Enhanced attentional bias towards sexually explicit cues in individuals with and without compulsive sexual behaviours.

Compulsive sexual behaviour (CSB) is relatively common and has been associated with significant distress and psychosocial impairments. CSB has been conceptualized as either an impulse control disorder or a non-substance 'behavioural' addiction. Substance use disorders are commonly associated with attentional biases to drug cues which are believed to reflect processes of incentive salience. Here we assess male CSB subjects compared to age-matched male healthy controls using a dot probe task to assess attentional bias to sexually explicit cues. We show that compared to healthy volunteers, CSB subjects have enhanced attentional bias to explicit cues but not neutral cues particularly for early stimuli latency. Our findings suggest enhanced attentional bias to explicit cues possibly related to an early orienting attentional response. This finding dovetails with our recent observation that sexually explicit videos were associated with greater activity in a neural network similar to that observed in drug-cue-reactivity studies. Greater desire or wanting rather than liking was further associated with activity in this neural network. These studies together provide support for an incentive motivation theory of addiction underlying the aberrant response towards sexual cues in CSB.This is the published version of the manuscript. It is originally published by PLoS in PLoS ONE here: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0105476

Jumping the Gun: Mapping Neural Correlates of Waiting Impulsivity and Relevance Across Alcohol Misuse.

BACKGROUND: Why do we jump the gun or speak out of turn? Waiting impulsivity has a preclinical basis as a predictor for the development of addiction. Here, we mapped the intrinsic neural correlates of waiting and dissociated it from stopping, both fundamental mechanisms of behavioral control. METHODS: We used a recently developed translational task to assess premature responding and assess response inhibition using the stop signal task. We mapped the neural correlates in 55 healthy volunteers using a novel multi-echo resting-state functional magnetic resonance imaging sequence and analysis, which robustly boosts signal-to-noise ratio. We further assessed 32 young binge drinkers and 36 abstinent subjects with alcohol use disorders. RESULTS: Connectivity of limbic and motor cortical and striatal nodes mapped onto a mesial-lateral axis of the subthalamic nucleus. Waiting impulsivity was associated with lower connectivity of the subthalamic nucleus with ventral striatum and subgenual cingulate, regions similarly implicated in rodent lesion studies. This network was dissociable from fast reactive stopping involving hyperdirect connections of the pre-supplementary area and subthalamic nucleus. We further showed that binge drinkers, like those with alcohol use disorders, had elevated premature responding and emphasized the relevance of this subthalamic network across alcohol misuse. Using machine learning techniques we showed that subthalamic connectivity differentiates binge drinkers and individuals with alcohol use disorders from healthy volunteers. CONCLUSIONS: We highlight the translational and clinical relevance of dissociable functional systems of cortical, striatal, and hyperdirect connections with the subthalamic nucleus in modulating waiting and stopping and their importance across dimensions of alcohol misuse.The study was funded by the Wellcome Trust Fellowship grant for VV (093705/Z/10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. The BCNI is supported by a WT and MRC grant. ETB is employed part-time by the University of Cambridge and part-time by GSK PLC and is a shareholder of GSK. TWR is a consultant for Cambridge Cognition, Eli Lilly, GSK, Merck, Sharpe and Dohme, Lundbeck, Teva and Shire Pharmaceuticals. He is or has been in receipt of research grants from Lundbeck, Eli Lilly and GSK and is an editor for Springer-Verlag (Psychopharmacology). The remaining authors declare no competing financial interests.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.biopsych.2015.06.00

Fronto-striatal organization: Defining functional and microstructural substrates of behavioural flexibility.

Discrete yet overlapping frontal-striatal circuits mediate broadly dissociable cognitive and behavioural processes. Using a recently developed multi-echo resting-state functional MRI (magnetic resonance imaging) sequence with greatly enhanced signal compared to noise ratios, we map frontal cortical functional projections to the striatum and striatal projections through the direct and indirect basal ganglia circuit. We demonstrate distinct limbic (ventromedial prefrontal regions, ventral striatum - VS, ventral tegmental area - VTA), motor (supplementary motor areas - SMAs, putamen, substantia nigra) and cognitive (lateral prefrontal and caudate) functional connectivity. We confirm the functional nature of the cortico-striatal connections, demonstrating correlates of well-established goal-directed behaviour (involving medial orbitofrontal cortex - mOFC and VS), probabilistic reversal learning (lateral orbitofrontal cortex - lOFC and VS) and attentional shifting (dorsolateral prefrontal cortex - dlPFC and VS) while assessing habitual model-free (SMA and putamen) behaviours on an exploratory basis. We further use neurite orientation dispersion and density imaging (NODDI) to show that more goal-directed model-based learning (MBc) is also associated with higher mOFC neurite density and habitual model-free learning (MFc) implicates neurite complexity in the putamen. This data highlights similarities between a computational account of MFc and conventional measures of habit learning. We highlight the intrinsic functional and structural architecture of parallel systems of behavioural control.VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. LM is in receipt of an MRC studentship. The BCNI is supported by a WT and MRC grant. ETB is employed part-time by the University of Cambridge and part-time by GSK PLC and is a shareholder of GSK. TWR is a consultant for Cambridge Cognition, Eli Lilly, GSK, Merck, Sharpe and Dohme, Lundbeck, Teva and Shire Pharmaceuticals. He is or has been in receipt of research grants from Lundbeck, Eli Lilly and GSK and is an editor for Springer-Verlag (Psychopharmacology). The remaining authors declare no competing financial interests. The study was funded by the Wellcome Trust Fellowship grant for VV (093705/Z/10/Z) and Cambridge NIHR Biomedical Research Centre.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.cortex.2015.11.00

Reward sensitivity and waiting impulsivity: shift towards reward valuation away from action control

Background Impulsivity and reward expectancy are commonly inter-related. Waiting impulsivity, measured using the rodent 5-Choice Serial Reaction Time (5-CSRT) task, predicts compulsive cocaine seeking and sign (or cue) tracking. Here we assess human waiting impulsivity using a novel translational task, the 4-CSRT, and the relationship with reward cues. Methods Healthy volunteers (n=29) performed the monetary incentive delay task as a functional MRI study where subjects observe a cue predicting reward (cue) and wait to respond for high (£5), low (£1) or no reward. Waiting impulsivity was tested with the 4-CSRT. Results For high reward prospects (£5 – no reward), greater waiting impulsivity on the 4-CSRT correlated with greater medial orbitofrontal cortex (OFC) and lower supplementary motor area (SMA) activity to cues. In response to high reward cues, greater waiting impulsivity was associated with greater subthalamic nucleus connectivity with OFC and greater subgenual cingulate connectivity with anterior insula but decreased connectivity with regions implicated in action selection and preparation. Conclusion These findings highlight a shift towards regions implicated in reward valuation and a shift towards compulsivity away from higher level motor preparation and action selection and response. We highlight the role of reward sensitivity and impulsivity, mechanisms potentially linking human waiting impulsivity with incentive approach and compulsivity, theories highly relevant to disorders of addiction.status: publishe

The Successful Measurement of Clitoral Pulse Amplitude Using a New Clitoral Photoplethysmograph: A Pilot Study

BACKGROUND: Although the clitoris is more sensitive to stimulation and its innervation more conducive to sensory feedback than the vagina, the field of sexual psychophysiology, which uses psychophysiological methods including genital response measures to study sexual arousal, relies heavily on the measurement of vaginal, rather than clitoral, pulse amplitude. AIM: To develop and test a new clitoral photoplethysmograph for the measurement of clitoral pulse amplitude (CPA). METHODS: 2 versions of the new device, which differed in the orientation of the sensor and light source (parallel vs angled), were tested in 15 premenopausal, sexually functional women. Vaginal pulse amplitude (VPA) was assessed simultaneously. The women viewed a 3-minute erotic and an anxiety-inducing film segment with each clitoral sensor, interspersed with neutral video excerpts. In addition, they were asked to indicate their subjective level of sexual arousal during and after erotic video presentations. OUTCOMES: The main outcome measures are CPA, VPA, and subjective sexual arousal. RESULTS: The clitoral photoplethysmograph successfully detected CPA. The quality of the signals was best for the angled sensor. Main effects of the film and the interaction between the film and epoch were stronger for the clitoral than for the vaginal device. In addition, CPA followed more closely changes in intensity of sexual films than VPA. Within- and between-subject correlations between genital response and subjective sexual arousal were higher for the clitoral than for the vaginal device. CLINICAL TRANSLATION: Comparison of CPA with other genital blood flow measures in clinical samples is indicated and may contribute to improved physiological assessments of sexual response in women. STRENGTHS AND LIMITATIONS: Our sample was small and consisted of healthy volunteers. Future research could examine test-retest reliability, by including multiple recording sessions, and further explore the specificity of CPA by comparing sexual and non-sexual stimuli with positive valence. CONCLUSION: This study presents the first instrument to successfully measure CPA. Mechelmans DJ, Sachtler WL, von Wiegand TE, et al. The Successful Measurement of Clitoral Pulse Amplitude Using a New Clitoral Photoplethysmograph: A Pilot Study. J Sex Med 2020;17:1118-1125.status: publishe

The successful measurement of clitoral pulse amplitude using a new clitoral plethysmograph

Background: Although the clitoris is more sensitive to stimulation than the vagina, and its innervation more conducive to sensory feedback, the field of sexual psychophysiology relies heavily on the measurement of vaginal pulse amplitude (VPA). This is most likely due to the availability of an instrument, the vaginal photoplethysmograph, that is easy to place and that allows for relatively stable measurement. Recently, two studies (Gerritsen et al., 2009; Suschinsky et al., 2015) have used clitoral photoplethysmography to assess blood flow in the clitoris. However, only clitoral blood volume (CBV), thought to represent general clitoral vasocongestion, was reported rather than clitoral pulse amplitude (CPA). In the current study, we developed and tested a new clitoral photoplethysmograph for the measurement of CPA. Methods: After several design iterations, we selected two different versions of the new device, which differed in their orientation of the sensor and light source (i.e. parallel and angled). We tested the two newly developed clitoral sensors in 15 premenopausal, sexually functional women (mean age = 26.6, SD = 4.7). Vaginal pulse amplitude (VPA) was assessed simultaneously using a standard vaginal photoplethysmograph. Women wore elastic spandex shorts to enable stable placement of the instruments. The women viewed a three-minute erotic and an anxiety-inducing film segment with each clitoral sensor, and were presented with neutral video excerpts prior to the first and after each subsequent video. In addition, they were asked to use a lever to indicate their subjective level of sexual arousal during the erotic video presentations. Results: Due to technical problems, the data of three women could not be used. For the remaining participants we obtained satisfactory signals, especially when using the non-parallel clitoral device, which detected clear pulse waves in all women. Less than 2% of the clitoral and vaginal device data were impacted by artifacts. Main effects of Film and the interaction between Film and Epoch were stronger, in terms of effect size, for the clitoral than for the vaginal device. Furthermore, CPA followed more closely the changes in intensity of the sexual films than VPA: The clitoral pulse signal grew more steadily throughout the three-minute erotic video sequence, showing a substantial increase during the third minute, when vaginal intercourse was depicted. The vaginal pulse wave, on the other hand, showed the fastest and strongest increase during early parts of the erotic video (depicting petting and oral sex). Both within- and between-subject correlations between genital response and subjective sexual arousal were higher for the clitoral than for the vaginal device. Key Words: clitoral pulse amplitude, clitoral photoplethysmography, sexual arousal, vaginal pulse amplitudestatus: accepte

Neural correlates of waiting impulsivity: a dimensional approach to alcohol misuse

Objective Why do we “jump the gun”, speak out of turn, or run a red light? Waiting and stopping are fundamental mechanisms of behavioural control. Here we assess waiting impulsivity, or anticipatory premature responding before target onset, dimensionally across social drinkers, binge drinkers, and alcohol use disorders. We further focus on the characterization of neural correlates underlying waiting impulsivity in healthy volunteers. Special interest falls on the subthalamic nucleus (STN), a major relay structure within the indirect inhibitory pathway of striatal circuitry which also receives hyper-direct projections directly from cortical regions. This rich convergence of cortical inputs together with its principal gating of basal ganglia output implicates the STN as a crucial mediator of more complex control of motor and cognitive function. Method Towards a multi-faceted investigation of waiting impulsivity, we examined its neural correlates using a novel 4-choice serial reaction time task (4-CSRT), tested off-line, and differentiated that network from another underlying well-characterized form of motor impulsivity measured using the stop-signal task. To examine the intrinsic neural correlates of waiting and stopping, we use multi-echo resting state fMRI sequence and independent components analysis (ME-ICA) which has been shown to have up to four-fold enhancements in signal-to-noise ratio relative to conventional fMRI scans. Using machine learning classification, we explored the extent to which STN network connectivity would allow for classification of binge drinkers (BD) and those with alcohol use disorders (AUD) from healthy volunteers. For robust data-driven classifications between groups, we used a support vector machine. Supervised machine learning methods such as support vector machines provide robust characterizations at the individual rather than group level. Its use in classification of neuroimaging data is emerging, with studies demonstrating applications based on structural and functional data, supporting its potential as a diagnostic tool with high translational relevance. Results We show that greater premature responding in humans using the novel 4-CSRT task is associated with decreased intrinsic connectivity in a network involving bilateral STN, bilateral subgenual cingulate and right ventral striatum. These findings are dissociable from motor response inhibition or action cancellation as captured by the SSRT, which was associated with lower connectivity between hyper-direct projections of the right pre-SMA and left STN along with dorsal caudate and STN connectivity. We further show translational potential of these findings in alcohol misuse. In young adult BD subjects at greater risk for subsequent alcohol use problems, there was enhanced premature responding relative to matched healthy volunteers. Furthermore, in healthy social drinkers (healthy volunteers), we show that the degree of alcohol severity correlates negatively with connectivity between the bilateral STN and subgenual cingulate. Using machine learning predictive classification, the degree of STN connectivity predicted the differentiation of BD and AUD from social drinkers (healthy volunteers). Conclusion Our findings implicate dissociable parallel functional systems of the corticostriatal pathway and hyper-direct connections in modulating waiting and stopping. Our findings support a dimensional approach towards alcohol misuse from heavy social drinking to young adult binge drinkers to AUD and suggest the neural correlates of premature responding may be endophenotypic markers of alcohol misuse

Dot probe task and attentional bias.

<p>Dot probe task. The cues (A, B) represent either a sexually explicit, erotic or neutral woman cue paired with a neutral furniture cue randomly presented on either side. Subjects are required to indicate the side in which the green target appears using one of two key presses. The graph represents attentional bias ((Reaction time (RT) for control – RT test cue)/(RT control + RT test cue)) for the early stimulus latency compared between subjects with compulsive sexual behavior (CSB) and healthy volunteers (HV). The error bars represent standard error of the mean.</p

Stimulus latency and raw reaction time scores.

<p>A. Stimulus latency. The attentional bias score is shown for subjects with compulsive sexual behavior (CSB) and healthy volunteers (HV) as a function of stimulus latency (Early: 250–350 msec; Late 350–450 msec). B. Raw reaction time for cues and control stimuli for CSB and HV subjects. The error bars represent standard error of the mean.</p