针刺外关穴的脑区激活：功能磁共振成像证据

Objective: To observe the cerebral activation of needling Waiguan (SJ5) by fMRI with the controlled studies of sham needling and needling in a sham point. Methods: Eighteen volunteers were randomly divided into 3 groups of true needling in true acupoint Waiguan (SJ5)(group A), sham needling in true acupoint SJ5 (group B) and true needling in a sham point (group C). During the stimulation, each subject received fMRI functional cerebral imaging scan. The collected data were processed by SPM2. Results: Compared with sham needling, true needling in SJ5 could activate the areas of BA8 and left cerebellum; Compared with needling in the sham point, needling in SJ5 could activate the areas of BA2 and bilateral cerebellum. Conclusion: Needling in SJ5 acupoint activated different cerebral areas compared with sham needling in the same acupoint or true needling in a sham acupoint based on the scanning of fMRI cerebral functional imaging.     

Acupuncture at Waiguan （SJ5） and sham points influences activation of functional brain areas of ischemic stroke patients： a functional magnetic resonance imaging study

Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group （true acupuncture at right Waiguan （SJ5）） and sham point group （sham acupuncture）. Results of functional magnetic resonance imaging revealed activation in right parietal lobe （Brodmann areas 7 and 19）, the right temporal lobe （Brodmann area 39）, the right limbic lobe （Brodmann area 23） and bilateral oc-cipital lobes （Brodmann area 18）. Furthermore, inhibition of bilateral frontal lobes （Brodmann area 4, 6, and 45）, right parietal lobe （Brodmann areas 1 and 5） and left temporal lobe （Brodmann area 21 ） were observed in the true point group. Activation in the precuneus of right parietal lobe （Brodmann area 7） and inhibition of the left superior frontal gyrus （Brodmann area 10） was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex （Brodmann area 5） is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.     

Activated and deactivated functional brain areas in the Deqi state: A functional MRI study

We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1, 2, 3, 4, 5, 6, 7, 9, 10, 18, 24, 31, 40 and 46.     

不同穴位皮部浅刺与常规针刺在fMRI脑功能成像中的差异

Few studies have examined the effects of different stimuli at a single acupoint using functional magnetic resonance imaging.The present study applied acupuncture at the Neiguan(PC 6),Waiguan(SJ 5),Zhigou(SJ 6) and Yanglingquan(GB 34) acupoints in healthy volunteers.fMRI was used to examine the activation of brain areas in response to different types of acupuncture(cutaneous or routine acupuncture) at each acupoint.There were no significant differences in the distribution of activation in the regions of interest between cutaneous and routine acupuncture at the Neiguan,Waiguan,and Zhigou acupoints,but some differences were observed between the two methods of acupuncture at the Yanglingquan acupoint.There were no significant differences in the intensity of induced activation between cutaneous and routine acupuncture at the Neiguan,Zhigou and Yanglingquan acupoints,but the activation intensity in the right cerebellum induced by routine acupuncture at the Waiguan acupoint was greater than that induced by cutaneous acupuncture.Results confirmed that cutaneous and routine acupuncture at the Neiguan,Waiguan,Zhigou and Yanglingquan acupoints activated different functional brain areas,and caused activation of different intensities in some areas.     

Acupuncture for ischemic stroke:cerebellar activation may be a central mechanism following Deqi

The needling sensation of Deqi during acupuncture is a key factor of influencing acupuncture outcome.Recent studies have mainly focused on the brain function effects of Deqi in a physiological state.Functional magnetic resonance imaging(f MRI)on the effects of acupuncture at Waiguan(SJ5)in pathological and physiological states is controversial.In this study,12 patients with ischemic stroke received acupuncture at Waiguan(SJ5)and simultaneously underwent f MRI scanning of the brain,with imaging data of the activated areas obtained.Based on the patient’s sensation,imaging data were allocated to either the Deqi group or non-Deqi group.In the Deqi group,the activated/deactivated areas were the left superior temporal gyrus(BA39)/right anterior lobe of the cerebellum and left thalamus.In the non-Deqi group,the activated areas included the medial frontal gyrus of the right frontal lobe(BA11),right limbic lobe(BA30,35),and left frontal lobe(BA47),while the only deactivated area was the right parietal lobe(BA40).Compared with the non-Deqi group,the Deqi group exhibited marked activation of the right anterior lobe of the cerebellum and right limbic lobe(BA30).These findings confirm that the clinical effect of Deqi during acupuncture is based on brain functional changes.Cerebellar activation may be one of the central mechanisms of acupuncture in the treatment of ischemic stroke.     

Long-term acupuncture treatment has a multi-targeting regulation on multiple brain regions in rats with Alzheimer's disease: a positron emission tomography study

The acute effect of acupuncture on Alzheimer’s disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer’s disease is unclear.Therefore,in this study,we performed long-term needling at Zusanli(ST36)or a sham point(1.5 mm lateral to ST36)in a rat Alzheimer’s disease model,for 30 minutes,once per day,for 30 days.The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning.Positron emission tomography images were processed with SPM2.The brain areas activated after needling at ST36 included the left hippocampus,the left orbital cortex,the left infralimbic cortex,the left olfactory cortex,the left cerebellum and the left pons.In the sham-point group,the activated regions were similar to those in the ST36 group.However,the ST36 group showed greater activation in the cerebellum and pons than the sham-point group.These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer’s disease.     

Nitrogen monoxide vector of ultrasonic atomizing inhalation improves vertebro-basilar artery insufficiency Hemodynamic changes are detected by transcranial Doppler test

BACKGROUND: Latest researches at home and abroad indicate that glycerol trinitrate plays its function because it can metabolize into nitrogen monoxide (NO) in vivo. OBJECTIVE: To study the therapeutic effects of NO vector of ultrasonic atomizing inhalation on vertebro-basilar artery insufficiency (VBI) through transcranial Doppler (TCD) detection and serum NO content and indirect effect of TCD on cerebral blood flow changes. DESIGN: Randomized grouping and controlled clinical study. SETTING: Department of Neurology, the Fourth People's Hospital of Jinan. PARTICIPANTS: A total of 130 patients who were diagnosed as VBI were selected from Department of Neurology, the Fourth People's Hospital of Jinan from December 2001 to December 2005. The involved inpatients were checked by CT and MRI, and met the VBI diagnostic standard enacted by the Fourth National Academic Meeting of Cerebrovascular Disease in 1995. All patients and their relatives provided the confirmed consent. They were randomly divided into low-dose treatment group (n =60), high-lose treatment group (n =30) and control group (n =40). METHODS: Patients in the low-dose and high-dose treatment groups were given ultrasonic atomizing inhalation of 3 mg and 5 mg glycerol trinitrate, respectively, for 20 minutes, once a day. In addition, ligustrazine and energy mixture were used once a day for three days in a course. Cases in the control group were only given ligustrazine and energy mixture. All selected cases accepted TCD, blood NO content was checked at the time of beginning, after the first time and after a period of treatment.　According to the TCD test, VBI patients were divided into two groups (high-low flow velocity). The vertebral artery (VA) and basal artery (BA) of left or right sides were detected by 2 Hz detector via occipital window. MAIN OUTCOME MEASURES: ① Blood flow velocity of systolic phase, blood flow velocity of diastole phase and vascular resistance in left and right VA and BA detected by using TCD before treatment, after treatment for one course; ② content of serum NO indirectly measured by using nitric acid disoxidation technique. RESULTS: All 130 VBI patients were involved in the final analysis. ① Changes of hemodynamic indexes: Systolic phase of VA and diastole phase of BA were higher in low-dose treatment group than that in the control group after first treatment, and there was significant difference (P < 0.05); meanwhile, systolic phase and diastole phase of VA and systolic phase of BA were also higher in treatment group than that in the control group after one course (P < 0.05). However, both systolic phase and diastole phase of VA and BA were lower in high-dose treatment group than that in the control group after first treatment and one course, and there was significant difference (P < 0.05). ② Content of serum NO: After first treatment, there was no significant difference between low-dose treatment group and high-dose treatment group (P > 0.05); but both groups were higher than control group, and there was significant difference (P < 0.05, 0.01). CONCLUSION: NO vector of ultrasonic atomizing inhalation can improve VBI so as to improve cerebral blood-supply state.     

A central analgesic mechanism of acupuncture for migraine An ongoing functional MRI study

Shaoyang acupoints are the most frequently used in migraine treatment. However, the central anal- gesic mechanism remains poorly understood. Studies have demonstrated that single stimulus of the verum acupuncture in healthy subjects can induce significant connectivity or activity changes in pain- related central networks compared with sham acupuncture. However, these findings are not indicative of the central analgesic mechanism of acupuncture at Shaoyang acupoints. Thus, we recruited 100 migraine sufferers and randomly assigned them into five groups： Shaoyang uncommon acupoint, Shaoyang common acupoint, Yangming uncommon acupoint, non-acupoint control, and blank control groups. Subjects were subjected to evaluation of curative effects and functional MRI prior to and after 10 and 20 acupuncture treatments. All subjects were diagnosed by physicians and enrolled following clinical physical examination. Subjects were observed during 1-4 weeks after inclusion. At the fifth week, the first clinical evaluation and resting functional MRI were conducted. The Shaoyang uncom- mon acupoint, Shaoyang common acupoint, Yangming uncommon acupoint, and non-acupoint control grousp then were treated with acupuncture, five times per week, 20 times in total over 4 weeks. The second and third clinical evaluations and resting functional MRI screenings were conducted following 10 and 20 acupuncture treatments. The blank control group was observed during the 5 to 8 week pe- riod, followed by clinical evaluation and resting functional MRI. The aim of this study was to examine changes in brain functional activity and central networks in subjects with migraine undergoing acu- puncture at Shaoyang uncommon acupoints. This study provides a further explanation of the central analgesic mechanism by which acupuncture at Shaoyang acupoints treats migraine,     

Botulinum toxin type A plus rehabilitative training for improving the motor function of the upper limbs and activities of daily life in patients with stroke and brain injury

BACKGROUND: Botulinum toxin type A (BTX-A) is mostly to be used to treat various diseases of motor disorders, whereas its effect on muscle spasm after stroke and brain injury needs further observation. OBJECTIVE: To observe the effect of BTX-A plus rehabilitative training on treating muscle spasm after stroke and brain injury. DESIGN: A randomized controlled observation. SETTINGS: Department of Rehabilitation, Department of Neurology and Department of Neurosurgery, the Second Hospital of Hebei Medical University. PARTICIPANTS: Sixty inpatients with brain injury and stroke were selected from the Department of Rehabilitation, Department of Neurology and Department of Neurosurgery, the Second Hospital of Hebei Medical University from January 2001 to August 2006. They were all confirmed by CT and MRI, and had obvious increase of spastic muscle strength in upper limbs, their Ashworth grades were grade 2 or above. The patients were randomly divided into treatment group (n =30) and control group (n =30). METHODS: ① Patients in the treatment group undertook comprehensive rehabilitative trainings, and they were administrated with domestic BTX-A, which was provided by Lanzhou Institute of Biological Products, Ministry of Health (S10970037), and the muscles of flexion spasm were selected for upper limbs, 20-25 IU for each site. ② Patients in the treatment group were assessed before injection and at 1 and 2 weeks, 1 and 3 months after injection respectively, and those in the control group were assessed at corresponding time points. The recovery of muscle spasm was assessed by modified Ashworth scale (MAS, grade 0-Ⅳ; Grade 0 for without increase of muscle strength; Grade Ⅳ for rigidity at passive flexion and extension); The recovery of motor function of the upper limbs was evaluated with Fugl-Meyer Assessment (FMA, total score was 226 points, including 100 for exercise, 14 for balance, 24 for sense, 44 for joint motion, 44 for pain and 66 for upper limb); The ADL were evaluated with Barthel index, the total score was 100 points, 60 for mild dysfunction, 60-41 for moderate dysfunction, < 40 for severe dysfunction). MAIN OUTCOME MEASURES: Changes of MAS grade, FMA scores and Barthel index before and after BTX-A injection. RESULTS: All the 60 patients with brain injury and stroke were involved in the analysis of results. ① FMA scores of upper limbs: The FMA score in the treatment group at 2 weeks after treatment was higher than that before treatment [(14.98±10.14), (13.10±9.28) points, P < 0.05], whereas there was no significant difference at corresponding time point in the control group. The FMA scores at 1 and 3 months in the treatment group [(23.36±10.69), (35.36±11.36) points] were higher than those in the control group [(20.55±10.22), (30.33±10.96) points, P < 0.01]. ② MAS grades of upper limbs: There were obviously fewer cases of grade Ⅲ in MAS at 2 weeks after treatment than before treatment in the treatment group (0, 9 cases, P < 0.05), whereas there was no obvious difference in the control group. There were obviously fewer cases of grade Ⅲ in MAS at 2 weeks and 1 month after treatment in the treatment group (0, 0 case) than the control group (5, 2 cases, P < 0.01). ③ Barthel index of upper limbs: The Barthel index at 2 weeks after treatment was higher than that before treatment in the treatment group [(30.36±22.25), (28.22±26.21) points, P < 0.05], whereas there was no significant difference in the control group. The Barthel indexes at 1 and 3 months after treatment in the treatment group were obviously higher than those in the control group [(20.55±10.22), (30.33±10.96) points, P < 0.01]. CONCLUSION: BTX-A has obvious efficacy on decreasing muscle tension after stroke and brain injury, and relieving muscle spasm; Meanwhile, the combination with rehabilitative training can effectively ameliorate the motor function of upper limbs and ADL of the patients.     

Botulinum toxin type A plus rehabilitative training for improving the motor function of the upper limbs and activities of daily life in patients with stroke and brain injury

BACKGROUND: Botulinum toxin type A (BTX-A) is mostly to be used to treat various diseases of motor disorders, whereas its effect on muscle spasm after stroke and brain injury needs further observation. OBJECTIVE: To observe the effect of BTX-A plus rehabilitative training on treating muscle spasm after stroke and brain injury. DESIGN: A randomized controlled observation. SETTINGS: Department of Rehabilitation, Department of Neurology and Department of Neurosurgery, the Second Hospital of Hebei Medical University. PARTICIPANTS: Sixty inpatients with brain injury and stroke were selected from the Department of Rehabilitation, Department of Neurology and Department of Neurosurgery, the Second Hospital of Hebei Medical University from January 2001 to August 2006. They were all confirmed by CT and MRI, and had obvious increase of spastic muscle strength in upper limbs, their Ashworth grades were grade 2 or above. The patients were randomly divided into treatment group (n =30) and control group (n =30). METHODS: ① Patients in the treatment group undertook comprehensive rehabilitative trainings, and they were administrated with domestic BTX-A, which was provided by Lanzhou Institute of Biological Products, Ministry of Health (S10970037), and the muscles of flexion spasm were selected for upper limbs, 20-25 IU for each site. ② Patients in the treatment group were assessed before injection and at 1 and 2 weeks, 1 and 3 months after injection respectively, and those in the control group were assessed at corresponding time points. The recovery of muscle spasm was assessed by modified Ashworth scale (MAS, grade 0-Ⅳ; Grade 0 for without increase of muscle strength; Grade Ⅳ for rigidity at passive flexion and extension); The recovery of motor function of the upper limbs was evaluated with Fugl-Meyer Assessment (FMA, total score was 226 points, including 100 for exercise, 14 for balance, 24 for sense, 44 for joint motion, 44 for pain and 66 for upper limb); The ADL were evaluated with Barthel index, the total score was 100 points, 60 for mild dysfunction, 60-41 for moderate dysfunction, < 40 for severe dysfunction). MAIN OUTCOME MEASURES: Changes of MAS grade, FMA scores and Barthel index before and after BTX-A injection. RESULTS: All the 60 patients with brain injury and stroke were involved in the analysis of results. ① FMA scores of upper limbs: The FMA score in the treatment group at 2 weeks after treatment was higher than that before treatment [(14.98±10.14), (13.10±9.28) points, P < 0.05], whereas there was no significant difference at corresponding time point in the control group. The FMA scores at 1 and 3 months in the treatment group [(23.36±10.69), (35.36±11.36) points] were higher than those in the control group [(20.55±10.22), (30.33±10.96) points, P < 0.01]. ② MAS grades of upper limbs: There were obviously fewer cases of grade Ⅲ in MAS at 2 weeks after treatment than before treatment in the treatment group (0, 9 cases, P < 0.05), whereas there was no obvious difference in the control group. There were obviously fewer cases of grade Ⅲ in MAS at 2 weeks and 1 month after treatment in the treatment group (0, 0 case) than the control group (5, 2 cases, P < 0.01). ③ Barthel index of upper limbs: The Barthel index at 2 weeks after treatment was higher than that before treatment in the treatment group [(30.36±22.25), (28.22±26.21) points, P < 0.05], whereas there was no significant difference in the control group. The Barthel indexes at 1 and 3 months after treatment in the treatment group were obviously higher than those in the control group [(20.55±10.22), (30.33±10.96) points, P < 0.01]. CONCLUSION: BTX-A has obvious efficacy on decreasing muscle tension after stroke and brain injury, and relieving muscle spasm; Meanwhile, the combination with rehabilitative training can effectively ameliorate the motor function of upper limbs and ADL of the patients.     

Baseline functional connectivity may predict placebo responses to accelerated rTMS treatment in major depression

Although in theory sham repetitive transcranial magnetic stimulation (rTMS) has no inherent therapeutic value, nonetheless, such placebo stimulations may have relevant therapeutic effects in clinically depressed patients. On the other hand, antidepressant responses to sham rTMS are quite heterogeneous across individuals and its neural underpinnings have not been explored yet. The current brain imaging study aims to detect baseline neural fingerprints resulting in clinically beneficial placebo rTMS treatment responses. We collected resting‐state functional magnetic resonance imaging data prior to a registered randomized clinical trial of accelerated placebo stimulation protocol in patients documented with treatment‐resistant depression ( http://clinicaltrials.gov/show/NCT01832805 ). In addition to global brain connectivity and rostral anterior cingulate cortex (rACC) seed‐based functional connectivity (FC), elastic‐net regression and cross‐validation procedures were used to identify baseline intrinsic brain connectivity biomarkers for sham‐rTMS responses. Placebo responses to accelerated sham rTMS were correlated with baseline global brain connectivity in the rACC/ventral medial prefrontal cortex (vmPFC). Concerning the rACC seed‐based FC analysis, the placebo response was associated positively with the precuneus/posterior cingulate (PCun/PCC) cortex and negatively with the middle frontal gyrus. Our findings provide first brain imaging evidence for placebo responses to sham stimulation being predictable from rACC rsFC profiles, especially in brain areas implicated in (re)appraisal and self‐focus processes.     

Brain structural properties predict psychologically mediated hypoalgesia in an 8‐week sham acupuncture treatment for migraine

Neuroimaging studies described brain structural changes that comprise the mechanisms underlying individual differences in migraine development and maintenance. However, whether such interindividual variability in migraine was observed in a pretreatment scan is a predisposition for subsequent hypoalgesia to placebo treatment that remains largely unclear. Using T1‐weighted imaging, we investigated this issue in 50 healthy controls (HC) and 196 patients with migraine without aura (MO). An 8‐week double‐blinded, randomized, placebo‐controlled acupuncture was used, and we only focused on the data from the sham acupuncture group. Eighty patients participated in an 8‐weeks sham acupuncture treatment, and were subdivided (50% change in migraine days from baseline) into recovering (MOr) and persisting (MOp) patients. Optimized voxel‐based morphometry (VBM) and functional connectivity analysis were performed to evaluate brain structural and functional changes. At baseline, MOp and MOr had similar migraine activity, anxiety and depression; reduced migraine days were accompanied by decreased anxiety in MOr. In our findings, the MOr group showed a smaller volume in the left medial prefrontal cortex (mPFC), and decreased mPFC‐related functional connectivity was found in the default mode network. Additionally, the reduction in migraine days after placebo treatment was significantly associated with the baseline gray matter volume of the mPFC which could also predict post‐treatment groups with high accuracy. It indicated that individual differences for the brain structure in the pain modulatory system at baseline served as a substrate on how an individual facilitated or diminished hypoalgesia responses to placebo treatment in migraineurs. Hum Brain Mapp 38:4386–4397, 2017. © 2017 Wiley Periodicals, Inc.     

Differential effects of sham feeding and meal ingestion on ghrelin and pancreatic polypeptide levels: evidence for vagal efferent stimulation mediating ghrelin release.

Ghrelin has been suggested to function as an appetite-stimulating signal from the gastrointestinal tract to the brain acting through a vagal afferent pathway. Ghrelin levels rise before meals and fall after meal ingestion. The purpose of this study was to investigate factors which regulate ghrelin release into the circulation by determining changes in systemic ghrelin concentrations after sham feeding and meal ingestion. METHODS: Fifteen normal subjects underwent sham feeding of a bacon and cheese toasted sandwich. Serial blood samples were obtained before and every 5 min for another 30 min during sham feeding and for 30 min after actual meal ingestion. Radioimmunoassay was used to measure plasma ghrelin and pancreatic polypeptide concentrations. RESULTS: During sham feeding, plasma ghrelin concentration increased from 1730+/-237 to 1917+/-269 pg/mL (P<0.05) and plasma pancreatic polypeptide increased from 417+/-50 to 841+/-97 pg/mL (P<0.01). Subsequent meal ingestion was characterized by an increase in pancreatic polypeptide from 782+/-88 to 1710+/-119 pg/mL (P<0.01), but no significant change in ghrelin levels. CONCLUSIONS: Plasma ghrelin and pancreatic polypeptide concentrations increase with sham feeding. This suggests a vagal efferent pathway mediating ghrelin release. In contrast to pancreatic polypeptide which rises with actual meal ingestion, ghrelin levels did not change.     

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression

Abstract

Background and aim: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD).

Methods: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10?Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1?Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks.

Results: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression.

Conclusions: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.     

The time course of ineffective sham‐blinding during low‐intensity (1 mA) transcranial direct current stimulation

Studies using transcranial direct current stimulation (tDCS) typically compare an active protocol relative to a shorter sham (placebo) protocol. Both protocols are presumed to be perceptually identical on the scalp, and thus represent an effective method of delivering double‐blinded experimental designs. However, participants often show above‐chance accuracy when asked which condition involved active/sham retrospectively. We assessed the time course of sham‐blinding during active and sham tDCS. We predicted that participants would be aware that the current is switched on for longer in the active versus sham protocol. Thirty‐two adults were tested in a preregistered, double‐blinded, within‐subjects design. A forced‐choice reaction time task was undertaken before, during and after active (10 min 1 mA) and sham (20 s 1 mA) tDCS. The anode was placed over the left primary motor cortex (C3) to target the right hand, and the cathode on the right forehead. Two probe questions were asked every 30 s: “Is the stimulation on?” and “How sure are you?”. Distinct periods of non‐overlapping confidence intervals were identified between conditions, totalling 5 min (57.1% of the total difference in stimulation time). These began immediately after sham ramp‐down and lasted until the active protocol had ended. We therefore show a failure of placebo control during 1 mA tDCS. These results highlight the need to develop more effective methods of sham‐blinding during transcranial electrical stimulation protocols, even when delivered at low‐intensity current strengths.