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Pharmacological intervention is a mainstay for treatment of epilepsy. However, a third of patients with epilepsy remain drug resistant. Behavioural treatments such as biofeedback training can be potential effective alternative interventions for drug resistant epilepsy. This paper describes a biofeedback therapy in which the training of patients to control peripheral autonomic tone (galvanic skin response) changes in central control of seizure occurrence. This paper introduces; 1) the theoretical development of methodology, 2) the effect of GSR biofeedback in reducing seizure frequency in drug resistant epilepsy, 3) insights into the neural mechanisms of effective GSR biofeedback through neuromodulatory autonomic control and 3) future prospects of this approach as a therapeutic tool instantiated as an Autonomic Cognitive Rehabituation Training (ACRT)., (Copyright © 2019. Published by Elsevier B.V.)

Background: Thirty-percent of patients with epilepsy are drug-resistant, and might benefit from effective noninvasive therapeutic interventions. Evidence is accumulating on the efficacy of autonomic biofeedback therapy using galvanic skin response (GSR; an index of sympathetic arousal) in treating epileptic seizures. This study aimed to extend previous controlled clinical trials of autonomic biofeedback therapy with a larger homogeneous sample of patients with temporal lobe epilepsy. In addition, we used neuroimaging to characterize neural mechanisms of change in seizure frequency following the therapy., Methods: Forty patients with drug-resistant temporal lobe epilepsy (TLE) (age: 18 to 70years old), on stable doses of anti-epileptic medication, were recruited into a controlled and parallel-group trial from three screening centers in the UK. Patients were allocated to either an active intervention group, who received therapy with GSR biofeedback, or a control group, who received treatment as usual. Allocation to the group was informed, in part, by whether patients could travel to attend repeated therapy sessions (non-randomized). Measurement of outcomes was undertaken by an assessor blinded to the patients' group membership. Resting-state functional and structural MRI data were acquired before and after one month of therapy in the therapy group, and before and after a one-month interval in the control group. The percentage change of seizure frequency was the primary outcome measure. The analysis employed an intention-to-treat principle. The secondary outcome was the change in default mode network (DMN) and limbic network functional connectivity tested for effects of therapy. The trial was registered with the National Institute for Health Research (NIHR) portfolio (ID 15967)., Findings: Data were acquired between May 2014 and October 2016. Twenty participants were assigned to each group. Two patients in the control group dropped out before the second scan, leaving 18 control participants. There was a significant difference in reduction of seizure frequency between the therapy and control groups (p<0.001: Mann Whitney U Test). The seizure frequency in the therapy group was significantly reduced (p<0.001: Wilcoxon Signed Rank Test) following GSR biofeedback, with a mean seizure reduction of 43% (SD=± 32.12, median=-37.26, 95% CI -58.02% to -27.96%). No significant seizure reduction was observed in the control group, with a mean increase in seizure frequency of 31% (SD=±88.27, median=0, 95% CI -12.83% to 74.96%). The effect size of group comparison was 1.14 (95% CI 0.44 to 1.82). 45% of patients in the therapy group showed a seizure reduction of >50%. Neuroimaging analysis revealed that post-therapy seizure reduction was linearly correlated with enhanced functional connectivity between right amygdala and both the orbitofrontal cortex (OFC) and frontal pole (FP)., Interpretation: Our clinical study provides evidence for autonomic biofeedback therapy as an effective and potent behavioral intervention for patients with drug-resistant epilepsy. This approach is non-pharmacological, non-invasive and seemingly side-effect free., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Biofeedback training is a technique through which one can learn to control usually uncontrollable inner body functions, such as brain waves, heart rate or electrodermal activity (EDA). These 'hidden' biological signals are measured from a participant and fed back during the training, e.g., through visual and auditory changes on a computer screen. With practice, the participant learns to control this feedback, and ultimately to control their bodily responses without needing the feedback. In this article, the application of EDA biofeedback will be introduced as a therapy for specific neurological conditions.

Pharmacological treatment is the mainstay for the treatment of epilepsy. However concerns regarding long-term side effects of drugs are increasingly voiced. Behavioral treatments including biofeedback, represents an alternative management option for the control of epilepsy. Biofeedback is a non-invasive bio-behavioral procedure through which patients can learn to gain psychophysiological control over seizures. This article will first overview seizure precipitation from a psychological perspective, and then introduce three major biofeedback treatments. Sensory motor rhythm (SMR) and slow cortical potential(SCP) biofeedback uses electroencephalographic parameters and are categorized as neurofeedback. Electrodermal activity (EDA) biofeedback focuses on modulation of peripheral sympathetic tone. The neural mechanisms underlying biofeedback treatment will be discussed in relation to thalamo-cortical regulation(of neural excitability across brain networks).

Objective: To study the clinical effectiveness of biofeedback treatment in reducing tics in patients with Tourette syndrome., Background: Despite advances in the pharmacologic treatment of patients with Tourette syndrome, many remain troubled by their tics, which may be resistant to multiple medications at tolerable doses. Electrodermal biofeedback is a noninvasive biobehavioral intervention that can be useful in managing neuropsychiatric and neurologic conditions., Methods: We conducted a randomized controlled trial of electrodermal biofeedback training in 21 patients with Tourette syndrome., Results: After training the patients for 3 sessions a week over 4 weeks, we observed a significant reduction in tic frequency and improved indices of subjective well-being in both the active-biofeedback and sham-feedback (control) groups, but there was no difference between the groups in these measurements. Furthermore, the active-treatment group did not demonstrably learn to reduce their sympathetic electrodermal tone using biofeedback., Conclusions: Our findings indicate that this form of biofeedback training was unable to produce a clinical effect greater than placebo. The main confounding factor appeared to be the 30-minute duration of the training sessions, which made it difficult for patients to sustain a reduction in sympathetic tone when their tics themselves were generating competing phasic electrodermal arousal responses. Despite a negative finding in this study, electrodermal biofeedback training may have a role in managing tics if optimal training schedules can be identified.

We report data from two patients, followed over 3 years after electrodermal biofeedback treatment. Patients were trained three times each week for four weeks to increase their sympathetic arousal using electrodermal biofeedback. This treatment was directed at enabling the patients to change their psychophysiological state as a countermeasure to prevent seizures. Both patients voluntarily kept a record of seizure frequency over the year preceding the treatment and continued to record their seizures for up to 3 years after the termination of biofeedback treatment. Both patients showed a marked reduction in seizure frequency (54.9% and 59.8%) during the month of biofeedback treatment. This improvement was maintained over the subsequent years. We highlight the therapeutic potential of biofeedback interventions that enable patients to volitionally control their state of physiological arousal in the management of drug-resistant epilepsy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Biofeedback is a noninvasive behavioral treatment that enables a patient to gain volitional control over a physiological process. As a treatment for epilepsy, biofeedback interventions were explored from as early as the 1970s, concentrating on sensory motor rhythm (SMR) as a neurophysiologic parameter. Whereas SMR biofeedback aims to modulate frequency components of the electroencephalography (EEG), slow cortical potential (SCP) biofeedback (which was introduced in the 1990s) focuses on the regulation of the amplitude of cortical potential changes (DC shift). In its application to epilepsy, biofeedback using galvanic skin response (GSR), an electrodermal measure of sympathetic activity, is a relatively new cost-effective methodology. The present article first reviews biofeedback using SMR and SCP, for which efficacy and neural mechanisms are relatively well characterized. Then recent data regarding promising applications of GSR biofeedback will be introduced and discussed in detail.

Anti-epileptic drugs are the mainstay in the management of epilepsy. However, approximately 30% of patients continue to have seizures despite optimal drug therapy. Behavioural interventions that include biofeedback have become increasingly popular over the last 3 decades, and the results have mostly been encouraging. Biofeedback is a non-invasive behavioural treatment that enables a patient to gain volitional control over a physiological process. In epilepsy, targeted parameters for biofeedback include electroencephalographic (EEG) measures of cortical activity, such as different EEG frequencies or cortical potentials (i.e., neurofeedback), and peripheral autonomic activity, such as Galvanic Skin Response (GSR). In this review, biofeedback using Sensory Motor Rhythm (SMR), Slow Cortical Potentials (SCP), and GSR are discussed. SMR biofeedback was established in the 1970s and is the most prominent methodology for biofeedback treatment of epilepsy in published literature. The technique is now regaining its popularity. SCP biofeedback was introduced in the 1990s. In contrast to SMR biofeedback, which modulates the frequency components of EEG, SCP biofeedback focuses on the regulation of potential changes (amplitude of DC shift). The clinical trials conducted using SCP biofeedback were larger than those conducted using SMR biofeedback, and their overall outcomes were promising. GSR biofeedback is a relatively new methodology in its application to epilepsy and focuses on the modulation of electrodermal measures of sympathetic activity. Compared to the neurofeedback approach, GSR biofeedback is much easier to implement, and evidence suggests that its clinical benefits can be achieved more rapidly. Although the biofeedback treatment may never achieve the status of an alternative to pharmacotherapy for epilepsy, current research findings strongly suggest that biofeedback has the potential to become a potent adjunctive non-pharmacological approach to reduce seizure frequency in patient with drug-resistant epilepsy. Further research, especially a well-controlled large clinical trial, is necessary and anticipated.

Objectives: To examine the immediate and sustained effects of volitional sympathetic modulation, using galvanic skin response (GSR) biofeedback training on cortical excitability in patients with drug-resistant epilepsy., Methods: Ten patients undertook 12 sessions of GSR biofeedback training over 1 month, during which they were trained to increase sympathetic arousal, using GSR biofeedback. Contingent negative variation (CNV) (a slow cortical potential reflecting cortical arousal and excitability) and the related post imperative negative variation (PINV) were quantified before and after biofeedback treatment., Results: A significant reduction in CNV amplitude was observed in both the short-term (within the first session, after 10 minutes of GSR biofeedback) and long-term (sustained after 12 training sessions). Specifically, the change in baseline CNV amplitude after the 12 training sessions correlated with a percentage reduction in seizure frequency. Furthermore, changes in baseline amplitude of the PINV also correlated with seizure reduction., Conclusions: Our findings demonstrate that behavioral enhancement of peripheral sympathetic tone (GSR) is associated with modulation of indices of cortical excitability. Moreover, GSR biofeedback training over repeated sessions was associated with a chronic baseline reduction in slow cortical potentials and concurrent therapeutic improvement.

We investigated the effect of galvanic skin response (GSR) biofeedback training on seizure frequency in patients with treatment-resistant epilepsy. Eighteen patients with drug-refractory epilepsy were randomly assigned either to an active GSR biofeedback group (n = 10) or to a sham control biofeedback group (n = 8). Biofeedback training significantly reduced seizure frequency in the active biofeedback group (P = 0.017), but not the control group (P > 0.10). This was manifest as a significant between-group difference in seizure reduction (P 0.01). Furthermore, there was a correlation between degree of improvement in biofeedback performance and reduction of seizure frequency (rho = 0.736, P = 0.001), confirming that the effect of biofeedback treatment was related to physiological change. Our findings highlight the potential therapeutic value of GSR biofeedback in reducing seizure frequency in patients with drug-resistant epilepsy.