Neurochemistry of response inhibition and interference in gambling disorder: a preliminary study of γ-aminobutyric acid (GABA+) and glutamate-glutamine (Glx).

BACKGROUND: Neurobehavioral research on the role of impulsivity in gambling disorder (GD) has produced heterogeneous findings. Impulsivity is multifaceted with different experimental tasks measuring different subprocesses, such as response inhibition and distractor interference. Little is known about the neurochemistry of inhibition and interference in GD. METHODS: We investigated inhibition with the stop signal task (SST) and interference with the Eriksen Flanker task, and related performance to metabolite levels in individuals with and without GD. We employed magnetic resonance spectroscopy (MRS) to record glutamate-glutamine (Glx/Cr) and inhibitory, γ-aminobutyric acid (GABA+/Cr) levels in the dorsal ACC (dACC), right dorsolateral prefrontal cortex (dlPFC), and an occipital control voxel. RESULTS: We found slower processing of complex stimuli in the Flanker task in GD (P < .001, η2p = 0.78), and no group differences in SST performance. Levels of dACC Glx/Cr and frequency of incongruent errors were correlated positively in GD only (r = 0.92, P = .001). Larger positive correlations were found for those with GD between dACC GABA+/Cr and SST Go error response times (z = 2.83, P = .004), as well as between dACC Glx/Cr and frequency of Go errors (z = 2.23, P = .03), indicating general Glx-related error processing deficits. Both groups expressed equivalent positive correlations between posterror slowing and Glx/Cr in the right dlPFC (GD: r = 0.74, P = .02; non-GD: r = .71, P = .01). CONCLUSION: Inhibition and interference impairments are reflected in dACC baseline metabolite levels and error processing deficits in GD.

Acute and repetitive fronto-cerebellar tDCS stimulation improves mood in non-depressed participants.

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation, which allows for selective inhibition or excitation of neural structures. It has demonstrated some efficacy in the treatment of mood disorders. However, these studies have predominately focused on stimulation of the prefrontal cortex (PFC). The cerebellum has an increasingly recognized role in emotional control, affective state, and some psychopathologies. As such, tDCS research into mood modulation needs to expand beyond conventional PFC-focused paradigms. Using a contralateral stimulation electrode placement [anodal left dorsolateral(dl)PFC, cathodal right cerebellum], and a single-blind, repeated-measures design, we initially assessed changes in the mood of healthy participants in response to acute stimulation (n = 44) and three repeated stimulations delivered second-daily (n = 21). In a second experiment, we separately investigated the influence of reversed polarity upon these same measures, in response to acute stimulation (n = 23) and repeated stimulation (n = 11). We observed a systematic elevation of mood in both active conditions following single and repeated tDCS, the latter of which displayed a progressive elevation of mood from baseline. No mood change was noted in response to either single or repeated stimulation in the sham condition. Frontocerebellar tDCS stimulation advantageously influences mood in healthy participants, with an accumulative and potentiated effect following successive stimulations. The possibility that frontocerebellar stimulation may provide a novel therapeutic adjunctive or pre-emptive intervention in stress-related disorders and mood-related psychopathologies should be considered.

Subtraction artifacts and frequency (mis-)alignment in J-difference GABA editing.

PURPOSE: To compare the repeatability of γ-aminobutyric acid (GABA) measurements using J-difference editing, before and after spectral realignment-a technique which has previously been demonstrated to improve the quality of J-difference GABA spectra. MATERIALS AND METHODS: We performed in vivo measurements in three brain regions (occipital, sensorimotor, and dorsolateral prefrontal cortex [DLPFC]), and analyzed these using alternative alignment approaches to evaluate the impact of alignment on repeatability: "Independent alignment" (aligning each subspectrum independently) and "Pairwise alignment" (aligning each on and off subspectrum as a pair) were compared. RESULTS: Pairwise alignment improved the group mean coefficient of variation in all regions; 0.4% in occipital, 1.1% in sensorimotor, and 1.1% in DLPFC. Independent alignment resulted in subtraction artifacts in the majority of cases, and increased the coefficient of variation in the DLPFC by 9.4%. Simulations demonstrate that the GABA quantification error in datasets with high B0 drift, is 4.5% without alignment, but <1% with optimal alignment. CONCLUSION: Pairwise alignment improves the repeatability of GABA spectroscopy data. However, independently aligning all on and off subspectra can lead to artifacts and worse repeatability when compared with nonaligned data.

Unconscious inhibition separates two forms of cognitive control.

In the human brain, cognitive-control processes are generally considered distinct from the unconscious mechanisms elicited by subliminal priming. Here, we show that cognitive control engaged in situations of response conflict interacts with the negative (inhibitory) phase of subliminal priming. Thus, cognitive control may surprisingly share common processes with nonconscious brain mechanisms. In contrast, our findings reveal that subliminal inhibition does not, however, interact with control adaptation--the supposed modulation of current control settings by previous experience of conflict. Therefore, although influential models have grouped immediate cognitive control and control adaptation together as products of the same conflict detection and control network, their relationship to subliminal inhibition separates them. Overall, these results suggest that the important distinction lies not between cognitive or top-down processes on the one hand and nonconscious priming mechanisms on the other hand but between responsive (poststimulus) mechanisms that deal with sensorimotor activation after it has occurred and preparatory (prestimulus) mechanisms that are modulated before stimulus arrival.

Narrative Economics, Public Policy and Mental Health.

General public's mental health can be affected by the public policy response to a pandemic threat. Britain, Italy and Sweden have had very distinct approaches to the COVID-19 pandemic: early lock-down, delayed lock-down and no-lock-down. We develop a novel narrative economics of language Culture-Based Development approach, and using Google trend data for seed keywords, death and suicide, we reach two main conclusions: (i) while countries had a pre-existing culturally relative disposition towards death-related anxiety, the sensitivity to the public policy towards COVID-19 was also country specific; (ii) however, significant spillovers from one specific national lockdown public policy to another country's mental health are identified.

Tracking online searches for gambling activities and operators in the United Kingdom during the COVID-19 pandemic: A Google Trends™ analysis.

Background: Whilst some research has explored the impact of COVID-19 on gambling behaviour, little is yet known about online search behaviours for gambling during this period. The current study explored gambling-related online searches before, during and after the outbreak of the COVID-19 pandemic in the UK. We also assessed whether search trends were related to Gambling Commission behavioural data over the same period. Methods: Google Trends™ search data, covering thirty months from January 2020 to June 2022, for five gambling activities and five gambling operators were downloaded. Graphical displays of the weekly relative search values over this period were then produced to visualise trends in search terms, with key dates in COVID-19 policy and sporting events highlighted. Cross-correlations between seasonally adjusted monthly search data and behavioural indices were conducted. Results: Sharp increases in internet searches for poker, slots, and bingo were evident during the first lockdown in the UK, with operator searches sharply decreasing over this period. No changes in gambling activity searches were highlighted during subsequent lockdowns, although small increases in operator-based searches were detected. Strong positive correlations were found between search data and industry data for sports betting and poker but not for slots. Conclusions: Google Trends™ data may act as an indicator of population-level gambling behaviour. Substitution of preferred gambling activities for others may have occurred during the first lockdown when opportunities for sports betting were limited. Further research is needed to assess the effectiveness of internet search data in predicting gambling-related harm.

Supplementary motor area activations in unconscious inhibition of voluntary action.

It is widely accepted that regions within the dorsal medial frontal cortex are involved in the control of voluntary action. However, recent evidence suggests that a subset of these regions may also be important for unconscious and involuntary motor processes. Indeed, Sumner et al. (Neuron 54:697-711, 2007) showed that two patients with micro-lesions of the supplementary motor area (SMA) and supplementary eye field (SEF) demonstrated an absence of unconscious inhibition as evoked by masked-prime stimuli, while pre-SMA damage had no such effect. Here, we employ fMRI and a similar masked-prime task to test whether SMA and pre-SMA are similarly dissociated in healthy volunteers. Reaction times (RT) revealed that responses to compatible trials were slower than those to incompatible trials (negative compatibility effect, NCE), indicating automatic inhibition in every participant. BOLD signals in the SMA were modulated by prime compatibility, showing greater signal for compatible trials, but there was no change in pre-SMA. There was also no modulation in the hand motor cortex (HMC). These findings imply that the SMA is involved in automatic suppression of manual motor plans.

Influence of expectation on postural disturbance evoked by proprioceptive stimulation.

Recent experiments have shown that the vestibular channel of balance control differs fundamentally from the visual channel. Whereas the response to a visual perturbation can be suppressed if the subject has awareness that an upcoming disturbance is likely to be caused by an external agent rather than by self-motion, a similar assumption cannot be made concerning the vestibular system. The present experiment investigated whether postural responses evoked by a proprioceptive perturbation (vibration of the Achilles' tendon at 90 Hz for 2.2 s) are either automatic and immune to expectation (similarly to vestibular responses) or cognitively penetrable (similarly to visual responses). Subjects (n = 12) stood on a force platform while stimuli were delivered either by the subject himself (self-triggered condition) or by the experimenter. For the latter condition, the stimulus was delivered either without warning (unpredictable condition) or at a fixed interval (500 ms) following an auditory cue (precue condition). Results showed that the backward CoP displacement induced by vibration was delayed by approximately 500 ms in the expected and self-triggered conditions compared to the unexpected condition. However, once initiated, the velocity of the backward displacement was higher in the self-triggered condition as compared to the unexpected condition. After a period of 2.2 s of vibration, the amplitude of this backward CoP displacement was similar in the three experimental conditions. Therefore, although expectation appears to delay the upcoming of the main backward body sway, it does not appear to be able to weight the impact of the proprioceptive stimulation. This suggested that afferents provided by the different sensory channels involved in postural control are not similarly susceptible to high level processes such as expectation.

Incorporation of recent waking-life experiences in dreams correlates with frontal theta activity in REM sleep.

Rapid eye movement (REM) sleep and its main oscillatory feature, frontal theta, have been related to the processing of recent emotional memories. As memories constitute much of the source material for our dreams, we explored the link between REM frontal theta and the memory sources of dreaming, so as to elucidate the brain activities behind the formation of dream content. Twenty participants were woken for dream reports in REM and slow wave sleep (SWS) while monitored using electroencephalography. Eighteen participants reported at least one REM dream and 14 at least one SWS dream, and they, and independent judges, subsequently compared their dream reports with log records of their previous daily experiences. The number of references to recent waking-life experiences in REM dreams was positively correlated with frontal theta activity in the REM sleep period. No such correlation was observed for older memories, nor for SWS dreams. The emotional intensity of recent waking-life experiences incorporated into dreams was higher than the emotional intensity of experiences that were not incorporated. These results suggest that the formation of wakefulness-related dream content is associated with REM theta activity, and accords with theories that dreaming reflects emotional memory processing taking place in REM sleep.

Guiding the surgical gesture using an electro-tactile stimulus array on the tongue: a feasibility study.

Under conventional "open-" surgery, the physician has to take care of the patient, interact with other clinicians and check several monitoring devices. Nowadays, the computer assisted surgery proposes to integrate 3-D cameras in the operating theatre in order to assist the surgeon in performing minimally invasive surgical punctures. The cameras localize the needle and the computer guides the surgeon towards an intracorporeal clinically defined target. A visualization system (screen) is employed to provide the surgeon with indirect visual spatial information about the intracorporeal positions of the needle. The present work proposes to use another sensory modality to guide the surgeon, thus keeping the visual modality fully dedicated to the surgical gesture. For this, the sensory substitution paradigm using the Bach-y-Rita's "Tongue Display Unit" (TDU) is exploited to provide to the surgeon information of the position tool. The TDU device is composed of a 6 x 6 matrix of electrodes transmitting electrotactile information on the tongue surface. The underlying idea consists in transmitting information about the deviation of the needle movement with regard to a preplanned "optimal" trajectory. We present an experiment assessing the guidance effectiveness of an intracorporeal puncture under TDU guidance with respect to the performance evidenced under a usual visual guidance system.

Response inhibition in the parametric go/no-go task and its relation to impulsivity and subclinical psychopathy.

The current study utilizes the parametric go/no-go task (PGNG), a task that examines changes in inhibitory performance as executive function load increases, to examine the link between psychopathic traits, impulsivity, and response inhibition in a cohort of healthy participants. The results show that as executive function load increased, inhibitory ability decreased. High scores on the Cognitive Complexity subscale of the Barratt Impulsivity Scale (BIS-11) predict poor inhibitory ability in the PGNG. Similarly, high scores on the Psychopathy Personality Inventory-Revised (PPI-R) Blame Externalization subscale predict response inhibition deficits in the PGNG, which loads more on the executive functions than the standard go/no-go task. The remaining BIS-11 as well as PPI-R subscales did not interact with inhibitory performance in the PGNG highlighting the specificity of associations between aspects of personality and impulsivity with inhibitory performance as cognitive load is increased. These data point towards the sensitivity of the PGNG in studying response inhibition in the context of highly impulsive populations and its utility as a measure of impulsivity.

Response inhibition in the parametric Go/No-Go task in psychopathic offenders.

Previous research on response inhibition in psychopaths has failed to find consistent evidence for aberrant inhibitory ability, despite strong expectations to the contrary. However, previous examinations have utilised inhibition paradigms that suffer from critical shortcomings, such as a lack of ecological validity and overly simplistic response criteria. To assess inhibition under conditions close to the demands of everyday settings, the current study employs a parametric Go/No-go task in male offenders (n77). Additionally, rather than treating psychopathy as a categorical descriptor, a dimensional approach is taken to assess the relationship between individual psychopathic traits and response inhibition performance. Results indicate significant relationships between response inhibition and individual facets of psychopathy as measured by the Psychopathy Checklist: Screening Version. A positive relationship was found between inhibitory ability and interpersonal aspects of psychopathy, reflecting an enhancement of inhibitory functioning for those scoring high on this facet. In addition, a negative association was found between psychopathic lifestyle characteristics and response inhibition. Whereas the negative association mirrors the conceptualisation of the lifestyle facet, the positive association between interpersonal psychopathic aspects and response inhibition might reflect a propensity for adaptive behaviour that enables psychopaths to adequately manipulate their victims and mask their true nature.

Cathodal tDCS improves task performance in participants high in Coldheartedness.

OBJECTIVE: It is investigated whether personality-related inter-individual differences modulate tDCS effects on response inhibition. Psychopathic personality traits have been associated with a reduced ability to inhibit prepotent responses and as such it is likely that these traits may modulate the effect tDCS has on response inhibition. This study represents the first investigation into the effect of psychopathic traits on tDCS effects in the context of response inhibition, and based on previous research, the psychopathic traits Blame Externalization and Coldheartedness were elected as potential candidates for modulating tDCS effects to right dorsolateral prefrontal cortex. METHODS: Eighteen healthy participants underwent tDCS stimulation (sham, anodal, cathodal) before completing a response inhibition task, the parametric Go/No-go task. This task measures response inhibition under conditions of low and high cognitive load. TDCS stimulation was applied to F4 (international 10-20 system), corresponding to right dorsolateral prefrontal cortex, for 20min with an intensity of 1.5mA. Analysis of covariance was performed to assess how changes in response inhibition performance across difficulty level and stimulation condition were related to individual differences in psychopathy scores as measured via the Psychopathic Personality Inventory-Revised questionnaire. RESULTS: A positive relationship was found between greater scores on the Psychopathic Personality Inventory-Revised subscale of Coldheartedness and improvement in Go/No-go task performance after application of cathodal tDCS. This effect specifically related to the high load condition of the Go/No-go task. CONCLUSION: The psychopathic personality trait Coldheartedness may represent an imbalance of excitatory and inhibitory inputs to dlPFC. Improvement in functioning on inhibitory tasks after cathodal tDCS may be a result of a shift of excitatory glutamate levels to a more optimal level. SIGNIFICANCE: The current results demonstrate the utility of tDCS as a tool to assess how differences in cortical responsivity are associated with specific personality traits. Additionally, this study represents the first investigation into the influence of psychopathic traits on tDCS effects on dlPFC, and we observed beneficial changes in response inhibition as a result of, especially, cathodal stimulation in participants scoring high on Coldheartedness.

Prefrontal Electrical Stimulation in Non-depressed Reduces Levels of Reported Negative Affects from Daily Stressors.

Negative emotional responses to the daily life stresses have cumulative effects which, in turn, impose wide-ranging negative constraints on emotional well being and neurocognitive performance (Kalueff and Nutt, 2007; Nadler et al., 2010; Charles et al., 2013). Crucial cognitive functions such as memory and problem solving, as well more short term emotional responses (e.g., anticipation of- and response to- monetary rewards or losses) are influenced by mood. The negative impact of these behavioral responses is felt at the individual level, but it also imposes major economic burden on modern healthcare systems. Although much research has been undertaken to understand the underlying mechanisms of depressed mood and design efficient treatment pathways, comparatively little was done to characterize mood modulations that remain within the boundaries of a healthy mental functioning. In one placebo-controlled experiment, we applied daily prefrontal transcranial Direct Current Stimulation (tDCS) at five points in time, and found reliable improvements on self-reported mood evaluation. Using a new team of experimenters, we replicated this finding in an independent double-blinded placebo-controlled experiment and showed that stimulation over a shorter period of time (3 days) is sufficient to create detectable mood improvements. Taken together, our data show that repeated bilateral prefrontal tDCS can reduce psychological distress in non-depressed individuals.

Visibility predicts priming within but not between people: a cautionary tale for studies of cognitive individual differences.

With resurgent interest in individual differences in perception, cognition and behavioral control as early indicators of disease, endophenotypes, or a means to relate brain structure to function, behavioral tasks are increasingly being transferred from within-subject settings to between-group or correlational designs. The assumption is that where we know the mechanisms underlying within-subject effects, these effects can be used to measure individual differences in those same mechanisms. However, between-subjects variability can arise from an entirely different source from that driving within-subject effects, and here we report a clear-cut demonstration of this. We examined the debated relationship between the visibility of a masked-prime stimulus and the direction of priming it causes (positive or reversed). Such reversal of priming has been hypothesized to reflect an automatic inhibitory mechanism that controls partially activated responses and allows behavioral flexibility. Within subjects, we found an unambiguous systematic transition from reversed priming to positive priming as prime visibility increased, replicated 7 times, and using different stimulus manipulations. However, across individuals there was never a relationship between prime discrimination ability and priming. Specifically, these data resolve the controversial debate on visibility and reversed priming, indicating that they arise from independent processes relying on partially shared stimulus signals. More generally, they stand as an exemplar case in which variance between individuals arises from a different source from that produced by stimulus manipulations.

The relationship between reversed masked priming and the tri-phasic pattern of the lateralised readiness potential.

One of the potential explanations for negative compatibility effects (NCE) in subliminal motor priming tasks has been perceptual prime-target interactions. Here, we investigate whether the characteristic tri-phasic LRP pattern associated with the NCE is caused by these prime-target interactions. We found that both the prime-related phase and the critical reversal phase remain present even on trials where the target is omitted, confirming they are elicited by the prime and mask, not by prime-target interactions. We also report that shape and size of the reversal phase are associated with response speed, consistent with a causal role for the reversal for the subsequent response latency. Additionally, we analysed sequential modulation of the NCE by previous conflicting events, even though such conflict is subliminal. In accordance with previous literature, this modulation is small but significant.

Automatic motor activation in the executive control of action.

Although executive control and automatic behavior have often been considered separate and distinct processes, there is strong emerging and convergent evidence that they may in fact be intricately interlinked. In this review, we draw together evidence showing that visual stimuli cause automatic and unconscious motor activation, and how this in turn has implications for executive control. We discuss object affordances, alien limb syndrome, the visual grasp reflex, subliminal priming, and subliminal triggering of attentional orienting. Consideration of these findings suggests automatic motor activation might form an intrinsic part of all behavior, rather than being categorically different from voluntary actions.

Dorsolateral prefrontal γ-aminobutyric acid in men predicts individual differences in rash impulsivity.

BACKGROUND: Impulsivity is a multifaceted personality construct associated with numerous psychiatric disorders. Recent research has characterized four facets of impulsivity: "urgency" (the tendency to act rashly especially in the context of distress or cravings); "lack of premeditation" (not envisaging the consequences of actions); "lack of perseverance" (not staying focused on a task); and "sensation seeking" (engaging in exciting activities). Urgency is particularly associated with clinical populations and problematic disinhibited behavior. METHODS: We used magnetic resonance spectroscopy to measure concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the dorsolateral prefrontal cortex (DLPFC) in two cohorts of 12 and 13 participants. RESULTS: We find that variation in trait urgency in healthy men correlates with GABA concentration in the DLPFC. The result was replicated in an independent cohort. More GABA predicted lower urgency scores, consistent with a role in self-control for GABA-mediated inhibitory mechanisms in DLPFC. CONCLUSIONS: These findings help account for individual differences in self-control and thus clarify the relationship between GABA and a wide range of psychiatric disorders associated with impaired self-control.

Tight coupling between positive and reversed priming in the masked prime paradigm.

When associations between certain visual stimuli and particular actions are learned, those stimuli become capable of automatically and unconsciously activating their associated action plans. Such sensorimotor priming is assumed to be fundamental for efficient responses, and can be reliably measured in masked prime studies even when the primes are not consciously perceived. However, when the delay between prime and target is increased, reversed priming effects are often found instead (the negative compatibility effect, NCE). The main accounts of the NCE assume that it too is a sensorimotor phenomenon, predicting that it should occur only when the initial positive priming phase also occurs. Alternatively, reversed priming may reflect a perceptual process entirely independent from positive motor priming (which is simply evident at a different temporal delay), in which case no dependency is expected between the NCE and positive priming. We tested these predictions while new sensorimotor associations were learned, and found a remarkable symmetry between positive and reversed priming during all such learning phases, supporting the idea that reversed priming is a sensorimotor process that automatically follows the positive priming phase.