Effects Of High-definition Transcranial Direct Current Stimulation On Attentional Bias And Alpha Oscillations In Patients With Chronic Low Back Pain

BackgroundChronic low back pain（CLBP）is a major cause of disability worldwide and is influenced by biology,psychology,attentional processes and the experience or anticipation of past acquired pain.Recent studies have observed that abnormal neural oscillations in CLBP,especially endogenous alpha oscillations（8-12 Hz）,play an important role in CLBP.This phenomenon can be explained by thalamocortical dysrhythmia（TCD）,suggesting that alpha activity may be a biomarker indicator of pain recovery.In the psychological aspect of chronic pain,CLBP is more prone to allocate more attention to painful stimuli in the environment（e.g.,pain-related pictures）,the so-called pain attention bias.A new attentional bias modification（ABM）training has been derived based on attentional dysfunction.Since pain and cognition share neural substrates,ABM training for cognitive function may be effective in improving pain as well.Modulation of brain alpha oscillations by transcranial direct current stimulation（tDCS）has been shown to reduce pain in patients with chronic pain.However,in the field of CLBP,the modulatory potential of tDCS-targeted stimulation,especially in combination with ABM,on alpha oscillations,as well as the causal relationship and specific mechanisms between CLBP and brain rhythms are not yet clear and need to be further investigated.Therefore,the aim of this study was to investigate the association between clinical indicators of CLBP from physiological and psychological aspects,and to investigate the effects of HD-tDCS combined with ABM on alpha oscillations and pain attention bias in CLBP and the possible underlying neural mechanisms for improving clinical symptoms.MethodThis study was a randomized,double-blind,parallel,controlled clinical trial.A total of46 patients with CLBP were recruited,and finally 40 completed the trial,19 in the real HD-tDCS combined with ABM group and 21 in the sham HD-tDCS combined with ABM group.All subjects completed baseline behavioral scale assessments,including the numeric pain rating scale（NRS）;the Oswestry disability index（ODI）;and the pain catastrophizing scale（PCS）.Next,resting-state electroencephalography（EEG）and dot-probe task were acquired.The dorsolateral prefrontal cortex（DLPFC）was then targeted for real/sham HD-tDCS combined with ABM.Immediately after treatment,dot-probe task and resting-state EEG acquisition were repeated.EEG data pre-processing and statistical analysis were performed based on MATLAB,EEGLAB and self-written codes.αoscillation power was obtained by averaging the power spectral density（PSD）around individualαfrequencies using the pwelch.The power spectral density of alpha oscillations was obtained by averaging the power spectral density（PSD）around individual alpha frequencies and calculating the alpha power spectral density in six regions of interest（ROI）using the pwelch function.Independent samples t-test was used if the difference values between groups conformed to normal distribution,and rank sum test was used for skewed information.Pearson correlation analysis or multi-factor linear regression was used to assess the relationship between alpha oscillations and clinical behavioral indicators.ResultsThere was a significant positive correlation between NRS and ODI（r=0.42,p=0.007）;alpha oscillations in the parietal region showed a significant negative correlation with NRS（r=-0.32,p=0.041）and a marginally negative correlation between alpha oscillations in the occipital region and NRS（r=-0.31,p=0.053）.Under the DLPFC stimulation condition,the increase inαoscillations in each ROI region was significantly higher than in the SHAM group.The most significant difference was found in the parietal region（t=-3.01,p=0.004）,followed by the occipital region（t=-2.66,p=0.01）.Multifactorial linear regression equations were constructed by incorporating the amount of change in alpha oscillations（Post-Pre）,gender,age and ODI in the DLPFC and SHAM groups,respectively.The results showed statistically significant differences in the effect of ODI on the amount of change in alpha oscillations in the left prefrontal region（b=0.12,t=2.31,p=0.04）and the right prefrontal region（b=0.11,t=2.72,p=0.02）in the DLPFC group only.There was no significant effect in the SHAM group.The change in reaction time of point probes before and after the intervention was statistically significant in the DLPFC group(t-_consistent=2.39,p=0.03;t-_inconsistent=2.28,p=0.04);in the SHAM group the reaction time of point probes before and after the intervention was statistically significant in the consistent condition(t-_consistent=2.18,p=0.04;t-_inconsistent=1.19,p=0.06).Before the intervention,the pain attentional bias index was 0.25（SD=5.44）in the DLPFC group and-0.26（SD=5.17）in the SHAM group,and after the intervention,there was no significant change in the attentional bias scores of the two groups（t=0.056,p=0.96）.No serious adverse events were reported in all CLBP patients who received HD-tDCS.However,five（12.5%）reported very mild to mild adverse reactions during stimulation in the form of pain,pruritus and burning under the anodal electrodes.Severity was rated according to a Likert scale（0-5）,which showed no significant difference in the severity of adverse reactions between the two groups（p=0.81）.Patients with CLBP were asked to rate their perceived confidence in HD-tDCS on a scale of 0-100.There was no significant difference in mean scores between the DLPFC and SHAM groups（p=0.08）,indicating the success of the blinded method.ConclusionsThis study is the first research on HD-tDCS combined with ABM training and high-density EEG for CLBP patients.In CLBP,there is a negative correlation between pain intensity and lumbar spine dysfunction.Pain intensity inhibits endogenous alpha oscillations.HD-tDCS successfully identifies and modulates alpha oscillations in CLBP patients,and only the changes of alpha oscillations in the target stimulation area,namely the prefrontal cortex,is affected by the degree of lumbar spine dysfunction in CLBP,indicating the importance of individual differences in neurophysiology and helping to explain the inconsistent effects among different studies.In addition,HD-tDCS combined with ABM training did not effectively improve the pain attention bias score in CLBP,and the dot-probe test showed a significant learning effect.Overall,this study provides new evidence for the potential benefits of HD-tDCS combined with ABM training for CLBP,and this target-specific method combined with EEG can provide insights into the mechanisms of chronic pain,emphasizing the importance of targeting specific neural mechanisms in developing effective interventions,which will also provide support and evidence for the personalized customization of non-invasive stimulation targeting specific brain areas.