Thalamic regulation of frontal interactions in human cognitive flexibility.

Interactions across frontal cortex are critical for cognition. Animal studies suggest a role for mediodorsal thalamus (MD) in these interactions, but the computations performed and direct relevance to human decision making are unclear. Here, inspired by animal work, we extended a neural model of an executive frontal-MD network and trained it on a human decision-making task for which neuroimaging data were collected. Using a biologically-plausible learning rule, we found that the model MD thalamus compressed its cortical inputs (dorsolateral prefrontal cortex, dlPFC) underlying stimulus-response representations. Through direct feedback to dlPFC, this thalamic operation efficiently partitioned cortical activity patterns and enhanced task switching across different contingencies. To account for interactions with other frontal regions, we expanded the model to compute higher-order strategy signals outside dlPFC, and found that the MD offered a more efficient route for such signals to switch dlPFC activity patterns. Human fMRI data provided evidence that the MD engaged in feedback to dlPFC, and had a role in routing orbitofrontal cortex inputs when subjects switched behavioral strategy. Collectively, our findings contribute to the emerging evidence for thalamic regulation of frontal interactions in the human brain.

Stroke-derived neutrophils demonstrate higher formation potential and impaired resolution of CD66b + driven neutrophil extracellular traps.

BACKGROUND: Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients. METHODS: We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples were functionally analyzed for their formation and clearance of Neutrophil-Extracellular-Traps. The composition of retrieved thrombi has been immunologically analyzed. RESULTS: Peripheral blood of stroke patients showed significantly elevated levels of DNAse-I (p < 0.001), LDG (p = 0.003), CD4 (p = 0.005) as well as the pro-inflammatory cytokines IL-17 (p < 0.001), INF-γ (p < 0.001) and IL-22 (p < 0.001) compared to controls, reflecting a TH1/TH17 response. Increased counts of DNAse-I in sera (p = 0.045) and Neutrophil-Extracellular-Traps in thrombi (p = 0.032) have been observed in patients with onset time of symptoms longer than 4,5 h. Lower values of CD66b in thrombi were independently associated with greater improvement of NIHSS after mechanical thrombectomy (p = 0.045). Stroke-derived neutrophils show higher potential for Neutrophil-Extracellular-Traps formation after stimulation and worse resolution under DNAse-I treatment compared to neutrophils derived from healthy individuals. CONCLUSIONS: Our data provide new insight in the role of activated neutrophils and Neutrophil-Extracellular-Traps in ischemic stroke. Future larger studies are warranted to further investigate the role of immunothrombosis in the cascades of stroke. TRIAL REGISTRATION: DRKS, DRKS00013278, Registered 15 November 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013278.

Modulations of Insular Projections by Prior Belief Mediate the Precision of Prediction Error during Tactile Learning.

Awareness for surprising sensory events is shaped by prior belief inferred from past experience. Here, we combined hierarchical Bayesian modeling with fMRI on an associative learning task in 28 male human participants to characterize the effect of the prior belief of tactile events on connections mediating the outcome of perceptual decisions. Activity in anterior insular cortex (AIC), premotor cortex (PMd), and inferior parietal lobule (IPL) were modulated by prior belief on unexpected targets compared with expected targets. On expected targets, prior belief decreased the connection strength from AIC to IPL, whereas it increased the connection strength from AIC to PMd when targets were unexpected. Individual differences in the modulatory strength of prior belief on insular projections correlated with the precision that increases the influence of prediction errors on belief updating. These results suggest complementary effects of prior belief on insular-frontoparietal projections mediating the precision of prediction during probabilistic tactile learning.SIGNIFICANCE STATEMENT In a probabilistic environment, the prior belief of sensory events can be inferred from past experiences. How this prior belief modulates effective brain connectivity for updating expectations for future decision-making remains unexplored. Combining hierarchical Bayesian modeling with fMRI, we show that during tactile associative learning, prior expectations modulate connections originating in the anterior insula cortex and targeting salience-related and attention-related frontoparietal areas (i.e., parietal and premotor cortex). These connections seem to be involved in updating evidence based on the precision of ascending inputs to guide future decision-making.

Confidence in Decision-Making during Probabilistic Tactile Learning Related to Distinct Thalamo-Prefrontal Pathways.

The flexibility in adjusting the decision strategy from trial to trial is a prerequisite for learning in a probabilistic environment. Corresponding neural underpinnings remain largely unexplored. In the present study, 28 male humans were engaged in an associative learning task, in which they had to learn the changing probabilistic strengths of tactile sample stimuli. Combining functional magnetic resonance imaging with computational modeling, we show that an unchanged decision strategy over successively presented trials related to weakened functional connectivity between ventralmedial prefrontal cortex (vmPFC) and left secondary somatosensory cortex. The weaker the connection strength, the faster participants indicated their choice. If the decision strategy remained unchanged, participant's decision confidence (i.e., prior belief) was related to functional connectivity between vmPFC and right pulvinar. While adjusting the decision strategy, we instead found confidence-related connections between left orbitofrontal cortex and left thalamic mediodorsal nucleus. The stronger the participant's prior belief, the weaker the connection strengths. Together, these findings suggest that distinct thalamo-prefrontal pathways encode the confidence in keeping or changing the decision strategy during probabilistic learning. Low confidence in the decision strategy demands more thalamo-prefrontal processing resources, which is in-line with the theoretical accounts of the free-energy principle.

Encoding schemes in somatosensation: From micro- to meta-topography.

Encoding schemes are systematic large-scale arrangements that convert incoming sensory information into a format required for further information processing. The increased spatial resolution of brain images obtained with ultra-high field magnetic resonance imaging at 7 T (7T-MRI) and above increases the granularity and precision of processing units that mediate the link between neuronal encoding and functional readouts. Here, these new developments are reviewed with a focus on human tactile encoding schemes derived from small-scale processing units (in the order of 0.5-5 mm) that are relevant for theoretical and practical concepts of somatosensory encoding and cortical plasticity. Precisely, we review recent approaches to characterize meso-scale maps, layer units, and cortical fields in the sensorimotor cortex of the living human brain and discuss their impact on theories of perception, motor control, topographic encoding, and cortical plasticity. Finally, we discuss concepts on the integration of small-scale processing units into functional networks that span multiple topographic maps and multiple cortical areas. Novel research areas are highlighted that may help to bridge the gap between cortical microstructure and meta-topographic models on brain anatomy and function.

Homeostatic, reward and executive brain functions after gastric bypass surgery.

Obesity in part arises from the regular overconsumption of palatable, caloric-dense foods. This maladaptive eating behavior has been described as impulsive, compulsive and even addictive, and has its origins in molecular and cellular aberrations in the gut and brain. Mounting evidence from human and rodent studies suggests that Roux-en-Y gastric bypass (RYGB) surgery persistantly promotes lower caloric intake by modifying gut-brain communication. In this Review, we discuss how the changes in gut hormones, nutrient sensing andmicrobiota brought about by RYGB together favourably regulate homeostatic, reward and executive brain functions. We further speculate on how this lastingly establishes a negative whole-body energy balance in the face of plenty. Future studies will more completely characterize the role of modified gut-brain communication in the healthier eating behavior following RYGB, possibly facilitating the development of more effective, non-surgical weight loss treatments.

Visually-Driven Maps in Area 3b.

Sensory perception relies on the precise neuronal encoding of modality-specific environmental features in primary sensory cortices. Some studies have reported the penetration of signals from other modalities even into early sensory areas. So far, no comprehensive account of maps induced by "foreign sources" exists. We addressed this question using surface-based topographic mapping techniques applied to ultra-high resolution fMRI neuroimaging data, measured in female participants. We show that fine-grained finger maps in human primary somatosensory cortex, area 3b, are somatotopically activated not only during tactile mechanical stimulation, but also when viewing the same fingers being touched. Visually-induced maps were weak in amplitude, but overlapped with the stronger tactile maps tangential to the cortical sheet when finger touches were observed in both first- and third-person perspectives. However, visually-induced maps did not overlap tactile maps when the observed fingers were only approached by an object but not actually touched. Our data provide evidence that "foreign source maps" in early sensory cortices are present in the healthy human brain, that their arrangement is precise, and that their induction is feature-selective. The computations required to generate such specific responses suggest that counterflow (feedback) processing may be much more spatially specific than has been often assumed.SIGNIFICANCE STATEMENT Using ultra-high field fMRI, we provide empirical evidence that viewing touches activates topographically aligned single finger maps in human primary somatosensory cortical area 3b. This shows that "foreign source maps" in early sensory cortices are topographic, precise, and feature-selective in healthy human participants with intact sensory pathways.

Brain structural differences in monozygotic twins discordant for body mass index.

BACKGROUND: Substantial efforts have been made to investigate the neurobiological underpinnings of human obesity with a number of studies indicating a profound influence of increased body weight on brain structure. Although body weight is known to be highly heritable, uncertainty remains regarding the respective contribution of genetic and environmental influences. METHODS: In this study we used structural magnetic resonance imaging (MRI) data from the Human Connectome Project (HCP). Voxel-based morphometry (VBM) was applied to study BMI-associated differences in gray matter volume (GMV) within monozygotic (MZ) twin pairs discordant for BMI (ΔBMI â€‹> â€‹2.5 â€‹kg*m-2, n = 68 pairs). In addition, we investigated the relationship of ΔBMI (entire range) with GMV differences within the entire sample of MZ twin pairs (n = 153 pairs). RESULTS: Analyses of BMI discordant twin pairs yielded less GMV in heavier twin siblings (p < 0.05 FWETFCE; paired t-Test) within the occipital and cerebellar cortex, the prefrontal cortex and the bilateral striatum including the nucleus accumbens. A highly converging pattern was found in regression analyses across the entire sample of MZ twin pairs, with ΔBMI being associated with less GMV in heavier MZ twins. CONCLUSION: While MZ twins share the same genetic background, our findings indicate that non-genetic influences and the mere presence of a higher BMI constitute relevant factors in the context of body weight related structural brain alterations.

Gastric-bypass surgery induced widespread neural plasticity of the obese human brain.

Bariatric surgery has become the gold standard for the treatment of morbid obesity (body mass index (BMI) ≥ 40 kg/m2), but only few studies investigated its plastic influences on the obese brain. In this longitudinal study, we combined structural and functional magnetic resonance brain imaging (MRI) in 27 patients (BMI 47.8 ± 5.5 kg/m2) undergoing gastric-bypass surgery and 14 non-obese matched controls (BMI 24.7 ± 3.4 kg/m2). Over the first year after surgery, patients presented widespread changes in white matter density (WMD) as well as gray matter density (GMD) in the cerebral cortex of all lobes, subcortical structures, the brainstem as well as the cerebellum, but no changes in white matter water diffusivity throughout the brain. Voxel-by-voxel regression analyses revealed that all GMD and WMD changes were well associated with elevated regional homogeneity of spontaneous neural activity (ReHo) in blood-oxygenation level-dependent signals. Spatial-temporal integration of structural and functional MRI suggests that gastric-bypass surgery induces widespread plastic changes in brain structure that concurrently homogenizes the functional profile of the cortex, subcortical regions as well as white matter structures.

Intermittent compared to continuous real-time fMRI neurofeedback boosts control over amygdala activation.

Real-time fMRI neurofeedback is a feasible tool to learn the volitional regulation of brain activity. So far, most studies provide continuous feedback information that is presented upon every volume acquisition. Although this maximizes the temporal resolution of feedback information, it may be accompanied by some disadvantages. Participants can be distracted from the regulation task due to (1) the intrinsic delay of the hemodynamic response and associated feedback and (2) limited cognitive resources available to simultaneously evaluate feedback information and stay engaged with the task. Here, we systematically investigate differences between groups presented with different variants of feedback (continuous vs. intermittent) and a control group receiving no feedback on their ability to regulate amygdala activity using positive memories and feelings. In contrast to the feedback groups, no learning effect was observed in the group without any feedback presentation. The group receiving intermittent feedback exhibited better amygdala regulation performance when compared with the group receiving continuous feedback. Behavioural measurements show that these effects were reflected in differences in task engagement. Overall, we not only demonstrate that the presentation of feedback is a prerequisite to learn volitional control of amygdala activity but also that intermittent feedback is superior to continuous feedback presentation.

Satiety-induced enhanced neuronal activity in the frontal operculum relates to the desire for food in the obese female brain.

In the present pilot study, we questioned how eating to satiety affects cognitive influences on the desire for food and corresponding neuronal activity in the obese female brain. During EEG recording, lean (n = 10) and obese women (n = 10) self-rated the ability to reappraise visually presented food. All women were measured twice, when hungry and after eating to satiety. After eating to satiety, reappraisal of food was easier than when being hungry. Comparing the EEG data of the sated to the hungry state, we found that only in obese women the frontal operculum was involved not only in the reappraisal of food but also in admitting the desire for the same food. The right frontal operculum in the obese female brain, assumed to primarily host gustatory processes, may be involved in opposing cognitive influences on the desire for food. These findings may help to find potential brain targets for non-invasive brain stimulation or neurofeedback studies that aim at modulating the desire for food.

How Visual Body Perception Influences Somatosensory Plasticity.

The study of somatosensory plasticity offers unique insights into the neuronal mechanisms that underlie human adaptive and maladaptive plasticity. So far, little attention has been paid on the specific influence of visual body perception on somatosensory plasticity and learning in humans. Here, we review evidence on how visual body perception induces changes in the functional architecture of the somatosensory system and discuss the specific influence the social environment has on tactile plasticity and learning. We focus on studies that have been published in the areas of human cognitive and clinical neuroscience and refer to animal studies when appropriate. We discuss the therapeutic potential of socially mediated modulations of somatosensory plasticity and introduce specific paradigms to induce plastic changes under controlled conditions. This review offers a contribution to understanding the complex interactions between social perception and somatosensory learning by focusing on a novel research field: socially mediated sensory plasticity.

Connections between intraparietal sulcus and a sensorimotor network underpin sustained tactile attention.

Previous studies on sustained tactile attention draw conclusions about underlying cortical networks by averaging over experimental conditions without considering attentional variance in single trials. This may have formed an imprecise picture of brain processes underpinning sustained tactile attention. In the present study, we simultaneously recorded EEG-fMRI and used modulations of steady-state somatosensory evoked potentials (SSSEPs) as a measure of attentional trial-by-trial variability. Therefore, frequency-tagged streams of vibrotactile stimulations were simultaneously presented to both index fingers. Human participants were cued to sustain attention to either the left or right finger stimulation and to press a button whenever they perceived a target pulse embedded in the to-be-attended stream. In-line with previous studies, a classical general linear model (GLM) analysis based on cued attention conditions revealed increased activity mainly in somatosensory and cerebellar regions. Yet, parametric modeling of the BOLD response using simultaneously recorded SSSEPs as a marker of attentional trial-by-trial variability quarried the intraparietal sulcus (IPS). The IPS in turn showed enhanced functional connectivity to a modality-unspecific attention network. However, this was only revealed on the basis of cued attention conditions in the classical GLM. By considering attentional variability as captured by SSSEPs, the IPS showed increased connectivity to a sensorimotor network, underpinning attentional selection processes between competing tactile stimuli and action choices (press a button or not). Thus, the current findings highlight the potential value by considering attentional variations in single trials and extend previous knowledge on the role of the IPS in tactile attention.

Rapid and specific gray matter changes in M1 induced by balance training.

Training-induced changes in cortical structure can be observed non-invasively with magnetic resonance imaging (MRI). While macroscopic changes were found mainly after weeks to several months of training in humans, imaging of motor cortical networks in animals revealed rapid microstructural alterations after a few hours of training. We used MRI to test the hypothesis of immediate and specific training-induced alterations in motor cortical gray matter in humans. We found localized increases in motor cortical thickness after 1h of practice in a complex balancing task. These changes were specific to motor cortical effector representations primarily responsible for balance control in our task (lower limb and trunk) and these effects could be confirmed in a replication study. Cortical thickness changes (i) linearly increased across the training session, (ii) occurred independent of alterations in resting cerebral blood flow and (iii) were not triggered by repetitive use of the lower limbs. Our findings show that motor learning triggers rapid and specific gray matter changes in M1.

The perception of touch and the ventral somatosensory pathway.

In humans, touching the skin is known to activate, among others, the contralateral primary somatosensory cortex on the postcentral gyrus together with the bilateral parietal operculum (i.e. the anatomical site of the secondary somatosensory cortex). But which brain regions beyond the postcentral gyrus specifically contribute to the perception of touch remains speculative. In this study we collected structural magnetic resonance imaging scans and neurological examination reports of patients with brain injuries or stroke in the left or right hemisphere, but not in the postcentral gyrus as the entry site of cortical somatosensory processing. Using voxel-based lesion-symptom mapping, we compared patients with impaired touch perception (i.e. hypoaesthesia) to patients without such touch impairments. Patients with hypoaesthesia as compared to control patients differed in one single brain cluster comprising the contralateral parietal operculum together with the anterior and posterior insular cortex, the putamen, as well as subcortical white matter connections reaching ventrally towards prefrontal structures. This finding confirms previous speculations on the 'ventral pathway of somatosensory perception' and causally links these brain structures to the perception of touch.

Cerebellar-parietal connections underpin phonological storage.

Previous research has accumulated convincing evidence to show that the human cerebellum contributes to the short-term storage of verbal information, but its specific role in brain networks involved in phonological storage remains uncertain. In a randomized, crossover and sham-controlled design, we here combined transcranial direct current stimulation (tDCS), applied to the right cerebellum, with fMRI to investigate systematically the contribution of the human cerebellum to encoding, maintenance, and retrieval of verbal information. After anodal, but not cathodal, tDCS, we found a reduced item recognition capacity together with an attenuated neural signal from the right cerebellar lobule VIIb, specifically during the late encoding phase. Within this phase, tDCS furthermore affected task-associated functional connections between right cerebellar lobule VIIb and the posterior parietal cortex. These findings suggest that the right cerebellar lobule VIIb interacts with the posterior parietal cortex, specifically during the late stages of verbal encoding, when verbal information enters phonological storage.

Brain imaging in the context of food perception and eating.

PURPOSE OF REVIEW: Eating behavior depends heavily on brain function. In recent years, brain imaging has proved to be a powerful tool to elucidate brain function and brain structure in the context of eating. In this review, we summarize recent findings in the fast growing body of literature in the field and provide an overview of technical aspects as well as the basic brain mechanisms identified with imaging. Furthermore, we highlight findings linking neural processing of eating-related stimuli with obesity. RECENT FINDINGS: The consumption of food is based on a complex interplay between homeostatic and hedonic mechanisms. Several hormones influence brain activity to regulate food intake and interact with the brain's reward circuitry, which is partly mediated by dopamine signaling. Additionally, it was shown that food stimuli trigger cognitive control mechanisms that incorporate internal goals into food choice. The brain mechanisms observed in this context are strongly influenced by genetic factors, sex and personality traits. SUMMARY: Overall, a complex picture arises from brain-imaging findings, because a multitude of factors influence human food choice. Although several key mechanisms have been identified, there is no comprehensive model that is able to explain the behavioral observations to date. Especially a careful characterization of patients according to genotypes and phenotypes could help to better understand the current and future findings in neuroimaging studies.

Pain Relief-Related Structural Brain Alterations in Trigeminal Neuralgia Induced by Noninvasive Stereotactic Radiosurgery: A Pilot Study.

PURPOSE: Trigeminal neuralgia (TN) is a chronic pain disorder defined by unilateral shock-like pain in at least one division of the trigeminal nerve. Although several studies have investigated structural brain plasticity in patients with TN, treatment-induced alterations remain largely uninvestigated. METHODS AND MATERIALS: Combining T1-weighted magnetic resonance imaging with voxel-based morphometry and multiple-regression analyses, we assessed gray matter maps of patients with TN to investigate changes in gray matter volume (GMV) before and 6 months after stereotactic radiosurgery (SRS). RESULTS: Comparison of pre- and post-SRS GMV of 25 patients with TN (16 women; mean age 67 years) did not yield any significant clusters, suggesting that the effect of SRS intervention itself on gray matter structure may be negligible. Regarding SRS-induced pain relief, we found a significant GMV increase in the left superior frontal gyrus associated with greater degree of pain relief (P = .024) and a trend toward an increase in GMV in the left dorsolateral prefrontal cortex (P = .097). CONCLUSIONS: In this pilot study, we observed significant increases in GMV in the left superior frontal gyrus with SRS-induced improvements in pain and a trend toward an increase in GMV in the dorsolateral prefrontal cortex. Future studies are indicated to validate these findings and determine whether SRS-induced decrease in distracting pain events and subsequent increases in GMV result in improved functionality, decreased dependence on "top-down" control, and improved cognitive/executive balance with amelioration of pain events.

Dynamic causal modeling suggests serial processing of tactile vibratory stimuli in the human somatosensory cortex--an fMRI study.

Sensitivity to location and frequency of tactile stimuli is a characterizing feature of human primary (S1), and secondary (S2) somatosensory cortices. Recent evidence suggests that S1 is predominantly receptive to stimulus location, while S2 is attuned to stimulus frequency. Although it is well established in humans that tactile frequency information is relayed serially from S1 to S2, a recent study, using functional magnetic resonance imaging (fMRI) in combination with dynamic causal modeling (DCM), suggested that somatosensory inputs are processed in parallel in S1 and S2. In the present fMRI/DCM study, we revisited this controversy and investigated the specialization of the human somatosensory cortical areas with regard to tactile stimulus representations, as well as their effective connectivity. During brain imaging, 14 participants performed a somatosensory discrimination task on vibrotactile stimuli. Importantly, the model space for DCM was chosen to allow for direct inference on the question of interest by systematically varying the information transmission from pure parallel to pure serial implementations. Bayesian model comparison on the level of model families strongly favors a serial, instead of a parallel processing route for tactile stimulus information along the somatosensory pathway. Our fMRI/DCM data thus support previous suggestions of a sequential information transmission from S1 to S2 in humans.