Selective accessibility mechanisms indicate that anchoring effects are results of selective retrieval of working memory. Neuroimaging studies have revealed that the right dorsolateral prefrontal cortex (DLPFC) is closely related to memory retrieval and performance. However, no research has investigated the effect of changing the cortical excitability in right DLPFC on anchoring effects. Transcranial direct current stimulation (tDCS) can modulate the excitability of the human cerebral cortex, while anodal and cathodal tDCS are postulated to increase or decrease cortical activity, respectively. (...) In this study, we used tDCS to investigate whether effects of increased or decreased right DLPFC excitability influence anchoring effects in willingness to pay (WTP) experiments. Ninety participants were first randomly assigned to receive either anodal, cathodal, or sham stimulation of 15 minutes, then they performed a valuation task regarding WTP. The results showed that anchoring effects were negatively related to activities of right DLPFC: the anodal stimulation diminished anchoring effects while the cathodal stimulation increased anchoring effects. These outcomes provide one of the first instances of neural evidence for the role of the right DLPFC in anchoring effects and support psychological explanations of the selective accessibility mechanisms and cognitive sets. (shrink)

The use of transcranial Electrical Stimulation in the modulation of cognitive brain functions to improve neuropsychiatric conditions has extensively increased over the decades. tES techniques have also raised new challenges associated with study design, stimulation protocol, functional specificity, and dose-response relationship. In this paper, we addressed challenges through the emerging methodology to investigate the dose-response relationship of High Definition-transcranial Direct Current Stimulation, identifying the role of negative valence in tinnitus perception. In light of the neurofunctional testable framework (...) and tES application, hypotheses were formulated to measure clinical and surrogate endpoints. We posited that conscious pairing adequately pleasant stimuli with tinnitus perception results in correction of the loudness misperception and would be reinforced by concurrent active HD-tDCS on the left Dorsolateral Prefrontal Cortex. The dose-response relationship between HD-tDCS specificity and the loudness perception is also modeled. We conducted a double-blind, randomized crossover pilot study with six recruited tinnitus patients. Accrued data was utilized to design a well-controlled adaptive seamless Bayesian dose-response study. The sample size and optimum interims were anticipated for adaptive decision-making about efficacy, safety, and single session dose parameters. Furthermore, preliminary pilot study results were sufficient to show a significant difference within the longitudinally detected self-report tinnitus loudness between before and under positive emotion induction. This study demonstrated a research methodology used to improve emotion regulation in tinnitus patients. In the projected method, positive emotion induction is essential for promoting functional targeting under HD-tDCS anatomical specificity to indicate the efficacy and facilitate the dose-finding process. The continuous updating of prior knowledge about efficacy and dose during the exploratory stage adapts the anticipated dose-response model. Consequently, the effective dose range to make superiority neuromodulation in correcting loudness misperception of tinnitus will be redefined. Highly effective dose adapts the study to a standard randomized trial and transforms it into the confirmatory stage in which active HD-tDCS protocol is compared with a sham trial. Establishing the HD-tDCS intervention protocols relying on this novel method provides reliable evidence for regulatory agencies to approve or reject the efficacy and safety. Furthermore, this paper supports a technical report for designing multimodality data-driven complementary investigations in emotion regulation, including EEG-driven neuro markers, Stroop-driven attention biases, and neuroimaging-driven brain network dynamics. (shrink)

Objective: To examine changes in patients’ desired control of the deep brain stimulator and perception of global life control throughout DBS.Methods: A consecutive cohort of 52 patients with Parkinson’s disease was recruited to participate in a prospective longitudinal study over three assessment points. Semi-structured interviews assessing participants’ desire for stimulation control and perception of global control were conducted at all three points. Qualitative data were coded using content analysis. Visual analog scales were embedded in the interviews to quantify participants’ (...) perceptions of control over time.Results: Participants reported significant increases in their perception of global control over time and significant declines in their desired control of the stimulation. These changes were unrelated to improvements in motor symptoms. Improvements in global control were negatively correlated with a decline in desired stimulation control. Qualitative data indicate that participants have changed, nuanced levels of desired control over their stimulators. Increased global life control following DBS may be attributed to increased control over PD symptoms, increased ability to engage in valued activities, and increased overall self-regulation, while other domains related to global control remained unaffected by DBS.Conclusions: There are few empirical data documenting patients’ desire for stimulation control throughout neuromodulation and how stimulation control is related to other aspects of control despite the growing application of neuromodulation devices to treat a variety of disorders. Our data highlight distinctions in different types of control and have implications for the development of patient-controlled neurostimulation devices. (shrink)

Background: Ideas always have and always will change the world; with ideas-engagement enabling individuals to become more knowledgeable, better able to make good decisions and better positioned to re-align their values in response to new progressive norms and beliefs. Given these potential benefits, of primary interest is how citizens can be most effectively encouraged to engage with new ideas. Methods: With this study we test the efficacy of two approaches designed to enhance citizen’s perceptions regarding the value of ideas-engagement. Specifically, (...) we recontextualise a previously undertaken small-scale randomised control trial designed to stimulate states of either curiosity or pragmatic prospection amongst two randomly allocated groups of respondents. Our target variables involve the importance respondents attribute to staying up to date, as well as to four related attitudinal variables. Our target audience is the voting age population of England. Results: 515 participants took part in the experiment, with 269 receiving the curiosity stimulating intervention and 246, the prospection intervention. Our findings suggest that, by the end of four weeks, only the intervention designed to promote pragmatic prospection had significantly impacted on the importance respondents attribute to staying up to date. It also positively impacted the value- scores for one of the secondary attitudinal variables (relating to the importance of supporting physical and mental-health). Conclusions: While this study provides useful insight regarding ideas-engagement, further work is needed. In particular, future studies will require a larger sample, so as to ascertain the impact of these approaches on ‘ideas refusers’. Also required is the inclusion of a control group to provide a definitive counter factual. Furthermore, since positive changes in attitudes towards ideas- engagement also ideally leads to changes in behaviours, questions are also needed to examine the sources of ideas respondents subsequently engage with (or not) as a result of these interventions. (shrink)

Galvanic vestibular stimulation is a non-invasive method of electrically stimulating the vestibular system. We investigated whether the application of GVS can alter the learning of new functional mobility and manual control tasks and whether learning can be retained following GVS application. In a between-subjects experiment design, 36 healthy subjects performed repeated trials, capturing the learning of either a functional mobility task, navigating an obstacle course on a compliant surface with degraded visual cues or a manual control task, using a (...) joystick to null self-roll tilt against a pseudo-random disturbance while seated in the dark. In the “learning” phase of trials, bilateral, bipolar GVS was applied continuously. The GVS waveform also differed between subjects in each task group: white noisy galvanic vestibular stimulation at 0.3 mA high-level random GVS at 0.7 mA, or with the absence of stimulation. Following the “learning” trials, all subjects were blindly transitioned to sham GVS, upon which they immediately completed another series of trials to assess any aftereffects. In the functional mobility task, we found nGVS significantly improved task learning. Further, improvements in learning the functional mobility task with nGVS were retained, even once the GVS application was stopped. The benefits in learning with nGVS were not observed in the manual control task. High level GVS tended to inhibit learning in both tasks, but not significantly so. Even once the high-level stimulation was stopped, the impaired performance remained. Improvements in learning with nGVS may be due to increased information throughput resulting from stochastic resonance. The benefit of nGVS for functional mobility, but not manual control nulling, may be due to the multisensory, strategic, motor coordination, or spatial awareness aspects of the former task. Learning improvements with nGVS have the potential to benefit individuals who perform functional mobility tasks, such as astronauts, firefighters, high performance athletes, and soldiers. (shrink)

Inhibitory control training is a promising method to improve individual performance of inhibitory control. Recent studies have suggested transcutaneous vagus nerve stimulation as a novel approach to affect cognitive function owing to its ability to modulate the locus coeruleus-noradrenaline system. To examine the synergistic effects of combining ICT with tVNS, 58 young males in college were randomly assigned to four groups: ICT + tVNS, ICT + sham tVNS, sham ICT + tVNS, and sham ICT + sham tVNS. Participants were (...) instructed to complete three sessions that comprised pre-training tests, a training session, and post-training tests sequentially. Results showed that the ICT + tVNS group significantly improved training and near-transfer effects on the stop-signal and Go/No-go tasks, and these effects were larger than those of the other groups. However, none of the groups exhibited the far-transfer effect on the color-word Stroop task. These results suggest that tVNS augments the intervention effects of training and similar inhibition tasks to achieve the synergistic effect; however, it does not modulate the effects of non-training tasks and obtain the far-transfer effect. ICT combined with tVNS may be a valuable intervention for improving IC in healthy individuals in certain industries and offers novel research ideas for using tVNS for cognitive improvement. (shrink)

Chronic migraine is a difficult disease to diagnose, and its pathophysiology remains undefined. Its symptoms affect the quality of life and daily living tasks of the affected person, leading to momentary disability. This is a pilot, randomized, controlled, double-blind clinical trial study with female patients between 18 and 65 years old with chronic migraine. The patients underwent twelve mindfulness sessions paired with anodal transcranial direct-current stimulation over the left dorsolateral prefrontal cortex, with current intensity of 2 mA applied for (...) 20 min, three times a week for 4 weeks. In addition, 20 min of mindfulness home practices were performed by guided meditation audio files. A total of 30 participants were evaluated after the treatment, and these were subdivided into two groups—active tDCS and sham tDCS, both set to mindfulness practice. The FFMQ-BR, MIDAS, and HIT-6 questionnaires were used to evaluate the outcomes. After the treatment, the active mindfulness and tDCS group showed better results in all outcomes. The sham group also showed improvements, but with smaller effect sizes compared to the active group. The only significant difference in the intergroup analysis was the outcome evaluated by HIT-6 in the post treatment result. Our results provide the first therapeutic evidence of mindfulness practices associated with left DLPFC anodal tDCS with a consequent increase in the level of full attention and analgesic benefits in the clinical symptoms of patients with chronic migraine. (shrink)

IntroductionTranscranial magnetic stimulation is a consolidated procedure for the treatment of depression, with several meta-analyses demonstrating its efficacy. Theta-burst stimulation is a modification of TMS with similar efficacy and shorter session duration. The geriatric population has many comorbidities and a high prevalence of depression, but few clinical trials are conducted specifically for this age group. TBS could be an option in this population, offering the advantages of few side effects and no pharmacological interactions. Therefore, our aim is to (...) investigate the efficacy of TBS in geriatric depression.Clinical trial registration[https://clinicaltrials.gov/ct2/], identifier [NCT04842929]. (shrink)

Auditory stimulation training (AST) has been proposed as a potential treatment for chil-dren with specific language impairments (SLI). The current study was designed to test this as-sumption by using an AST with technically modulated musical material (ASTM) in a random-ized control group design. A total of 101 preschool children (62 male, 39 females; mean age = 4.52 years, SD = 0.62) with deficits in speech comprehension and poor working memory ca-pacity were randomly allocated into one of two treatment groups (...) or a control group. Children in the ASTM group (n = 40) received three 30-minute sessions per week over 12 weeks, whereas children in the comparison group received pedagogical activities during these intervals (n = 24). Children in the control group (n = 37) received no treatment. Working memory, phoneme dis-crimination and speech perception skills were tested prior to (baseline) and after treatment. Chil-dren in the ASTM group showed significantly greater working memory capacity, speech per-ception, and phoneme discrimination skills after treatment, whereas children in the other groups did not show such improvement. Taken together, these results suggest that ASTM can enhance auditory cognitive performance in children with SLI. (shrink)

The phenomenological effects of deep brain stimulation (DBS) on the self of the patient remains poorly understood and under described in the literature, despite growing evidence that a significant number of patients experience postoperative neuropsychiatric changes. To address this lack of phenomenological evidence, we conducted in-depth, semistructured interviews with 17 patients with Parkinson's disease who had undergone DBS. Exploring the subjective character specific to patients' experience of being implanted gives empirical and conceptual understanding of the potential phenomenon of DBS-induced (...) self-estrangement. Our study concluded that (1) the more patients preoperatively felt alienated by their illness, the more they experienced postoperative self-estrangement, and (2) the notion of self-estrangement seems to exist in association with certain common qualitative characters, namely, loss of control, which reflects a deteriorative estrangement, and distorted perception of capacities, which reveals a restorative estrangement. These findings indicate that subjective self-reports help us to understand some aspects of the potential phenomenon of DBS-induced self-estrangement. (shrink)

Stimulants have been shown to be safe and effective for reduction of the symptoms of attention deficit hyperactivity disorder. Despite much debate, however, there has been little empirical evidence as to whether stimulants affect authenticity and moral agency in children. Singh presents evidence that stimulants do not undercut children's' sense of self and increase their experience of agency. These findings are consistent with laboratory evidence that stimulant drugs in therapeutic doses improve cognitive control over thought and behavior.

Elevations in brain stimulation reward (BSR) thresholds have been observed in rats undergoing nicotine withdrawal and have been proposed as a sensitive measure of the negative affective state associated with nicotine withdrawal. mGluR are presynaptic autoreceptors that decrease glutamate release when stimulated. The aim of this study was to examine the role of glutamate neurotransmission in nicotine dependence. The mGluR agonist LY314582 (2.5–7.5 mg/kg) precipitated nicotine withdrawal as measured by elevations in BSR thresholds in nicotine-treated rats but not in (...) controls. It was hypothesized that LY314582 precipitated nicotine withdrawal by decreasing glutamatergic tone at postsynaptic glutamate receptors. Therefore, the effects of MPEP (0.5–2 mg/kg), an mGluR antagonist, and MK-801 (0.01–1 mg/kg), an NMDA receptor antagonist, were examined. MPEP elevated BSR thresholds by an equal magnitude in control and nicotine-treated rats. At low doses, MK-801 (0.01–0.2 mg/kg) lowered BSR thresholds to a similar extent in control and nicotine-treated rats. At higher doses, MK-801 (0.25–1 mg/kg) disrupted performance in nicotine-treated and control rats. These data indicate that mGluR and NMDA receptors regulate BSR in opposite directions in non-dependent animals, and chronic nicotine treatment does not alter these effects. Most importantly, the data demonstrate that the mGluR is involved in nicotine dependence, but mGluR and NMDA receptors do not mediate mGluR actions in nicotine dependence. (shrink)

There is preliminary evidence, from case reports and investigational studies, to suggest that Deep Brain Stimulation could be used to treat some patients with Anorexia Nervosa. Although this research is at an early stage, the invasive nature of the intervention and the vulnerability of the potential patients are such that anticipatory ethical analysis is warranted. In this paper, we first show how different treatment mechanisms raise different philosophical and ethical questions. We distinguish three potential mechanisms alluded to in the (...) neuroscientific literature, relating to desire, control, and emotion, respectively. We explain why the precise nature of the mechanism has important implications for the patient’s autonomy and personal identity. In the second part of the paper, we consider practical dimensions of offering DBS to patients with AN in certain cases. We first discuss some limited circumstances where the mere offering of the intervention might be perceived as exerting a degree of coercive pressure that could serve to undermine the validity of the patient’s consent. Finally, we consider the implications of potential effects of DBS for the authenticity of the patient’s choice to continue using stimulation to ameliorate their condition. (shrink)

We can understand viewed scenes and extract task-relevant information within a few hundred milliseconds. This process is generally supported by three cortical regions that show selectivity for scene images: parahippocampal place area (PPA), medial place area (MPA) and occipital place area (OPA). Prior studies have focused on the visual information each region is responsive to, usually within the context of recognition or navigation. Here, we move beyond these tasks to investigate gaze allocation during scene viewing. Eye movements rely on a (...) scene’s visual representation to direct saccades, and thus foveal vision. In particular, we focus on the contribution of OPA, which is i) located in occipito-parietal cortex, likely feeding information into parts of the dorsal pathway critical for eye movements, and ii) contains strong retinotopic representations of the contralateral visual field. Participants viewed scene images for 1034 ms while their eye movements were recorded. On half of the trials, a 500 ms train of five transcranial magnetic stimulation (TMS) pulses was applied to the participant’s cortex, starting at scene onset. TMS was applied to the right hemisphere over either OPA or the occipital face area (OFA), which also exhibits a contralateral visual field bias but shows selectivity for face stimuli. Participants generally made an overall left-to-right, top-to-bottom pattern of eye movements across all conditions. When TMS was applied to OPA, there was an increased saccade latency for eye movements toward the contralateral relative to the ipsilateral visual field after the final TMS pulse (400ms). Additionally, TMS to the OPA biased fixation positions away from the contralateral side of the scene compared to the control condition, while the OFA group showed no such effect. There was no effect on horizontal saccade amplitudes. These combined results suggest that OPA might serve to represent local scene information that can then be utilized by visuomotor control networks to guide gaze allocation in natural scenes. (shrink)

BackgroundTemporal interference (TI) stimulation is a novel technique that enables the non-invasive modulation of deep brain regions. However, the implementation of this technology in humans has not been well-characterized or examined, including its safety and feasibility.ObjectiveWe aimed to examine the feasibility, safety, and blinding of using TI on human participants in this pilot study.Materials and methodsIn a randomized, single-blinded, and sham-controlled pilot study, healthy young participants were randomly divided into four groups [TI and transcranial alternating current stimulation (tACS) (...) targeting the right frontoparietal region, TI-sham, and tACS-sham]. Each participant was asked to complete N-back (N = 1 to 3) tasks before, during, and after one session of stimulation to assess their working memory (WM). The side effects and blinding efficacy were carefully assessed. The accuracy, reaction time (RT), and inverse efficiency score (IES, reaction time/accuracy) of the N-back tasks were measured.ResultsNo severe side effects were reported. Only mild-to-moderate side effects were observed in those who received TI, which was similar to those observed in participants receiving tACS. The blinding efficacy was excellent, and there was no correlation between the severity of the reported side effects and the predicted type of stimulation that the participants received. WM appeared to be only marginally improved by TI compared to tACS-sham, and this improvement was only observed under high-load cognitive tasks. WM seemed to have improved a little in the TI-sham group. However, it was not observed significant differences between TI and TI-sham or TI and tACS in all N-back tests.ConclusionOur pilot study suggests that TI is a promising technique that can be safely implemented in human participants. Studies are warranted to confirm the findings of this study and to further examine the effects of TI-sham stimulation as well as the effects of TI on deeper brain regions. (shrink)

Deep brain stimulation (DBS) of the globus pallidus interna and subthalamic nucleus has restored some degree of motor control in many patients in advanced stages of Parkinson’s disease. DBS has also been used to treat dystonia, essential tremor (progressive neurological condition causing trembling), chronic pain, obsessive-compulsive disorder, Tourette’s syndrome, major depressive disorder, obesity, cerebral palsy, and the minimally conscious state. Although the underlying mechanisms of the technique are still not clear, DBS can modulate underactive or overactive neural circuits and (...) restore disrupted communication between and among groups of neurons in interacting regions of the brain. This can control and relieve many symptoms associated with a range of neurological and psychiatric disorders.But the procedures of implanting and stimulating the electrodes are brain-invasive and entail significant risks. Some patients receiving DBS have experienced intracerebral hemorrhage, infection, cognitive disturbances such as impulsive behavior, and affective disturbances such as mania. It is not known whether continuous electrical stimulation of the brain would reshape synaptic connectivity and permanently alter neural circuits in ways that may not be salutary. The risk of these effects indicates that DBS should be used only when a patient’s condition is refractory to all other interventions and when there is a high probability that the technique will benefit the patient and improve his or her quality of life. If a patient’s quality of life is poor and all other treatment options have been exhausted, then the likelihood of benefit can justify physicians’ exposing patients to some risk. The clinical and ethical significance of the risk in DBS underscores the obligation of physicians to obtain fully informed consent from patients undergoing the procedure. (shrink)

The essential role of creativity has been highlighted in several human knowledge areas. Regarding the neural underpinnings of creativity, there is evidence about the role of left dorsolateral prefrontal cortex (DLPFC) and left inferior frontal gyrus (IFG) on divergent thinking (DT) and convergent thinking (CT). Transcranial stimulation studies suggest that the left DLPFC is associated with both DT and CT, whereas left IFG is more related to DT. However, none of the previous studies have targeted both hubs simultaneously and (...) compared transcranial direct current stimulation (tDCS) and random noise stimulation (tRNS). Additionally, given the relationship between cognitive flexibility and creativity, we included it in order to check if the improvement in creativity may be mediated by cognitive flexibility. In this double-blind, between-subjects study, 66 healthy participants were randomly assigned to one of three groups (N = 22) that received a transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), or sham for 20 min. The tDCS group received 1.5 mA with the anode over the left DLPFC and cathode over the left IFG. Locations in tRNS group were the same and they received 1.5 mA of high frequency tRNS (100–500 Hz). Divergent thinking was assessed before (baseline) and during stimulation with unusual uses (UU) and picture completion (PC) subtests from Torrance Creative thinking Test, whereas convergent thinking was evaluated with the remote association test (RAT). Stroop test was included to assess cognitive flexibility. ANCOVA results of performance under stimulation (controlling for baseline performance) showed that there were significant differences in PC (F = 3.35, p = 0.042, np2 = 0.10) but not in UU (F = 0.61, p = 0.546) and RAT (F = 2.65, p = 0.079) scores. Post-hoc analyses showed that tRNS group had significantly higher scores compared to sham (p = 0.004) in PC. More specifically, tRNS showed higher performance in fluency (p = 0.012) and originality (p = 0.021) dimensions of PC compared to sham. Regarding cognitive flexibility, we did not find any significant effect of any of the stimulation groups (F = 0.34, p = 0.711). Therefore, no further mediation analyses were performed. Finally, the group that received tDCS reported more adverse effects than sham group (F = 3.46, p = 0.035). Altogether, these results suggest that tRNS may have some advantages over tDCS in DT. (shrink)

Childhood self-control is currently receiving great scientific and public attention because it could predict much of adult’s life success and well-being. Specialized interventions based on findings in social psychology and neuroscience potentially enhance children’s capacity to exercise self-control. This perspective triggers hopes that self-control enhancement allows us to say good-bye for good to potentially unsafe psychopharmacological agents and electronic brain stimulants. This chapter provides an in-depth ethical analysis of pediatric self-control enhancement and points toward a series of serious conceptual and (...) ethical concerns. First, it gives an overview of current psychological as well as neuroscientific research on self-control, and it presents longitudinal studies that emphasize the importance of childhood self-control for adult life success. Second, it critically discusses the concept of self-control presupposed in these approaches and points to crucial limitations. Going beyond an understanding of self-control as a sophisticated means of goal-achievement, I will argue for a comprehensive understanding that takes the inherent normativity of self-controlled behavior seriously. In that context, self-control enhancement appears as not necessarily desirable and occasionally even detrimental. Finally, this chapter questions the notion of childhood implicit in current research and how values typically put on this phase of life could get affected by self-control enhancement. I finish with an exploration of the conditions under which pediatric self-control enhancement is either impermissible, permissible, or maybe obligatory. (shrink)

'Brainjacking’ refers to the exercise of unauthorized control of another’s electronic brain implant. Whilst the possibility of hacking a Brain–Computer Interface (BCI) has already been proven in both experimental and real-life settings, there is reason to believe that it will soon be possible to interfere with the software settings of the Implanted Pulse Generators (IPGs) that play a central role in Deep Brain Stimulation (DBS) systems. Whilst brainjacking raises ethical concerns pertaining to privacy and physical or psychological harm, we (...) claim that the possibility of brainjacking DBS raises particularly profound concerns about individual autonomy, since the possibility of hacking such devices raises the prospect of third parties exerting influence over the neural circuits underpinning the subject’s cognitive, emotional and motivational states. However, although it seems natural to assume that brainjacking represents a profound threat to individual autonomy, we suggest that the implications of brainjacking for individual autonomy are complicated by the fact that technologies targeted by brainjacking often serve to enhance certain aspects of the user’s autonomy. The difficulty of ascertaining the implications of brainjacking DBS for individual autonomy is exacerbated by the varied understandings of autonomy in the neuroethical and philosophical literature. In this paper, we seek to bring some conceptual clarity to this area by mapping out some of the prominent views concerning the different dimension of autonomous agency, and the implications of brainjacking DBS for each dimension. Drawing on three hypothetical case studies, we show that there could plausibly be some circumstances in which brainjacking could potentially be carried out in ways that could serve to enhance certain dimensions of the target’s autonomy. Our analysis raises further questions about the power, scope, and necessity of obtaining prior consent in seeking to protect patient autonomy when directly interfering with their neural states, in particular in the context of self-regulating closed-loop stimulation devices. (shrink)

Rationale: Deep brain stimulation (DBS) of the hippocampus is proposed for enhancement of memory impaired by injury or disease. Many pre-clinical DBS paradigms can be addressed in epilepsy patients undergoing intracranial monitoring for seizure localization, since they already have electrodes implanted in brain areas of interest. Even though epilepsy is usually not a memory disorder targeted by DBS, the studies can nevertheless model other memory-impacting disorders, such as Traumatic Brain Injury (TBI). Methods: Human patients undergoing Phase II invasive monitoring (...) for intractable epilepsy were implanted with depth electrodes capable of recording neurophysiological signals. Subjects performed a delayed-match-to-sample (DMS) memory task while hippocampal ensembles from CA1 and CA3 cell layers were recorded to estimate a multi-input, multi-output (MIMO) model of CA3-to-CA1 neural encoding and a memory decoding model (MDM) to decode memory information from CA3 and CA1 neuronal signals. After model estimation, subjects again performed the DMS task while either MIMO-based or MDM-based patterned stimulation was delivered to CA1 electrode sites during the encoding phase of the DMS trials. Each subject was sorted (post hoc) by prior experience of repeated and/or mild-to-moderate brain injury (RMBI), TBI, or no history (control) and scored for percentage successful delayed recognition (DR) recall on stimulated vs. non-stimulated DMS trials. The subject’s medical history was unknown to the experimenters until after individual subject memory retention results were scored. Results: When examined compared to control subjects, both TBI and RMBI subjects showed increased memory retention in response to both MIMO and MDM-based hippocampal stimulation. Furthermore, effects of stimulation were also greater in subjects who were evaluated as having pre-existing mild-to-moderate memory impairment. Conclusion: These results show that hippocampal stimulation for memory facilitation was more beneficial for subjects who had previously suffered a brain injury (other than epilepsy), compared to control (epilepsy) subjects who had not suffered a brain injury. This study demonstrates that the epilepsy/intracranial recording model can be extended to test the ability of DBS to restore memory function in subjects who previously suffered a brain injury other than epilepsy, and support further investigation into the beneficial effect of DBS in TBI patients. (shrink)

Paired associative stimulation at the spinal cord has been shown to increase muscle force and dexterity by strengthening the corticomuscular connection, through spike timing dependent plasticity. Typically, transcranial magnetic stimulation and transcutaneous peripheral nerve electrical stimulation are often used in spinal PAS. PNS targets superficial nerve branches, by which the number of applicable muscles is limited. Alternatively, a muscle can be activated by positioning the stimulation electrode on the “motor point”, which is the most sensitive location (...) of a muscle to electrical stimulation. Although this can increase the number of applicable muscles for spinal PAS, nobody has tested whether MPS can be used for the spinal PAS to date. Here we investigated the feasibility of using MPS instead of PNS for spinal PAS. Ten healthy male individuals received spinal PAS on two separate days with different stimulation timings expected to induce facilitation of corticospinal excitability or no effect on the soleus. The motor evoked potentials response curve in the soleus was measured prior to the spinal PAS, immediately after and at 10, 20, 30 min post-intervention as a measure of corticospinal excitability. The post-intervention MEP response curve areas were larger in the REAL condition than the CONTROL conditions. Further, the post-intervention MEP response curve areas were significantly larger than pre-intervention in the REAL condition but not in the CONTROL condition. We conclude that MPS can facilitate corticospinal excitability through spinal PAS. (shrink)

The notion that there exists a fundamental need to exert control over or to influence one’s environment has enjoyed a long history in psychology (e.g., DeCharms, 1968; Heider, 1958) and has stimulated considerable theoretical work. Such a need has been characterized by theorists at multiple levels of analysis. Control motivation, for example, has been characterized broadly in terms of proactive (White, 1959) or reactive (e.g., Abramson, Seligman, & Teasdale, 1978; Brehm, 1966; Brehm & Brehm, 1981) strivings for control over general (...) or specific (Brehm & Brehm, 1981) and central or peripheral outcomes (Thompson, 1993). Additionally, various types of control strategies used to gain or maintain a sense of personal control have been proposed (e.g., Averill, 1973; Heckhausen & Schulz, 1995; Rothbaum, Weisz, & Snyder, 1982; Thompson, 1981). Modes of control, for instance, have been categorized as either primary or secondary. Primary strategies involve direct action undertaken to produce desirable and avoid undesirable outcomes in the external world, whereas secondary strategies employ primarily cognitive processes undertaken to produce a change within the person. Recently, Heckhausen and Schulz (1995) have further delineated these primary and secondary forms of control according to whether they are based on veridical or illusory causal understandings of the world and whether they are functional or dysfunctional. While most control theorists view primary control as preferable to secondary control, the latter is viewed as critical in the process of adaptation to control failures and in the promotion of future primary control attempts. (shrink)

Transcranial direct current stimulation has been previously used to investigate the causal relationships between the dorsolateral prefrontal cortex and task switching but has delivered inconclusive results that may be due to different switching tasks involving different cognitive control processes. In the current study, we manipulated task types and task predictability to investigate the role of DLPFC in task-switching performances. Notably, we distinguished the specific effects of anodal-tDCS on two types of tasks. Forty-eight participants were randomly assigned to four task (...) groups as follows; Group I who was assigned right anode parity/magnitude tasks, Group II who were assigned sham parity/magnitude tasks, Group III who were assigned RA parity/vowel-consonant tasks, and Group IV who were assigned sham parity/vowel-consonant tasks. Participants were asked to complete both predictable and unpredictable tasks. In the parity/magnitude task, we demonstrated a lower switch cost for the RA group compared to the sham group for unpredictable tasks. In contrast, in the parity/vowel-consonant task, the switch cost was higher for the RA group compared to the sham group for unpredictable and predictable tasks. These findings confirmed an anodal-tDCS-induced effect over the right DLPFC both in the parity/magnitude and parity/vowel-consonant tasks. Our data indicated that anodal tDCS may have a stronger influence on task-switching performance over the right DLPFC by changing the irrelevant task-set inhibition process. Also, the right DLPFC is unlikely to act by performing exogenous adjustment of predictable task switching. (shrink)

Online controlled experiments, also known as A/B tests, have become ubiquitous. While many practical challenges in running experiments at scale have been thoroughly discussed, the ethical dimension of A/B testing has been neglected. This article fills this gap in the literature by introducing a new, soft ethics and governance framework that explicitly recognizes how the rise of an experimentation culture in industry settings brings not only unprecedented opportunities to businesses but also significant responsibilities. More precisely, the article (a) introduces a (...) set of principles to encourage ethical and responsible experimentation to protect users, customers, and society; (b) argues that ensuring compliance with the proposed principles is a complex challenge unlikely to be addressed by resorting to a one-solution response; (c) discusses the relevance and effectiveness of several mechanisms and policies in educating, governing, and incentivizing companies conducting online controlled experiments; and (d) offers a list of prompting questions specifically designed to help and empower practitioners by stimulating specific ethical deliberations and facilitating coordination among different groups of stakeholders. (shrink)

Deep Brain Stimulation is currently being investigated as an experimental treatment for patients suffering from treatment-refractory AN, with an increasing number of case reports and small-scale trials published. Although still at an exploratory and experimental stage, initial results have been promising. Despite the risks associated with an invasive neurosurgical procedure and the long-term implantation of a foreign body, DBS has a number of advantageous features for patients with SE-AN. Stimulation can be fine-tuned to the specific needs of the (...) particular patient, is relatively reversible, and the technique also allows for the crucial issue of investigating and comparing the effects of different neural targets. However, at a time when DBS is emerging as a promising investigational treatment modality for AN, lesioning procedures in psychiatry are having a renaissance. Of concern it has been argued that the two kinds of interventions should instead be understood as rivaling, yet “mutually enriching paradigms” despite the fact that lesioning the brain is irreversible and there is no evidence base for an effective target in AN. We argue that lesioning procedures in AN are unethical at this stage of knowledge and seriously problematic for this patient group, for whom self-control is particularly central to wellbeing. They pose a greater risk of major harms that cannot justify ethical equipoise, despite the apparent superiority in reduced short term surgical harms and lower cost. (shrink)

Tremor of the upper extremity is a significant cause of disability in some patients with multiple sclerosis. The MS tremor is complex because it contains an ataxic intentional tremor component due to the involvement of the cerebellum and cerebellar outflow pathways by MS plaques, which makes the MS tremor, in general, less responsive to medications or deep brain stimulation than those associated with essential tremor or Parkinson's disease. The cerebellar component has been thought to be the main reason for (...) making DBS less effective, although it is not clear whether it is due to the lack of suppression of the ataxic tremor by DBS or else. The goal of this study was to clarify the effect of DBS on cerebellar tremor compared to non-cerebellar tremor in a patient with MS. By wearing an accelerometer on the index finger of each hand, we were able to quantitatively characterize kinetic tremor by frequency and amplitude, with cerebellar ataxia component on one hand and that without cerebellar component on the other hand, at the beginning and end of the hand movement approaching a target at DBS Off and On status. We found that cerebellar tremor surprisingly had as good a response to DBS as the tremor without a cerebellar component, but the function control on cerebellar tremor was not as good due to its distal oscillation, which made the amplitude of tremor increasingly greater as it approached the target. This explains why cerebellar tremor or MS tremor with cerebellar component has a poor functional transformation even with a good percentage of tremor control. This case study provides a better understanding of the effect of DBS on cerebellar tremor and MS tremor by using a wearable device, which could help future studies improve patient selection and outcome prediction for DBS treatment of this disabling tremor. (shrink)

Background and objectives: Developmental coordination disorder is a neurodevelopmental motor disorder occurring in 5-6% of school-aged children. It is suggested that children with DCD show deficits in motor learning. Transcranial direct current stimulation enhances motor learning in adults and children but is unstudied in DCD. We aimed to investigate if tDCS, paired with motor skill training, facilitates motor learning in a pediatric sample with DCD.Methods: Twenty-eight children with diagnosed DCD were randomized and placed into a treatment or sham group. (...) Anodal tDCS was applied in conjunction with fine manual training over 5 consecutive days. Children's motor functioning was assessed with the Purdue Pegboard Test and Jebsen-Taylor Hand Function Test at baseline, post-intervention and 6 weeks following intervention. Group differences in rates of motor learning and skill transfer/retention were examined using linear mixed modeling and repeated measures ANOVAs, respectively.Results: There were no serious adverse events or drop-outs and procedures were well-tolerated. Independent of group, all participants demonstrated improved motor scores over the 5 training days [F, p < 0.001, 95% CI ], with no skill decay observed at retention. There was no interaction between intervention group and day [F, p = 0.086, 95% CI ].Conclusion: Children with DCD demonstrate motor learning with long-term retention of acquired skill. Motor cortex tDCS did not enhance motor learning as seen in other populations. Before conclusions of tDCS efficacy can be drawn, additional carefully designed trials with reproducible results are required.Clinical Trial Registration:ClinicalTrials.gov: NCT03453983. (shrink)

This study investigated the neuromodulatory effects of transspinal stimulation on soleus H-reflex excitability and electromyographic activity during stepping in humans with and without spinal cord injury. Thirteen able-bodied adults and 5 individuals with SCI participated in the study. EMG activity from both legs was determined for steps without, during, and after a single-pulse or pulse train transspinal stimulation delivered during stepping randomly at different phases of the step cycle. The soleus H-reflex was recorded in both subject groups under (...) control conditions and following single-pulse transspinal stimulation at an individualized exactly similar positive and negative conditioning-test interval. The EMG activity was decreased in both subject groups at the steps during transspinal stimulation, while intralimb and interlimb coordination were altered only in SCI subjects. At the steps immediately after transspinal stimulation, the physiological phase-dependent EMG modulation pattern remained unaffected in able-bodied subjects. The conditioned soleus H-reflex was depressed throughout the step cycle in both subject groups. Transspinal stimulation modulated depolarization of motoneurons over multiple segments, limb coordination, and soleus H-reflex excitability during assisted stepping. The soleus H-reflex depression may be the result of complex spinal inhibitory interneuronal circuits activated by transspinal stimulation and collision between orthodromic and antidromic volleys in the peripheral mixed nerve. The soleus H-reflex depression by transspinal stimulation suggests a potential application for normalization of spinal reflex excitability after SCI. (shrink)

ObjectiveProcessing Speed, the ability to perceive and react fast to stimuli in the environment, has been shown to be impaired in children with attention deficit hyperactivity disorder. However, it is unclear whether PS can be improved following targeted treatments for ADHD. Here we examined potential changes in PS following application of transcranial electric stimulation combined with cognitive training in children with ADHD. Specifically, we examined changes in PS in the presence of different conditions of mental fatigue.MethodsWe used a randomized (...) double-blind active-controlled crossover study of 19 unmedicated children with ADHD. Participants received either anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex or transcranial random noise stimulation, while completing CT, and the administration order was counterbalanced. PS was assessed before and after treatment using the MOXO-CPT, which measures PS in the presence of various conditions of mental fatigue and cognitive load.ResultstRNS combined with CT yielded larger improvements in PS compared to tDCS combined with CT, mainly under condition of increased mental fatigue. Further improvements in PS were also seen in a 1-week follow up testing.ConclusionThis study provides initial support for the efficacy of tRNS combined with CT in improving PS in the presence of mental fatigue in pediatric ADHD. (shrink)

BackgroundPublic health guidelines have recommended that elective medical procedures, including deep brain stimulation surgery for Parkinson’s disease, should not be scheduled during the coronavirus pandemic to prevent further virus spread and overload on health care systems. However, delaying DBS surgery for PD may not be in the best interest of individual patients and is not called for in regions where virus spread is under control and inpatient facilities are not overloaded.MethodsWe administered a newly developed phone questionnaire to 20 consecutive (...) patients with PD who received DBS surgery in Ruijin Hospital in Shanghai during the COVID-19 pandemic. The questionnaire was designed to gather the patients’ experiences and perceptions on the impact of COVID-19 on their everyday activities and access to medical care.ResultsMost of the patients felt confident about the preventive measures taken by the government and hospitals, and they have changed their daily living activities accordingly. Moreover, a large majority of patients felt confident obtaining access to regular and COVID-19-related health care services if needed. Routine clinical referral, sense of security in the hospital during the outbreak, and poor control of PD symptoms were the three main reasons given by patients for seeking DBS surgery during the COVID-19 pandemic.ConclusionThe COVID-19 pandemic has considerably impacted medical care and patients’ lives but elective procedures, such as DBS surgery for PD, do not need to be rescheduled when the health care system is not overloaded and adequate public health regulations are in place. (shrink)

Deep brain stimulation is an invasive technique designed to stimulate certain deep brain regions for therapeutic purposes and is currently used mainly in patients with neurodegenerative disorders, such as Parkinson’s disease. However, DBS is also used increasingly for other experimental applications, such as the treatment of psychiatric disorders, weight reduction. Apart from its therapeutic potential, DBS can cause severe adverse effects, some that might also have a significant impact on the patient’s personality and autonomy by the external stimulation (...) of DBS which effects lie beyond the individual’s control and free will. The article’s purpose is to outline the procedures of DBS currently used in therapeutic and experimental applications and to discuss the ethical concerns regarding this procedure. It will address the clinical benefit-risk-ratio, the particular ethics of research in this field, and the ethical issues raised by affecting a patient’s or an individual’s personality and autonomous behaviour. Moreover, a potential ethical guideline, the Ulysses contract is discussed for the field of clinical application as well as the question of responsibility. (shrink)

Sustained peripheral somatosensory stimulations, such as high-frequency repetitive somatosensory stimulation (HF-RSS) and vibrated stimulation, are effective in altering the balance between excitation and inhibition in the somatosensory cortex (S1) and motor cortex (M1). A recent study reported that whole-hand water flow (WF) stimulation induced neural disinhibition in the M1. Based on previous results, we hypothesized that whole-hand WF stimulation would lead to neural disinhibition in the S1 because there is a strong neural connection between M1 and (...) S1 and aimed to examine whether whole-hand WF stimulation would change the neural balance between excitation and inhibition in the S1. Nineteen healthy volunteers were studied by measuring excitation and inhibition in the S1 before and after each of the four 15-min interventions. The excitation and inhibition in the S1 were assessed using somatosensory evoked potentials (SEPs) and paired-pulse inhibition (PPI) induced by single- and paired-pulse stimulations, respectively. The four interventions were as follows: control, whole-hand water immersion, whole-hand WF, and HF-RSS. The results showed no significant changes in SEPs and PPI following any intervention. However, changes in PPI with an interstimulus interval (ISI) of 30 ms were significantly correlated with the baseline value before whole-hand WF. Thus, the present findings indicated that the whole-hand WF stimulation had a greater decreased neural inhibition in participants with higher neural inhibition in the S1 at baseline. Considering previous results on M1, the present results possibly show that S1 has lower plasticity than M1 and that the duration (15 min) of each intervention may not have been enough to alter the balance of excitation and inhibition in the S1. (shrink)

Reduced Environmental Stimulation Therapy (REST) alters the balance of sensory input to the nervous system by systematically attenuating sensory signals from visual, auditory, thermal, tactile, vestibular, and proprioceptive channels. Previous research from our group has shown that REST via floatation acutely reduces anxiety and blood pressure while simultaneously heightening interoceptive awareness in clinically anxious populations. Anorexia nervosa (AN) is an eating disorder characterized by elevated anxiety, distorted body representation, and abnormal interoception, raising the question of whether REST might positively (...) impact these symptoms. However, this approach has never been studied in eating disorders and it is unknown whether exposure to REST might worsen AN symptoms. To examine these possibilities we conducted an open-label study to investigate the safety and tolerability of REST in AN. We also explored the impact of REST on affective symptoms, body image disturbance, and interoception. Twenty-one partially weight-restored AN outpatients completed a protocol involving four sequential sessions of REST: reclining in a zero-gravity chair, floating in an open pool, and two sessions of floating in an enclosed pool. All sessions were 90 minutes, approximately one week apart. We measured orthostatic blood pressure before and immediately after each session (primary outcome), in addition to collecting blood pressure readings every 10 minutes during the session using a wireless waterproof system as a secondary outcome measure. Each participant's affective state, awareness of interoceptive sensations, and body image was assessed before and after every session (exploratory outcomes). There was no evidence of orthostatic hypotension following floating, and no adverse events (primary outcome). Secondary analyses revealed that REST induced statistically significant reductions in blood pressure, anxiety and negative affect, heightened awareness of cardiorespiratory but not gastrointestinal sensations, and reduced body image dissatisfaction. The findings from this initial trial suggest that individuals with AN can safely tolerate the physical effects of REST via floatation. Future randomized controlled trials will need to investigate whether these initial observations of improved anxiety, interoception, and body image disturbance can be effectively extended to acutely ill AN populations. (shrink)

It is hypothesized that repeated, non‐invasive stimulation of the vestibular (balance) system, via a small electrical current to the skin behind the ears, will cause the brain centers that control energy homeostasis to shift the body toward a leaner physique. This is because these centers integrate multiple inputs to, in effect, fix a set‐point for body fat, which though difficult to alter is not immutable. They will interpret repeated stimulation of the parts of the vestibular system that detect (...) acceleration as a state of chronic activity. During such a physiologically challenging time it is preferable, from an energy homeostasis viewpoint, to both utilize fat reserves, and reduce the volume of these reserves and thus the energy cost of carrying them around. Hence, this type of vestibular stimulation could potentially be a therapeutic option for metabolic syndrome disorders such as obesity. This hypothesis is eminently testable via a clinical trial. (shrink)