Continuous theta-burst stimulation over the right dorsolateral prefrontal cortex disrupts fear memory reconsolidation in humans.
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ABSTRACT:
SUBMITTER: Su S
PROVIDER: S-EPMC8786637 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Continuous theta-burst stimulation over the right dorsolateral prefrontal cortex disrupts fear memory reconsolidation in humans.
Su Sizhen S Deng Jiahui J Yuan Kai K Gong Yimiao Y Zhang Yuxin Y Li Hui H Cao Kexin K Huang Xiaolin X Lin Xiao X Wu Ping P Xue Yanxue Y Bao Yanping Y Shi Jie J Shi Le L Lu Lin L
iScience 20211211 1
Continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation technique, can induce long-lasting changes in synaptic plasticity, vital for memory reconsolidation. For this study, a total of 170 participants completed four experiments by a randomized controlled design. Succeeding fear conditioning, the subjects received cTBS over the right dorsolateral prefrontal cortex (dlPFC) or vertex (control) with or without exposure to the conditioned stimulus to reactivate the original fear m ...[more]
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Project description:BackgroundConvergent neuroimaging and neuromodulation studies implicate the right dorsolateral prefrontal cortex (dlPFC) as a key region involved in anxiety-cognition interactions. However, neuroimaging data are correlational, and neuromodulation studies often lack appropriate methodological controls. Accordingly, this work was designed to explore the role of right prefrontal cognitive control mechanisms in the expression/regulation of anxiety using continuous theta-burst transcranial magnetic stimulation (cTBS) and threat of unpredictable shock. Based on prior neuromodulation studies, we hypothesized that the right dlPFC contributed to anxiety expression, and that cTBS should downregulate this expression.MethodsWe measured potentiated startle and performance on the Sternberg working memory paradigm in 28 healthy participants before and after 4 sessions (600 pulses/session) of active or sham cTBS. Stimulation was individualized to the right dlPFC site of maximal working memory-related activity and optimized using electric-field modeling.ResultsCompared with sham cTBS, active cTBS, which is thought to induce long-term depression-like synaptic changes, increased startle during threat of shock, but the effect was similar for predictable and unpredictable threat. As a measure of target (dis)engagement, we also showed that active but not sham cTBS decreased accuracy on the Sternberg task.ConclusionsCounter to our initial hypothesis, cTBS to the right dlPFC made individuals more anxious, rather than less anxious. Although preliminary, these results are unlikely to be due to transient effects of the stimulation, because anxiety was measured 24 hours after cTBS. In addition, these results are unlikely to be due to off-target effects, because target disengagement was evident from the Sternberg performance data.
| S-EPMC10382694 | biostudies-literature
Project description:Theta-burst stimulation (TBS) over the dorsolateral prefrontal cortex (DLPFC) may be more effective for modulating cortical excitability compared to standard repetitive transcranial magnetic stimulation. However, the impact of intermittent (iTBS) and continuous TBS (cTBS) on working memory (WM) is poorly studied. The aim of our study was to compare the effects of iTBS and cTBS on WM over the left and right DLPFC. iTBS, cTBS or sham stimulation was administered over the right and left hemisphere of fifty-one healthy human subjects. WM was assessed before and after TBS using the 1-back, 2-back, and 3-back tasks. We found classical practice effects in the iTBS and the sham group: WM performance improved following stimulation as measured by the discriminability index. However, this effect could not be observed in the cTBS group. We did not find any hemisphere-dependent effects, suggesting that the practice effect is not lateralized, and TBS affects WM performance in a comparable manner if administered either over the left or the right hemisphere. We propose that our findings represent a useful addition to the literature of TBS-induced effects on WM. Moreover, these results indicate the possibility of clarifying processes underlying WM performance changes by using non-invasive brain stimulation.
| S-EPMC6172210 | biostudies-literature
Project description:Repetitive transcranial magnetic stimulation (rTMS) treatment protocols targeting the right dlPFC have been effective in reducing anxiety symptoms comorbid with depression. However, the mechanism behind these effects is unclear. Further, it is unclear whether these results generalize to non-depressed individuals. We conducted a series of studies aimed at understanding the link between anxiety potentiated startle and the right dlPFC, following a previous study suggesting that continuous theta burst stimulation (cTBS) to the right dlPFC can make people more anxious. Based on these results we hypothesized that intermittent TBS (iTBS), which is thought to have opposing effects on plasticity, may reduce anxiety when targeted at the same right dlPFC region. In this double-blinded, cross-over design, 28 healthy subjects underwent 12 study visits over a 4-week period. During each of their 2 stimulation weeks, they received four 600 pulse iTBS sessions (2/day), with a post-stimulation testing session occurring 24 h following the final iTBS session. One week they received active stimulation, one week they received sham. Stimulation weeks were separated by a 1-week washout period and the order of active/sham delivery was counterbalanced across subjects. During the testing session, we induced anxiety using the threat of unpredictable shock and measured anxiety potentiated startle. Contrary to our initial hypothesis, subjects showed increased startle reactivity following active compared to sham stimulation. These results replicate work from our two previous trials suggesting that TMS to the right dlPFC increases anxiety potentiated startle, independent of both the pattern of stimulation and the timing of the post stimulation measure. Although these results confirm a mechanistic link between right dlPFC excitability and startle, capitalizing upon this link for the benefit of patients will require future exploration.
| S-EPMC11319663 | biostudies-literature
Project description:IntroductionCognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology.MethodsWe enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS).ResultsDominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample.ConclusionAcute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.
| S-EPMC7006239 | biostudies-literature
Project description:Theta burst stimulation is increasingly growing in popularity as a non-invasive method of moderating corticospinal networks. Theta burst stimulation uses gamma frequency trains applied at the rhythm of theta, thus, mimicking theta-gamma coupling involved in cognitive processes. The dorsolateral prefrontal cortex has been found to play a crucial role in numerous cognitive processes. Here, we include 25 studies for review to determine the cognitive effects of continuous theta burst stimulation over the dorsolateral prefrontal cortex; 20 of these studies are healthy participant and five are patient (pharmacotherapy-resistant depression) studies. Due to the heterogeneous nature of the included studies, only a descriptive approach is used and meta-analytics ruled out. The cognitive effect is measured on various cognitive domains: attention, working memory, planning, language, decision making, executive function, and inhibitory and cognitive control. We conclude that continuous theta burst stimulation over the dorsolateral prefrontal cortex mainly inhibits cognitive performance. However, in some instances, it can lead to improved performance by inhibiting the effect of distractors or other competing irrelevant cognitive processes. To be precise, continuous theta burst stimulation over the right dorsolateral prefrontal cortex impaired attention, inhibitory control, planning, and goal-directed behavior in decision making but also improved decision making by reducing impulsivity. Conversely, continuous theta burst stimulation over the left dorsolateral prefrontal cortex impaired executive function, working, auditory feedback regulation, and cognitive control but accelerated the planning, decision-making process. These findings constitute a useful contribution to the literature on the cognitive effects of continuous theta burst stimulation over the dorsolateral prefrontal cortex.
| S-EPMC7417340 | biostudies-literature
Project description:BackgroundPrevious studies have identified the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on cravings of patients with methamphetamine use disorder (MUD). However, the mechanism underlying the treatment effect remains largely unknown. A potential candidate mechanism could be that rTMS over the dorsolateral prefrontal cortex (DLPFC) modulates the attention bias to methamphetamine-related cues. The purpose of this study is therefore to determine the modulation of rTMS on methamphetamine-related attention bias and the corresponding electrophysiological changes.MethodsForty-nine patients with severe MUD were included for analysis. The subjects were randomized to receive the active intermittent theta-burst stimulation (iTBS) or sham iTBS targeting DLPFC for 20 sessions. Participants performed the Addiction Stroop Task before and after the treatment while being recorded by a 64-channel electroencephalogram. Baseline characteristics were collected through the Addiction Severity Index.ResultsPost-treatment evaluations showed a reduced error rate in discriminating the color of methamphetamine words in the active iTBS group compared with the sham iTBS group. Following rTMS treatment, we found the significant time-by-group effect for the N1 amplitude (methamphetamine words > neutral words) and P3 latency (methamphetamine words > neutral words). The change of N1 amplitude was positively correlated with cravings in the active group. Moreover, reduced power of neural oscillation in the beta band, manifesting at frontal central areas, was also found in the active group.ConclusionThis study suggests that attention bias and the beta oscillation during the attentional processing of methamphetamine words in patients with MUD could be modulated by iTBS applied to left DLPFC.
| S-EPMC8370756 | biostudies-literature
Project description:Most neuroimaging studies on planning report bilateral activations of the dorsolateral prefrontal cortex (dlPFC). Recently, these concurrent activations of left and right dlPFC have been shown to double dissociate with different cognitive demands imposed by the planning task: Higher demands on the extraction of task-relevant information led to stronger activation in left dlPFC, whereas higher demands on the integration of interdependent information into a coherent action sequence entailed stronger activation of right dlPFC. Here, we used continuous theta-burst stimulation (cTBS) to investigate the supposed causal structure-function mapping underlying this double dissociation. Two groups of healthy subjects (left-lateralized stimulation, n = 26; right-lateralized stimulation, n = 26) were tested within-subject on a variant of the Tower of London task following either real cTBS over dlPFC or sham stimulation over posterior parietal cortex. Results revealed that, irrespective of specific task demands, cTBS over left and right dlPFC was associated with a global decrease and increase, respectively, in initial planning times compared to sham stimulation. Moreover, no interaction between task demands and stimulation type (real vs. sham) and/or stimulation side (left vs. right hemisphere) were found. Together, against expectations from previous neuroimaging data, lateralized cTBS did not lead to planning-parameter specific changes in performance, but instead revealed a global asymmetric pattern of faster versus slower task processing after left versus right cTBS. This global asymmetry in the absence of any task-parameter specific impact of cTBS suggests that different levels of information processing may span colocalized, but independent axes of functional lateralization in the dlPFC.
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Project description:IntroductionRepetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.Materials and methodsWe performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.ResultsSeven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.ConclusionWe report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).
| S-EPMC9433314 | biostudies-literature
Project description:Individuals show marked variation in their responses to threat. Such individual differences in behavioral inhibition play a profound role in mental and physical well-being. Behavioral inhibition is thought to reflect variation in the sensitivity of a distributed neural system responsible for generating anxiety and organizing defensive responses to threat and punishment. Although progress has been made in identifying the key constituents of this behavioral inhibition system in humans, the involvement of dorsolateral prefrontal cortex (DLPFC) remains unclear. Here, we acquired self-reported Behavioral Inhibition System Sensitivity scores and high-resolution electroencephalography from a large sample (n= 51). Using the enhanced spatial resolution afforded by source modeling techniques, we show that individuals with greater tonic (resting) activity in right-posterior DLPFC rate themselves as more behaviorally inhibited. This observation provides novel support for recent conceptualizations of behavioral inhibition and clues to the mechanisms that might underlie variation in threat-induced negative affect.
| S-EPMC2858783 | biostudies-literature
Project description:BackgroundPolydrug abuse is common among opioid users. Individuals who use both heroin and methamphetamine (MA) have been shown to experience a wide range of cognitive deficits. Previous research shows that repetitive transcranial magnetic stimulation (rTMS) can change cerebral cortical excitability and regulate neurotransmitter concentration, which could improve cognitive function in drug addiction. However, the stimulation time, location, and possible mechanisms of rTMS are uncertain.Methods56 patients with polydrug use disorder were randomized to receive 20 sessions of 10 Hz rTMS (n = 19), iTBS (n = 19), or sham iTBS (n = 18) to the left DLPFC. All patients used MA and heroin concurrently. Cognitive function was assessed and several related proteins including EPI, GABA-Aα5, IL-10, etc. were quantified by ELISA before and after the treatment.ResultsBaseline RBANS scores were lower than normal for age (77.25; IQR 71.5-85.5). After 20 treatment sessions, in the iTBS group, the RBANS score increased by 11.95 (95% CI 0.02-13.90, p = 0.05). In particular, there were improvements in memory and attention as well as social cognition. Following treatment, serum EPI and GABA-Aα5 were reduced and IL-10 was elevated. The improvement of immediate memory was negatively correlated with GABA-Aα5 (r = -0.646, p = 0.017), and attention was positively correlated with IL-10 (r = 0.610, p = 0.027). In the 10 Hz rTMS group, the improvement of the RBANS total score (80.21 ± 14.08 before vs.84.32 ± 13.80 after) and immediate memory (74.53 ± 16.65 before vs.77.53 ± 17.78 after) was statistically significant compared with the baseline (p < 0.05). However, compared with the iTBS group, the improvement was small and the difference was statistically significant. There was no statistically significant change in the sham group (78.00 ± 12.91 before vs.79.89 ± 10.92 after; p > 0.05).ConclusionIntermittent theta burst stimulation to the left DLPFC may improve cognitive function in polydrug use disorder patients. Its efficacy appears to be better than that of 10 Hz rTMS. The improvement of cognitive function may be related to GABA-Aα5 and IL-10. Our findings preliminarily demonstrate the clinical value of iTBS to the DLPFC to augment neurocognitive recovery in polydrug use disorders.
| S-EPMC10248467 | biostudies-literature