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Background: Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA)., Aims/methods: This study, conducted in 30 healthy volunteers, examined the acute effects of GABA A (lorazepam: 1 mg) and GABA B receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety., Results: Compared to placebo, lorazepam reduced ERP indices of sensory gating by attenuating response to S1. Although not directly impacting P50 inhibition, baclofen-induced changes in gating (relative to placebo) were negatively correlated with trait but not state anxiety., Conclusions: These preliminary findings support the involvement of GABA in sensory gating and tentatively suggest a role for GABA B receptor signaling in anxiety-associated gating dysregulation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Long-term cannabis use has been associated with the appearance of psychotic symptoms and schizophrenia-like cognitive impairments; however these studies may be confounded by concomitant use of tobacco by cannabis users. We aimed to determine if previously observed cannabis-associated deficits in sensory gating would be seen in cannabis users with no history of tobacco use, as evidenced by changes in the P50, N100, and P200 event-related potentials. A secondary objective of this study was to examine the effects of acute nicotine administration on cannabis users with no tobacco use history., Methods: Three components (P50, N100, P200) of the mid-latency auditory-evoked response (MLAER) were elicited by a paired-stimulus paradigm in 43 healthy, non-tobacco smoking male volunteers between the ages of 18-30. Cannabis users (CU, n = 20) were administered nicotine (6 mg) and placebo gum within a randomized, double-blind design. Non-cannabis users (NU, n = 23) did not receive nicotine., Results: Between-group sensory gating effects were only observed for the N100, with CUs exhibiting a smaller N100 to S 1 of the paired stimulus paradigm, in addition to reduced dN100 (indicating poorer gating). Results revealed no significant sensory gating differences with acute administration of nicotine compared to placebo cannabis conditions., Conclusions: These findings suggest a relationship between gating impairment and cannabis use; however, acute nicotine administration nicotine does not appear to impact sensory gating function., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The COVID-19 pandemic has resulted in a number of negative health related consequences, including impacts on mental health. More than 22% of Canadians reported that they had felt depressed in the last week, in response to a December 2020 national survey. Given the need to physically distance during the pandemic, and the increase in demand for mental health services, digital interventions that support mental health and wellness may be beneficial., Objective: The purpose of this research was to identify digital interventions that could be used to support the mental health of the Canadian general population during the COVID-19 pandemic. The objectives were to identify (1) the populations these interventions were developed for, inclusive of exploring areas of equity such as socioeconomic status, sex/gender, race/ethnicity and culture, and relevance to Indigenous peoples and communities; (2) the effect of the interventions; and (3) any barriers or facilitators to the use of the intervention., Methods: This study was completed using a Cochrane Rapid Review methodology. A search of Embase, PsycInfo, Medline, and Web of Science, along with Google, Million Short, and popular mobile app libraries, was conducted. Two screeners were involved in applying inclusion criteria using Covidence software. Academic articles and mobile apps identified were screened using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields resource, the American Psychiatric Association App Evaluation Framework, and the Mental Health Commission of Canada's guidance on app assessment and selection., Results: A total of 31 mobile apps and 114 web-based resources (eg, telemedicine, virtual peer support groups, discussion forums, etc) that could be used to support the mental health of the Canadian population during the pandemic were identified. These resources have been listed on a publicly available website along with search tags that may help an individual make a suitable selection. Variability exists in the populations that the interventions were developed for, and little assessment has been done with regard to areas of equity. The effect of the interventions was not reported for all those identified in this synthesis; however, for those that did report the effect, it was shown that they were effective in the context that they were used. A number of barriers and facilitators to using these interventions were identified, such as access, cost, and connectivity., Conclusions: A number of digital interventions that could support population mental health in Canada during the global COVID-19 pandemic were identified, indicating that individuals have several options to choose from. These interventions vary in their purpose, approach, design, cost, and targeted user group. While some research and digital interventions addressed equity-related considerations, more research and focused attention should be given to this area., (©Gillian Strudwick, Sanjeev Sockalingam, Iman Kassam, Lydia Sequeira, Sarah Bonato, Alaa Youssef, Rohan Mehta, Nadia Green, Branka Agic, Sophie Soklaridis, Danielle Impey, David Wiljer, Allison Crawford. Originally published in JMIR Mental Health (http://mental.jmir.org), 02.03.2021.)

The high prevalence of concomitant cannabis and nicotine use has implications for sensory and cognitive processing. While nicotine tends to enhance function in these domains, cannabis use has been associated with both sensory and cognitive impairments, though the underlying mechanisms are unclear. Additionally, the interaction of the nicotinic (nAChR) and cannabinoid (CB 1 ) receptor systems has received limited study in terms of sensory/cognitive processes. This study involving healthy volunteers assessed the acute separate and combined effects of nabilone (a CB 1 agonist) and nicotine on sensory processing as assessed by auditory deviance detection and indexed by the mismatch negativity (MMN) event-related potential. It was hypothesized that nabilone would impair auditory discriminability as shown by diminished MMN amplitudes, but not when administered in combination with nicotine. 20 male non-smokers and non-cannabis-users were assessed using a 5-stimulus 'optimal' multi-feature MMN paradigm within a randomized, placebo controlled design (placebo; nabilone [0.5 mg]; nicotine [6 mg]; and nicotine + nabilone). Treatment effects were region- and deviant-dependent. At the temporal regions (mastoid sites), MMN was reduced by nabilone and nicotine separately, whereas co-administration resulted in no impairment. At the frontal region, MMN was enhanced by co-administration of nicotine and nabilone, with no MMN effects being found with separate treatment. These neural effects have relevance for sensory/cognitive processes influenced by separate and simultaneous use of cannabis and tobacco and may have treatment implications for disorders associated with sensory dysfunction and impairments in endocannabinoid and nicotinic cholinergic neurotransmission., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cognitive impairment has been proposed to be the core feature of schizophrenia (Sz). Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which can improve cognitive function in healthy participants and in psychiatric patients with cognitive deficits. tDCS has been shown to improve cognition and hallucination symptoms in Sz, a disorder also associated with marked sensory processing deficits. Recent findings in healthy controls demonstrate that anodal tDCS increases auditory deviance detection, as measured by the brain-based event-related potential, mismatch negativity (MMN), which is a putative biomarker of Sz that has been proposed as a target for treatment of Sz cognition. This pilot study conducted a randomized, double-blind assessment of the effects of pre- and post-tDCS on MMN-indexed auditory discrimination in 12 Sz patients, moderated by auditory hallucination (AH) presence, as well as working memory performance. Assessments were conducted in three sessions involving temporal and frontal lobe anodal stimulation (to transiently excite local brain activity), and one control session involving 'sham' stimulation (meaning with the device turned off, i.e., no stimulation). Results demonstrated a trend for pitch MMN amplitude to increase with anodal temporal tDCS, which was significant in a subgroup of Sz individuals with AHs. Anodal frontal tDCS significantly increased WM performance on the 2-back task, which was found to positively correlate with MMN-tDCS effects. The findings contribute to our understanding of tDCS effects for sensory processing deficits and working memory performance in Sz and may have implications for psychiatric disorders with sensory deficits.

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a weak constant current to alter cortical excitability and activity temporarily. tDCS-induced increases in neuronal excitability and performance improvements have been observed following anodal stimulation of brain regions associated with visual and motor functions, but relatively little research has been conducted with respect to auditory processing. Recently, pilot study results indicate that anodal tDCS can increase auditory deviance detection, whereas cathodal tDCS decreases auditory processing, as measured by a brain-based event-related potential (ERP), mismatch negativity (MMN). As evidence has shown that tDCS lasting effects may be dependent on N-methyl-D-aspartate (NMDA) receptor activity, the current study investigated the use of dextromethorphan (DMO), an NMDA antagonist, to assess possible modulation of tDCS's effects on both MMN and working memory performance. The study, conducted in 12 healthy volunteers, involved four laboratory test sessions within a randomised, placebo and sham-controlled crossover design that compared pre- and post-anodal tDCS over the auditory cortex (2 mA for 20 minutes to excite cortical activity temporarily and locally) and sham stimulation (i.e. device is turned off) during both DMO (50 mL) and placebo administration. Anodal tDCS increased MMN amplitudes with placebo administration. Significant increases were not seen with sham stimulation or with anodal stimulation during DMO administration. With sham stimulation (i.e. no stimulation), DMO decreased MMN amplitudes. Findings from this study contribute to the understanding of underlying neurobiological mechanisms mediating tDCS sensory and memory improvements.

Schizophrenia (SZ) is a psychiatric disorder characterized by cognitive dysfunction within the realm of attentional processing. Reduced P3a and P3b event-related potentials (ERPs), indexing involuntary and voluntary attentional processing respectively, have been consistently observed in SZ patients who also express prominent cholinergic deficiencies. The involvement of the brain's cholinergic system in attention has been examined for several decades; however, further inquiry is required to further comprehend how abnormalities in this system affect neighbouring neurotransmitter systems and contribute to neurocognitive deficits. The objective of this pilot study was to examine the moderating role of the CHRNA4 (rs1044396), CHRNA7 (rs3087454), and SLC5A7 (rs1013940) genes on ERP indices of attentional processing in healthy volunteers (N=99; Caucasians and non-Caucasians) stratified by genotype and assessed using the auditory P300 "oddball" paradigm. Results indicated significantly greater P3a and P3b-indexed attentional processing for CT (vs. CC) CHRNA4 carriers and greater P3b for AA (vs. CC) CHRNA7 carriers. SLC5A7 allelic variants did not show significant differences in P3a and P3b processing. These findings expand our knowledge on the moderating effect of cholinergic genes on attention and could help inform targeted drug developments aimed at restoring attention deficits in SZ patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a very weak constant current to temporarily excite (anodal stimulation) or inhibit (cathodal stimulation) activity in the brain area of interest via small electrodes placed on the scalp. Currently, tDCS of the frontal cortex is being used as a tool to investigate cognition in healthy controls and to improve symptoms in neurological and psychiatric patients. tDCS has been found to facilitate cognitive performance on measures of attention, memory, and frontal-executive functions. Recently, a short session of anodal tDCS over the temporal lobe has been shown to increase auditory sensory processing as indexed by the Mismatch Negativity (MMN) event-related potential (ERP). This preliminary pilot study examined the separate and interacting effects of both anodal and cathodal tDCS on MMN-indexed auditory pitch discrimination. In a randomized, double blind design, the MMN was assessed before (baseline) and after tDCS (2mA, 20min) in 2 separate sessions, one involving 'sham' stimulation (the device is turned off), followed by anodal stimulation (to temporarily excite cortical activity locally), and one involving cathodal stimulation (to temporarily decrease cortical activity locally), followed by anodal stimulation. Results demonstrated that anodal tDCS over the temporal cortex increased MMN-indexed auditory detection of pitch deviance, and while cathodal tDCS decreased auditory discrimination in baseline-stratified groups, subsequent anodal stimulation did not significantly alter MMN amplitudes. These findings strengthen the position that tDCS effects on cognition extend to the neural processing of sensory input and raise the possibility that this neuromodulatory technique may be useful for investigating sensory processing deficits in clinical populations., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults., (Copyright © 2016. Published by Elsevier B.V.)

Chronic cannabis use may interact with factors, such as age of onset of cannabis use, family history, and genetic factors, to elicit schizophrenia (SZ)-like symptoms, including sensory and cognitive deficits. However, evidence of a relationship between cannabis use and cognitive impairment is confounded by concomitant use of tobacco. The objective of this study was to compare tobacco-naïve cannabis users with individuals without a history of tobacco/cannabis use on the auditory mismatch negativity (MMN) event-related potential (ERP), a neural measure of auditory deviance detection which is diminished in SZ. An exploratory arm of the study, conducted within a randomized, double-blind, placebo controlled design, examined the acute effects of nicotine gum (6mg) on MMN in cannabis users. MMN was recorded in response to 5 deviant stimuli within an optimal MMN paradigm in 44 healthy, non-tobacco smoking volunteers aged 18-26. Cannabis users (n=21) started smoking cannabis prior to age 17, at least 1 joint per month. To examine the effects of chronicity, users were grouped into relatively heavy long-term (HLT; n=11) users and light short-term (LST; n=10) users. Impaired deviance detection was shown in cannabis users vs. nonusers as reflected by a smaller MMN to duration deviants. Chronicity of use was also associated with MMN alterations, as HLTs displayed a reduced duration and gap MMN vs. LSTs. Compared with placebo, nicotine treatment enhanced select MMN deviants in cannabis user subgroups. As deficits associated with early and persistent cannabis use are similar to those seen in SZ, these dose-dependant disturbances in early sensory processing with cannabis use may be one cognitive pathway which mediates an increased risk for SZ in vulnerable youth, and be influenced by concurrent cigarette smoking behavior., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Membrane potentials and brain plasticity are basic modes of cerebral information processing. Both can be externally (non-invasively) modulated by weak transcranial direct current stimulation (tDCS). Polarity-dependent tDCS-induced reversible circumscribed increases and decreases in cortical excitability and functional changes have been observed following stimulation of motor and visual cortices but relatively little research has been conducted with respect to the auditory cortex. The aim of this pilot study was to examine the effects of tDCS on auditory sensory discrimination in healthy participants (N = 12) assessed with the mismatch negativity (MMN) brain event-related potential (ERP). In a randomized, double-blind, sham-controlled design, participants received anodal tDCS over the primary auditory cortex (2 mA for 20 min) in one session and 'sham' stimulation (i.e., no stimulation except initial ramp-up for 30 s) in the other session. MMN elicited by changes in auditory pitch was found to be enhanced after receiving anodal tDCS compared to 'sham' stimulation, with the effects being evidenced in individuals with relatively reduced (vs. increased) baseline amplitudes and with relatively small (vs. large) pitch deviants. Additional studies are needed to further explore relationships between tDCS-related parameters, auditory stimulus features and individual differences prior to assessing the utility of this tool for treating auditory processing deficits in psychiatric and/or neurological disorders.

Novel pharmacological treatments targeting alpha 7 nicotinic acetylcholine receptor (α7 nAChR) hypofunction in schizophrenia have shown mixed success in ameliorating cognitive impairments associated with this disorder. Choline, a selective agonist at α7 receptors is increased with oral administration of cytidine 5'-diphosphocholine (CDP-choline), the cognitive effects of which were assessed in healthy volunteers. Using the CogState test battery, behavioral performance in schizophrenia-relevant cognitive domains was assessed in 24 male participants following a single low (500mg) and moderate (1000mg) dose of CDP-choline. Relative to placebo, CDP-choline improved processing speed, working memory, verbal learning, verbal memory, and executive function in low baseline performers, while exerting no effects in medium baseline performers, and diminishing cognition in high baseline performers. Dose effects varied with cognitive domain but were evident with both the 500mg and 1000mg doses. These preliminary findings of cognitive enhancement in relatively impaired performers are consistent with the α7 receptor mechanism and support further trials with CDP-choline as a potential pro-cognitive strategy for cognitive impairment in schizophrenia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

CDP-choline (cytidine-5'-diphosphocholine) is a phospholipid used to treat cognitive disorders, presumably repairing and maintaining brain cell membranes. Additional mechanisms may include enhanced cholinergic neurotransmission as the α7 nicotinic receptor actions of choline and increased acetylcholine synthesis accompanying CDP-choline administration may modulate brain oscillations underlying cognitive processes. This study utilizes electroencephalographic (EEG) recordings in healthy volunteers to evaluate CDP-choline induction of an oscillatory response profile associated with nicotinic stimulation. Resting state EEG was acquired in 24 male volunteers administered low (500mg) and moderate (1000mg) doses of CDP-choline in a randomized placebo-controlled, crossover trial. Consistent with nicotinic agonist treatment, spectral analysis showed dose-dependent reductions in delta and increases in alpha oscillations, which were also accompanied by decreases in beta and gamma oscillatory activity. These findings support the posit that CDP-choline cognitive enhancement involves multiple mechanisms including facilitated nicotinic cholinergic action., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Diminished auditory sensory gating and associated neurocognitive deficits in schizophrenia have been linked to altered expression and function of the alpha-7 nicotinic acetycholinergic receptor (α7 nAChR), the targeting of which may have treatment potential. Choline is a selective α7 nAChR agonist and the aim of this study was to determine whether cytidine 5'-diphosphocholine (CDP-choline), or citicoline, a dietary source of choline, increases sensory gating and cognition in healthy volunteers stratified for gating level. In a randomized, placebo-controlled, double-blind design involving acute administration of low, moderate doses (500 mg, 1000 mg) of CDP-choline, 24 healthy volunteers were assessed for auditory gating as indexed by suppression of the P50 event-related potential (ERP) in a paired-stimulus (S1, S2) paradigm, and for executive function as measured by the Groton Maze Learning Task (GMLT) of the CogState Schizophrenia Battery. CDP-choline improved gating (1000 mg) and suppression of the S2 P50 response (500 mg, 1000 mg), with the effects being selective for individuals with low gating (suppression) levels. Tentative support was also shown for increased GMLT performance (500 mg) in low suppressors. These preliminary findings with CDP-choline in a healthy, schizophrenia-like surrogate sample are consistent with a α7 nAChR mechanism and support further trials with choline as a pro-cognitive strategy., (© The Author(s) 2014.)

Objective: Cognitive enhancement resulting from nicotinic acetylcholine receptor stimulation may be evidenced by increased efficiency of the auditory-frontal cortex network of auditory discrimination, which is impaired in schizophrenia, a cognitive disorder associated with excessive tobacco use. Investigating automatic (preattentive) detection of acoustic change with the mismatch negativity (MMN) brain event-related potential in response to nicotine in individuals with varying baseline levels of auditory discrimination may provide useful insight into the cholinergic regulation of this neural network and its potential amelioration with novel nicotinic agents., Methods: Sixty healthy, non-smoking male volunteers were presented with an 'optimal' multi-feature MMN paradigm in a randomized, placebo controlled double-blind design with 6 mg of nicotine gum., Results: Participants with low, medium, and high baseline amplitudes responded differently to nicotine (vs. placebo), and nicotine response was feature specific. Whereas MMN in individuals with high amplitudes was diminished by nicotine, MMN increased in those with low amplitudes. Nicotine effects were not shown in medium amplitude participants., Conclusions: These findings provide preliminary support for the role of nicotinic neurotransmission in sensory memory processing of auditory change and suggest that nicotinic receptor modulation can both enhance and diminish change detection, depending on baseline MMN and its eliciting stimulus feature., (Copyright © 2014 John Wiley & Sons, Ltd.)

Cholinergic stimulation produces cognitive effects that vary across individuals, and stimulus/task conditions. As of yet, the role of individual differences in moderating the effects of the nicotinic acetylcholine receptor agonist nicotine on specific attentional functions and their neural and behavioral correlates is not fully understood. In this randomized, double-blind, placebo-controlled study of 64 healthy non-smokers, we address the contribution of baseline-dependence to inter-individual variability in response to nicotine gum (6 mg) assessed with event-related brain potential (ERP) indices of involuntary (the anteriorly distributed P3a) and voluntary (the posteriorly distributed P3b) attention derived from an active 3-stimulus auditory oddball paradigm involving listening to standard and novel stimuli and detection and response to target stimuli. Nicotine enhanced the amplitude of P3a elicited during the processing of novel stimuli but only in individuals with relatively low baseline P3a amplitudes. Exhibiting an inverted-U nicotine response profile, target P3b and standard N1 amplitudes were increased and decreased in participants with low and high baseline amplitudes, respectively. In all, the findings corroborate the involvement of nicotinic mechanisms in attention, generally acting to increase attentional capacity in relatively low attentional functioning (reduced baseline ERPs) individuals, while having negative or detrimental effects in those with medium/high attentional levels (increased baseline ERPs), and in a manner that is differentially expressed during bottom-up (involuntary) attentional capture and top-down (voluntary) attentional allocation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Reduced suppression of the P50 auditory event-related potential in schizophrenia patients relative to normal controls is indicative of a sensory gating deficit and is one of the most robust findings reported for functional brain abnormalities in this disorder. However, there is considerable gating variability in patients and controls and there is little understanding as to how inter-individual differences moderate gating responses to drugs and nicotinic agonists in particular, which have shown potential to reverse gating deficits. In this study the effects of acutely administered nicotine (gum, 6 mg) on sensory gating in a paired (S₁-S₂) auditory stimulus paradigm were investigated in 57 healthy, non-smoking volunteers stratified as low (n = 19), medium (n = 19) and high (n = 19) P50 suppressors on the basis of three separate baseline derived gating indices, P50 ratios, P50 difference scores, and gating difference waveforms. Relative to placebo, nicotine consistently improved gating in low suppressors as stratified with all three gating indices, exerted no effects in medium suppressors and reduced gating in high suppressors. Analysis of individual stimulus (S₂, S₂) amplitudes showed distinctly different mechanisms of action underlying nicotine effects in individuals with low and high baseline suppression. The results parallel similar findings of baseline-dependency in the gating effects of several antipsychotic drugs in healthy volunteers and support the use of group segmentation as a translational model in novel cognitive drug development for schizophrenia.

Enhanced cortical cholinergic signaling associated with nicotinic acetylcholine receptor (nAChR) stimulation has been linked with pro-cognitive actions in a variety of performance domains, including attentional tasks. Improvements in stimulus selection with the nAChR agonist nicotine have been reported but its effects on visual spatial selective attention are unclear. Employing a double-blind, placebo-controlled design, this study examined the acute actions of nicotine (6 mg) in 24 non-smokers performing a visual search task of spatial attention that was probed with behavioral performance measures and the N2pc component of the event-related potentials (ERPs), which served as a neural index of spatial attentional selection. Nicotine did not affect behavioral performance indices. In high symptomatic subjects (as indexed by greater increases in heart rate post-administration), nicotine was associated with an N2pc amplitude enhancement while in low symptomatic individuals it was associated with an N2pc difference amplitude decrease. Nicotine modulation of the ERP marker of spatial attentional selection corroborates in general the attentional effects of nAChR agonists and extends these properties to include altered selective mechanisms during visual spatial processing., (Copyright © 2011 Elsevier Inc. All rights reserved.)