Treatment for obesity is extensive, often invasive and involves a difficult path to recovery. Current treatment methods involve psychological therapies, medication use and even high-risk surgeries. Now a team of researchers suggest that deep transcranial magnetic stimulation (dTMS) could be a safer, more effective option.
Brain stimulation, also known as neurostimulation, has long been an area of interest in the treatment of a variety of different medical conditions, including obesity, eating disorders and others associated with addictive behaviour. In order to understand how this technique works when it comes to the treatment of obesity, one needs to understand the mechanisms that lead to the development of this condition.
Overeating is just one of many contributing factors to excess weight gain and is linked to a ‘neurological reward system’ associated with addictive behavioural patterns. Food cravings, characterised as an intense urge to consume a specific food, are something we’re all familiar with and experience from time to time. For some the difference between ‘a little’ and ‘a lot’ is a very fine line, and a simple urge becomes something of a serious splurge.
When overindulgence reaches excessive proportions, problems begin to mount. Cravings and the need to satisfy them can become a major roadblock in a person’s ability to maintain a healthy weight or successfully lose the significant excess that has accumulated over time.
Understanding the brain’s reward system as it relates to food
In essence, the brain’s reward system, which is located at the centre of the brain and involves many parts of it (including the ventral tegmental area, the nucleus accumbens, and the prefrontal cortex), is essential to survival. The reward pathway is also linked to areas of the brain responsible for memory and behaviour. So, the pleasant sensations (rewards) experienced when eating, drinking or having sex provide positive reinforcement of these important activities which will be remembered in order to increase the likelihood of them being repeated in future. Likewise, this system serves to help humans to avoid harmful behaviours.
When it comes to food, the brain’s reward system has a mechanism that drives the desire for food (i.e. wanting food) and one that is associated with the pleasurable properties of food (i.e. liking food). While eating is a reward in itself as it ensures that the body’s caloric requirements are met, enabling us to survive, humans often eat in the absence of appetite and purely for pleasure. Certain foods, especially fatty or sugary foods are perceived by the brain as rewards due to the chemicals (neurotransmitters) and hormones released in the body and brain as a result. The way we feel when eating these foods may promote further consumption thereof, even when our bodies do not require the caloric intake for energy. Our brains thus learn to associate these foods (the stimuli) with feeling good (the reward).
For some individuals struggling with obesity, it has been suggested that the reward pathway response is linked to brain alterations that heighten ‘the need to feed’. This then amplifies pleasure-related eating to levels that lead to excess weight gain and counteract acceptable weight loss progress when any attempts at dieting are made. This leaves some obese individuals more vulnerable to experiencing cravings and if these are indulged, this could lead to the very opposite of what any treatment is structured to achieve.
What if a stimulation mechanism could be used on the brain to assist in altering this ‘neurological reward system’ and thereby help to treat behaviours which ultimately result in unhealthy weight gain?
Could such a stimulation mechanism be a safer alternative to invasive and risky surgeries, or harmful medication side-effects?
Newly presented research at this year’s European Society of Endocrinology annual meeting (European Congress of Endocrinology / ECE 2018 held between 19 and 22 May 2018) has shown positive results in these regards and has led the team of researchers involved to believe that brain stimulation could indeed be offered as a safer treatment alternative for those suffering from obesity.
The European Society of Endocrinology is a scientific society which brings together specialists in the field who share knowledge in order to advance health technologies. Improving medical advancements is core to the organisation’s ethos, and the annual congress is aimed at sharing new insights among all specialists who attend from across Europe.
Is there really a need for safer alternative obesity treatments?
The adverse medical and psychological effects on very overweight and obese individuals contribute to poor quality of life and premature mortality. Mounting health problems associated with excessive weight gain contribute to a reduction in life expectancy. Treatment responses which involve behavioural, pharmacotherapy (medication) and surgical measures can be effective, but many physicians and specialists have found that success rates vary. Some patients respond well to the combination of conservative treatment (proactive changes in exercise activity, nutrition plans and cognitive behavioural therapy sessions) and medication use or more invasive means, like bariatric surgery. However, this is not the case for all patients, particularly in the long-term.
Livio Luzi (MD, PhD, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato and the University of Milan, Italy) who was involved in the latest study addresses some of the core issues - "Given the distressing effects of obesity in patients and socioeconomic burden, it is increasingly urgent to identify new strategies to counteract the current obesity trends. dTMS (deep transcranial magnetic stimulation) could present a much safer and cheaper alternative to treat obesity compared with drugs or surgery."
Obesity as a disease is a growing epidemic affecting millions of adults and children around the world. The World Health Organization (WHO) estimates that the problem has tripled globally since 1975, and for a medical condition that is preventable, this is alarming to say the least. (1) Several million people across the globe are believed to succumb to obesity related complications and comorbid health conditions each year.
The neurobiology behind negative eating behaviours and eating disorders has been studied quite extensively already, with researchers exploring how portions of the brain may be targeted in a way that stimulates a positive and sustainable reaction. Deep brain stimulation (DBS) could form part of an overall treatment plan in a way that may effectively get the better of one of the many contributing factors to obesity – food cravings.
Deep brain stimulation is traditionally a procedure that works by delivering electrical pulses to targeted portions of the brain with the use of electrodes. These electrodes are connected to an IPG (implantable pulse generator), a battery-powered micro-electronic device that is implanted into the body and delivers small electrical pulses that either block or stimulate nerve signals within the nervous system. Similar techniques have already proven effective in the treatment of various neurological conditions, like that of Parkinson’s disease, as well as circuit-based neuropsychiatric problems like major depression, OCD (obsessive-compulsive disorder), Alzheimer’s disease and even Tourette’s syndrome. This has led to scientific explorations regarding eating disorders and obesity too.
It has been found that brain stimulation affects the mesolimbic pathway (also known as the ‘reward pathway’). This dopaminergic pathway connects structures in the midbrain and the ventral striatum (a part of the brain that consists of the nucleus accumbens and the olfactory tubercle and is involved in various aspects of reward processes and motivation). Stimulation also affects the mesostriatal pathways involved, prompting midbrain dopamine projections into the cortex and striatum. This dopaminergic system plays a key role in the emotional processing (or limbic) and motor functions. Abnormal dopaminergic activity and cortical excitability (activity in the cerebral cortex) are associated with addictive behaviours, including food cravings.
Deep brain stimulation is also linked to the treatment of cravings associated with smoking habits. Repetitive transcranial magnetic stimulation (rTMS) has been researched as a non-invasive technique with the ability to block behaviours associated with addictive habits in nicotine-dependant individuals. A single dose of high-frequency rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) could reduce cravings and thereby contribute to successful habit cessation. (2)
What is dTMS?
The latest study looks at the use of deep brain stimulation in the form of dTMS (deep transcranial magnetic stimulation). While traditional deep brain stimulation is invasive and requires the surgical implantation of an electrode in the brain, a neurostimulator device in the chest and internal lead wire that runs from the brain, behind the ear, down the back of the neck and over the shoulder to connect to it, dTMS is non-invasive (as no incisions or implants are required) and does not require the administration of drugs. Instead, deep, repetitive pulses are delivered to the prefrontal cortex, penetrating the scalp, via a helmet that is filled with electric coils. Patients are conscious and do not experience any pain during the procedure.
The use of magnetic energy (electrical currents) stimulates the brain’s neurons (cells) and assists in balancing chemistry within this complex organ. The potential mechanism that drives alterations in the brain in relation to cravings during this process has only been delved into recently and for the time being, dTMS is only approved for research purposes when working with obese patients.
The research team from the Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Italy, conducted an analysis of blood biomarkers (metabolic and neuroendocrine parameters) following just one session of dTMS and deduced that such a procedure may be helpful in reducing food cravings in individuals struggling with obesity, when delivered with high-frequency stimulation. The team theorise that if food cravings could be sufficiently reduced, weight management protocols may be somewhat easier to implement and thereby contribute to more effective weight loss in obese patients.
This research follows a pilot study conducted (by the same team) over a period of 9 weeks in 2016, using 16 obese participants. Repetitive transcranial magnetic stimulation was conducted and suggested a strong enough possibility for weight loss. An average of 4.5 kg (or 9 to 10 pounds) could be lost with at least a 34% food craving reduction being reported following the procedure. The patients were followed-up on and it was found that the weight lost as a result of this procedure could be maintained for at least 6 and 12 months thereafter. (3)
At the time the researchers involved noted that further study, using larger participant groups for a longer period of time to assess the efficacy and success rate of these methods was required, and researchers then delved a little deeper into this type of technique in the studies that followed. One such study commenced in 2015 and involved 50 obese patients. Once more the objective was to assess the impact of dTMS on weight control and satiety. (4)
How could dTMS help those struggling with obesity?
The new research was presented by the Italian team on 21 May 2018 at this year’s ECE. (5) The team later published a press release outlining brief points regarding their research (a full version does not seem to be publicly available as yet). (6)
In a similar way to previous studies, this team noted that dTMS could assist with weight loss goals, targeting food cravings by modulating metabolic pathways in relation to activity within the hypothalamus, pituitary and adrenal glands. They then set out to analyse just what effect dTMS could have on a person’s appetite and satiety levels.
The study was conducted using 40 patients who were classified as obese (the participant group consisted of 29 women and 11 men). A person with a BMI (body mass index) that is calculated as 30 or higher is typically classified as obese. The average BMI of the study participants was 36.3.
The patients were divided into groups and each given a single dTMS session for a period of 30 minutes. The sessions incorporated comparisons between high-frequency (18 Hz), low-frequency (1 Hz) and sham stimulation groups. In the sham group, patients experienced similar effects to real frequency stimulation without actual significant currents being applied (this control group was established in order to account for any placebo effects experienced during treatment). Low-frequency stimulation suppresses cortical activity, while high-frequency stimulates it.
When assessing the blood biomarkers of each patient, it was noted that those who were exposed to high-frequency stimulation experienced an 18% increase in norepinephrine levels (also referred to as noradrenaline which helps to suppress appetite) in comparison to low-frequency stimulation participants. High-frequency patients also experienced a 13.9% increase in beta-endorphin levels (neurotransmitters which lead to heightened feeling of reward when food is eaten) when compared with low-frequency stimulated participants. Other notable differences included a 7% increase in blood glucose levels and a 16.3% reduction in levels of leptin – also referred to as the ‘starvation hormone’, the hormone which signals to the brain that a sufficient calorie intake has occurred, and no further ingestion of food is required, helping to balance or regulate energy in the body.
The research team also noted a 20.7% decrease in thyroid stimulating hormone (a pituitary hormone in the brain which stimulates the thyroid gland to produce thyroxine for metabolism regulation) and a 16.3% reduction in levels of prolactin (a protein hormone also produced in the pituitary gland). Patients exposed to low-frequency stimulation showed reduced levels of salivary cortisol (29.4%) after just the one session too.
Some variations were noted between the genders when it came to analysing the blood biomarkers. To the researchers this suggested that there may be some variances between the genders when it comes to food craving vulnerability, an area which could form part of the focus for future studies. If such vulnerabilities (like differences in blood glucose levels) can be better determined, this could help scientists and medical professionals gain a better understanding of some of the neurological influences in a patient’s ability to successfully lose weight.
In short, high-frequency stimulation (even just one 30-minute session) could stimulate increases in beta-endorphins which directly impact heightened feelings of reward in an individual. By activating and stimulating this sense of reward following the ingestion of food, a person could feel more satisfied during meal times, reducing the cravings experienced in which make weight loss even more difficult to achieve. Stimulation appears to modify neuronal connectivity which could be linked with gut microbiota too – another area future research could focus on for further clarity.
The analysis of blood biomarkers following dTMS treatment is but one step forward in understanding the mechanisms for reducing food cravings and the associated addictive habits. This team is likely to go on to use brain imaging as a next phase for their research to determine just how and why treatment using high-frequency stimulation appears to make a difference. Such research will assess the structure and function of the brain in both the short-term (just after a treatment) and further down the line. Modified neuronal connectivity and its possible link with the gut could be more clearly analysed too.
If the more precise questions around these areas of interest can be answered, dTMS treatment could very well become part of a standard treatment plan for obese patients in the future. If effective enough, the need for multiple pharmacological therapy and surgical procedures may be significantly reduced, and thereby the many adverse reactions a person is at risk of when undergoing these types of treatment.
The research team believe that dTMS treatment is a safer alternative to the currently used methods, especially as it can be done more than once. They also believe that such treatment could even be considered to prevent overweight individuals from becoming obese. In this way, obesity could perhaps be prevented in individuals with unhealthy eating tendencies.
For now, the equipment used is not authorised in this capacity but could be a viable option down the line if such treatment is found to be successful among obese patients. If it does prove to be effective, invasive surgical procedures may become a last resort and medication use that often results in multiple side-effects can be significantly reduced.
Is dTMS treatment the answer to food cravings and obesity? Scientists involved in the research (this study and others) certainly see strong potential and continue to find ways to prove it.
References:
1. World Health Organization. 18 October 2017. Obesity and overweight - Key facts: http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight [Accessed 25.05.2018]
2. Biological Psychiatry Journal. 15 April 2013. Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Reduces Nicotine Cue Craving: https://www.biologicalpsychiatryjournal.com/article/S0006-3223(13)00038-3/abstract [Accessed 25.05.2018]
3. American Diabetes Association’s 76th Scientific Sessions. 10 - 14 June 2016. 266-OR / 266 - Efficacy of Deep Transcranial Magnetic Stimulation on Satiety and Body Weight: http://www.abstractsonline.com/pp8/#!/4008/presentation/43719 [Accessed 25.05.2018]
4. ClinicalTrials.gov. January 2017. Transcranial Magnetic Stimulation (TMS) in Obesity: https://clinicaltrials.gov/ct2/show/NCT03009695 [Accessed 25.05.2018]
5. Endocrine Abstracts. 2018. Deep transcranial magnetic stimulation acutely modulates neuro-endocrine pathways underlying obesity: https://www.endocrine-abstracts.org/ea/0056/ea0056oc6.2 [Accessed 25.05.2018]
6. European Society of Endocrinology. 21 May 2018. Brain stimulation may reduce food cravings as obesity treatment: https://www.ese-hormones.org/media/1503/brain-stimulation-may-reduce-food-cravings-as-obesity-treatment.pdf [Accessed 25.05.2018]