Effect of yoga on cortical inhibition in healthy individuals: A pilot study using Transcranial Magnetic Stimulation

Sir:

The practice of yoga – a multicomponent process of synchronized physical postures, respiratory control strategies, and deep relaxation e has been studied as an adjuvant treatment to improve cognitive, affective and behavioral symptoms of psychiatric disorders. Meta-analyses of randomized controlled trials demonstrate short-term therapeutic benefits in mood and anxiety disorders [1] and improved quality of life in schizophrenia [2]. However, there are limited studies that have examined the neurobiological mechanistic pathways that yoga engages, modulates and harnesses in the process of bringing about therapeutic gains. Among the many effects reported with yoga, a blunted physiological response to stress e cortisol release following activation of the hypothalamopituitary-adrenal (HPA)-axis e is most commonly examined [3]. Interestingly, the HPA-axis is under the regulatory control of gamma-amino-butyric acid (GABA)-mediated cortical inhibition [4]. It is therefore conceivable that yoga blunts the physiological response to stress by enhancing GABA-mediated cortical inhibitory tone.

Magnetic resonance spectroscopy (MRS) and Transcranial Magnetic Stimulation (TMS) have been employed as in vivo techniques of studying GABA-functions. As compared to a control intervention (walking), yoga practice for 12-weeks enhanced MRS-measured GABA concentrations in the left thalamus, which correlated positively with subjective reports of mood improvements in healthy individuals [5]. However, these findings were not replicated in another study [6]. While MRS provides information on GABA concentrations, TMS provides an index of cortical inhibitory function, specific to the GABA-receptor subtype. Identifying whether yoga engages GABA_A or GABA_B receptor-mediated cortical inhibition can potentially improve replicability by providing a more nuanced investigational approach. In this study, we, therefore, aimed to examine the changes in short interval intracortical inhibition (SICI) and cortical silent period (CSP) e two distinct TMS-derived measures of cortical inhibition that are mediated by GABA_A and GABA_B sub-receptors, respectively [7], after yoga training in healthy individuals. We hypothesized enhancement of SICI and CSP after yoga training.

Fifteen healthy volunteers who enrolled for month-long yoga training in a beginners' yoga appreciation course were recruited over a period of two years. They had a mean age of 32.2 ± 8.5 years and 17 ± 2 years of education. 60% (n = 9) were females and all 15 subjects completed an average of 17.5 ± 4 (median 18) sessions of 60-min duration yoga training. The Institute Ethics Committee approved the study protocol and all participants were recruited after they provided a written informed consent. Subjects with current psychiatric diagnoses or on any psychotropic medications were excluded. Subjects were also asked to avoid stimulants like tea/coffee at least 1-h prior to the experiment.

The yoga-training module included asanas or postures, pranayama or controlled breathing and guided deep relaxation, and was imparted by a qualified yoga therapist six days a week for one month. Before and after the yoga training, subjects underwent a TMS experiment, during which, they were seated comfortably in a chair, with their elbows flexed at 90-degrees and hands rested on the armrest of the chair in prone position. TMS pulses were delivered using a 70-mm figure-of-eight coil (MagPro R30 with MagOption; MagVenture, Farum, Denmark) positioned tangentially over the hand area of the left motor cortex, with the handle pointing posterolaterally. Locating the left motor cortex hand area and determining the resting motor threshold (RMT) and stimulus intensity to elicit 1mV amplitude of motor evoked potentials (SI_1mV) were done according to standard guidelines [8] as electromyography recordings were obtained from the right first dorsal interosseous muscle. Data acquisition and analysis were done using Signal-4 Software (Cambridge Electronic Devices, Cambridge, UK).

To measure SICI, a subthreshold conditioning stimulus (80% of RMT) was given 3 milliseconds before a suprathreshold test stimulus (SI_1mV) with the right hand at rest [9]. Ten trials each were performed using this paired-pulse paradigm and with test-pulse (SI_1mV) alone. SICI was expressed as the percentage of inhibition of the test-pulse with the conditioned stimulus. CSP duration (in milliseconds) was measured in a tonically active right FDI by stimulating the left motor cortex with ten trials of 120% and 140% RMT each. The CSP duration was defined as the time from the MEP offset to the return of any voluntary EMG activity. Two raters independently measured the CSP manually from the average waveforms obtained separately from the ten recordings using two stimulation intensities. Both raters were not aware whether the CSP recordings were pre or post yoga as they received coded files for measurement of CSP duration. The intra-class correlation coefficient for pre- and post-yoga CSP measurements with both the stimulation intensities performed by the two raters ranged between 0.979-0.996. An average CSP duration obtained from measurements of both raters was then used in the analyses.

Paired t-test revealed significant enhancement of CSP duration measured using both intensities following yoga training (figure-1). SICI increased following yoga training (19.6 ± 45.5% to 35.2 ± 28.05%) but this was not statistically significant (P = 0.051). Number of yoga training sessions had a positive correlation with the change in CSP measured using 120%RMT (r = 0.54; p = 0.03) and 140%RMT (r = 0.51; p = 0.05). Together, these findings suggest that yoga training adaptively modulates cortical inhibition, specifically the GABA_B-receptor-mediated CSP; a possible dose-response relationship was also observed. Though preliminary, our results are in keeping with an earlier study that demonstrated greater enhancement of CSP following single-session of meditation, compared to television watching [10], and therefore support the hypothesis of GABA_B-modulation by yoga therapy.

Fig. 1. Box-plots representing cortical silent period duration before and after the month-long yoga training.

The change in cortical silent period duration (CSP) remained significant for both stimulus intensities used to elicit CSP after applying a Bonferroni correction (P < 0.016). CSP120 and CSP140 refer to cortical silent period measured using stimulus intensity of 120% and 140% resting motor thresholds respectively. In the boxplots, the central lines and crosses represent medians and means respectively; box-limits are at 25th and 75th percentiles; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles; data points are plotted as black open circles.

Important limitations of these findings include the lack of a control arm, smaller number (ten) of pulses to record SICI and CSP, and absence of behavioral data to correlate with the change in cortical inhibition. Even though cortical inhibition improved when measured using SICI and CSP, it was statistically significant for CSP alone. Future controlled treatment trials of yoga in larger samples can employ these in vivo measurements of GABA function to demonstrate potential biological systems engagement as a mediator of treatment response.