Miguel Alonso-Alonso

Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain–behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies.

Safety and Behavioral Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation in Stroke

Background and Purpose— Electromagnetic brain stimulation might have value to reduce motor deficits after stroke. Safety and behavioral effects of higher frequencies of repetitive transcranial magnetic stimulation (rTMS) require detailed assessment. Methods— Using an active treatment-only, unblinded, 2-center study design, patients with chronic stroke received 20 minutes of 20 Hz rTMS to the ipsilesional primary motor cortex hand area. Patients were assessed before, during the hour after, and 1 week after rTMS. Results— The 12 patients were 4.7±4.9 years poststroke (mean±SD) with moderate–severe arm motor deficits. In terms of safety, rTMS was well tolerated and did not cause new symptoms; systolic blood pressure increased from pre- to immediately post-rTMS by 7 mm Hg (P=0.043); and none of the behavioral measures showed a decrement. In terms of behavioral effects, modest improvements were seen, for example, in grip strength, range of motion, and pegboard performance, up to 1 week after rTMS. The strongest predictor of these motor gains was lower patient age. Conclusions— A single session of high-frequency rTMS to the motor cortex was safe. These results require verification with addition of a placebo group and thus blinded assessments across a wide spectrum of poststroke deficits and with larger doses of 20 Hz rTMS.

Computational modeling of transcranial direct current stimulation (tDCS) in obesity: Impact of head fat and dose guidelines☆

Recent studies show that acute neuromodulation of the prefrontal cortex with transcranial direct current stimulation (tDCS) can decrease food craving, attentional bias to food, and actual food intake. These data suggest potential clinical applications for tDCS in the field of obesity. However, optimal stimulation parameters in obese individuals are uncertain. One fundamental concern is whether a thick, low-conductivity layer of subcutaneous fat around the head can affect current density distribution and require dose adjustments during tDCS administration. The aim of this study was to investigate the role of head fat on the distribution of current during tDCS and evaluate whether dosing standards for tDCS developed for adult individuals in general are adequate for the obese population. We used MRI-derived high-resolution computational models that delineated fat layers in five human heads from subjects with body mass index (BMI) ranging from “normal-lean” to “super-obese” (20.9 to 53.5 kg/m2). Data derived from these simulations suggest that head fat influences tDCS current density across the brain, but its relative contribution is small when other components of head anatomy are added. Current density variability between subjects does not appear to have a direct and/or simple link to BMI. These results indicate that guidelines for the use of tDCS can be extrapolated to obese subjects without sacrificing efficacy and/or treatment safety; the recommended standard parameters can lead to the delivery of adequate current flow to induce neuromodulation of brain activity in the obese population.

Modulation of synchrony between single motor units during precision grip tasks in humans

During precision grip, coherence between motor cortex and hand muscle EMG oscillatory activity in the 15‐30 Hz range covaries with the compliance of the manipulated object. The current study investigated whether short‐term synchrony and coherence between discharges of single motor units (SMUs) in the first dorsal interosseous (1DI) muscle were similarly modulated by object compliance during precision grip. Eight subjects used index finger and thumb to grip two levers that were under robotic control. Guided by visual feedback of the lever force levels, subjects held the levers against a steady force of 1.3 N for 8 s; they then linearly increased the force to 1.6 N over a 2 s period and held for a further 8 s before linearly decreasing the force back to the 1.3 N level over another 2 s period. Subjects performed the task at two different levels of compliance, each with identical grip force levels. Both surface EMG and SMU activity were recorded from the 1DI muscle. Short‐term synchrony between the discharges of pairs of SMUs was assessed in the time domain by cross‐correlation and in the frequency domain by coherence analysis. Coherence was seen in two frequency ranges: 6‐12 Hz and 15‐30 Hz. The compliance of the gripped object had a significant effect on both short‐term synchronisation and coherence in the 15‐30 Hz range between SMUs; both were greater for the more compliant condition. There was no change in the 6‐12 Hz coherence.

The neurocognitive connection between physical activity and eating behaviour.

As obesity rates increase worldwide, healthcare providers require methods to instill the lifestyle behaviours necessary for sustainable weight loss. Designing effective weight‐loss interventions requires an understanding of how these behaviours are elicited, how they relate to each other and whether they are supported by common neurocognitive mechanisms. This may provide valuable insights to optimize existing interventions and develop novel approaches to weight control. Researchers have begun to investigate the neurocognitive underpinnings of eating behaviour and the impact of physical activity on cognition and the brain. This review attempts to bring these somewhat disparate, yet interrelated lines of literature together in order to examine a hypothesis that eating behaviour and physical activity share a common neurocognitive link. The link pertains to executive functions, which rely on brain circuits located in the prefrontal cortex. These advanced cognitive processes are of limited capacity and undergo relentless strain in the current obesogenic environment. The increased demand on these neurocognitive resources as well as their overuse and/or impairment may facilitate impulses to over‐eat, contributing to weight gain and obesity. This impulsive eating drive may be counteracted by physical activity due to its enhancement of neurocognitive resources for executive functions and goal‐oriented behaviour. By enhancing the resources that facilitate ‘top‐down’ inhibitory control, increased physical activity may help compensate and suppress the hedonic drive to over‐eat. Understanding how physical activity and eating behaviours interact on a neurocognitive level may help to maintain a healthy lifestyle in an obesogenic environment.

Brain Stimulation in Poststroke Rehabilitation

Brain stimulation techniques provide a powerful means to modulate the function of specific neural structures, and show potential for future applications in the rehabilitation of stroke patients. Recent studies have started to translate to the bedside the body of data gathered over the last few years on mechanisms underlying brain plasticity and stroke recovery. Both noninvasive and invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation, transcranial direct current stimulation and direct cortical stimulation with epidural electrodes, have recently been tested in small studies with stroke patients. The results to date are very promising. Nonetheless, we are still at an early stage in the field and further evidence is needed to assess the clinical impact of this new approach. In this review, we provide readers with a basic introduction to the field, summarize preliminary studies and discuss future directions.

Obesity and the Neurocognitive Basis of Food Reward and the Control of Intake

With the rising prevalence of obesity, hedonic eating has become an important theme in obesity research. Hedonic eating is thought to be that driven by the reward of food consumption and not metabolic need, and this has focused attention on the brain reward system and how its dysregulation may cause overeating and obesity. Here, we begin by examining the brain reward system and the evidence for its dysregulation in human obesity. We then consider the issue of how individuals are able to control their hedonic eating in the present obesogenic environment and compare 2 contrasting perspectives on the control of hedonic eating, specifically, enhanced control of intake via higher cognitive control and loss of control over intake as captured by the food addiction model. We conclude by considering what these perspectives offer in terms of directions for future research and for potential interventions to improve control over food intake at the population and the individual levels.

Neuromodulation targeted to the prefrontal cortex induces changes in energy intake and weight loss in obesity

Obesity is associated with decreased activity in the prefrontal cortex. Transcranial direct current stimulation (tDCS) modifies cortical excitability and may facilitate improved control of eating. The energy intake (EI) and body weight in subjects who received cathodal versus sham (study 1) and subsequent anodal versus sham (study 2) tDCS aimed at the left dorsolateral prefrontal cortex (LDLPFC) were measured.

Brain responses to food images during the early and late follicular phase of the menstrual cycle in healthy young women: relation to fasting and feeding

BACKGROUND Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown. OBJECTIVE The objective was to examine whether brain activation during food visualization is affected by changes in estradiol concentration in the fasted and fed conditions. DESIGN Nine eumenorrheic, lean young women [mean (±SD) age: 26.2 ± 3.2 y; body mass index (in kg/m(2)): 22.4 ± 1.2] completed 2 visits, one in the early (low estradiol) and one in the late (high estradiol) follicular phase of their menstrual cycle. At each visit, subjects underwent functional magnetic resonance imaging while they viewed food and nonfood images, before and after a standardized meal. Region-of-interest analysis was used to examine the effect of follicular phase and prandial state on brain activation (food > nonfood contrast) and its association with estradiol concentration. RESULTS Differences were identified in the inferior frontal and fusiform gyri. In these areas, visualization of food elicited greater activation in the fed state than during fasting but only in the late follicular phase, when estradiol concentration was high. The change in estradiol concentration across the follicular phase (late minus early) was inversely correlated with the change in fusiform gyrus activation in the fasted state but not in the fed state. CONCLUSION Our findings suggest that estradiol may reduce food intake by decreasing sensitivity to food cues in the ventral visual pathway under conditions of energy deprivation. This trial was registered at clinicaltrials.gov as NCT00130117.

Long-term effects of contralesional rTMS in severe stroke: Safety, cortical excitability, and relationship with transcallosal motor fibers

BACKGROUND Contralesional hemispheric repetitive transcranial magnetic stimulation (rTMS) may improve motor function in mild to moderate stroke and effects are considered to be mediated through transcallosal motor fibers. OBJECTIVE This study aimed to investigate the safety of contralesional rTMS in a selected group of severe chronic stroke patients. METHODS Ten sessions of 1 Hz rTMS were applied to contralesional primary motor cortex (M1) using neuronavigated stimulation and changes in motor impairment were evaluated before, during and after rTMS applications and at 4-weeks follow-up. Neurophysiological response to stimulation was assessed through cortical excitability evaluations. The relationship between functional and neurophysiological response to rTMS and microstructural integrity of transcallosal motor fibers were searched using diffusion tensor imaging (DTI) based fractional anisotropy (FA). RESULTS rTMS was well-tolerated with high compliance and no dropouts; no seizures or motor worsening occurred. Transcallosal FA values revealed a positive linear relationship with the mild motor improvement detected after rTMS while higher FA values were observed in subjects with better motor outcome. Cortical excitability showed a significant change in contralesional short-interval intracortical inhibition indicating altered plasticity following rTMS. CONCLUSIONS Our results suggest that noninvasive neuromodulation of the contralesional hemisphere may present a possibility to assist adaptive neuroplastic changes in severe chronic stroke. Implementation of DTI-derived measures of transcallosal microstructural integrity may allow for individually-tailored interventions to guide processes of interhemispheric neuroplasticity. Further research is warranted to establish the clinical value of these findings in neurorehabilitation settings for subjects with chronic severe stroke.