Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods.

Felipe Fregni , Fernanda Orsati , Waldelle Pedrosa , Shirley Fecteau , Fatima A M Tome , Michael A Nitsche , Tatiana Mecca , Elizeu C Macedo , Alvaro Pascual-Leone , Paulo S Boggio

Appetite. 2007 Dec 23; : 18243412

We aimed to assess whether modulation of the dorsolateral prefrontal cortex (DLFPC) with noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS), modifies food craving in healthy subjects. We performed a randomized sham-controlled cross-over study in which 23 subjects received sham and active tDCS (anode left/cathode right and anode right/cathode left) of the DLPFC. Subjects were exposed to food and also watched a movie of food associated with strong craving. Desire for food consumption was evaluated by visual analogue scales (VAS) and food consumption before and after treatment. In addition we measured visual attention to food using an eye tracking system. Craving for viewed foods as indexed by VAS was reduced by anode right/cathode left tDCS. After sham stimulation, exposure to real food or food-related movie increased craving; whereas after anode left/cathode right tDCS, the food-related stimuli did not increase craving levels, as revealed by the VAS scale. Moreover, compared with sham stimulation, subjects fixated food-related pictures less frequently after anode right/cathode left tDCS and consumed less food after both active stimulation conditions. These changes were not related to mood changes after any type of tDCS treatment. The effects of tDCS on food craving might be related to a modulation of neural circuits associated with reward and decision-making.

Bartholow, Sciamanna, Alberti: Pioneers in the Electrical Stimulation of the Exposed Human Cerebral Cortex.

Stefano Zago , Roberta Ferrucci , Felipe Fregni , Alberto Priori

Neuroscientist. 2008 Jan 24; : 18219054

Although the past 25 years have witnessed increasing interest in human brain stimulation, its historical development is marked by phases of fascination and obscurity. Its history dates back to the 19th century when the first reports describing application of an electric current to an isolated point on the exposed brain made brain stimulation a major neuroscientific novelty of the time. In this article, the authors present and discuss a number of early experiments involving electrical stimulation of the exposed human brain. In this important, albeit unexplored, historical chapter of brain stimulation, the 3 investigators, Bartholow, Sciamanna, and Alberti, were the first to reproduce findings in animals with electrical brain stimulation in humans.

Focusing Effect of Acetylcholine on Neuroplasticity in the Human Motor Cortex.

Min-Fang Kuo , Jan Grosch , Felipe Fregni , Walter Paulus , Michael A Nitsche

J Neurosci. 2007 Dec 26;27 (52):14442-14447 18160652

Cholinergic neuromodulation is pivotal for arousal, attention, and cognitive processes. Loss or dysregulation of cholinergic inputs leads to cognitive impairments like those manifested in Alzheimer's disease. Such dysfunction can be at least partially restored by an increase of acetylcholine (ACh). In animal studies, ACh selectively facilitates long-term excitability changes induced by feed-forward afferent input. Consequently, it has been hypothesized that ACh enhances the signal-to-noise ratio of input processing. However, the neurophysiological foundation for its ability to enhance cognition in humans is not well documented. In this study we explore the effects of rivastigmine, a cholinesterase inhibitor, on global and synapse-specific forms of cortical plasticity induced by transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) on 10-12 healthy subjects, respectively. Rivastigmine essentially blocked the induction of the global excitability enhancement elicited by anodal tDCS and revealed a tendency to first reduce and then stabilize cathodal tDCS-induced inhibitory aftereffects. However, ACh enhanced the synapse-specific excitability enhancement produced by facilitatory PAS and consolidated the inhibitory PAS-induced excitability diminution. These findings are in line with a cholinergic focusing effect that optimizes the detection of relevant signals during information processing in humans.

New Insights Into Neuromodulatory Approaches for the Treatment of Pain.

Mark P Jensen , Shahin Hakimian , Leslie H Sherlin , Felipe Fregni

J Pain. 2007 Dec 18; : 18096437

Two lines of evidence about the association between the experience of pain and brain state (measured via electroencephalogram or EEG) have recently come to light. First, research from a number of sources suggests a link between brain EEG activity and the experience of pain. Specifically, this research suggests that the subjective experience of pain is associated with relatively lower amplitudes of slower wave (delta, theta, and alpha) activity and relatively higher amplitudes of faster wave (beta) activity. Second, there has been a recent increase in interest in interventions that impact the cortical neuromodulation of pain, including behavioral treatments (such as self-hypnosis training and neurofeedback) and both invasive and noninvasive brain stimulation. Although a direct causal link between experience of pain and brain activity as measured by EEG has not been established, the targeting of pain treatment at a cortical level by trying to affect EEG rhythms directly is an intriguing possibility. PERSPECTIVE: Preliminary evidence suggests the possibility, which has not yet adequately tested or proven, that the experience of chronic pain is linked to cortical activity as assessed via an electroencephalogram. Support for this hypothesis would have important implications for understanding the mechanisms that underlie a number of pain treatments, and for developing new innovative treatments for chronic pain management.

Transcranial direct stimulation and fluoxetine for the treatment of depression.

Sergio P Rigonatti , Paulo S Boggio , Martin L Myczkowski , Emma Otta , Juliana T Fiquer , Rafael B Ribeiro , Michael A Nitsche , Alvaro Pascual-Leone , Felipe Fregni

Eur Psychiatry. 2007 Nov 15; : 18023968

Diminishing Risk-Taking Behavior by Modulating Activity in the Prefrontal Cortex: A Direct Current Stimulation Study.

Shirley Fecteau , Daria Knoch , Felipe Fregni , Natasha Sultani , Paulo Boggio , Alvaro Pascual-Leone

J Neurosci. 2007 Nov 14;27 (46):12500-12505 18003828

Studies have shown increased risk taking in healthy individuals after low-frequency repetitive transcranial magnetic stimulation, known to transiently suppress cortical excitability, over the right dorsolateral prefrontal cortex (DLPFC). It appears, therefore, plausible that differential modulation of DLPFC activity, increasing the right while decreasing the left, might lead to decreased risk taking, which could hold clinical relevance as excessively risky decision making is observed in clinical populations leading to deleterious consequences. The goal of the present study was to investigate whether risk-taking behaviors could be decreased using concurrent anodal transcranial direct current stimulation (tDCS) of the right DLPFC, which allows upregulation of brain activity, with cathodal tDCS of the left DLPCF, which downregulates activity. Thirty-six healthy volunteers performed the risk task while they received either anodal over the right with cathodal over the left DLPFC, anodal over the left with cathodal over the right DLPFC, or sham stimulation. We hypothesized that right anodal/left cathodal would decrease risk-taking behavior compared with left anodal/right cathodal or sham stimulation. As predicted, during right anodal/left cathodal stimulation over the DLPFC, participants chose more often the safe prospect compared with the other groups. Moreover, these participants appeared to be insensitive to the reward associated with the prospects. These findings support the notion that the interhemispheric balance of activity across the DLPFCs is critical in decision-making behaviors. Most importantly, the observed suppression of risky behaviors suggests that populations with boundless risk-taking behaviors leading to negative real-life consequences, such as individuals with addiction, might benefit from such neuromodulation-based approaches.

Site-specific Effects of Transcranial Direct Current Stimulation on Sleep and Pain in Fibromyalgia: A Randomized, Sham-controlled Study.

Suely Roizenblatt , Felipe Fregni , Rafaela Gimenez , Thiago Wetzel , Sergio P Rigonatti , Sergio Tufik , Paulo S Boggio , Angela C Valle

Pain Pract. 2007 Nov 6; : 17986164

Objective: To investigate whether active anodal transcranial direct current stimulation (tDCS) (of dorsolateral prefrontal cortex [DLPFC] and primary motor cortex [M1]) as compared to sham treatment is associated with changes in sleep structure in fibromyalgia. Methods: Thirty-two patients were randomized to receive sham stimulation or active tDCS with the anode centered over M1 or DLPFC (2 mA, 20 minutes for five consecutive days). A blinded evaluator rated the clinical symptoms of fibromyalgia. All-night polysomnography was performed before and after five consecutive sessions of tDCS. Results: Anodal tDCS had an effect on sleep and pain that was specific to the site of stimulation: such as that M1 and DLPFC treatments induced opposite effects on sleep and pain, whereas sham stimulation induced no significant sleep or pain changes. Specifically, whereas M1 treatment increased sleep efficiency (by 11.8%, P = 0.004) and decreased arousals (by 35.0%, P = 0.001), DLPFC stimulation was associated with a decrease in sleep efficiency (by 7.5%, P = 0.02), an increase in rapid eye movement (REM) and sleep latency (by 47.7%, P = 0.0002, and 133.4%, P = 0.02, respectively). In addition, a decrease in REM latency and increase in sleep efficiency were associated with an improvement in fibromyalgia symptoms (as indexed by the Fibromyalgia Impact Questionnaire). Finally, patients with higher body mass index had the worse sleep outcome as indexed by sleep efficiency changes after M1 stimulation. Interpretation: Our findings suggest that one possible mechanism to explain the therapeutic effects of tDCS in fibromyalgia is via sleep modulation that is specific to modulation of primary M1 activity.

Brain stimulation in poststroke rehabilitation.

Miguel Alonso-Alonso , Felipe Fregni , Alvaro Pascual-Leone

Cerebrovasc Dis. 2007 ;24 Suppl 1 :157-66 17971652

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.