Markus Gschwind

White-Matter Connectivity between Face-Responsive Regions in the Human Brain

Face recognition is of major social importance and involves highly selective brain regions thought to be organized in a distributed functional network. However, the exact architecture of interconnections between these regions remains unknown. We used functional magnetic resonance imaging to identify face-responsive regions in 22 participants and then employed diffusion tensor imaging with probabilistic tractography to establish the white-matter pathways between these functionally defined regions. We identified strong white-matter connections between the occipital face area (OFA) and fusiform face area (FFA), with a significant right-hemisphere predominance. We found no evidence for direct anatomical connections between FFA and superior temporal sulcus (STS) or between OFA and STS, contrary to predictions based on current cognitive models. Instead, our findings point to segregated processing along a ventral extrastriate visual pathway to OFA-FFA and another more dorsal system connected to STS and frontoparietal areas. In addition, early occipital areas were found to have direct connections to the amygdala, which might underlie a rapid recruitment of limbic brain areas by visual inputs bypassing more elaborate extrastriate cortical processing. These results unveil the structural neural architecture of the human face recognition system and provide new insights on how distributed face-responsive areas may work together.

Processing social aspects of human gaze: a combined fMRI-DTI study.

Human gaze is a critical social cue that can reveal intentions and dispositions of others. The right posterior superior temporal sulcus (pSTS) is thought to be critically involved in processing eye gaze information. We combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to identify direct neural connections of right pSTS and to determine how these connections are modulated by the social significance of perceived gaze shifts. Participants saw faces with direct or averted gaze during event-related fMRI. Half of these faces remained static, and half displayed a dynamic gaze shift either towards or away from the subject. Social attention (dynamic gaze shifts towards the observer) not only increased activity in right pSTS, but also its functional connectivity with the right anterior insula (aIns) and right fusiform gyrus (FG). However, direct fiber connections from pSTS were demonstrated by DTI for the right aIns, but not the right FG. Moreover, the right FG responded to eye motion irrespective of direction and social significance; whereas the right aIns was selectively sensitive to social significance (i.e. gaze shifts towards the observer), but not generally to eye motion. We conclude that the social aspects of mutual gaze contact are processed by direct fiber pathways between right pSTS and right aIns; whereas increased connectivity with FG could reflect an enhanced perceptual analysis of changing facial features in dynamic gaze conditions and involves indirect fiber pathways with pSTS, perhaps via motion-selective regions in middle temporal (MT) gyrus that exhibited strong white-matter connections with both pSTS and FG and could thus provide inputs to these two areas.

Classifying minimally disabled multiple sclerosis patients from resting state functional connectivity

Multiple sclerosis (MS), a variable and diffuse disease affecting white and gray matter, is known to cause functional connectivity anomalies in patients. However, related studies published to-date are post hoc; our hypothesis was that such alterations could discriminate between patients and healthy controls in a predictive setting, laying the groundwork for imaging-based prognosis. Using functional magnetic resonance imaging resting state data of 22 minimally disabled MS patients and 14 controls, we developed a predictive model of connectivity alterations in MS: a whole-brain connectivity matrix was built for each subject from the slow oscillations (<0.11 Hz) of region-averaged time series, and a pattern recognition technique was used to learn a discriminant function indicating which particular functional connections are most affected by disease. Classification performance using strict cross-validation yielded a sensitivity of 82% (above chance at p<0.005) and specificity of 86% (p<0.01) to distinguish between MS patients and controls. The most discriminative connectivity changes were found in subcortical and temporal regions, and contralateral connections were more discriminative than ipsilateral connections. The pattern of decreased discriminative connections can be summarized post hoc in an index that correlates positively (ρ=0.61) with white matter lesion load, possibly indicating functional reorganisation to cope with increasing lesion load. These results are consistent with a subtle but widespread impact of lesions in white matter and in gray matter structures serving as high-level integrative hubs. These findings suggest that predictive models of resting state fMRI can reveal specific anomalies due to MS with high sensitivity and specificity, potentially leading to new non-invasive markers.

Bilateral dorsal and ventral fiber pathways for the processing of affective prosody identified by probabilistic fiber tracking

Dorsal and ventral pathways for syntacto-semantic speech processing in the left hemisphere are represented in the dual-stream model of auditory processing. Here we report new findings for the right dorsal and ventral temporo-frontal pathway during processing of affectively intonated speech (i.e. affective prosody) in humans, together with several left hemispheric structural connections, partly resembling those for syntacto-semantic speech processing. We investigated white matter fiber connectivity between regions responding to affective prosody in several subregions of the bilateral superior temporal cortex (secondary and higher-level auditory cortex) and of the inferior frontal cortex (anterior and posterior inferior frontal gyrus). The fiber connectivity was investigated by using probabilistic diffusion tensor based tractography. The results underscore several so far underestimated auditory pathway connections, especially for the processing of affective prosody, such as a right ventral auditory pathway. The results also suggest the existence of a dual-stream processing in the right hemisphere, and a general predominance of the dorsal pathways in both hemispheres underlying the neural processing of affective prosody in an extended temporo-frontal network.

Multiple sclerosis decreases explicit counterfactual processing and risk taking in decision making

Introduction Deficits in decision making (DM) are commonly associated with prefrontal cortical damage, but may occur with multiple sclerosis (MS). There are no data concerning the impact of MS on tasks evaluating DM under explicit risk, where different emotional and cognitive components can be distinguished. Methods We assessed 72 relapsing-remitting MS (RRMS) patients with mild to moderate disease and 38 healthy controls in two DM tasks involving risk with explicit rules: (1) The Wheel of Fortune (WOF), which probes the anticipated affects of decisions outcomes on future choices; and (2) The Cambridge Gamble Task (CGT) which measures risk taking. Participants also underwent a neuropsychological and emotional assessment, and skin conductance responses (SCRs) were recorded. Results In the WOF, RRMS patients showed deficits in integrating positive counterfactual information (p<0.005) and greater risk aversion (p<0.001). They reported less negative affect than controls (disappointment: p = 0.007; regret: p = 0.01), although their implicit emotional reactions as measured by post-choice SCRs did not differ. In the CGT, RRMS patients differed from controls in quality of DM (p = 0.01) and deliberation time (p = 0.0002), the latter difference being correlated with attention scores. Such changes did not result in overall decreases in performance (total gains). Conclusions The quality of DM under risk was modified by MS in both tasks. The reduction in the expression of disappointment coexisted with an increased risk aversion in the WOF and alexithymia features. These concomitant emotional alterations may have implications for better understanding the components of explicit DM and for the clinical support of MS patients.

Structural white-matter connections mediating distinct behavioral components of spatial neglect in right brain-damaged patients

Spatial neglect is a neuropsychological syndrome in which patients fail to perceive and orient to stimuli located in the space contralateral to the lesioned hemisphere. It is characterized by a wide heterogeneity in clinical symptoms which can be grouped into distinct behavioral components correlating with different lesion sites. Moreover, damage to white-matter (WM) fiber tracts has been suggested to disconnect brain networks that mediate different functions associated with spatial cognition and attention. However, it remains unclear what WM pathways are associated with functionally dissociable neglect components. In this study we examined nine patients with a focal right hemisphere stroke using a series of neuropsychological tests and diffusion tensor imaging (DTI) in order to disentangle the role of specific WM pathways in neglect symptoms. First, following previous work, the behavioral test scores of patients were factorized into three independent components reflecting perceptual, exploratory, and object-centered deficits in spatial awareness. We then examined the structural neural substrates of these components by correlating indices of WM integrity (fractional anisotropy) with the severity of deficits along each profile. Several locations in the right parietal and frontal WM correlated with neuropsychological scores. Fiber tracts projecting from these locations indicated that posterior parts of the superior longitudinal fasciculus (SLF), as well as nearby callosal fibers connecting ipsilateral and contralateral parietal areas, were associated with perceptual spatial deficits, whereas more anterior parts of SLF and inferior fronto-occipital fasciculus (IFOF) were predominantly associated with object-centered deficits. In addition, connections between frontal areas and superior colliculus were found to be associated with the exploratory deficits. Our results provide novel support to the view that neglect may result from disconnection lesions in distributed brain networks, but also extend these notions by highlighting the role of dissociable circuits in different functional components of the neglect syndrome. However these preliminary findings require replication with larger samples of patients.

Sleep sharpens sensory stimulus coding in human visual cortex after fear conditioning.

Efficient perceptual identification of emotionally-relevant stimuli requires optimized neural coding. Because sleep contributes to neural plasticity mechanisms, we asked whether the perceptual representation of emotionally-relevant stimuli within sensory cortices is modified after a period of sleep. We show combined effects of sleep and aversive conditioning on subsequent discrimination of face identity information, with parallel plasticity in the amygdala and visual cortex. After one night of sleep (but neither immediately nor after an equal waking interval), a fear-conditioned face was better detected when morphed with another identity. This behavioral change was accompanied by increased selectivity of the amygdala and face-responsive fusiform regions. Overnight neural changes can thus sharpen the representation of threat-related stimuli in cortical sensory areas, in order to improve detection in impoverished or ambiguous situations. These findings reveal an important role of sleep in shaping cortical selectivity to emotionally-relevant cues and thus promoting adaptive responses to new dangers.

Ecstatic Epileptic Seizures: A Glimpse into the Multiple Roles of the Insula

Ecstatic epileptic seizures are a rare but compelling epileptic entity. During the first seconds of these seizures, ecstatic auras provoke feelings of well-being, intense serenity, bliss, and “enhanced self-awareness.” They are associated with the impression of time dilation, and can be described as a mystic experience by some patients. The functional neuroanatomy of ecstatic seizures is still debated. During recent years several patients presenting with ecstatic auras have been reported by others and us (in total n = 52); a few of them in the setting of presurgical evaluation including electrical brain stimulation. According to the recently recognized functions of the insula, and the results of nuclear brain imaging and electrical stimulation, the ecstatic symptoms in these patients seem to localize to a functional network centered around the anterior insular cortex, where we thus propose to locate this rare ictal phenomenon. Here we summarize the role of the multiple sensory, autonomic, affective, and cognitive functions of the insular cortex, which are integrated into the creation of self-awareness, and we suggest how this system may become dysfunctional on several levels during ecstatic aura.

Seizure Onset Zone Localization from Ictal High-Density EEG in Refractory Focal Epilepsy

Epilepsy surgery is the most efficient treatment option for patients with refractory epilepsy. Before surgery, it is of utmost importance to accurately delineate the seizure onset zone (SOZ). Non-invasive EEG is the most used neuroimaging technique to diagnose epilepsy, but it is hard to localize the SOZ from EEG due to its low spatial resolution and because epilepsy is a network disease, with several brain regions becoming active during a seizure. In this work, we propose and validate an approach based on EEG source imaging (ESI) combined with functional connectivity analysis to overcome these problems. We considered both simulations and real data of patients. Ictal epochs of 204-channel EEG and subsets down to 32 channels were analyzed. ESI was done using realistic head models and LORETA was used as inverse technique. The connectivity pattern between the reconstructed sources was calculated, and the source with the highest number of outgoing connections was selected as SOZ. We compared this algorithm with a more straightforward approach, i.e. selecting the source with the highest power after ESI as the SOZ. We found that functional connectivity analysis estimated the SOZ consistently closer to the simulated EZ/RZ than localization based on maximal power. Performance, however, decreased when 128 electrodes or less were used, especially in the realistic data. The results show the added value of functional connectivity analysis for SOZ localization, when the EEG is obtained with a high-density setup. Next to this, the method can potentially be used as objective tool in clinical settings.

Transcranial direct-current stimulation as treatment in epilepsy

ABSTRACT Introduction: Neuromodulation (NM) is a complementary therapy for patients with drug-resistant epilepsy. Vagal nerve stimulation and deep brain stimulation of the anterior thalamus are established techniques and have shown their efficacy in lowering seizure frequency, but they are invasive and rarely render patients seizure-free. Non-invasive NM techniques are therefore increasingly investigated in a clinical context. Areas covered: Current knowledge about transcranial direct-current stimulation (tDCS) and other non-invasive NM in patients with epilepsy, based on the available animal and clinical studies from PubMed search. Expert commentary: tDCS modulates neuronal membrane potentials, and consequently alters cortical excitability. Cathodal stimulation leads to cortical inhibition, which is of particular importance in epilepsy treatment. The antiepileptic efficacy is promising but still lacks systematic studies. The beneficial effect, seen in ~20%, outlasts the duration of stimulation, indicating neuronal plasticity and is therefore of great interest to obtain long-term effects.