrontal cortex (MPFC) known to be involved in the supramodal coordination of perceptual and cognitive processes. Secondly, directing someone else's gaze toward an object activated the ventral striatum which-in light of ratings obtained from participants-appears to underlie the hedonic aspects of sharing attention. The data, therefore, support the idea that other-initiated joint attention relies upon recruitment of MPFC previously related to the "meeting of minds." In contrast, self-initiated joint attention leads to a differential increase of neural activity in reward-related brain areas, which might contribute to the uniquely human motivation to engage in the sharing of experiences.
353 citations
TL;DR: Connectivity analyses suggest that both a reduction of pathological transcallosal influences (originating from contralesional M1) and a restitution of ipsilesional effective connectivity between SMA and M1 underlie improved motor performance.
298 citations
TL;DR: A newly developed adaptation of a method which uses eyetracking data obtained from participants in real time to control visual stimulation during functional magnetic resonance imaging is presented, providing an innovative tool to generate gaze-contingent stimuli in spite of the constraints of this experimental setting.
Abstract: The field of social neuroscience has made remarkable progress in elucidating the neural mechanisms of social cognition. More recently, the need for new experimental approaches has been highlighted that allow studying social encounters in a truly interactive manner by establishing 'online' reciprocity in social interaction. In this article, we present a newly developed adaptation of a method which uses eyetracking data obtained from participants in real time to control visual stimulation during functional magnetic resonance imaging, thus, providing an innovative tool to generate gaze-contingent stimuli in spite of the constraints of this experimental setting. We review results of two paradigms employing this technique and demonstrate how gaze data can be used to animate a virtual character whose behavior becomes 'responsive' to being looked at allowing the participant to engage in 'online' interaction with this virtual other in real-time. Possible applications of this setup are discussed highlighting the potential of this development as a new 'tool of the trade' in social cognitive and affective neuroscience.
149 citations
TL;DR: Simulation results suggest that preprocessing without a strong prior about the artifact to be removed disturbs the information content and time ordering of the data and leads to spurious and missed causalities.
139 citations
TL;DR: Investigating the neural mechanisms of empathy in ASD and familial contributions to empathy correlates found shared abnormalities in fusiform gyrus activation in affected adolescents and first-degree relatives suggest that this dysfunction constitutes a fundamental deviation in ASD.
125 citations
TL;DR: The data suggest that context, in which an action verb is encountered, modulates the neural activity within key areas of the motor system, implying that motor simulation (or motor planning) rather than semantic processing per se may underlie previously observed motor system activation related to action verb processing.
98 citations
TL;DR: The data suggest that noninvasive longitudinal monitoring and quantification of endogenous neural stem cell activation in the brain is feasible and that [18F]FLT-PET could be used to monitor the effects of drugs aimed at expanding the Neural stem cell niche.
Abstract: Neural stem cells reside in two major niches in the adult brain [i.e., the subventricular zone (SVZ) and the dentate gyrus of the hippocampus]. Insults to the brain such as cerebral ischemia result in a physiological mobilization of endogenous neural stem cells. Since recent studies showed that pharmacological stimulation can be used to expand the endogenous neural stem cell niche, hope has been raised to enhance the brain9s own regenerative capacity. For the evaluation of such novel therapeutic approaches, longitudinal and intraindividual monitoring of the endogenous neural stem cell niche would be required. However, to date no conclusive imaging technique has been established. We used positron emission tomography (PET) and the radiotracer 3′-deoxy-3′-[ 18 F]fluoro-l-thymidine ([ 18 F]FLT) that enables imaging and measuring of proliferation to noninvasively detect endogenous neural stem cells in the normal and diseased adult rat brain in vivo . This method indeed visualized neural stem cell niches in the living rat brain, identified as increased [ 18 F]FLT-binding in the SVZ and the hippocampus. Focal cerebral ischemia and subsequent damage of the blood–brain barrier did not interfere with the capability of [ 18 F]FLT-PET to visualize neural stem cell mobilization. Moreover, [ 18 F]FLT-PET allowed for an in vivo quantification of increased neural stem cell mobilization caused by pharmacological stimulation or by focal cerebral ischemia. The data suggest that noninvasive longitudinal monitoring and quantification of endogenous neural stem cell activation in the brain is feasible and that [ 18 F]FLT-PET could be used to monitor the effects of drugs aimed at expanding the neural stem cell niche.
90 citations
TL;DR: It is found that DCS facilitates declarative learning as well as blood-oxygen level dependent activity levels in the probabilistically defined cornu ammonis region of the hippocampus.
88 citations
TL;DR: The present data suggest that in patients with recurrent GBM the metabolically active tumour volume may be substantially underestimated by Gd-DTPA enhancement, and the findings support the notion that complementary information derived from MET uptake andGd- DTPA enhancement may be helpful in developing individualized, patient-tailored therapy strategies in patientswith recurrent G BM.
Abstract: Purpose
We investigated the relationship between three-dimensional volumetric data of the metabolically active tumour volume assessed using [11C]-methionine positron emission tomography (MET-PET) and the area of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement assessed using magnetic resonance imaging (MRI) in patients with recurrent glioblastoma (GBM).
83 citations
TL;DR: The data suggest that stimulating noradrenergic mechanisms may rearrange the functional network architecture within and across the hemispheres, for example, by synaptic gating, thereby optimizing motor behavior.
Abstract: Both animal and human data suggest that stimulation of the noradrenergic system may influence neuronal excitability in regions engaged in sensory processing and visuospatial attention. We tested the hypothesis that the neural mechanisms subserving motor performance in tasks relying on the visuomotor control of goal-directed hand movements might be modulated by noradrenergic influences. Healthy subjects were stimulated using the selective noradrenaline reuptake inhibitor reboxetine (RBX) in a placebo-controlled crossover design. Functional magnetic resonance imaging and dynamic causal modeling (DCM) were used to assess drug-related changes in blood oxygen level-dependent activity and interregional connectivity while subjects performed a joystick task requiring goal-directed movements. Improved task performance under RBX was associated with increased activity in right visual, intraparietal and superior frontal cortex (premotor/frontal eye field). DCM revealed that the neuronal coupling among these regions was significantly enhanced when subjects were stimulated with RBX. Concurrently, right intraparietal cortex and right superior frontal cortex exerted a stronger driving influence on visuomotor areas of the left hemisphere, including SMA and M1. These effects were independent from task difficulty. The data suggest that stimulating noradrenergic mechanisms may rearrange the functional network architecture within and across the hemispheres, for example, by synaptic gating, thereby optimizing motor behavior.
79 citations
TL;DR: The hypothesis that heterozygous PINK1 mutations act as a susceptibility factor to develop at least subtle Parkinson disease motor and nonmotor signs is strengthened, as supported by the finding of a reduced striatal dopaminergic FDOPA uptake not only in homozygous but also, albeit to a lesser extent, inheterozygous mutation carriers.
Abstract: Background: While homozygous mutations in the PINK1 gene cause recessively inherited early-onset Parkinson disease (PD), heterozygous mutations have been suggested as a susceptibility factor. Methods: To evaluate this hypothesis, 4 homozygous PINK1 patients with PD and 10 asymptomatic carriers of a single heterozygous mutation from a large German family (family W) were included in this study. Clinical follow-up of the heterozygous mutation carriers 3 years after the initial visit included a detailed videotaped neurologic examination using the Unified Parkinson9s Disease Rating Scale III protocol and smell and color discrimination testing. At follow-up, PET with 18-fluorodopa (FDOPA) of 13 family members was obtained in order to evaluate the clinical phenotype in light of nigostriatal dopaminergic functioning. The clinical and PET data were compared to those of healthy controls. Results: While there was mild worsening of clinical signs in previously affected heterozygous mutation carriers upon follow-up, 3 additional individuals had newly developed signs of possible PD. Hyposmia was found in 7 of the heterozygous mutation carriers, diminished color discrimination in 4. The homozygous mutation carriers who were all definitely affected with PD showed a severe, 60% decrease of caudate and putaminal FDOPA uptake; heterozygous offspring also had a significant 20% putaminal FDOPA uptake reduction compared to controls. Conclusions: Our findings strengthen the hypothesis that heterozygous PINK1 mutations act as a susceptibility factor to develop at least subtle Parkinson disease motor and nonmotor signs, as supported by the finding of a reduced striatal dopaminergic FDOPA uptake not only in homozygous but also, albeit to a lesser extent, in heterozygous mutation carriers.
TL;DR: In this paper, the authors found specific but distinct patterns of cerebral dysfunction associated with interference control and TD processing in ADHD, characterized by both reduced neural activation in regions critical for task performance and reduced co-activation of frontal cortex.
Abstract: Objective Both executive functions and time perception are typically impaired in subjects with attention-deficit/hyperactivity disorder (ADHD). However, the exact neural mechanisms underlying these deficits remain to be investigated. Method Fourteen subjects with ADHD and 14 age- and IQ-matched controls (aged 9 through 15 years) were assessed with functional magnetic resonance imaging while they performed a combined spatial stimulus–response compatibility (SRC) and time duration discrimination (TD) paradigm using identical stimuli for all experimental conditions. Results Children with ADHD performed less accurately in the SRC but not in the TD task compared with controls. On the brain level, subjects with ADHD showed significantly reduced neural activity in the left putamen during SRC and reduced fronto-cerebellar activation during TD when compared with the baseline conditions. Compared with subjects with ADHD, control subjects had increased activation in a left-hemispheric fronto-parietal network during the SRC task and in the right superior-frontal gyrus during the TD task. Functional connectivity analyses revealed abnormal fronto-parietal coupling during the SRC task and reduced fronto-cerebellar connectivity during the TD task in the ADHD group compared with controls. Conclusions Our findings suggest specific but distinct patterns of cerebral dysfunction associated with interference control and TD processing in ADHD, characterized by both reduced neural activation in regions critical for task performance and reduced co-activation of frontal cortex. Group differences on the behavioral level were controlled by several methodological approaches. Nonetheless, given the use of a block design, we cannot rule out the possibility that between-group differences in behavior confounded the neural activation patterns.
TL;DR: The data suggest that motion processing in ASD results in deviant activations in both the lower and higher processing stages of the dorsal pathway, which might reflect differences in the perception of visual stimuli in ASD, which possibly result in impaired integration of motion signals.
TL;DR: The results suggest that the hMNS is recruited during a low-level stage of animacy judgment representing a basic disposition to detect the salience of movements, whereas the SNN appears to be a high-level processing component serving evaluation in social and mental inference.
TL;DR: The data show time-modulated neural substrates during recent and remote memories in women and suggest that a specific MPFC activation underlies the autonoetic, emotional and self-related character of recent AMs.
TL;DR: The very early start of the attenuation already about 30 ms after stimulation onset is in line with the hypothesis of forward mechanisms, based on motor commands, as the basis of differentiation between self-produced and externally produced tactile sensations.
Abstract: Sensory stimulation resulting from one's own behavior or the outside world is easily differentiated by healthy persons who are able to predict the sensory consequences of their own actions. This ability has been related to cortical attenuation of activation elicited by self-produced stimulation. To date, however, the neural processes underlying this modulation remain to be elucidated. We therefore recorded whole-scalp magnetoencephalographic (MEG) signals from 10 young adults either when they were touched by another person with a brush or when they touched themselves with the same device. The main MEG responses peaked at the primary somatosensory cortex at 54+/-2 ms. Signals and source strengths were about a fifth weaker to self-produced than external touch. Importantly, attenuation was present in each subject. Control recordings indicated that the suppression was neither caused by hand movements as such nor by visual cues. The very early start of the attenuation already about 30 ms after stimulation onset is in line with the hypothesis of forward mechanisms, based on motor commands, as the basis of differentiation between self-produced and externally produced tactile sensations.
TL;DR: This study is the first to show developmental changes in the neural mechanisms supporting empathy from childhood to early adulthood, and may have important implications for the development of novel therapeutic interventions in clinical conditions characterized by empathy deficits, such as autism spectrum disorder.
Abstract: Although empathy is rooted early in life, the ability to understand and share the emotions of others continues to develop after childhood. Here, we aimed at exploring developmental changes in the neural mechanisms underlying empathy from childhood to early adulthood. Using functional magnetic resonance imaging, 47 healthy male subjects aged 8–27 years were investigated during an explicit empathy task. Emotional faces were presented and participants were either asked to infer the emotional state from the face (other-task) or to judge their own emotional response to the face (self-task). A perceptual decision on the width of faces was used as a control condition. Age-related activity increases were observed in the fusiform gyrus and inferior frontal gyrus, depending on whether subjects attributed emotions to self or other. During the self-task, activity in the right precuneus and right intraparietal sulcus decreased as a function of age. No age-related differences were observed in behavioral performance measures. Increased activity in the fusiform gyrus and in the frontal component of the human mirror neuron system with increasing age may be explained by greater experience and expertise accumulated during socio-emotional interactions. Greater recruitment of right parietal structures in younger as compared to older subjects might reflect developmental differences in the cognitive strategies to infer one’s own emotional response. This study is the first to show developmental changes in the neural mechanisms supporting empathy. Our findings may have important implications for the development of novel therapeutic interventions in clinical conditions characterized by empathy deficits, such as autism spectrum disorder.
TL;DR: In this article, the authors investigated whether a period of continuous theta burst stimulation (cTBS) induces cortical plasticity and thus improves bradykinesia of the upper limb in Parkinson's disease.
Abstract: The purpose of this study was to investigate whether a period of continuous theta burst stimulation (cTBS) induces cortical plasticity and thus improves bradykinesia of the upper limb in Parkinson’s disease. In eight patients with Parkinson’s disease (two females; mean age: 68.5 ± 5 years; disease duration: 4 ± 3 years) electrophysiological (motor evoked potentials, contralateral and ipsilateral silent period) and behavioural (Purdue pegboard test, UPDRS motor subscore) parameters were evaluated before (baseline condition) and after a 40-s period of (1) real or (2) sham continuous theta burst stimulation over the primary motor cortex contralateral to the more affected body side off dopaminergic drugs. Compared to baseline, cTBS did change neither measures of cortical excitability nor behavioural measures. cTBS over the primary motor cortex does not impact on cortical excitability or motor function of the upper limb in Parkinson’s disease. We interpret these data to reflect impaired cortical plasticity in Parkinson’s disease. This study is an important contribution to the knowledge about impaired plasticity in Parkinson’s disease.
TL;DR: It is concluded that cytoarchitectonic maps of striate and extrastriate visual areas may provide a valuable method for assigning functional group activations and thus add valuable a priori knowledge to the analysis of functional imaging data of the visual cortex.
TL;DR: In Parkinson’s disease the beneficial effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple finger, hand and pointing movements is reduced by preconditioning with cathodal tDCS, but not with anodAL tDCS.
Abstract: To investigate whether a period of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over M1 preconditioned by tDCS improves bradykinesia of the upper limb in Parkinson's disease (PD). Fifteen patients with PD performed index finger, hand tapping and horizontal pointing movements as well as reach-to-grasp movements with either hand before (baseline conditions) and after a period of 1 Hz rTMS preconditioned by (1) sham, (2) anodal or (3) cathodal tDCS over the primary motor cortex contralateral to the more affected body side. Movement kinematics was analysed using an ultrasound-based motion analyser at baseline, immediately after and 30 min after each stimulation session. Dopaminergic medication was continued. Compared to baseline, 1 Hz rTMS significantly increased the frequency of index finger and hand tapping as well as horizontal pointing movements performed with the contralateral hand. Movement frequency increased up to 40% over 30 min after cessation of the stimulation. Preconditioning with cathodal tDCS, but not with anodal tDCS, reduced the effectiveness of 1 Hz rTMS to improve tapping and pointing movements. There was no significant increase of movement frequencies of the ipsilateral hand induced by 1 Hz rTMS preconditioned by either tDCS session. Movement kinematics of reach-to-grasp movements were not significantly influenced by either stimulation session. In PD the beneficial effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple finger, hand and pointing movements is reduced by preconditioning with cathodal tDCS, but not with anodal tDCS. Preconditioning with tDCS is a powerful tool to modulate the behavioural effect of 1 Hz rTMS over the primary motor cortex in PD.
TL;DR: The key problems of neuronavigation for TMS are delineated and how they can be addressed by modern neuronavigational strategies.
TL;DR: In this article, the effects of APOE genotype on spatial contextual memory encoding and retrieval success in healthy older adults were investigated using event-related functional magnetic resonance imaging (fMRI) data.
TL;DR: The data suggest a specific topography of ‘tremor clusters’ for rest and postural tremor in PD, and presume that the same tremor mechanisms exist in patients with tremor‐dominant and akinetic‐rigid PD, but to different degrees.
Abstract: Implantation of electrodes in the subthalamic nucleus (STN) for deep brain stimulation is a well-established method to ameliorate motor symptoms in patients suffering from Parkinson's disease (PD). This study investigated the pathophysiology of rest and postural tremor in PD. In 14 patients with PD, we recorded intraoperatively local field potentials (LFPs) in the STN (at different recording depths) and electromyographic signals (EMGs) of the contralateral forearm. Using coherence analysis we analysed tremor epochs both at rest and hold conditions in patients of the akinetic-rigid or of the tremor-dominant PD subtype. Data analysis revealed significant LFP-EMG coherence during periods of rest and postural tremor. However, strong differences between both tremor types were observed: local maxima (cluster) of rest and postural tremor did not match. Additionally, during rest tremor coherence occurred significantly more frequently at single tremor frequency than at double tremor frequency in tremor-dominant as well as in akinetic-rigid patients. In contrast, during postural tremor in patients with akinetic-rigid PD coherence was predominantly at double tremor frequency. The data suggest a specific topography of 'tremor clusters' for rest and postural tremor. Furthermore, we presume that the same tremor mechanisms exist in patients with tremor-dominant and akinetic-rigid PD, but to different degrees.
TL;DR: The time course and the location of the activations suggest that the mechanisms involved in generating the Müller-Lyer illusion are closely linked to the ones associated with object perception, consistent with theories considering a relevant contribution of higher visual areas to the generation of the Müllers-Lyers illusion.
Abstract: By attaching arrows to a line's ends, the Muller-Lyer illusion can be used to modulate perceived line length. In the present study, we investigated the dynamics of the brain processes underlying this illusion using magnetoencephalography. Subjects were presented with a horizontal line with arrows attached to its ends. Across trials, the angles formed by the arrows were repeatedly changed such that 2 variants of the Muller-Lyer length illusion were either induced or not. The onset of both variants of the illusion revealed consistent activations in visual areas between 85 and 130 ms after stimulus onset, as well as strong and longer lasting activations along the ventral visual processing stream including inferior occipital, inferior temporal, and fusiform gyrus within the range of 195--220 ms. Subsequent neural activation was observed in the right superior temporal cortex, as well as in the right inferior parietal and the right inferior frontal cortex. The time course and the location of the activations suggest that the mechanisms involved in generating the Muller-Lyer illusion are closely linked to the ones associated with object perception, consistent with theories considering a relevant contribution of higher visual areas to the generation of the Muller-Lyer illusion.
TL;DR: The macrosphere model closely resembles the characteristical dynamics of postischemic inflammation previously observed in human stroke and is suggested to be highly appropriate for studying the pathophysiology of stroke in a translational approach from rodent to human.
Abstract: Neuroinflammation evolves as a multi-facetted response to focal cerebral ischemia. It involves activation of resident glia cell populations, recruitment of blood-derived leucocytes as well as humoral responses. Among these processes, phagocyte accumulation has been suggested to be a surrogate marker of neuroinflammation. We previously assessed phagocyte accumulation in human stroke by MRI. We hypothesize that phagocyte accumulation in the macrosphere model may resemble the temporal and spatial patterns observed in human stroke. In a rat model of permanent focal ischemia by embolisation of TiO2-spheres we assessed key features of post-ischemic neuroinflammation by the means of histology, immunocytochemistry of glial activation and influx of hematogeneous cells, and quantitative PCR of TNF-α, IL-1, IL-18, and iNOS mRNA. In the boundary zone of the infarct, a transition of ramified microglia into ameboid phagocytic microglia was accompanied by an up-regulation of MHC class II on the cells after 3 days. By day 7, a hypercellular infiltrate consisting of activated microglia and phagocytic cells formed a thick rim around the ischemic infarct core. Interestingly, in the ischemic core microglia could only be observed at day 7. TNF-α was induced rapidly within hours, IL-1β and iNOS peaked within days, and IL-18 later at around 1 week after ischemia. The macrosphere model closely resembles the characteristical dynamics of postischemic inflammation previously observed in human stroke. We therefore suggest that the macrosphere model is highly appropriate for studying the pathophysiology of stroke in a translational approach from rodent to human.
TL;DR: The data suggest an age-associated functional reorganization in the neural networks underlying long-term declarative memory, which could reflect changes in visuospatial processing during episodic memory retrieval in older adults.
TL;DR: It is concluded that the newly developed ADL-based neglect battery provides an economic and ecologically valid tool for the assessment of neglect and can be used to assess and quantify neglect in everyday activities, and thus to monitor realistically rehabilitative needs of neglect patients.
TL;DR: Investigation of lesion anatomy underlying perceptual and response bias using a manual response Landmark task in 68 patients with right-hemispheric stroke suggests that perceptual/attentional and motor/intentional aspects of neglect are independent components of the syndrome with differential neural underpinnings in fronto-parietal and subcortical brain regions.
TL;DR: It is contended that the anterior intraparietal area and the dorsal premotor cortex are both involved albeit at different phases during the mapping of arbitrary visual cues with goal directed grasp and transport movements.
TL;DR: Contrary to the existing basal ganglia model and the current concept of Parkinson’s disease pathophysiology, it is found the subthalamic nucleus to receive more ‘afferences’ than it emitted ‘efferences”, suggesting that its role is more complex than a simple driving nucleus in the basal Ganglia loop.
Abstract: Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, although its precise mechanisms remain poorly understood. To gain further insight into the mechanisms underlying deep brain stimulation, we analysed the causal relationship between forearm muscle activity and local field potentials derived from the subthalamic nucleus. In 19 patients suffering from Parkinson’s disease of the akinetic-rigid subtype, we calculated the squared partial directed coherence between muscles of the contralateral forearm and the subthalamic nucleus or zona incerta during both a rest and a hold condition of the arm. For both recording regions, data analysis revealed that, during the rest condition, electromyographic activity was significantly more often ‘Granger-causal’ for the local field potentials than the opposite causation. In contrast, during the hold condition, no significant difference was found in the occurrence of causalities. Contrary to the existing basal ganglia model and the current concept of Parkinson’s disease pathophysiology, we found the subthalamic nucleus to receive more ‘afferences’ than it emitted ‘efferences’, suggesting that its role is more complex than a simple driving nucleus in the basal ganglia loop. Therefore, the effect of deep brain stimulation in the subthalamic nucleus could, at least in part, result from a blockade of pathological afferent input.