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.

Modulation of prefrontal couplings by prior belief-related responses in ventromedial prefrontal cortex.

Humans and other animals can maintain constant payoffs in an uncertain environment by steadily re-evaluating and flexibly adjusting current strategy, which largely depends on the interactions between the prefrontal cortex (PFC) and mediodorsal thalamus (MD). While the ventromedial PFC (vmPFC) represents the level of uncertainty (i.e., prior belief about external states), it remains unclear how the brain recruits the PFC-MD network to re-evaluate decision strategy based on the uncertainty. Here, we leverage non-linear dynamic causal modeling on fMRI data to test how prior belief-dependent activity in vmPFC gates the information flow in the PFC-MD network when individuals switch their decision strategy. We show that the prior belief-related responses in vmPFC had a modulatory influence on the connections from dorsolateral PFC (dlPFC) to both, lateral orbitofrontal (lOFC) and MD. Bayesian parameter averaging revealed that only the connection from the dlPFC to lOFC surpassed the significant threshold, which indicates that the weaker the prior belief, the less was the inhibitory influence of the vmPFC on the strength of effective connections from dlPFC to lOFC. These findings suggest that the vmPFC acts as a gatekeeper for the recruitment of processing resources to re-evaluate the decision strategy in situations of high uncertainty.

Human orbitofrontal cortex signals decision outcomes to sensory cortex during behavioral adaptations.

The ability to respond flexibly to an ever-changing environment relies on the orbitofrontal cortex (OFC). However, how the OFC associates sensory information with predicted outcomes to enable flexible sensory learning in humans remains elusive. Here, we combine a probabilistic tactile reversal learning task with functional magnetic resonance imaging (fMRI) to investigate how lateral OFC (lOFC) interacts with the primary somatosensory cortex (S1) to guide flexible tactile learning in humans. fMRI results reveal that lOFC and S1 exhibit distinct task-dependent engagement: while the lOFC responds transiently to unexpected outcomes immediately following reversals, S1 is persistently engaged during re-learning. Unlike the contralateral stimulus-selective S1, activity in ipsilateral S1 mirrors the outcomes of behavior during re-learning, closely related to top-down signals from lOFC. These findings suggest that lOFC contributes to teaching signals to dynamically update representations in sensory areas, which implement computations critical for adaptive behavior.

Classical conditioning of faciliatory paired-pulse TMS.

In this proof-of-concept study, we questioned whether the influence of TMS on cortical excitability can be applied to classical conditioning. More specifically, we investigated whether the faciliatory influence of paired-pulse TMS on the excitability of the human motor cortex can be transferred to a simultaneously presented auditory stimulus through conditioning. During the conditioning phase, 75 healthy young participants received 170 faciliatory paired TMS pulses (1st pulse at 95% resting motor threshold, 2nd at 130%, interstimulus interval 12 ms), always presented simultaneously with one out of two acoustic stimuli. In the test phase, 20 min later, we pseudorandomly applied 100 single TMS pulses (at 130% MT), 50 paired with the conditioned tone-50 paired with a control tone. Using the Wilcoxon-Signed Rank test, we found significantly enhanced median amplitudes of motor evoked potentials (MEPs) paired with the conditioned tone as compared to the control tone, suggesting successful conditioning (p = 0.031, responder rate 55%, small effect size of r = - 0.248). The same comparison in only those participants with a paired-pulse amplitude < 2 mV in the conditioning phase, increased the responder rate to 61% (n = 38) and effect size to moderate (r = - 0.389). If we considered only those participants with a median paired-pulse amplitude < 1 mV, responder rate increased further to 79% (n = 14) and effect size to r = - 0.727 (i.e., large effect). These findings suggest increasingly stronger conditioning effects for smaller MEP amplitudes during paired-pulse TMS conditioning. These proof-of-concept findings extend the scope of classical conditioning to faciliatory paired-pulse TMS.

Analogous cognitive strategies for tactile learning in the rodent and human brain.

Evolution has molded individual species' sensory capacities and abilities. In rodents, who mostly inhabit dark tunnels and burrows, the whisker-based somatosensory system has developed as the dominant sensory modality, essential for environmental exploration and spatial navigation. In contrast, humans rely more on visual and auditory inputs when collecting information from their surrounding sensory space in everyday life. As a result of such species-specific differences in sensory dominance, cognitive relevance and capacities, the evidence for analogous sensory-cognitive mechanisms across species remains sparse. However, recent research in rodents and humans yielded surprisingly comparable processing rules for detecting tactile stimuli, integrating touch information into percepts, and goal-directed rule learning. Here, we review how the brain, across species, harnesses such processing rules to establish decision-making during tactile learning, following canonical circuits from the thalamus and the primary somatosensory cortex up to the frontal cortex. We discuss concordances between empirical and computational evidence from micro- and mesoscopic circuit studies in rodents to findings from macroscopic imaging in humans. Furthermore, we discuss the relevance and challenges for future cross-species research in addressing mutual context-dependent evaluation processes underpinning perceptual learning.

Nutrition claims influence expectations about food attributes, attenuate activity in reward-associated brain regions during tasting, but do not impact pleasantness.

INTRODUCTION: Nutrition claims are one of the most common tools used to improve food decisions. Previous research has shown that nutrition claims impact expectations; however, their effects on perceived pleasantness, valuation, and their neural correlates are not well understood. These claims may have both intended and unintended effects on food perception and valuation, which may compromise their effect on food decisions. METHODS: We investigated the effects of nutrition claims on expectations, perceptions, and valuation of milk-mix drinks in a behavioral (n = 110) and an fMRI (n = 39) study. In the behavioral study, we assessed the effects of a "fat-reduced" and a "protein-rich" nutrition claim on expected and perceived food attributes of otherwise equal food products. In the fMRI study, we investigated the effect of a "protein-rich" claim on taste pleasantness perception and valuation, and on their neural correlates during tasting and swallowing. RESULTS: We found that both nutrition claims increased expected and perceived healthiness and decreased expected but not perceived taste pleasantness. The "protein-rich" claim increased expected but not perceived satiating quality ratings, while the "fat-reduced" claim decreased both expected and perceived satiating quality ratings. In the absence vs. presence of the "protein-rich" claim, we observed an increased activity in a cluster extending to the left nucleus accumbens during tasting and an increased functional connectivity between this cluster and a cluster in right middle frontal gyrus during swallowing. CONCLUSION: Altogether, we found that nutrition claims impacted expectations and attenuated reward-related responses during tasting but did not negatively affect perceived pleasantness. Our findings support highlighting the presence of nutrients with positive associations and exposure to foods with nutrition claims to increase their acceptance. Our study offers insights that may be valuable in designing and optimizing the use of nutrition claims.

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.

Distinct Behavior of Traumatic versus Nontraumatic Intracerebral Hematomas: Different Biology or Impact of Age?

BACKGROUND AND STUDY AIMS: Patients with large intracerebral hematomas (ICH) may demonstrate different demographics and underlying brain and systemic diseases, as well as different radiologic courses and distinct outcomes. It remains unclear whether their different behavior attributes to a different biology of the ICH or to the asymmetric characteristics of the two populations. To analyze and adjust for potential sources of selection and treatment bias, our study compared age-matched patients with traumatic and nontraumatic ICH in a single cohort diagnosed and treated in the same surgical department. MATERIAL AND METHODS: We analyzed 135 consecutive patients with traumatic (n = 90) or spontaneous ICH (n = 45) undergoing treatment at a surgical intensive care unit of an urban university hospital. We documented their differences before and after adjustment for age in terms of demographics, the therapies applied, their radiologic (i.e., volume and rate of ICH expansion [HE]) and clinical (patients' outcome at 30 days) course, the length of hospital and ICU stay, as well as the hospital costs. RESULTS: Patients with traumatic ICH demonstrated more favorable clinical and radiologic characteristics at admission, that is, higher Glasgow Coma Scale score (p < 0.001), less frequently dilated pupil (p = 0.028), lower Charlson Comorbidity Index (p < 0.001), smaller ICH volume (p < 0.001), noneloquent (p < 0.001) or nonintraventricular (p = 0.003) ICH locations, as well as underwent fewer neurosurgical interventions (p < 0.001) and showed a better outcome (p = 0.041), defined as Glasgow Outcome Scale 4 and 5. After adjustment for age, no different outcomes were observed. Of note, elderly patients on novel oral anticoagulants (NOACs) were more likely to develop an HE compared with those on vitamin K antagonists (VKAs, p = 0.05) after traumatic brain injury (TBI) but not after spontaneous ICH. CONCLUSION: Our data reveal a significant heterogeneity within the traumatic series. Whereas younger patients show an excellent outcome, the elderly population of the traumatic cases demonstrates a poor outcome similar to that of the nontraumatic cohort. HE under NOACs rather than under VKAs is more likely in the elderly after TBI. Larger prospective trials are warranted to elucidate the potential individual underlying molecular mechanisms for the development of an ICH and HE in these diseases.

A Systematic Review of Obesity and Binge Eating Associated Impairment of the Cognitive Inhibition System.

Altered functioning of the inhibition system and the resulting higher impulsivity are known to play a major role in overeating. Considering the great impact of disinhibited eating behavior on obesity onset and maintenance, this systematic review of the literature aims at identifying to what extent the brain inhibitory networks are impaired in individuals with obesity. It also aims at examining whether the presence of binge eating disorder leads to similar although steeper neural deterioration. We identified 12 studies that specifically assessed impulsivity during neuroimaging. We found a significant alteration of neural circuits primarily involving the frontal and limbic regions. Functional activity results show BMI-dependent hypoactivity of frontal regions during cognitive inhibition and either increased or decreased patterns of activity in several other brain regions, according to their respective role in inhibition processes. The presence of binge eating disorder results in further aggravation of those neural alterations. Connectivity results mainly report strengthened connectivity patterns across frontal, parietal, and limbic networks. Neuroimaging studies suggest significant impairment of various neural circuits involved in inhibition processes in individuals with obesity. The elaboration of accurate therapeutic neurocognitive interventions, however, requires further investigations, for a deeper identification and understanding of obesity-related alterations of the inhibition brain system.

Intake of NOAC is associated with hematoma expansion of intracerebral hematomas after traumatic brain injury.

PURPOSE: Novel oral anticoagulants are increasingly replacing vitamin K antagonists in the prophylaxis of thromboembolism as they are associated with lower incidence of spontaneous intracerebral hematomas and they do not require drug level monitoring. However, management dilemmas are apparent in patients on novel oral anticoagulants who have developed intracerebral hematomas after traumatic brain injury, since clinical experience with their reversal strategies is limited. METHODS: We retrospectively studied 90 patients with traumatic intracerebral hematomas undergoing treatment at the surgical intensive care unit of the BG University Clinic Bergmannsheil in Bochum between 2015 and 2018. We analyzed potential prognostic factors for their radiological (expansion of intracerebral hematoma) and clinical (patients' outcome) course, in particular the role of novel oral anticoagulants. RESULTS: 71.1% of patients were male; mean age was 67.3 years. Hematoma's expansion occurred in 35.9% of our patients, whereas 62.2% of our cohort showed a favorable outcome, defined as Glasgow Outcome Scale 4 and 5. Intake of novel oral anticoagulants was associated with a higher rate of hematoma's expansion compared to patients on vitamin K antagonists (p = 0.05) or to patients with normal coagulation status (p = 0.002). A younger age (p < 0.001) was identified as the sole independent prognostic factor for a more favorable outcome, after excluding our cases, who underwent a cardiopulmonary resuscitation. CONCLUSIONS: Our data showed a higher rate of hematoma's expansion in patients with traumatic intracerebral hematomas on novel oral anticoagulants vs. vitamin K antagonists and recommend the consideration of prophylactic reversal of the novel oral anticoagulants at admission. Larger prospective trials are warranted to conclude whether the current specific reversal protocols are safe and effective.

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.

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.

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.

Adiposity Related Brain Plasticity Induced by Bariatric Surgery.

Previous magnetic resonance imaging (MRI) studies revealed structural-functional brain reorganization 12 months after gastric-bypass surgery, encompassing cortical and subcortical regions of all brain lobes as well as the cerebellum. Changes in the mean of cluster-wise gray/white matter density (GMD/WMD) were correlated with the individual loss of body mass index (BMI), rendering the BMI a potential marker of widespread surgery-induced brain plasticity. Here, we investigated voxel-by-voxel associations between surgery-induced changes in adiposity, metabolism and inflammation and markers of functional and structural neural plasticity. We re-visited the data of patients who underwent functional and structural MRI, 6 months (n = 27) and 12 months after surgery (n = 22), and computed voxel-wise regression analyses. Only the surgery-induced weight loss was significantly associated with brain plasticity, and this only for GMD changes. After 6 months, weight loss overlapped with altered GMD in the hypothalamus, the brain's homeostatic control site, the lateral orbitofrontal cortex, assumed to host reward and gustatory processes, as well as abdominal representations in somatosensory cortex. After 12 months, weight loss scaled with GMD changes in right cerebellar lobule VII, involved in language-related/cognitive processes, and, by trend, with the striatum, assumed to underpin (food) reward. These findings suggest time-dependent and weight-loss related gray matter plasticity in brain regions involved in the control of eating, sensory processing and cognitive functioning.

Roux-en-Y gastric bypass surgery progressively alters radiologic measures of hypothalamic inflammation in obese patients.

There is increased interest in whether bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) achieve their profound weight-lowering effects in morbidly obese individuals through the brain. Hypothalamic inflammation is a well-recognized etiologic factor in obesity pathogenesis and so represents a potential target of RYGB, but clinical evidence in support of this is limited. We therefore assessed hypothalamic T2-weighted signal intensities (T2W SI) and fractional anisotropy (FA) values, 2 validated radiologic measures of brain inflammation, in relation to BMI and fat mass, as well as circulating inflammatory (C-reactive protein; CrP) and metabolic markers in a cohort of 27 RYGB patients at baseline and 6 and 12 months after surgery. We found that RYGB progressively increased hypothalamic T2W SI values, while it progressively decreased hypothalamic FA values. Regression analyses further revealed that this could be most strongly linked to plasma CrP levels, which independently predicted hypothalamic FA values when adjusting for age, sex, fat mass, and diabetes diagnosis. These findings suggest that RYGB has a major time-dependent impact on hypothalamic inflammation status, possibly by attenuating peripheral inflammation. They also suggest that hypothalamic FA values may provide a more specific radiologic measure of hypothalamic inflammation than more commonly used T2W SI values.

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.

Invasive and Non-invasive Stimulation of the Obese Human Brain.

Accumulating evidence suggests that non-invasive and invasive brain stimulation may reduce food craving and calorie consumption rendering these techniques potential treatment options for obesity. Non-invasive transcranial direct current stimulation (tDCS) or repetitive transcranial magnet stimulation (rTMS) are used to modulate activity in superficially located executive control regions, such as the dorsolateral prefrontal cortex (DLPFC). Modulation of the DLPFC's activity may alter executive functioning and food reward processing in interconnected dopamine-rich regions such as the striatum or orbitofrontal cortex. Modulation of reward processing can also be achieved by invasive deep brain stimulation (DBS) targeting the nucleus accumbens. Another target for DBS is the lateral hypothalamic area potentially leading to improved energy expenditure. To date, available evidence is, however, restricted to few exceptional cases of morbid obesity. The vagal nerve plays a crucial role in signaling the homeostatic demand to the brain. Invasive or non-invasive vagal nerve stimulation (VNS) is thus assumed to reduce appetite, rendering VNS another possible treatment option for obesity. Based on currently available evidence, the U.S. Food and Drug Administration recently approved VNS for the treatment of obesity. This review summarizes scientific evidence regarding these techniques' efficacy in modulating food craving and calorie intake. It is time for large controlled clinical trials that are necessary to translate currently available research discoveries into patient care.