Showing papers by "Gereon R. Fink published in 2012"

Deconstructing the Architecture of Dorsal and Ventral Attention Systems with Dynamic Causal Modeling

Abstract: Attentional orientation to a spatial cue and reorientation-after invalid cueing-are mediated by two distinct networks in the human brain. A bilateral dorsal frontoparietal network, comprising the intraparietal sulcus (IPS) and the frontal eye fields (FEF), controls the voluntary deployment of attention and may modulate visual cortex in preparation for upcoming stimulation. In contrast, reorienting attention to invalidly cued targets engages a right-lateralized ventral frontoparietal network comprising the temporoparietal junction (TPJ) and ventral frontal cortex. The present fMRI study investigated the functional architecture of these two attentional systems by characterizing effective connectivity during lateralized orienting and reorienting of attention, respectively. Subjects performed a modified version of Posner's location-cueing paradigm. Dynamic causal modeling (DCM) of regional responses in the dorsal and ventral network, identified in a conventional (SPM) whole-brain analysis, was used to compare different functional architectures. Bayesian model selection showed that top-down connections from left and right IPS to left and right visual cortex, respectively, were modulated by the direction of attention. Moreover, model evidence was highest for a model with directed influences from bilateral IPS to FEF, and reciprocal coupling between right and left FEF. Invalid cueing enhanced forward connections from visual areas to right TPJ, and directed influences from right TPJ to right IPS and IFG (inferior frontal gyrus). These findings shed further light on the functional organization of the dorsal and ventral attentional network and support a context-sensitive lateralization in the top-down (backward) mediation of attentional orienting and the bottom-up (forward) effects of invalid cueing.

Assessment of Treatment Response in Patients with Glioblastoma Using O-(2-18F-Fluoroethyl)-l-Tyrosine PET in Comparison to MRI

Abstract: 1048 Learning Objectives 1. Review the basic theory of operation of the decision support system (DSS). 2. Highlight the requirements for optimizing the efficiency of development of a DSS, and the ways in which the new software tool addresses these requirements. We previously reported development of a DSS to interpret radionuclide renal studies for the presence of left or right renal obstruction. The input consists of a set of quantitative values derived from dynamic renal scintigraphy performed with 99mTc mercaptoacetyltriglycine (MAG3). DSS software encapsulates the knowledge of a human expert into an “inference engine”, a series of if-then rules which operate on the input to infer presence or absence of obstruction for each kidney, with a numeric certainty factor, and provide justification for the findings. Our goal for this project was to improve the system by providing clinical history data for each patient. Because the DSS was originally implemented in software as a command line tool, adding the large number of data fields in our clinical database (342) and tracking these through their interactions in the inference engine, could be complex. To improve the efficiency of development and testing of the system, we undertook a re-organization of the programming code as well as development of a graphical user interface (UI) that could present a comprehensive display of the variables and calculations used by the DSS in determining presence or absence of obstruction for any individual patient study. Examples of features of the DSS development system and its UI, which are generalizable to any DSS, will be illustrated, including: 1) display of variables, boundary conditions and patient-specific values for renal functional parameters derived from MAG3 image processing, and for clinical history fields from the database, 2) inference results on a group of patients, 3) tabulation of results compared to the gold standard of consensus reading by human experts, 4) display of a history of previous tabulation results, to assess progress in development of the DSS. Research Support NIBIG/NIDDK grant R01-LM00759

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study

Abstract: Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke-affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke.

Multi-Session Transcranial Direct Current Stimulation (tDCS) Elicits Inflammatory and Regenerative Processes in the Rat Brain

Abstract: Transcranial direct current stimulation (tDCS) is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields are known to influence the migration of various cell types in vitro, but effects in vivo remain to be shown. Hypothesizing that tDCS might elicit the recruitment of cells to the cortex, we here studied the effects of tDCS in the rat brain in vivo. Adult Wistar rats (n = 16) were randomized to either anodal or cathodal stimulation for either 5 or 10 consecutive days (500 µA, 15 min). Bromodeoxyuridine (BrdU) was given systemically to label dividing cells throughout the experiment. Immunohistochemical analyses ex vivo included stainings for activated microglia and endogenous neural stem cells (NSC). Multi-session tDCS with the chosen parameters did not cause a cortical lesion. An innate immune response with early upregulation of Iba1-positive activated microglia occurred after both cathodal and anodal tDCS. The involvement of adaptive immunity as assessed by ICAM1-immunoreactivity was less pronounced. Most interestingly, only cathodal tDCS increased the number of endogenous NSC in the stimulated cortex. After 10 days of cathodal stimulation, proliferating NSC increased by ∼60%, with a significant effect of both polarity and number of tDCS sessions on the recruitment of NSC. We demonstrate a pro-inflammatory effect of both cathodal and anodal tDCS, and a polarity-specific migratory effect on endogenous NSC in vivo. Our data suggest that tDCS in human stroke patients might also elicit NSC activation and modulate neuroinflammation.

Structural brain abnormalities in adolescent anorexia nervosa before and after weight recovery and associated hormonal changes

Abstract: Objective The neurobiological mechanisms of structural brain abnormalities in patients with anorexia nervosa (AN) remain poorly understood. In particular, little is known about the changes in and the recovery of gray matter (GM) volumes after weight gain and the relation to hormonal normalization in adolescent patients with AN. Methods Nineteen female patients aged 12 to 17 years were assessed using magnetic resonance imaging at the time of admission to the hospital (T1) and after weight recovery (T2). Patients were compared with typically developing girls matched for age and intelligence quotient. Structural brain images were analyzed using a voxel-based morphometric approach. Circulating levels of cortisol and gonadotropins were assessed in blood samples. Results Compared with controls, patients with AN showed reduced GM in several brain regions along the cortical midline, reaching from the occipital cortex to the medial frontal areas. These GM reductions were mostly reversible at T1. Patients showed a GM increase from T1 to T2 along the cortical midline and in the occipital, temporal, parietal, and frontal lobes. GM increases at T2 correlated inversely with cortisol levels at T1 and positively with weight gain at T2. The strongest associations between regional GM increase and weight gain were found in the cerebellum. In addition, increases in GM volumes at T2 in the thalamus, hippocampus, and amygdala were associated with increases in follicle-stimulating hormone. Conclusions Our data suggest that brain alterations in adolescents with acute AN are mostly reversible at T1 and that GM recovery in specific brain regions is associated with weight and hormonal normalization.

Modulation of top-down control of visual attention by cathodal tDCS over right IPS.

Abstract: The right intraparietal sulcus (rIPS) is a key region for the endogenous control of selective visual attention in the human brain. Previous studies suggest that the rIPS is especially involved in top-down control and spatial distribution of attention across both visual hemifields. We further explored these attentional functions using transcranial direct current stimulation (tDCS) of the rIPS to modulate behavioral performance in a partial report task. Performance was analyzed according to the theory of visual attention (TVA) (Bundesen, 1990), which provides a computational framework to investigate different parameters of visuo-attentional processing such as top-down control, attentional weighting, capacity of visual short term memory, and processing speed. We investigated the effects of different tDCS current strengths (1 mA and 2 mA) in two experiments: 1 mA tDCS (anodal, cathodal, sham) did not affect any of the TVA parameters, but cathodal 2 mA stimulation significantly enhanced top-down control as evidenced by a reduction of the α parameter of TVA, regardless of hemifield. This differential impact on the top-down control component of attentional processing suggests that the horizontal rIPS is mainly involved in attentional selection as none of the spatial or resource variables of TVA were altered. Furthermore, the data add evidence to previous work highlighting (1) the importance of using appropriate current strength in stimulation protocols, and (2) that the often reported inhibitory effect of cathodal stimulation in e.g., motor tasks might not extend to cognitive paradigms.

Parkinson Subtypes Progress Differently in Clinical Course and Imaging Pattern

Abstract: Objective To elucidate whether Parkinson’s disease (PD) subtypes show a differential pattern of FP-CIT-SPECT binding during the disease course. Methods We examined 27 patients (10 female, 17 male, mean age 61.68±11.24 years, 14 tremordominant, 13 akinetic-rigid) with [123I]FP-CIT-SPECT and clinical ratings including UPDRS III after at baseline and after a mean period of 2.47 years. Patients had been classified at baseline as tremordominant or akinetic-rigid according to a “tremor score” and “non-tremor score”. These subgroups were compared for differences in disease progression. Means of clinical ratings and the quantitative analyses of FP-CIT-SPECT for ipsi- and contralateral putamen and caudate nucleus were calculated and compared between baseline and follow-up. Results There were no statistical differences concerning age, disease duration, L-Dopa equivalent dose, disease severity (UPDRS III) or dopaminergic uptake in FP-CIT-SPECT at baseline between both subgroups. At follow-up, akinetic-rigid patients showed a distinct and statistically significant reduction of the dopaminergic uptake associated with significant progression of the clinical symptoms (UPDRS III). In contrast, in tremor patients the aggravation of clinical symptoms and dopaminergic deficit was less pronounced without statistical significance among assessments. Conclusions This study shows for the first time a considerable progression of clinical symptoms and in-vivo dopaminergic deficit of akinetic-rigid compared to tremordominant PD patients over time. Our data may help to improve strategic planning of further therapeutic trials and to provide a clearer prognosis for patients regarding the perspective of their disease.

Theory of Mind and the Brain in Anorexia Nervosa: Relation to Treatment Outcome

Abstract: Objective Converging evidence suggests deficits in theory-of-mind (ToM) processing in patients with anorexia nervosa (AN). The present study aimed at elucidating the neural mechanisms underlying ToM-deficits in AN. Method A total of 19 adolescent patients with AN and 21 age-matched controls were investigated using functional magnetic resonance imaging during performance of a ToM-task at two time points (in-patients: admission to hospital and discharge after weight recovery). Clinical outcomes in patients were determined 1 year after admission. Results Irrespective of the time point, AN patients showed reduced activation in middle and anterior temporal cortex and in the medial prefrontal cortex. Hypoactivation in the medial prefrontal cortex at admission to hospital (T1) was correlated with clinical outcome at follow-up. Conclusions Hypoactivation in the brain network supporting theory of mind may be associated with a social–cognitive endophenotype reflecting impairments of social functioning in anorexia nervosa which is predictive for a poor outcome at 1-year follow-up.

Diagnosis and treatment of upper limb apraxia.

Abstract: Upper limb apraxia, a disorder of higher motor cognition, is a common consequence of left-hemispheric stroke. Contrary to common assumption, apraxic deficits not only manifest themselves during clinical testing but also have delirious effects on the patients’ everyday life and rehabilitation. Thus, a reliable diagnosis and efficient treatment of upper limb apraxia is important to improve the patients’ prognosis after stroke. Nevertheless, to date, upper limb apraxia is still an underdiagnosed and ill-treated entity. Based on a systematic literature search, this review summarizes the current tools of diagnosis and treatment strategies for upper limb apraxia. It furthermore provides clinicians with graded recommendations. In particular, a short screening test for apraxia, and a more comprehensive diagnostic apraxia test for clinical use are recommended. Although currently only a few randomized controlled studies investigate the efficacy of different apraxia treatments, the gesture training suggested by Smania and colleagues can be recommended for the therapy of apraxia, the effects of which were shown to extend to activities of daily living and to persist for at least 2 months after completion of the training. This review aims at directing the reader’s attention to the ecological relevance of apraxia. Moreover, it provides clinicians with appropriate tools for the reliable diagnosis and effective treatment of apraxia. Nevertheless, this review also highlights the need for further research into how to improve diagnosis of apraxia based on neuropsychological models and to develop new therapeutic strategies.

Convergence of human brain mapping tools: neuronavigated TMS Parameters and fMRI activity in the hand motor area

Abstract: Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are well-established tools for investigating the human motor system in-vivo. We here studied the relationship between movement-related fMRI signal changes in the primary motor cortex (M1) and electrophysiological properties of the hand motor area assessed with neuronavigated TMS in 17 healthy subjects. The voxel showing the highest task-related BOLD response in the left hand motor area during right hand movements was identified for each individual subject. This fMRI peak voxel in M1 served as spatial target for coil positioning during neuronavigated TMS. We performed correlation analyses between TMS parameters, BOLD signal estimates and effective connectivity parameters of M1 assessed with dynamic causal modeling (DCM). The results showed a negative correlation between the movement-related BOLD signal in left M1 and resting as well as active motor threshold (MT) obtained for left M1. The DCM analysis revealed that higher excitability of left M1 was associated with a stronger coupling between left supplementary motor area (SMA) and M1. Furthermore, BOLD activity in left M1 correlated with ipsilateral silent period (ISP), i.e. the stronger the task-related BOLD response in left M1, the higher interhemispheric inhibition effects targeting right M1. DCM analyses revealed a positive correlation between the coupling of left SMA with left M1 and the duration of ISP. The data show that TMS parameters assessed for the hand area of M1 do not only reflect the intrinsic properties at the stimulation site but also interactions with remote areas in the human motor system.

Intrinsic Network Connectivity Reflects Consistency of Synesthetic Experiences

Abstract: Studying cognitive processes underlying synesthesia, a condition in which stimulation of one sensory modality automatically leads to abnormal additional sensory perception, allows insights into the neural mechanisms of normal and abnormal cross-modal sensory processing. Consistent with the notion that synesthesia results from hyperconnectivity, functional connectivity analysis (adopting independent component analysis and seed-based correlation analysis) of resting-state functional magnetic resonance imaging data of 12 grapheme-color synesthetes and 12 nonsynesthetic control subjects revealed, in addition to increased intranetwork connectivity, both a global and a specific (medial and lateral visual networks to a right frontoparietal network) increase of intrinsic internetwork connectivity in grapheme-color synesthesia. Moreover, this increased intrinsic network connectivity reflected the strength of synesthetic experiences. These findings constitute the first direct evidence of increased functional network connectivity in synesthesia. In addition to this significant contribution to the understanding of the neural mechanisms of synesthesia, our results have important general implications. In combination with data derived from clinical populations, our data strongly suggest that altered differences in intrinsic network connectivity are directly related to the phenomenology of human experiences.

Neural mechanisms of attentional reorienting in three-dimensional space.

Abstract: How the human brain reconstructs the three-dimensional (3D) world from two-dimensional (2D) retinal images has received a great deal of interest as has how we shift attention in 2D space. In contrast, it remains poorly understood how visuospatial attention is shifted in depth. In this fMRI study, by constructing a virtual 3D environment in the MR scanner and by presenting targets either close to or far from the participants in an adapted version of the Posner spatial-cueing paradigm, we investigated the behavioral and neural mechanisms underlying visuospatial orienting/reorienting in depth. At the behavioral level, although covering the same spatial distance, attentional reorienting to objects unexpectedly appearing closer to the observer and in the unattended hemispace was faster than reorienting to unexpected objects farther away. At the neural level, we found that in addition to the classical attentional reorienting system in the right temporoparietal junction, two additional brain networks were differentially involved in aspects of attentional reorienting in depth. First, bilateral premotor cortex reoriented visuospatial attention specifically along the third dimension of visual space (i.e., from close to far or vice versa), compared with attentional reorienting within the same depth plane. Second, a network of areas reminiscent of the human "default-mode network," including posterior cingulate cortex, orbital prefrontal cortex, and left angular gyrus, was involved in the neural interaction between depth and attentional orienting, by boosting attentional reorienting to unexpected objects appearing both closer to the observer and in the unattended hemispace.

Disruption of motor network connectivity post-stroke and its noninvasive neuromodulation.

Abstract: PURPOSE OF REVIEW We review the latest evidence for the neural underpinnings of hand motor function recovery after stroke with particular emphasis on how the latter can be enhanced by noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS). RECENT FINDINGS New data from longitudinal studies in which rTMS of the lesioned or contralesional motor cortex was combined with motor training showed ambiguous effects: some patients improved whereas others did not show any rTMS effect (compared with control stimulation). In contrast, novel studies using tDCS point to a more consistent effect on distal upper limb function, especially for inhibitory (cathodal) tDCS applied over contralesional M1. Neuroimaging data reveal that the effects of rTMS/tDCS on the functional architecture of the motor system depend upon lesion location, degree of impairment and number of treatment sessions. Furthermore, analyses of regional brain activity and motor network connectivity allow prediction of the behavioural effects of brain stimulation. SUMMARY rTMS and tDCS can be used to modulate stroke-induced changes of motor network activity and connectivity thereby improving hand motor function. The interindividual variability in response to brain stimulation calls for the identification of treatment-associated surrogate markers, which may be provided by neuroimaging.

Hallucinations in Neurodegenerative Diseases

Abstract: SUMMARY Patients with neurodegenerative disease frequently experience hallucinations and illusionary perceptions. As early symptoms, hallucinations may even have diagnostic relevance (i.e., for the diagnosis of Lewy Body Dementia). In the later course of the disease, hallucinations may appear as characteristic symptoms and often constitute a particular challenge for therapeutic endeavors. Here, the distinction of disease-inherent hallucinations from medication-associated perceptual disturbances is particularly relevant. Synucleinopathies and tauopathies have different risk profiles for hallucinations. In synucleinopathies hallucinations are much more frequent and phenomenology is characterized by visual, short-lived hallucinations, with insight preserved for a long time. A “double hit” theory proposes that dysfunctionality of both associative visual areas and changes of limbic areas or the ventral striatum are required. In contrast, in tauopathies the hallucinations are more rare and mostly embedded in confusional states with agitation and with poorly defined or rapidly changing paranoia. The occurrence of hallucinations has even been proposed as an exclusion criterion for tauopathies with Parkinsonian features such as progressive supranuclear palsy. To date, treatment remains largely empirical, except the use of clozapine and cholinesterase inhibitors in synucleinopathies, which is evidence-based. The risk of increased neuroleptic sensitivity further restricts the treatment options in patients with Lewy Body Dementia. Coping Strategies and improvement of visual acuity and sleep quality may be useful therapeutic complements.

Clinical outcome of subthalamic stimulation in Parkinson's disease is improved by intraoperative multiple trajectories microelectrode recording.

Abstract: Background and Study Aims The use of multiple trajectories microelectrode recording (MER) during implantation of deep brain stimulation (DBS) electrodes into the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) is discussed controversially because of possible risks and unclear benefits The aim of the study is to investigate whether MER combined with intraoperative evaluation of stimulation effects improve clinical outcome in PD patients undergoing STN DBS surgery Material and Methods Prior to final DBS electrode implantation, we performed multiple trajectories MER and intraoperative test stimulations after magnetic resonance imaging (MRI)-guided planning in 32 PD patients In further 10 patients no MER (only intraoperative test stimulation) was used Results We found a significantly better clinical outcome (Unified Parkinson's Disease Rating Scale [UPDRS] III) in patients undergoing MER compared with non-MER patients In MER patients, DBS electrode placement was performed using the central trajectory in 73% Another than the central trajectory was taken in 27% of the patients No difference in clinical outcome between DBS electrodes implanted on the central or a decentral trajectory was observed Conclusions DBS surgery based on intraoperative multiple trajectories MER and test stimulation improves clinical outcome if compared with intraoperative test stimulation alone The data suggest that DBS surgery solely based on MRI and intraoperative test stimulation without MER may lead to nonoptimal placement of DBS electrodes and consequently poorer clinical outcome

Impaired self-awareness of motor deficits in Parkinson's disease: association with motor asymmetry and motor phenotypes.

Abstract: Background: This study investigated impaired self-awareness of motor deficits in nondemented, nondepressed Parkinson's disease (PD) patients during a defined clinical on state. Methods: Twenty-eight PD patients were examined. Patients' self-ratings and experts' ratings of patients' motor performance were compared. Patient–examiner discrepancies and level of impairment determined severity of impaired self-awareness. Motor exam assessed overall motor functioning, hemibody impairment, and 4 motor phenotypes. Neuropsychological tests were also conducted. Results: Signs of impaired self-awareness were present in 17 patients (60.7%). Higher severity of impaired self-awareness correlated significantly with higher postural-instability and gait-difficulty off scores (r = .575; P = .001), overall motor off scores (r = .569; P = .002), and higher left hemibody off scores (r = .490; P = .008). In multiple linear regression analyses, higher postural-instability and gait-difficulty off scores remained as the only significant predictor of impaired self-awareness severity. Conclusions: Postural instability and gait difficulties, disease severity, and right hemisphere dysfunction seem to contribute to impaired self-awareness. © 2012 Movement Disorder Society

Volumetry of [¹¹C]-methionine positron emission tomographic uptake as a prognostic marker before treatment of patients with malignant glioma.

Abstract: The purpose of this positron emission tomography (PET) study was to compare the prognostic value of pretreatment volume of ¹¹C]-methionine (MET) uptake and semiquantitative MET uptake ratio in patients with malignant glioma. The study population comprised 40 patients with malignant glioma. Pretreatment magnetic resonance imaging (MRI) and MET-PET imaging were performed before the initiation of glioma treatment in all patients. The pretreatment MET uptake ratios and volumes were assessed. To create prognostically homogeneous subgroups, patients' pretreatment prognostic factors were stratified according to the six classes of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA). Univariate and multivariate analyses were performed to determine significant prognostic factors. Survival analyses identified the pretreatment volume of MET uptake and a higher RTOG RPA class as significant predictors. In contrast, pretreatment maximum areas of contrast enhancement on MRI and semiquantitative MET uptake ratios could not be identified as significant prognostic factors. The patients' outcomes and Karnofsky Performance Scale scores were significantly correlated with pretreatment volume of MET uptake but not with semiquantitative MET uptake ratio. The data suggest that pretreatment volumetry of MET uptake but not the semiquantitative MET uptake ratio is a useful biologic prognostic marker in patients with malignant glioma.

Neural interaction between spatial domain and spatial reference frame in parietal-occipital junction

Abstract: On the basis of double dissociations in clinical symptoms of patients with unilateral visuospatial neglect, neuropsychological research distinguishes between different spatial domains (near vs. far) and different spatial reference frames (egocentric vs. allocentric). In this fMRI study, we investigated the neural interaction between spatial domains and spatial reference frames by constructing a virtual three-dimensional world and asking participants to perform either allocentric or egocentric judgments on an object located in either near or far space. Our results suggest that the parietal-occipital junction (POJ) not only shows a preference for near-space processing but is also involved in the neural interaction between spatial domains and spatial reference frames. Two dissociable streams of visual processing exist in the human brain: a ventral perception-related stream and a dorsal action-related stream. Consistent with the perception-action model, both far-space processing and allocentric judgments draw upon the ventral stream whereas both near-space processing and egocentric judgments draw upon the dorsal stream. POJ showed higher neural activity during allocentric judgments (ventral) in near space (dorsal) and egocentric judgments (dorsal) in far space (ventral) as compared with egocentric judgments (dorsal) in near space (dorsal) and allocentric judgments (ventral) in far space (ventral). Because representations in the dorsal and ventral streams need to interact during allocentric judgments (ventral) in near space (dorsal) and egocentric judgments (dorsal) in far space (ventral), our results imply that POJ is involved in the neural interaction between the two streams. Further evidence for the suggested role of POJ as a neural interface between the dorsal and ventral streams is provided by functional connectivity analysis.

Potential of Early [18F]-2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography for Identifying Hypoperfusion and Predicting Fate of Tissue in a Rat Embolic Stroke Model

Abstract: Background and Purpose—Experimental stroke models are essential to study in vivo pathophysiological processes of focal cerebral ischemia. In this study, an embolic stroke model in rats was applied (1) to characterize early development of regional cerebral blood flow and metabolism with positron emission tomography (PET) using [15O]H2O and [18F]-2-fluoro-2-deoxy-D-glucose (FDG); and (2) to identify potential parameters for predicting tissue fate. Methods—Remote occlusion of the middle cerebral artery was induced in 10 Wistar rats by injection of 4 TiO2 macrospheres. Sequential [15O]H2O-PET (baseline, 5, 30, 60 minutes after middle cerebral artery occlusion) and FDG-PET measurements (75 minutes after middle cerebral artery occlusion) were performed. [15O]H2O-PET data and FDG kinetic parameters were compared with MRIs and histology at 24 hours. Results—Regional cerebral blood flow decreased substantially within 30 minutes after middle cerebral artery occlusion (41% to 58% of baseline regional cerebral blood ...

Ventral and dorsal stream interactions during the perception of the müller-lyer illusion: Evidence derived from fmri and dynamic causal modeling

Abstract: The human visual system converts identically sized retinal stimuli into different-sized perceptions. For instance, the Muller-Lyer illusion alters the perceived length of a line via arrows attached to its end. The strength of this illusion can be expressed as the difference between physical and perceived line length. Accordingly, illusion strength reflects how strong a representation is transformed along its way from a retinal image up to a conscious percept. In this study, we investigated changes of effective connectivity between brain areas supporting these transformation processes to further elucidate the neural underpinnings of optical illusions. The strength of the Muller-Lyer illusion was parametrically modulated while participants performed either a spatial or a luminance task. Lateral occipital cortex and right superior parietal cortex were found to be associated with illusion strength. Dynamic causal modeling was employed to investigate putative interactions between ventral and dorsal visual streams. Bayesian model selection indicated that a model that involved bidirectional connections between dorsal and ventral stream areas most accurately accounted for the underlying network dynamics. Connections within this network were partially modulated by illusion strength. The data further suggest that the two areas subserve differential roles: Whereas lateral occipital cortex seems to be directly related to size transformation processes, activation in right superior parietal cortex may reflect subsequent levels of processing, including task-related supervisory functions. Furthermore, the data demonstrate that the observer's top-down settings modulate the interactions between lateral occipital and superior parietal regions and thereby influence the effect of illusion strength.

The Neural Basis of Anosognosia for Spatial Neglect After Stroke

Abstract: Background and Purpose—The present study investigated the lesion anatomy of anosognosia for visuospatial neglect resulting from right hemispheric stroke. Methods—In 63 patients, self-ratings of performance in paper-and-pencil tests were contrasted with external performance ratings. Lesion analysis was conducted on patient subgroups with different degrees of anosognosia but comparable visuospatial impairment. Results—Independent of the severity of visuospatial neglect per se, damage to the right angular and superior temporal gyrus was associated with higher levels of anosognosia. Conclusions—Using a novel assessment of anosognosia for spatial neglect, the present study relates stroke-induced self-awareness deficits to inferior parietal and superior temporal brain damage.

Nicotine effects on brain function during a visual oddball task: A comparison between conventional and eeg-informed fmri analysis

Abstract: In a previous oddball task study, it was shown that the inclusion of electrophysiology (EEG), that is, single-trial P3 ERP parameters, in the analysis of fMRI responses can detect activation that is not apparent with conventional fMRI data modeling strategies [Warbrick, T., Mobascher, A., Brinkmeyer, J., Musso, F., Richter, N., Stoecker, T., et al. Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task. Neuroimage, 47, 1532-1544, 2009]. Given that P3 is modulated by nicotine, including P3 parameters in the fMRI analysis might provide additional information about nicotine effects on brain function. A 1-mg nasal nicotine spray (0.5 mg each nostril) or placebo (pepper) spray was administered in a double-blind, placebo-controlled, within-subject, randomized, cross-over design. Simultaneous EEG-fMRI and behavioral data were recorded from 19 current smokers in response to an oddball-type visual choice RT task. Conventional general linear model analysis and single-trial P3 amplitude informed general linear model analysis of the fMRI data were performed. Comparing the nicotine with the placebo condition, reduced RTs in the nicotine condition were related to decreased BOLD responses in the conventional analysis encompassing the superior parietal lobule, the precuneus, and the lateral occipital cortex. On the other hand, reduced RTs were related to increased BOLD responses in the precentral and postcentral gyri, and ACC in the EEG-informed fMRI analysis. Our results show how integrated analyses of simultaneous EEG-fMRI data can be used to detect nicotine effects that would not have been revealed through conventional analysis of either measure in isolation. This emphasizes the significance of applying multimodal imaging methods to pharmacoimaging.