Neuromodulation directed at the prefrontal cortex of subjects with obesity reduces snack food intake and hunger in a randomized trial

Abstract

Background: Obesity is associated with reduced activation in the left dorsolateral prefrontal cortex (DLPFC), a region of the brain that plays a key role in the support of self-regulatory aspects of eating behavior and inhibitory control. Transcranial direct current stimulation (tDCS) is a noninvasive technique used to modulate brain activity.Objectives: We tested whether repeated anodal tDCS targeted at the left DLPFC (compared with sham tDCS) has an immediate effect on eating behavior during ad libitum food intake, resulting in weight change, and whether it might influence longer-term food intake-related appetite ratings in individuals with obesity.Design: In a randomized parallel-design study combining inpatient and outpatient assessments over 31 d, 23 individuals with obesity [12 men; mean ± SD body mass index (BMI; in kg/m2): 39.3 ± 8.42] received 15 sessions of anodal (i.e., enhancing cortical activity) or sham tDCS aimed at the left DLPFC. Ad libitum food intake was assessed through the use of a vending machine paradigm and snack food taste tests (SFTTs). Appetite was evaluated with a visual analog scale (VAS). Body weight was measured. We examined the effect of short-term (i.e., 3 sessions) and long-term (i.e., 15 sessions) tDCS on these variables.Results: Relative to sham tDCS, short-term anodal tDCS did not influence ad libitum intake of food from the vending machines. Accordingly, no effect on short-term or 4-wk weight change was observed. In the anodal tDCS group, compared with the sham group, VAS ratings for hunger and the urge to eat declined significantly more (P = 0.01 and P = 0.05, respectively), and total energy intake during an SFTT was relatively lower in satiated individuals (P = 0.01), after long-term tDCS.Conclusions: Short-term anodal tDCS of the left DLPFC did not have an immediate effect on ad libitum food intake or thereby weight change, relative to sham tDCS. Hunger and snack food intake were reduced only after a longer period of anodal tDCS in individuals with obesity. This trial was registered at clinicaltrials.gov as NCT00739362.

Keywords: ad libitum food intake; dorsolateral prefrontal cortex; eating in the absence of hunger; hunger; neuromodulation; obesity; snack food intake; transcranial direct current stimulation (tDCS); weight change.

© 2017 American Society for Nutrition.

Figures

FIGURE 1

Overview of study design. (A) Flowchart showing the number of individuals enrolled and admitted and the number of participants who completed the inpatient assessment and outpatient visits. Reasons for dropping out are listed on the right. For the inpatient assessment, 14 participants receiving anodal tDCS and 17 individuals receiving sham tDCS were analyzed to determine differences between the groups, whereas for the outpatient visits, 9 and 14 individuals in each group, respectively, were analyzed. In panel B, squares with numbers indicate the days of inpatient assessment, whereas squares with letters indicate weekdays when outpatient visits occurred. After receiving informed consent, the study physician enrolled the participants. Upon admission, before the vending machine paradigm (days 8, 9, and 10), subjects were administered an individualized WMD adjusted for body weight and sex (20% protein, 30% fat, 50% carbohydrate) (23). On day 2, eating-related behaviors and psychopathology were investigated through the administration of a Psy and a BQ, and fat-mass, fat-free mass, and percentage of body fat were estimated by DXA (DPX-1; Lunar Radiation Corp) (24). Glucose tolerance was determined on day 4. As a measure of ad libitum food intake and to assess taste preferences, an SFTT was performed on day 7 (25, 26). Study participants received anodal or sham tDCS of the left dorsolateral prefrontal cortex on days 8, 9, and 10. On these days, food intake was measured through the use of the vending machine paradigm. The SFTT, Psy, and BQ were repeated on day 11, and weight was measured at discharge. After the inpatient period, individuals were given instructions for a 25% calorie-reduced diet. Outpatient visits began the week after inpatient assessment. tDCS was performed for 4 consecutive weeks, 3 sessions/wk, each on a separate day. On the last day of the study, 1 d after the last outpatient stimulation, participants were fed breakfast on the clinical research unit and the Psy, BQ, and DXA were repeated. After lunch, participants completed the follow-up SFTT. *Except for the last week of outpatient visits, when a final tDCS was performed on a Thursday. BQ, behavioral questionnaire; DXA, dual X-ray absorptiometry; F, Friday; L, last day of the study (day after final transcranial direct current stimulation); M, Monday; OGTT, oral-glucose-tolerance test; Psy, psychological performance test; SFTT, snack food taste test; tDCS, transcranial direct current stimulation; W, Wednesday; WMD, weight-maintaining diet.

FIGURE 2

Effect of anodal compared with sham tDCS on food intake from vending machines. Mean energy intake (A) and mean total macronutrient intake [carbohydrates (B), fat (C), and protein (D), all in grams] for anodal (× n = 13) compared with sham (◆ n = 16) tDCS during a 3-d vending machine paradigm. The Student t test was used to discern differences in energy intake. Mixed models were used to test for a longitudinal effect of anodal stimulation on food intake. For mean energy intake (t value: 0.37), mean total carbohydrate intake (t value: 0.40), mean total fat intake (t value: 0.19), and mean total protein intake (t value: −0.13), no differences between the groups were observed (all P > 0.05; df: 27). Outliers in the anodal group for total mean energy intake (A) and mean total carbohydrate intake (B) were considered in the analyses and did not influence the significance of results. During the vending machine paradigm, no effect of anodal tDCS on mean food intake was observed compared with sham stimulation (all P > 0.05) (A–D). Daily energy intake (kilocalories per day) was determined through an assessment of ad libitum intake during the vending machine paradigm on days 1, 2, and 3 (E), adjusted for fat-free mass, with SEs indicated. No effect of anodal tDCS was observed on food intake from vending machines compared with sham stimulation (P > 0.05, df 56; F value: 0.02). tDCS, transcranial direct current stimulation.

FIGURE 3

Effect of anodal compared with sham tDCS on food intake during SFTT. Total energy intake (kilocalories; A) and candy consumed (grams; B) during SFTT 1 (first test during the baseline assessment; white columns), SFTT 2 (last test during the baseline assessment; striped columns), and SFTT 3 (test on the last day of the study during the outpatient visits; black columns). For baseline assessment (11 d), anodal and sham tDCS was performed in 13 and 16 subjects, respectively. Snack food intake could be analyzed in 8 and 13 individuals in the anodal and sham tDCS groups, respectively, during the outpatient assessment (4 consecutive weeks). SFTT1 and SFTT3 were compared and, relative to those who received sham tDCS, individuals who received anodal stimulation had significantly lower total energy intake (df: 1; t value: 2.77) and ate less candy (df: 1; t value: 2.95), as assessed with ANCOVA; this indicates an effect of anodal (compared with sham) tDCS on energy intake and thus indirectly on eating behavior in this setting. In a mixed model, time-by-treatment interaction for total energy intake and for candy consumed is P = 0.05. SFTT, snack food taste test; tDCS, transcranial direct current stimulation. *P < 0.05.

FIGURE 4

Effect of anodal compared with sham tDCS on VAS ratings during tDCS sessions. VAS ratings of hunger (A) and the urge to eat (B) during the inpatient assessment (tDCS study days 1–3) and outpatient visits (tDCS study days 8–31), comparing anodal (×) and sham (◆) stimulation, relative to study days after the first stimulation session. Means of ratings before and after tDCS are shown for all individuals within 1 study group. A total of 29 individuals completed the inpatient assessment (anodal tDCS, n = 13; sham tDCS, n = 16), and 23 completed the outpatient assessment (anodal tDCS, n = 9; sham tDCS, n = 14). Relative to the sham group, individuals receiving anodal tDCS had a greater decrease in VAS ratings for hunger and the urge to eat (P = 0.01; β: −0.61 VAS score/d; SE: 0.22 VAS score/d; df: 610; t value: 2.69; and P = 0.05; β: −0.46 VAS score/d; SE: 0.23 VAS score/d; df: 610; t value: 1.96, respectively) in a mixed model adjusted for age and sex, as indicated by the significant difference in the slope for these ratings comparing both groups over time (P = 0.01 and P = 0.05, respectively). Dotted lines represent trendlines for the decrease in ratings. For hunger ratings (A), the slopes of the trendlines for sham compared with anodal tDCS are −0.51 (P = 0.003) and −1.11 (P < 0.0001), respectively. VAS ratings for the urge to eat (B) display a steeper decrease in the anodal group (slope = −0.87; P < 0.0001) compared with the sham group (slope = −0.41; P = 0.02). Absolute VAS ratings of hunger and the urge to eat were consistently lower in the anodal group, including those ratings given before the first tDCS session. Because no identifiable baseline differences were found in the anodal and sham groups (all P > 0.05), consistently lower VAS ratings of hunger and the urge to eat in the anodal compared with the sham group is likely because of the relatively small study cohort. Of note, however, assessment of the greater declines in hunger and the urge to eat in mixed models accounted for the baseline ratings. tDCS, transcranial direct current stimulation; VAS, visual analog scale.