Accelerated intermittent theta burst stimulation in smoking cessation: No differences between active and placebo stimulation when using advanced placebo coil technology. A double-blind follow-up study

ObjectiveThis study aims to investigate the longer-term effects of accelerated intermittent theta burst stimulation (aiTBS) in smoking cessation and to examine whether there is a difference in outcome between active and placebo stimulation. The present study constitutes an ancillary study from a main Randomized Controlled Trial (RCT) evaluating the acute effects of aiTBS in smoking reduction.MethodA double-blind randomized control trial was conducted where 89 participants were randomly allocated to three groups (transcranial magnetic stimulation (TMS)&N group: active aiTBS stimulation combined with neutral videos; TMS&S group: active aiTBS stimulation combined with smoking-related videos; Placebo group: placebo stimulation combined with smoking-related videos). Nicotine dependence, tobacco craving, perceived stress and motivation to quit smoking were measured after completion of 20 aiTBS sessions and during various follow ups (post one week, post one month and post six months).ResultsOur results show that the positive effect on nicotine dependence and tobacco craving that occurred at the end of treatment lasts at least one month post treatment. This effect seems to dissipate six months post treatment. No significant differences were found between the three groups.ConclusionBoth active and placebo stimulation were equally effective in reducing nicotine dependence and tobacco craving up to one month after the end of treatment.     

Short theta burst stimulation to left frontal cortex prior to encoding enhances subsequent recognition memory

Deep semantic encoding of verbal stimuli can aid in later successful retrieval of those stimuli from long-term episodic memory. Evidence from numerous neuropsychological and neuroimaging experiments demonstrate regions in left prefrontal cortex, including left dorsolateral prefrontal cortex (DLPFC), are important for processes related to encoding. Here, we investigated the relationship between left DLPFC activity during encoding and successful subsequent memory with transcranial magnetic stimulation (TMS). In a pair of experiments using a 2-session within-subjects design, we stimulated either left DLPFC or a control region (Vertex) with a single 2-s train of short theta burst stimulation (sTBS) during a semantic encoding task and then gave participants a recognition memory test. We found that subsequent memory was enhanced on the day left DLPFC was stimulated, relative to the day Vertex was stimulated, and that DLPFC stimulation also increased participants’ confidence in their decisions during the recognition task. We also explored the time course of how long the effects of sTBS persisted. Our data suggest 2 s of sTBS to left DLPFC is capable of enhancing subsequent memory for items encoded up to 15 s following stimulation. Collectively, these data demonstrate sTBS is capable of enhancing long-term memory and provide evidence that TBS protocols are a potentially powerful tool for modulating cognitive function.     

Transient beneficial effects of excitatory theta burst stimulation in a patient with phonological agraphia after left supramarginal gyrus infarction

We report a patient showing isolated phonological agraphia after an ischemic stroke involving the left supramarginal gyrus (SMG). In this patient, we investigated the effects of focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the left SMG, corresponding to the Brodmann area (BA) 40. The patient and ten control subjects performed a dictational words and nonwords writing task before, and 5 and 30 min after they received excitatory intermittent TBS (iTBS) over the left BA 40, the right hemisphere homologous to BA 40, the Wernicke’s area, or the primary visual cortex.ITBS over the left SMG lead to a brief facilitation of phonological non-words writing to dictation. This case study report illustrates that rTMS is able to influence, among other language functions, the phonological loading processes during the written language production in stroke patients.     

Interfering with activity in the dorsomedial prefrontal cortex via TMS affects social impressions updating

In our everyday social interactions we often need to deal with others’ unpredictable behaviors. Integrating unexpected information in a consistent representation of another agent is a cognitively demanding process. Several neuroimaging studies point to the medial prefrontal cortex (mPFC) as a critical structure in mediating social evaluations. Our aim here was to shed light on the possible causal role of the mPFC in the dynamic process of forming and updating social impressions about others. We addressed this issue by suppressing activity in the mPFC by means of 1 Hz offline transcranial magnetic stimulation (TMS) prior to a task requiring participants to evaluate other agents’ trustworthiness after reading about their social behavior. In two different experiments, we found that inhibiting activity in the mPFC increased perceived trustworthiness when inconsistent information about one agent’s behavior was provided. In turn, when only negative or positive behaviors of a person were described, TMS over the mPFC did not affect judgments. Our results indicate that the mPFC is causally involved in mediating social impressions updating—at least in cases in which judgment is uncertain due to conflicting information to be processed.     

Parietal theta burst TMS: Functional fractionation observed during bistable perception not evident in attention tasks

When visual input is ambiguous, perception spontaneously alternates between interpretations: bistable perception. Studies have identified two distinct sites near the right intraparietal sulcus where inhibitory transcranial magnetic stimulation (TMS) affects the frequency of occurrence of these alternations, but strikingly with opposite directions of effect for the two sites. Lesion and TMS studies on spatial and sustained attention have also indicated a parcellation of right parietal cortex, into areas serving distinct attentional functions. We used the exact TMS procedure previously employed to affect bistable perception, yet measured its effect on spatial and sustained attention tasks. Although there was a trend for TMS to affect performance, trends were consistently similar for both parietal sites, with no indication of opposite effects. We interpret this as signifying that the previously observed parietal fractionation of function regarding the perception of ambiguous stimuli is not due to TMS-induced modification of spatial or sustained attention.     

Anterior cingulate cortex and cognitive control: Neuropsychological and electrophysiological findings in two patients with lesions to dorsomedial prefrontal cortex

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial prefrontal lesions, a hypothesis has been advanced claiming that the ACC is not involved in cognitive operations. In the current study, two comparably rare patients with unilateral lesions to dorsal medial prefrontal cortex (MPFC) encompassing the ACC were assessed with neuropsychological tests as well as Event-Related Potentials in two experimental paradigms known to engage prefrontal cortex (PFC). These included an auditory Novelty Oddball task and a visual Stop-signal task. Both patients performed normally on the Stroop test but showed reduced performance on tests of learning and memory. Moreover, altered attentional control was reflected in a diminished Novelty P3, whereas the posterior P3b to target stimuli was present in both patients. The error-related negativity, which has been hypothesized to be generated in the ACC, was present in both patients, but alterations of inhibitory behavior were observed. Although interpretative caution is generally called for in single case studies, and the fact that the lesions extended outside the ACC, the findings nevertheless suggest a role for MPFC in cognitive control that is not restricted to error monitoring.     

On the rate of stimulus occlusion during intermittent retinal stimulation

The CFF was determined with three sectored disks, each of which corresponded to one of the three rings in a Helmholtz disk. The fusion frequency is identical for all three rings of a Helmholtz disk but with the three sectored disks it was found that the rate of stimulus occlusion is a major factor in determining the CFF. It was tentatively concluded that the effect was not a consequence of different stimulus wave-forms. The phenomenon appears to have been reported late in the last century.     

Remembering specific features of emotional events across time: The role of REM sleep and prefrontal theta oscillations

When an episode of emotional significance is encountered, it often results in the formation of a highly resistant memory representation that is easily retrieved for many succeeding years. Recent research shows that beyond generic consolidation processes, rapid eye movement (REM) sleep importantly contributes to this effect. However, the boundary conditions of consolidation processes during REM sleep, specifically whether these extend to source memory, have not been examined extensively. The current study tested the effects of putative consolidation processes emerging during REM sleep and slow wave sleep (SWS) on item and source memory of negative and neutral images, respectively. Results demonstrate superior emotional relative to neutral item memory retention after both late night REM sleep and early night SWS. Emotional source memory, on the other hand, exhibited an attenuated decline following late night REM sleep, whereas neutral source memory was selectively preserved across early night SWS. This pattern of results suggests a selective preservation of emotional source memory during REM sleep that is functionally dissociable from SWS-dependent reprocessing of neutral source memory. This was further substantiated by a neurophysiological dissociation: Postsleep emotional source memory was selectively correlated with frontal theta lateralization (REM sleep), whereas postsleep neutral item memory was correlated with SWS spindle power. As such, the present results contribute to a more comprehensive characterization of sleep-related consolidation mechanisms underlying emotional and neutral memory retention. Subsidiary analysis of emotional reactivity to previously encoded material revealed an enhancing rather than attenuating effect of late night REM sleep on emotional responses.     

Transcranial direct current stimulation versus intermittent theta-burst stimulation for the improvement of working memory performance

Non-invasive brain stimulation (NIBS) techniques have been increasingly used over the dorsolateral prefrontal cortex (DLPFC) to enhance working memory (WM) performance. Notwithstanding, NIBS protocols have shown either small or inconclusive cognitive effects on healthy and neuropsychiatric samples. Therefore, we assessed working memory performance and safety of transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and both therapies combined vs placebo over the neuronavigated left DLPFC of healthy participants. Twenty-four subjects were included to randomly undergo four sessions of NIBS, once a week: tDCS alone, iTBS alone, combined interventions and placebo. The 2-back task and an adverse effect scale were applied after each NIBS session. Results revealed a significantly faster response for iTBS (b= -21.49, p= 0.04), but not for tDCS and for the interaction tDCS vs. iTBS (b= 13.67, p= 0.26 and b= 40.5, p= 0.20, respectively). No changes were observed for accuracy and no serious adverse effects were found among protocols. Although tolerable, an absence of synergistic effects for the combined protocol was seen. Nonetheless, future trials accessing different outcomes for the combined protocols, as well as studies investigating iTBS over the left DLPFC for cognition and exploring sources of variability for tDCS are encouraged.     

Observational learning in mice can be prevented by medial prefrontal cortex stimulation and enhanced by nucleus accumbens stimulation

The neural structures involved in ongoing appetitive and/or observational learning behaviors remain largely unknown. Operant conditioning and observational learning were evoked and recorded in a modified Skinner box provided with an on-line video recording system. Mice improved their acquisition of a simple operant conditioning task by observational learning. Electrical stimulation of the observer's medial prefrontal cortex (mPFC) at a key moment of the demonstration (when the demonstrator presses a lever in order to obtain a reward) cancels out the benefits of observation. In contrast, electrical stimulation of the observer's nucleus accumbens (NAc) enhances observational learning. Ongoing cognitive processes in the demonstrator could also be driven by electrical stimulation of these two structures, preventing the proper execution of the ongoing instrumental task (mPFC) or stopping pellet intake (NAc). Long-term potentiation (LTP) evoked in these two cortical structures did not prevent the acquisition or retrieval process--namely, mPFC and/or NAc stimulation only prevented, or modified, the ongoing behavioral process. The dorsal hippocampus was not involved in either of these two behavioral processes. Thus, both ongoing observational learning and performance of an instrumental task require the active contribution of the mPFC and/or the NAc.     

Alteration of hypnotic experience following transcranial electrical stimulation of the left prefrontal cortex

BackgroundRecent studies of neurostimulation reported alteration of hypnotizability and hypnotic phenomena after inhibition of the dorsolateral prefrontal cortex (DLPFC), but the different assessments of hypnosis and the stimulation parameters still left open many questions about the role of this brain region in hypnotizability. We aimed to administer inhibitory transcranial direct current stimulation (tDCS) over the left DLPFC to observe effects of stimulation on the hypnotic experience and the feeling of agency.Methodsa procedure of hypnotic induction with suggestions was repeated twice: before and after the unilateral cathodal tDCS over the left DLPFC. The experience was assessed through a phenomenological assessment of hypnosis and sense of agency in thirty-three participants randomly assigned to the sham or the active group.Resultsactive (inhibitory) tDCS enhanced the hypnotizability by 15.4% and altered a few dimensions of consciousness such as self-awareness and absorption. No changes emerged on the feeling of agency and pass rates for suggestions.ConclusionstDCS reflects a promising tool to alter the hypnotic phenomena and the responsiveness to hypnotic procedures. Neurocognitive implications are discussed for the construct of hypnotizability as well as for the role of the left DLPFC in the dimensions of consciousness such as self-awareness.     

Validity and reliability of electroencephalographic frontal alpha asymmetry and frontal midline theta as biomarkers for depression

Electroencephalographic (EEG) frontal alpha asymmetry (FAA) and frontal midline (FM) theta have been suggested as biomarkers for depression and anxiety, but have mostly been assessed in small and non‐clinical studies. In a clinical sample of 79 adults with depression (ICD‐10: F32), resting EEG and scales of depression (MADRS) and anxiety (HADS‐A) were measured at intake and after 3 months. FAA and FM theta values were referenced to a normative population database. Internal consistency, test‐retest reliability, and correlations with psychiatric tests were examined. Reliability was sufficient. However, FAA and FM theta values were close to the general population, and correlations with psychiatric tests were mostly small and non‐significant, with the exception of FAA on F7–F8 z‐scores and HADS‐A. We conclude that the validity of FAA and FM theta and therefore their potential as biomarkers for depression and anxiety remain unclear.     

Effects of stimulation by three-dimensional natural images on prefrontal cortex and autonomic nerve activity: a comparison with stimulation using two-dimensional images

Empirical evidence suggests that three-dimensional (3D) images of nature promote physiological relaxation in humans by providing more realistic effects compared with two-dimensional (2D) images. However, no studies have evaluated the physiological relaxation effects of nature-derived 3D images on prefrontal cortex and autonomic nerve activity. The present study aimed to clarify the physiological relaxation effects of visual stimulation by 3D flower images on prefrontal cortex and autonomic nerve activity. Nineteen male university students (22.2 ± 0.6 years) were presented with 3D and 2D images of the water lily for 90 s. Prefrontal cortex activity was measured using near-infrared spectroscopy, while autonomic nerve activity was measured using heart rate variability (HRV). Psychological effects were determined using a modified semantic differential method (SD). Compared with visual stimulation by 2D images, that by 3D images resulted in a significant decrease in oxyhemoglobin concentration in the right prefrontal cortex, lower sympathetic activity as calculated by the ratio of the low-frequency to high-frequency HRV component, and a significantly greater realistic feeling as evidenced by higher SD ratings. In conclusion, visual stimulation by realistic 3D floral images promotes physiological relaxation more effectively than the corresponding 2D image.     

Alpha2A-adrenoceptor stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals

The working-memory functions of the prefrontal cortex (PFC) are improved by stimulation of postsynaptic, alpha2A-adrenoceptors, especially in aged animals with PFC cognitive deficits. Thus, the alpha2A-adrenoceptor agonist, guanfacine, greatly improves working-memory performance in monkeys and rats following systemic administration or intra-PFC infusion. Alpha2A-adrenoceptors are generally coupled to Gi, which can inhibit adenylyl cyclases and reduce the production of cAMP. However, no study has directly examined whether the working-memory enhancement observed with guanfacine or other alpha2A-adrenoceptor agonists results from cAMP inhibition. The current study confirmed this hypothesis in both rats and monkeys, showing that treatments that increase cAMP-mediated signaling block guanfacine's beneficial effects. In aged rats, guanfacine was infused directly into the prelimbic PFC and was challenged with co-infusions of the cAMP analog, Sp-cAMPS. In aging monkeys, systemically administered guanfacine was challenged with the phosphodiesterase 4 inhibitor, rolipram, using intramuscular doses known to have no effect on their own. In both studies, agents that mimicked the actions of cAMP (rats) or increased endogenous cAMP (monkeys) completely blocked the enhancing effects of guanfacine on working-memory performance. These results are consistent with alpha2A-adrenoceptor stimulation enhancing PFC working-memory function via inhibition of cAMP-mediated signaling.     

右腹外侧前额叶对高抑郁水平成年人社会情绪调节的作用：一项tDCS研究

已有的经颅直流电刺激(transcranial direct current stimulation, tDCS)研究证明, 右腹外侧前额叶(right ventrolateral prefrontal cortex, RVLPFC)是社会情绪调节的重要脑区, 激活RVLPFC可显著降低人们对社会性负性情绪体验的强度。社会功能受损是抑郁症患者或抑郁倾向人群的重要特征之一。该群体对社会排斥的敏感性高, 且对负性社会情绪体验的情绪调节能力降低。在本研究中, 我们采用外显的情绪调节任务, 研究了高、低抑郁水平的两组成年人被试在RVLPFC接受阳性tDCS后其情绪调节能力的改变。结果表明, 虽然采用tDCS激活RVLPFC可帮助被试通过情绪调节(认知重评)减弱负性情绪体验, 但高抑郁水平被试的负性情绪强度下降程度明显小于低抑郁水平被试。另外本文还发现, 与源于个人的负性情绪相比, tDCS效应对源于社会的负性情绪(即社会排斥)更强。本研究是采用电或磁刺激提高抑郁人群社会情绪调节能力的首次尝试。实验结果表明, 高抑郁水平成年人的RVLPFC仅通过单次、短时间(34 min)的tDCS激活, 其情绪调节能力并未得到显著提升。这提示对抑郁倾向群体或抑郁症患者的干预或治疗需要多次施加tDCS。     

Hippocampal train stimulation modulates recall of fear extinction independently of prefrontal cortex synaptic plasticity and lesions

It has been shown that long-term potentiation (LTP) develops in the connection between the mediodorsal thalamus (MD) and the medial prefrontal cortex (mPFC) and between the hippocampus (HPC) and the mPFC following fear extinction, and correlates with extinction retention. However, recent lesion studies have shown that combined lesions of the MD and mPFC do not interfere with extinction learning and retention, while inactivation of the dorsal HPC disrupts fear extinction memory. Here we found in rats that immediate post-training HPC low-frequency stimulation (LFS) suppressed extinction-related LTP in the HPC-mPFC pathway and induced difficulties in extinction recall. HPC tetanus, applied several hours later, failed to re-establish mPFC LTP but facilitated recall of extinction. Delayed post-training HPC LFS also provoked mPFC depotentiation and difficulties with extinction recall. HPC tetanus abolished these two effects. We also found that damage to the mPFC induced fear return only in rats that received HPC LFS following extinction training. HPC tetanus also reversed this behavioral effect of HPC LFS in lesioned rats. These data suggest that the HPC interacts with the mPFC during fear extinction, but can modulate fear extinction independently of this interaction.