Showing papers by "Gereon R. Fink published in 2016"

Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy

Abstract: BACKGROUND: The aim of this study was to investigate the potential of dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET for differentiating local recurrent brain metastasis from radiation injury after radiotherapy since contrast-enhanced MRI often remains inconclusive. METHODS: Sixty-two patients (mean age, 55 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 76) on MRI after radiotherapy of brain metastases (predominantly stereotactic radiosurgery) were investigated with dynamic (18)F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) of (18)F-FET uptake were determined (20-40 min postinjection) as well as tracer uptake kinetics (ie, time-to-peak and slope of time-activity curves). Diagnoses were confirmed histologically (34%; 26 lesions in 25 patients) or by clinical follow-up (66%; 50 lesions in 37 patients). Diagnostic accuracies of PET parameters for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or the chi-square test. RESULTS: TBRs were significantly higher in recurrent metastases (n = 36) than in radiation injuries (n = 40) (TBRmax 3.3 ± 1.0 vs 2.2 ± 0.4, P < .001; TBRmean 2.2 ± 0.4 vs 1.7 ± 0.3, P < .001). The highest accuracy (88%) for diagnosing local recurrent metastasis could be obtained with TBRs in combination with the slope of time-activity curves (P < .001). CONCLUSIONS: The results of this study confirm previous preliminary observations that the combined evaluation of the TBRs of (18)F-FET uptake and the slope of time-activity curves can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. (18)F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Shaping Early Reorganization of Neural Networks Promotes Motor Function after Stroke

Abstract: Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1-16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis.

Where language meets meaningful action: a combined behavior and lesion analysis of aphasia and apraxia

Abstract: It is debated how language and praxis are co-represented in the left hemisphere (LH). As voxel-based lesion-symptom mapping in LH stroke patients with aphasia and/or apraxia may contribute to this debate, we here investigated the relationship between language and praxis deficits at the behavioral and lesion levels in 50 sub-acute stroke patients. We hypothesized that language and (meaningful) action are linked via semantic processing in Broca's region. Behaviorally, half of the patients suffered from co-morbid aphasia and apraxia. While 24% (n = 12) of all patients exhibited aphasia without apraxia, apraxia without aphasia was rare (n = 2, 4%). Left inferior frontal, insular, inferior parietal, and superior temporal lesions were specifically associated with deficits in naming, reading, writing, or auditory comprehension. In contrast, lesions affecting the left inferior frontal gyrus, premotor cortex, and the central region as well as the inferior parietal lobe were associated with apraxic deficits (i.e., pantomime, imitation of meaningful and meaningless gestures). Thus, contrary to the predictions of the embodied cognition theory, lesions to sensorimotor and premotor areas were associated with the severity of praxis but not language deficits. Lesions of Brodmann area (BA) 44 led to combined apraxic and aphasic deficits. Data suggest that BA 44 acts as an interface between language and (meaningful) action thereby supporting parcellation schemes (based on connectivity and receptor mapping) which revealed a BA 44 sub-area involved in semantic processing.

In vivo Patterns of Tau Pathology, Amyloid-β Burden, and Neuronal Dysfunction in Clinical Variants of Alzheimer's Disease.

Abstract: The clinical heterogeneity of Alzheimer's disease is not reflected in the rather diffuse cortical deposition of amyloid-β. We assessed the relationship between clinical symptoms, in vivo tau pathology, amyloid distribution, and hypometabolism in variants of Alzheimer's disease using novel multimodal PET imaging techniques. Tau pathology was primarily observed in brain regions related to clinical symptoms and overlapped with areas of hypometabolism. In contrast, amyloid-β deposition was diffusely distributed over the entire cortex. Tau PET imaging may thus serve as a valuable biomarker for the localization of neuronal injury in vivo and may help to validate atypical subtypes of Alzheimer's disease.

Impact of tau and amyloid burden on glucose metabolism in Alzheimer's disease.

Abstract: In a multimodal PET imaging approach, we determined the differential contribution of neurofibrillary tangles (measured with [18F]AV-1451) and beta-amyloid burden (measured with [11C]PiB) on degree of neurodegeneration (i.e., glucose metabolism measured with [18F]FDG-PET) in patients with Alzheimer's disease. Across brain regions, we observed an interactive effect of beta-amyloid burden and tau deposition on glucose metabolism which was most pronounced in the parietal lobe. Elevated beta-amyloid burden was associated with a stronger influence of tau accumulation on glucose metabolism. Our data provide the first in vivo insights into the differential contribution of Aβ and tau to neurodegeneration in Alzheimer's disease.

The right temporoparietal junction in attention and social interaction: A transcranial magnetic stimulation study.

Abstract: The right temporoparietal junction (rTPJ) has been associated with the ability to reorient attention to unexpected stimuli and the capacity to understand others' mental states (theory of mind [ToM]/false belief). Using activation likelihood estimation meta-analysis we previously unraveled that the anterior rTPJ is involved in both, reorienting of attention and ToM, possibly indicating a more general role in attention shifting. Here, we used neuronavigated transcranial magnetic stimulation to directly probe the role of the rTPJ across attentional reorienting and false belief. Task performance in a visual cueing paradigm and false belief cartoon task was investigated after application of continuous theta burst stimulation (cTBS) over anterior rTPJ (versus vertex, for control). We found that attentional reorienting was significantly impaired after rTPJ cTBS compared with control. For the false belief task, error rates in trials demanding a shift in mental state significantly increased. Of note, a significant positive correlation indicated a close relation between the stimulation effect on attentional reorienting and false belief trials. Our findings extend previous neuroimaging evidence by indicating an essential overarching role of the anterior rTPJ for both cognitive functions, reorienting of attention and ToM. Hum Brain Mapp 37:796-807, 2016. © 2015 Wiley Periodicals, Inc.

Transcranial Direct Current Stimulation Modulates Neurogenesis and Microglia Activation in the Mouse Brain.

Abstract: Transcranial direct current stimulation (tDCS) has been suggested as an adjuvant tool to promote recovery of function after stroke, but the mechanisms of its action to date remain poorly understood. Moreover, studies aimed at unraveling those mechanisms have essentially been limited to the rat, where tDCS activates resident microglia as well as endogenous neural stem cells. Here we studied the effects of tDCS on microglia activation and neurogenesis in the mouse brain. Male wild-type mice were subjected to multisession tDCS of either anodal or cathodal polarity; sham-stimulated mice served as control. Activated microglia in the cerebral cortex and neuroblasts generated in the subventricular zone as the major neural stem cell niche were assessed immunohistochemically. Multisession tDCS at a sublesional charge density led to a polarity-dependent downregulation of the constitutive expression of Iba1 by microglia in the mouse cortex. In contrast, both anodal and, to an even greater extent, cathodal tDCS induced neurogenesis from the subventricular zone. Data suggest that tDCS elicits its action through multifacetted mechanisms, including immunomodulation and neurogenesis, and thus support the idea of using tDCS to induce regeneration and to promote recovery of function. Furthermore, data suggest that the effects of tDCS may be animal- and polarity-specific.

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstract: Table of contentsA1 Functional advantages of cell-type heterogeneity in neural circuitsTatyana O. SharpeeA2 Mesoscopic modeling of propagating waves in visual cortexAlain DestexheA3 Dynamics and biomarkers of mental disordersMitsuo KawatoF1 Precise recruitment of spiking output at theta frequencies requires dendritic h-channels in multi-compartment models of oriens-lacunosum/moleculare hippocampal interneuronsVladislav Sekulić, Frances K. SkinnerF2 Kernel methods in reconstruction of current sources from extracellular potentials for single cells and the whole brainsDaniel K. Wójcik, Chaitanya Chintaluri, Dorottya Cserpán, Zoltán SomogyváriF3 The synchronized periods depend on intracellular transcriptional repression mechanisms in circadian clocks.Jae Kyoung Kim, Zachary P. Kilpatrick, Matthew R. Bennett, Kresimir JosićO1 Assessing irregularity and coordination of spiking-bursting rhythms in central pattern generatorsIrene Elices, David Arroyo, Rafael Levi, Francisco B. Rodriguez, Pablo VaronaO2 Regulation of top-down processing by cortically-projecting parvalbumin positive neurons in basal forebrainEunjin Hwang, Bowon Kim, Hio-Been Han, Tae Kim, James T. McKenna, Ritchie E. Brown, Robert W. McCarley, Jee Hyun ChoiO3 Modeling auditory stream segregation, build-up and bistabilityJames Rankin, Pamela Osborn Popp, John RinzelO4 Strong competition between tonotopic neural ensembles explains pitch-related dynamics of auditory cortex evoked fieldsAlejandro Tabas, André Rupp, Emili Balaguer-BallesterO5 A simple model of retinal response to multi-electrode stimulationMatias I. Maturana, David B. Grayden, Shaun L. Cloherty, Tatiana Kameneva, Michael R. Ibbotson, Hamish MeffinO6 Noise correlations in V4 area correlate with behavioral performance in visual discrimination taskVeronika Koren, Timm Lochmann, Valentin Dragoi, Klaus ObermayerO7 Input-location dependent gain modulation in cerebellar nucleus neuronsMaria Psarrou, Maria Schilstra, Neil Davey, Benjamin Torben-Nielsen, Volker SteuberO8 Analytic solution of cable energy function for cortical axons and dendritesHuiwen Ju, Jiao Yu, Michael L. Hines, Liang Chen, Yuguo YuO9 C. elegans interactome: interactive visualization of Caenorhabditis elegans worm neuronal networkJimin Kim, Will Leahy, Eli ShlizermanO10 Is the model any good? Objective criteria for computational neuroscience model selectionJustas Birgiolas, Richard C. Gerkin, Sharon M. CrookO11 Cooperation and competition of gamma oscillation mechanismsAtthaphon Viriyopase, Raoul-Martin Memmesheimer, Stan GielenO12 A discrete structure of the brain wavesYuri Dabaghian, Justin DeVito, Luca PerottiO13 Direction-specific silencing of the Drosophila gaze stabilization systemAnmo J. Kim, Lisa M. Fenk, Cheng Lyu, Gaby MaimonO14 What does the fruit fly think about values? A model of olfactory associative learningChang Zhao, Yves Widmer, Simon Sprecher,Walter SennO15 Effects of ionic diffusion on power spectra of local field potentials (LFP)Geir Halnes, Tuomo Mäki-Marttunen, Daniel Keller, Klas H. Pettersen,Ole A. Andreassen, Gaute T. EinevollO16 Large-scale cortical models towards understanding relationship between brain structure abnormalities and cognitive deficitsYasunori YamadaO17 Spatial coarse-graining the brain: origin of minicolumnsMoira L. Steyn-Ross, D. Alistair Steyn-RossO18 Modeling large-scale cortical networks with laminar structureJorge F. Mejias, John D. Murray, Henry Kennedy, Xiao-Jing WangO19 Information filtering by partial synchronous spikes in a neural populationAlexandra Kruscha, Jan Grewe, Jan Benda, Benjamin LindnerO20 Decoding context-dependent olfactory valence in Drosophila Laurent Badel, Kazumi Ohta, Yoshiko Tsuchimoto, Hokto KazamaP1 Neural network as a scale-free network: the role of a hubB. KahngP2 Hemodynamic responses to emotions and decisions using near-infrared spectroscopy optical imagingNicoladie D. TamP3 Phase space analysis of hemodynamic responses to intentional movement directions using functional near-infrared spectroscopy (fNIRS) optical imaging techniqueNicoladie D.Tam, Luca Pollonini, George ZouridakisP4 Modeling jamming avoidance of weakly electric fishJaehyun Soh, DaeEun KimP5 Synergy and redundancy of retinal ganglion cells in predictionMinsu Yoo, S. E. PalmerP6 A neural field model with a third dimension representing cortical depthViviana Culmone, Ingo BojakP7 Network analysis of a probabilistic connectivity model of the Xenopus tadpole spinal cordAndrea Ferrario, Robert Merrison-Hort, Roman BorisyukP8 The recognition dynamics in the brainChang Sub KimP9 Multivariate spike train analysis using a positive definite kernelTaro TezukaP10 Synchronization of burst periods may govern slow brain dynamics during general anesthesiaPangyu JooP11 The ionic basis of heterogeneity affects stochastic synchronyYoung-Ah Rho, Shawn D. Burton, G. Bard Ermentrout, Jaeseung Jeong, Nathaniel N. UrbanP12 Circular statistics of noise in spike trains with a periodic componentPetr MarsalekP14 Representations of directions in EEG-BCI using Gaussian readoutsHoon-Hee Kim, Seok-hyun Moon, Do-won Lee, Sung-beom Lee, Ji-yong Lee, Jaeseung JeongP15 Action selection and reinforcement learning in basal ganglia during reaching movementsYaroslav I. Molkov, Khaldoun Hamade, Wondimu Teka, William H. Barnett, Taegyo Kim, Sergey Markin, Ilya A. RybakP17 Axon guidance: modeling axonal growth in T-Junction assayCsaba Forro, Harald Dermutz, László Demkó, János VörösP19 Transient cell assembly networks encode persistent spatial memoriesYuri Dabaghian, Andrey BabichevP20 Theory of population coupling and applications to describe high order correlations in large populations of interacting neuronsHaiping HuangP21 Design of biologically-realistic simulations for motor controlSergio Verduzco-FloresP22 Towards understanding the functional impact of the behavioural variability of neuronsFilipa Dos Santos, Peter AndrasP23 Different oscillatory dynamics underlying gamma entrainment deficits in schizophreniaChristoph Metzner, Achim Schweikard, Bartosz ZurowskiP24 Memory recall and spike frequency adaptationJames P. Roach, Leonard M. Sander, Michal R. ZochowskiP25 Stability of neural networks and memory consolidation preferentially occur near criticalityQuinton M. Skilling, Nicolette Ognjanovski, Sara J. Aton, Michal ZochowskiP26 Stochastic Oscillation in Self-Organized Critical States of Small Systems: Sensitive Resting State in Neural SystemsSheng-Jun Wang, Guang Ouyang, Jing Guang, Mingsha Zhang, K. Y. Michael Wong, Changsong ZhouP27 Neurofield: a C++ library for fast simulation of 2D neural field modelsPeter A. Robinson, Paula Sanz-Leon, Peter M. Drysdale, Felix Fung, Romesh G. Abeysuriya, Chris J. Rennie, Xuelong ZhaoP28 Action-based grounding: Beyond encoding/decoding in neural codeYoonsuck Choe, Huei-Fang YangP29 Neural computation in a dynamical system with multiple time scalesYuanyuan Mi, Xiaohan Lin, Si WuP30 Maximum entropy models for 3D layouts of orientation selectivityJoscha Liedtke, Manuel Schottdorf, Fred WolfP31 A behavioral assay for probing computations underlying curiosity in rodentsYoriko Yamamura, Jeffery R. WickensP32 Using statistical sampling to balance error function contributions to optimization of conductance-based modelsTimothy Rumbell, Julia Ramsey, Amy Reyes, Danel Draguljić, Patrick R. Hof, Jennifer Luebke, Christina M. WeaverP33 Exploration and implementation of a self-growing and self-organizing neuron network building algorithmHu He, Xu Yang, Hailin Ma, Zhiheng Xu, Yuzhe WangP34 Disrupted resting state brain network in obese subjects: a data-driven graph theory analysisKwangyeol Baek, Laurel S. Morris, Prantik Kundu, Valerie VoonP35 Dynamics of cooperative excitatory and inhibitory plasticityEverton J. Agnes, Tim P. VogelsP36 Frequency-dependent oscillatory signal gating in feed-forward networks of integrate-and-fire neuronsWilliam F. Podlaski, Tim P. VogelsP37 Phenomenological neural model for adaptation of neurons in area ITMartin Giese, Pradeep Kuravi, Rufin VogelsP38 ICGenealogy: towards a common topology of neuronal ion channel function and genealogy in model and experimentAlexander Seeholzer, William Podlaski, Rajnish Ranjan, Tim VogelsP39 Temporal input discrimination from the interaction between dynamic synapses and neural subthreshold oscillationsJoaquin J. Torres, Fabiano Baroni, Roberto Latorre, Pablo VaronaP40 Different roles for transient and sustained activity during active visual processingBart Gips, Eric Lowet, Mark J. Roberts, Peter de Weerd, Ole Jensen, Jan van der EerdenP41 Scale-free functional networks of 2D Ising model are highly robust against structural defects: neuroscience implicationsAbdorreza Goodarzinick, Mohammad D. Niry, Alireza ValizadehP42 High frequency neuron can facilitate propagation of signal in neural networksAref Pariz, Shervin S. Parsi, Alireza ValizadehP43 Investigating the effect of Alzheimer’s disease related amyloidopathy on gamma oscillations in the CA1 region of the hippocampusJulia M. Warburton, Lucia Marucci, Francesco Tamagnini, Jon Brown, Krasimira Tsaneva-AtanasovaP44 Long-tailed distributions of inhibitory and excitatory weights in a balanced network with eSTDP and iSTDPFlorence I. Kleberg, Jochen TrieschP45 Simulation of EMG recording from hand muscle due to TMS of motor cortexBahar Moezzi, Nicolangelo Iannella, Natalie Schaworonkow, Lukas Plogmacher, Mitchell R. Goldsworthy, Brenton Hordacre, Mark D. McDonnell, Michael C. Ridding, Jochen TrieschP46 Structure and dynamics of axon network formed in primary cell cultureMartin Zapotocky, Daniel Smit, Coralie Fouquet, Alain TrembleauP47 Efficient signal processing and sampling in random networks that generate variabilitySakyasingha Dasgupta, Isao Nishikawa, Kazuyuki Aihara, Taro ToyoizumiP48 Modeling the effect of riluzole on bursting in respiratory neural networksDaniel T. Robb, Nick Mellen, Natalia ToporikovaP49 Mapping relaxation training using effective connectivity analysisRongxiang Tang

Spatiotopic neural representations develop slowly across saccades

Abstract: One of the long-standing unsolved mysteries of visual neuroscience is how the world remains apparently stable in the face of continuous movements of eyes, head and body. Many factors seem to contribute to this stability, including rapid updating mechanisms that temporarily remap the visual input to compensate for the impending saccade. However, there is also a growing body of evidence pointing to more long-lasting spatiotopic neural representations, which remain solid in external rather than retinal coordinates. In this study, we show that these spatiotopic representations take hundreds of milliseconds to build up robustly.

Noninvasive brain stimulation after stroke: it is time for large randomized controlled trials!

Abstract: Purpose of reviewWe here provide an update about studies published recently in the field of noninvasive neuromodulation of the motor system, aiming at facilitating recovery of function after stroke.Recent findingsA number of longitudinal studies have confirmed that repeated stimulation of the motor

Constructing Visual Perception of Body Movement with the Motor Cortex

Abstract: The human brain readily perceives fluent movement from static input. Using functional magnetic resonance imaging, we investigated brain mechanisms that mediate fluent apparent biological motion (ABM) perception from sequences of body postures. We presented body and nonbody stimuli varying in objective sequence duration and fluency of apparent movement. Three body postures were ordered to produce a fluent (ABC) or a nonfluent (ACB) apparent movement. This enabled us to identify brain areas involved in the perceptual reconstruction of body movement from identical lower-level static input. Participants judged the duration of a rectangle containing body/nonbody sequences, as an implicit measure of movement fluency. For body stimuli, fluent apparent motion sequences produced subjectively longer durations than nonfluent sequences of the same objective duration. This difference was reduced for nonbody stimuli. This body-specific bias in duration perception was associated with increased blood oxygen level-dependent responses in the primary (M1) and supplementary motor areas. Moreover, fluent ABM was associated with increased functional connectivity between M1/SMA and right fusiform body area. We show that perceptual reconstruction of fluent movement from static body postures does not merely enlist areas traditionally associated with visual body processing, but involves cooperative recruitment of motor areas, consistent with a “motor way of seeing”.

Neural correlates of reactive aggression in children with attention-deficit/hyperactivity disorder and comorbid disruptive behaviour disorders.

Abstract: OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is often linked with impulsive and aggressive behaviour, indexed by high comorbidity rates between ADHD and disruptive behaviour disorders (DBD). The present study aimed to investigate underlying neural activity of reactive aggression in children with ADHD and comorbid DBD using functional neuroimaging techniques (fMRI). METHOD: Eighteen boys with ADHD (age 9-14 years, 10 subjects with comorbid DBD) and 18 healthy controls were administered a modified fMRI-based version of the 'Point Subtraction Aggression Game' to elicit reactive aggressive behaviour. Trials consisted of an 'aggression phase' (punishment for a fictitious opponent) and an 'outcome phase' (presentation of the trial outcome). RESULTS: During the aggression phase, higher aggressive responses of control children were accompanied by higher activation of the ventral anterior cingulate cortex and the temporoparietal junction. Patients displayed inverted results. During the outcome phase, comparison between groups and conditions showed differential activation in the dorsal striatum and bilateral insular when subjects gained points. Losing points was accompanied by differential activation of regions belonging to the insula and the middle temporal sulcus. CONCLUSION: Data support the hypothesis that deficient inhibitory control mechanisms are related to increased impulsive aggressive behaviour in young people with ADHD and comorbid DBD. Language: en

Spatiotopic Adaptation in Visual Areas.

Abstract: The ability to perceive the visual world around us as spatially stable despite frequent eye movements is one of the long-standing mysteries of neuroscience. The existence of neural mechanisms processing spatiotopic information is indispensable for a successful interaction with the external world. However, how the brain handles spatiotopic information remains a matter of debate. We here combined behavioral and fMRI adaptation to investigate the coding of spatiotopic information in the human brain. Subjects were adapted by a prolonged presentation of a tilted grating. Thereafter, they performed a saccade followed by the brief presentation of a probe. This procedure allowed dissociating adaptation aftereffects at retinal and spatiotopic positions. We found significant behavioral and functional adaptation in both retinal and spatiotopic positions, indicating information transfer into a spatiotopic coordinate system. The brain regions involved were located in ventral visual areas V3, V4, and VO. Our findings suggest that spatiotopic representations involved in maintaining visual stability are constructed by dynamically remapping visual feature information between retinotopic regions within early visual areas. SIGNIFICANCE STATEMENT Why do we perceive the visual world as stable, although we constantly perform saccadic eye movements? We investigated how the visual system codes object locations in spatiotopic (i.e., external world) coordinates. We combined visual adaptation, in which the prolonged exposure to a specific visual feature alters perception, with fMRI adaptation, where the repeated presentation of a stimulus leads to a reduction in the BOLD amplitude. Functionally, adaptation was found in visual areas representing the retinal location of an adaptor but also at representations corresponding to its spatiotopic position. The results suggest that an active dynamic shift transports information in visual cortex to counteract the retinal displacement associated with saccade eye movements.

Numerosity perception after size adaptation.

Abstract: While some researchers propose the existence of a special numerosity sense, others challenge this view and argue that numerosity is derived from low-level features as density information. Here, we used size adaptation to manipulate the apparent area size of an object set without changing its physical density. After size adaptation, two probe patches were shown, each of which contained a specific numerosity of dots. Subjects were required to report, which probe patch contained more dots. Numerosity perception was compared between conditions where probe patches were adapted to appear smaller or larger. Size adaptation affected numerosity perception in a logarithmic fashion, increasing with the numerosity in the probe patch. No changes in density perception were found after size adaptation. Data suggest that size and density information play only a minor role in the estimation of low numerosities. In stark contrast, high numerosities strongly depend on size and density information. The data reinforce recent claims of separate mechanism for the perception of low and high numerosities.

Minocycline mitigates the gliogenic effects of proinflammatory cytokines on neural stem cells.

Abstract: Mobilizing endogenous neural stem cells (NSCs) in the adult brain is designed to enhance the brain's regenerative capacity after cerebral lesions, e.g., as a result of stroke. Cerebral ischemia elicits neuroinflammatory processes affecting NSCs in multiple ways, the precise mechanisms of which currently remain elusive. An inhibitory effect of minocycline on microglia activation, a hallmark of postischemic neuroinflammation, has already been demonstrated in clinical trials, showing minocycline to be safe and potentially effective in ischemic stroke. Here we investigate the direct effects of minocycline and of proinflammatory cytokines on the differentiation potential of NSCs in vitro and in vivo. Primary fetal rat NSCs were treated with minocycline plus a combination of the proinflammatory cytokines tumor necrosis factor-α, interleukin 1β, and interleukin 6. The differentiation fate of NSCs was assessed immunocytochemically. To investigate the effects of minocycline and inflammation in vivo, minocycline or lipopolysaccharides were injected intraperitoneally into adult rats, with subsequent immunohistochemistry. Minocycline alone did not affect the differentiation potential of NSCs in vivo or in vitro. In contrast, proinflammatory cytokines accelerated the differentiation of NSCs, promoting an astrocytic fate while inhibiting neurogenesis in vitro and in vivo. It is interesting to note that minocycline counteracted this cytokine-induced rapid astrocytic differentiation and restored the neurogenic and oligodendrogliogenic potential of NSCs. Data suggest that minocycline antagonizes the rapid glial differentiation induced by proinflammatory cytokines following cerebral ischemia but without having a direct effect on the differentiation potential of NSCs. Thus, minocycline constitutes a promising drug for stroke research, counteracting the detrimental effects of postischemic neuroinflammation in multiple ways.

Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

Abstract: Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson's disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson's Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson's disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.

Resting state default mode network connectivity in children and adolescents with ADHD after acute tryptophan depletion

Abstract: Objective Alterations of the default mode network (DMN) have been described in patients with neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), and the neurotransmitter serotonin (5-HT) is known to modulate DMN activity. This study aimed to explore the role of 5-HT on the DMN and its functional connectivity (FC) in young patients with ADHD. Methods Young male patients with ADHD (n = 12) and healthy controls (n = 10) (both aged 12–17 years) were subjected to acute tryptophan depletion (ATD) and subsequently diminished brain 5-HT synthesis. Three hours after challenge intake (ATD or a balanced control condition, BAL), resting state fMRI scans were obtained. Results In patients, ATD led to attenuated FC of the right superior premotor cortex (BA 6) with the DMN, comparable to the extent found in controls after BAL administration. ATD lowered FC of the left somatosensory cortex (BA 3) with the DMN, independently of the factor group, but with stronger effects in controls. Conclusions Data reveal a serotonergic modulation of FC between BA 6 and 3, known to be relevant for motor planning and sensory perception, and the DMN, thereby possibly pointing toward ATD acting beneficially on neural planning of motor activity in patients with ADHD.