TMS in combination with a pain directed intervention for the treatment of fibromyalgia - A randomized, double-blind, sham-controlled trial.

BACKGROUND: Fibromyalgia Syndrome (FMS) is a highly prevalent condition, that causes chronic pain and severe reduction in quality of life and productivity, as well as social isolation. Despite the significant morbidity and economic burden of FMS, current treatments are scarce. OBJECTIVE: To investigate whether stimulation of ACC -mPFC activity by dTMS enhances a pain-directed psychotherapeutic intervention. METHODS: 19 FMS patients were randomised to receive either 20 sessions of dTMS or sham stimulation, each followed by a pain-directed psychotherapeutic intervention. With the H7 HAC coil or sham stimulation, we targeted the ACC -mPFC; specific brain areas that play a central role in pain processing. Clinical response to treatment was assessed with the McGill Pain Questionnaire Short Form (SF-MPQ), the Visual Analogue Fibromyalgia Impact Questionnaire, the Brief Pain Inventory questionnaire, and the Hamilton Depression Rating Scale. RESULTS: DTMS treatment was safe and well tolerated by FMS patients. A significant decrease in the combined sensory and affective pain dimensions was specifically demonstrated in the dTMS cohort, as measured by the SF-MPQ (Significant group × time interaction [F(2, 32) = 3.51, p < .05,ηp2 = 0.18]; No significant changes were found in depressive symptoms in both the dTMS and sham groups. CONCLUSION: Our results suggest that a course of dTMS combined with a pain-directed psychotherapeutic intervention can alleviate pain symptoms in FMS patients. Beyond clinical possibilities, future studies are needed to substantiate the innovative hypothesis that it is not dTMS alone, but rather dTMS-induced plasticity of pain-related networks, that enables the efficacy of pain-directed psychotherapeutic interventions.

The Psychedelic Renaissance in Clinical Research: A Bibliometric Analysis of Three Decades of Human Studies with Psychedelics.

Psychedelics were used in the treatment of psychiatric conditions prior to their prohibition in the late 1960s. In the past three decades, there is a revived research interest in the therapeutic potential of psychedelic drugs with expected FDA approvals for treatment of various conditions. Given the exponential scientific growth of this field, we sought to characterize, analyze, and visualize trends in its top-cited articles. Bibliometric analyses are quantitative approaches to characterize a scientific field, including evaluation of the impact of academic literature. The bibliometric analysis and visualizations were conducted with R-tools for comprehensive science mapping. The top-cited 100 articles were cited between 82 and 668 times (median 125; mean 158). Fifty-four percent of the T100 articles were produced in the past decade (2010-2020). Network and author impact analysis highlighted key figures and primary collaboration networks within the top 100 publications. UK, USA, Switzerland, Spain, and Brazil lead the field. Results are discussed in terms of research growth, access, diversity, and the distribution of knowledge and experience in the field. These aggregated data and insights on the second wave of psychedelic research facilitate research evaluation, data-driven funding policies, and a practical map for researchers and clinicians entering the field.

Right prefrontal activation predicts ADHD and its severity: A TMS-EEG study in young adults.

OBJECTIVE: Here we bring a neurophysiological diagnostic tool, based on pathophysiologically-relevant brain region, that is critical for reducing the variability between clinicians, and necessary for quantitative measures of ADHD severity. METHODS: 54 healthy and 57 ADHD adults participated in the study. Electroencephalography (EEG) was recorded when combined with transcranial magnetic stimulation (TMS) over the right prefrontal cortex and also recorded during the Stop Signal task. RESULTS: TMS evoked potentials (TEPs) and the event related potential (ERP) components in the Stop Signal task were found to be significantly reduced in ADHD relative to the matched healthy controls. Stop signal reaction time (SSRT) and stopping accuracy was found to correlate with the ERP signal, and ADHD severity correlated with the TEP signal. Cortical activity (early TEP and Stop Signal ERP) diagnostic model yielded accuracy of 72%. CONCLUSION: TEPs and ERPs reveal that right PFC excitability was associated with ADHD severity, and with behavioral impulsivity - as a hallmark of ADHD pathology. This electrophysiological biomarker supports the potential of objective diagnosis for ADHD. SIGNIFICANCE: Such tools would allow better assessment of treatment efficacy and prognosis, may advance understanding of the pathophysiology of the disease and better the public's attitudes and stigma towards ADHD. TRIAL REGISTRATION: Trial to Evaluate the Efficacy of the HLPFC Coil Deep Transcranial Magnetic Stimulation System in Treating Attention Deficit and Hyperactivity Disorder (ADHD) in Adults, https://clinicaltrials.gov/ct2/show/NCT01737476, ClinicalTrials.govnumberNCT01737476.

Alleviation of ADHD symptoms by non-invasive right prefrontal stimulation is correlated with EEG activity.

Attention deficit hyperactivity disorder (ADHD) is a prevalent disorder with effective pharmacological treatment that benefits most patients. However, about one-third fail to benefit while others search non-pharmacological alternatives, and for those options are scarce. One alternative treatment option is to alter abnormal right prefrontal cortex (rPFC) activity, given that rPFC abnormality has been repeatedly implicated in ADHD neurophathology. Here, we evaluated whether targeting the rPFC with multiple sessions of repetitive transcranial magnetic stimulation (rTMS), which can modulate neuronal excitability, activity, and plasticity in a non-invasive manner, will affect clinical symptoms in adults suffering from ADHD. Concomitantly, we used EEG to characterize electrophysiological alterations induced by treatment and to search for correlation between baseline neuronal activity and clinical response. Forty-three drug free adults with ADHD were randomized to receive either Real, Active Control, or Sham treatment (13 females, age ranging 21-46; n = 15, 14, 14, respectively), and underwent three weeks of daily high-frequency (18 Hz) stimulation sessions. We found that Real treatment was safe and resulted in significant improvement of symptoms (η2p = 0.34; Cohen's d(against Sham) = 0.96; Cohen's d(against AC) = 0.68; p = 0.00085). Furthermore, based on EEG recorded within the first treatment session we established a novel biomarker, composed of the Alpha and Low-gamma power, which highly correlated the magnitude of the clinical outcome (r = 0.92, p = 0.0001). Taken together, the results of this pilot study indicate safety and effectiveness of rTMS directed to the rPFC for treatment of adult ADHD patients. The biomarker is suggested to reflect the responsiveness of the cortex to this rTMS intervention. Following validation of the results in larger samples, this study may represent a step towards a non-pharmacological treatment for adults with ADHD using EEG-based selection of optimal candidates for treatment.

Answering the missed call: Initial exploration of cognitive and electrophysiological changes associated with smartphone use and abuse.

BACKGROUND: Smartphone usage is now integral to human behavior. Recent studies associate extensive usage with a range of debilitating effects. We sought to determine whether excessive usage is accompanied by measurable neural, cognitive and behavioral changes. METHOD: Subjects lacking previous experience with smartphones (n = 35) were compared to a matched group of heavy smartphone users (n = 16) on numerous behavioral and electrophysiological measures recorded using electroencephalogram (EEG) combined with transcranial magnetic stimulation (TMS) over the right prefrontal cortex (rPFC). In a second longitudinal intervention, a randomly selected sample of the original non-users received smartphones for 3 months while the others served as controls. All measurements were repeated following this intervention. RESULTS: Heavy users showed increased impulsivity, hyperactivity and negative social concern. We also found reduced early TMS evoked potentials in the rPFC of this group, which correlated with severity of self-reported inattention problems. Heavy users also obtained lower accuracy rates than nonusers in a numerical processing. Critically, the second part of the experiment revealed that both the numerical processing and social cognition domains are causally linked to smartphone usage. CONCLUSION: Heavy usage was found to be associated with impaired attention, reduced numerical processing capacity, changes in social cognition, and reduced right prefrontal cortex (rPFC) excitability. Memory impairments were not detected. Novel usage over short period induced a significant reduction in numerical processing capacity and changes in social cognition.

Motor-evoked potentials reveal a motor-cortical readout of evidence accumulation for sensorimotor decisions.

Many everyday activities require time-pressured sensorimotor decision making. Traditionally, perception, decision, and action processes were considered to occur in series, but this idea has been successfully challenged, particularly by neurophysiological work in animals. However, the generality of parallel processing requires further elucidation. Here, we investigate whether the accumulation of a decision can be observed intrahemispherically within human motor cortex. Participants categorized faces as male or female, with task difficulty manipulated using morphed stimuli. Transcranial magnetic stimulation, applied during the reaction-time interval, produced motor-evoked potentials (MEPs) in two hand muscles that were the major contributors when generating the required pinch/grip movements. Smoothing MEPs using a Gaussian kernel allowed us to recover a continuous time-varying MEP average, comparable to an EEG component, permitting precise localization of the time at which the motor plan for the responding muscle became dominant. We demonstrate decision-related activity in the motor cortex during this perceptual discrimination task, suggesting ongoing evidence accumulation within the motor system even for two independent actions represented within one hemisphere.

Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial.

BACKGROUND: Tobacco smoking is the leading cause of preventable death in developed countries. Our previous studies in animal models and humans suggest that repeated activation of cue-induced craving networks followed by electromagnetic stimulation of the dorsal prefrontal cortex (PFC) can cause lasting reductions in drug craving and consumption. We hypothesized that disruption of these circuitries by deep transcranial magnetic stimulation (TMS) of the PFC and insula bilaterally can induce smoking cessation. METHODS: Adults (N = 115) who smoke at least 20 cigarettes/day and failed previous treatments were recruited from the general population. Participants were randomized to receive 13 daily sessions of high-frequency, low-frequency or sham stimulation following, or without, presentation of smoking cues. Deep TMS was administered using an H-coil version targeting the lateral PFC and insula bilaterally. Cigarette consumption was evaluated during the treatment by measuring cotinine levels in urine samples and recording participants' self-reports as a primary outcome variable. Dependence and craving were assessed using standardized questionnaires. RESULTS: High (but not low) frequency deep TMS treatment significantly reduced cigarette consumption and nicotine dependence. The combination of this treatment with exposure to smoking cues enhanced reduction in cigarette consumption leading to an abstinence rate of 44% at the end of the treatment and an estimated 33% 6 months following the treatment. CONCLUSIONS: This study further implicates the lateral PFC and insula in nicotine addiction and suggests the use of deep high-frequency TMS of these regions following presentation of smoking cues as a promising treatment strategy.

Are object affordances fully automatic? A case of covert attention.

Inspired in part by Gibson's (1979) ecological approach to perception, current neurocognitive theories of action suggest that the simple viewing of an object can automatically elicit motor programs for specific acts. However, the degree to which such affordances should be considered truly automatic is unknown. Here we explored the generation of motor plans afforded by pairs of cue objects that were viewed peripherally under different attentional states. Participants focused centrally while attending to just one of two peripheral cue objects that together had a strong significance for pinching, grasping, or both. They were instructed to ignore the objects and instead give power or precision grip responses to subsequent changes in background color. The data showed a significant interaction between type of response and type of object, indicating that object affordances are perceived even in nonfoveal vision. Critically, the generation of affordances was modulated by the locus of attention: Motor preparation was biased toward the attended object when two different categories of object appeared in the same trial, but the generation of affordances was also influenced by unattended stimuli. This finding demonstrates that object-action priming is not completely automatic, instead being constrained by processes of perceptual selection.

Binocular vision enhances a rapidly evolving affordance priming effect: behavioural and TMS evidence.

Extensive research has suggested that simply viewing an object can automatically prime compatible actions for object manipulation, known as affordances. Here we explored the generation of covert motor plans afforded by real objects with precision ('pinchable') or whole-hand/power ('graspable') grip significance under different types of vision. In Experiment 1, participants viewed real object primes either monocularly or binocularly and responded to orthogonal auditory stimuli by making precision or power grips. Pinchable primes facilitated congruent precision grip responses relative to incongruent power grips, and vice versa for graspable primes, but only in the binocular vision condition. To examine the temporal evolution of the binocular affordance effect, participants in Experiment 2 always viewed the objects binocularly but made no responses, instead receiving a transcranial magnetic stimulation pulse over their primary motor cortex at three different times (150, 300, 450ms) after prime onset. Motor evoked potentials (MEPs) recorded from a pinching muscle were selectively increased when subjects were primed with a pinchable object, whereas MEPs from a muscle associated with power grips were increased when viewing graspable stimuli. This interaction was obtained both 300 and 450ms (but not 150ms) after the visual onset of the prime, characterising for the first time the rapid development of binocular grip-specific affordances predicted by functional accounts of the affordance effect.

The truth-telling motor cortex: response competition in M1 discloses deceptive behaviour.

Neural circuits associated with response conflict are active during deception. Here we use transcranial magnetic stimulation to examine for the first time whether competing responses in primary motor cortex can be used to detect lies. Participants used their little finger or thumb to respond either truthfully or deceitfully regarding facial familiarity. Motor-evoked-potentials (MEPs) from muscles associated with both digits tracked the development of each motor plan. When preparing to deceive, the MEP of the non-responding digit (i.e. the plan corresponding to the truth) exceeds the MEP of the responding digit (i.e. the lie), whereas a mirror-reversed pattern occurs when telling the truth. This give away response conflict interacts with the time of stimulation during a speeded reaction period. Lies can even activate digit-specific cortical representations when only verbal responses are made. Our findings support neurobiological models which blend cognitive decision-making with motor programming, and suggest a novel index for discriminating between honest and intentionally false facial recognition.

Viewing objects and planning actions: on the potentiation of grasping behaviours by visual objects.

How do humans interact with tools? Gibson (1979) suggested that humans perceive directly what tools afford in terms of meaningful actions. This "affordances" hypothesis implies that visual objects can potentiate motor responses even in the absence of an intention to act. Here we explore the temporal evolution of motor plans afforded by common objects. We presented objects that have a strong significance for action (pinching and grasping) and objects with no such significance. Two experimental tasks involved participants viewing objects presented on a computer screen. For the first task, they were instructed to respond rapidly to changes in background colour by using an apparatus mimicking precision and power grip responses. For the second task, they received stimulation of their primary motor cortex using transcranial magnetic stimulation (TMS) while passively viewing the objects. Muscular responses (motor evoked potentials: MEPs) were recorded from two intrinsic hand muscles (associated with either a precision or power grip). The data showed an interaction between type of response (or muscle) and type of object, with both reaction time and MEP measures implying the generation of a congruent motor plan in the period immediately after object presentation. The results provide further support for the notion that the physical properties of objects automatically activate specific motor codes, but also demonstrate that this influence is rapid and relatively short lived.