Diffusion tensor imaging profiles reveal specific neural tract distortion in normal pressure hydrocephalus

BACKGROUND: The pathogenesis of normal pressure hydrocephalus (NPH) remains unclear which limits both early diagnosis and prognostication. The responsiveness to intervention of differing, complex and concurrent injury patterns on imaging have not been well-characterized. We used diffusion tensor imaging (DTI) to explore the topography and reversibility of white matter injury in NPH pre- and early after shunting. METHODS: Twenty-five participants (sixteen NPH patients and nine healthy controls) underwent DTI, pre-operatively and at two weeks post-intervention in patients. We interrogated 40 datasets to generate a full panel of DTI measures and corroborated findings with plots of isotropy (p) vs. anisotropy (q). RESULTS: Concurrent examination of DTI measures revealed distinct profiles for NPH patients vs. controls. PQ plots demonstrated that patterns of injury occupied discrete white matter districts. DTI profiles for different white matter tracts showed changes consistent with i) predominant transependymal diffusion with stretch/ compression, ii) oedema with or without stretch/ compression and iii) predominant stretch/ compression. Findings were specific to individual tracts and dependent upon their proximity to the ventricles. At two weeks post-intervention, there was a 6·7% drop in axial diffusivity (p = 0·022) in the posterior limb of the internal capsule, compatible with improvement in stretch/ compression, that preceded any discernible changes in clinical outcome. On PQ plots, the trajectories of the posterior limb of the internal capsule and inferior longitudinal fasciculus suggested attempted 'round trips'. i.e. return to normality. CONCLUSION: DTI profiling with p:q correlation may offer a non-invasive biomarker of the characteristics of potentially reversible white matter injury.Nicole C Keong was supported by a Joint Royal College of Surgeons of England and Dunhill Medical Trust Fellowship and a Tunku Abdul Rahman Centenary Grant and other from National Medical Research Council Transition Award Grant, Singapore (supporting ongoing work). A Medical Research Council Programme Grant [Wolfson Brain Imaging Centre Cooperative] supported the study imaging work. Marek Czosnyka was supported by grants from Johnson and Johnson – Codman, Integra, Sophysa and Aesculap. Zofia Czosnyka was supported by grants from Johnson and Johnson – Codman, Integra, Sophysa and Aesculap. Elise DeVito was funded by the Pinsent-Darwin Studentship in Mental Pathology. Charlotte Housden took up employment with Cambridge Cognition Ltd following her PhD. Barbara J Sahakian was supported by a Medical Research Council Grant and reports personal fees from Cambridge Cognition, Lundbeck, Servier, grants from Janssen/J&J, other from Otsuka and personal fees from Peak (Brainbow). JDP was supported by an NIHR Senior Investigator Award, a Medical Research Council Programme grant and an NIHR Cambridge Biomedical Research Centre grant [brain injury theme] and also wishes to declare the following - Past advisor to Codman and Medtronic international advisory board, Director (unpaid) of Medicam, Scientific Collaboration with GSK (unpaid), Trustee of Brain Research Trust, Patron of Headway Cambridgeshire, Honorary Director of National Institute for Health Research Brain Injury Healthcare Technology Cooperative

Reported patterns of vaping to support long-term abstinence from smoking: a cross-sectional survey of a convenience sample of vapers

Background: E-cigarettes are the most popular aid to smoking cessation attempts in England and the USA. This research examined associations between e-cigarette device characteristics and patterns of use, tobacco-smoking relapse, and smoking abstinence. Methods: A convenience sample of 371 participants with experience of vaping, and tobacco-smoking abstinence and/or relapse completed an online cross-sectional survey about e-cigarettes. Factors associated with smoking relapse were examined using multiple linear and logistic regression models. Results: Most participants were self-reported long-term abstinent smokers (86.3%) intending to continue vaping. Most initiated e-cigarette use with a vape pen (45.8%) or cig-a-like (38.7%) before moving onto a tank device (89%). Due to missing data, managed through pairwise deletion, only around 70 participants were included in some of the main analyses. Those using a tank or vape pen appeared less likely to relapse than those using a cig-a-like (tank vs. cig-a-like OR = 0.06, 95% CI 0.01-0.64, p = 0.019). There was an inverse association between starting self-reported e-cigarette liquid nicotine concentration and relapse, interacting with device type (OR = 0.79, 95% CI 0.63-0.99, p = 0.047), suggesting that risk of relapse may have been greater if starting with a low e-cigarette liquid nicotine concentration and/or cig-a-like device. Participants reported moving from tobacco-flavored cig-a-likes to fruit/sweet/food flavors with tank devices. Conclusions: Knowledge of how people have successfully maintained tobacco-smoking abstinence using vaping could help other tobacco smokers wishing to quit tobacco smoking through vaping

Decreased olfactory discrimination is associated with impulsivity in healthy volunteers

In clinical populations, olfactory abilities parallel executive function, implicating shared neuroanatomical substrates within the ventral prefrontal cortex. In healthy individuals, the relationship between olfaction and personality traits or certain cognitive and behavioural characteristics remains unexplored. We therefore tested if olfactory function is associated with trait and behavioural impulsivity in nonclinical individuals. Eighty-three healthy volunteers (50 females) underwent quantitative assessment of olfactory function (odour detection threshold, discrimination, and identifcation). Each participant was rated for trait impulsivity index using the Barratt Impulsiveness Scale and performed a battery of tasks to assess behavioural impulsivity (Stop Signal Task, SST; Information Sampling Task, IST; Delay Discounting). Lower odour discrimination predicted high ratings in non-planning impulsivity (Barratt Non-Planning impulsivity subscale); both, lower odour discrimination and detection threshold predicted low inhibitory control (SST; increased motor impulsivity). These fndings extend clinical observations to support the hypothesis that defcits in olfactory ability are linked to impulsive tendencies within the healthy population. In particular, the relationship between olfactory abilities and behavioural inhibitory control (in the SST) reinforces evidence for functional overlap between neural networks involved in both processes. These fndings may usefully inform the stratifcation of people at risk of impulse-control-related problems and support planning early clinical interventions

Methylphenidate Normalizes Fronto-Striatal Underactivation During Interference Inhibition in Medication-Naïve Boys with Attention-Deficit Hyperactivity Disorder

Youth with attention deficit hyperactivity disorder (ADHD) have deficits in interference inhibition, which can be improved with the indirect catecholamine agonist methylphenidate (MPH). Functional magnetic resonance imaging was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naïve ADHD boys. Medication-naïve boys with ADHD were scanned twice, in a randomized, double-blind design, under either a single clinical dose of MPH or placebo, while performing a Simon task that measures interference inhibition and controls for the oddball effect of low-frequency appearance of incongruent trials. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of healthy age-matched comparison boys. During incongruent trials compared with congruent–oddball trials, boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition, including right inferior prefrontal cortex, left striatum and thalamus, mid-cingulate/supplementary motor area, and left superior temporal lobe. MPH relative to placebo upregulated brain activation in right inferior prefrontal and premotor cortices. Under the MPH condition, patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions. Effect size comparison, furthermore, showed that these normalization effects were significant. MPH significantly normalized the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition, but did not affect medial frontal or temporal dysfunction. MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

Het nemen van beslissingen door volwassenen met ADHD:Een systematisch literatuuronderzoek

Personen met aandachtstekortstoornis met hyperactiviteit (ADHD) hebben een grotere kans om minder goede (levens)beslissingen te nemen en om risicovolle activiteiten te ondernemen dan personen zonder ADHD. Mogelijk komt dit doordat de kenmerken van ADHD van invloed zijn op het besluitvormingsproces. Hoewel beslissingsproblematiek reeds uitgebreid is onderzocht bij kinderen en adolescenten met ADHD, is er nog relatief weinig bekend over de besluitvorming van volwassenen met ADHD. Om die reden was het doel van dit literatuuronderzoek de aard en omvang van eventuele tekorten in het besluitvormingsproces van volwassenen met ADHD vast te stellen. Hiertoe is de bestaande literatuur, waarin de prestatie van volwassenen met ADHD op beslissingstaken werd vergeleken met de prestatie van een gezonde controlegroep, systematisch doorzocht, waartoe de databases PsycINFO, MEDLINE en PubMed zijn geraadpleegd. In totaal werden er 31 studies geïncludeerd. In de meerderheid van de studies (i.e. 55 %) weken de prestaties van volwassenen met ADHD af op een of meer van de gebruikte beslissingstaken in vergelijking met de controlegroep(en). Dit literatuuronderzoek levert daarmee voorzichtig bewijs voor het bestaan van verschillen in het besluitvormingsproces tussen gezonde individuen en volwassenen met ADHD. De grote inconsistentie in de bevindingen wordt deels verklaard door de verscheidenheid aan domeinen van besluitvorming die werden onderzocht, de comorbide stoornissen van de participanten en het medicatiegebruik in de ADHD-groepen. Het literatuuronderzoek besluit met een bespreking van de implicaties die de bevindingen hebben voor theorieën over de onderliggende mechanismen van ADHD

A preliminary study of the neural effects of behavioral therapy for substance use disorders.

BACKGROUND: The mechanisms by which behavioral therapies for substance use disorders (SUDs) exert their effects and the components of treatment that contribute most to substance use outcome remain unclear. Disruptions to aspects of impulse control and attention have been hypothesized to contribute to the development and maintenance of addiction; moreover, alterations in these processes may underlie responses to treatment. METHODS: Individuals participating in a randomized clinical trial evaluating computer-assisted cognitive behavioral therapy (CBT) for substance abuse participated in fMRI Stroop before and after treatment. A non-substance-using comparison group performed the same task under test-retest conditions. RESULTS: The patient group demonstrated decreased Stroop-related BOLD signal in regions including the anterior cingulate, inferior frontal gyrus and midbrain at post-treatment relative to pre-treatment, and displayed a greater decrease in the subthalamic nucleus and surrounding regions compared to healthy controls following test-retest. CONCLUSIONS: Behavioral therapies may be associated with reduction in substance use and effects on neural systems involved in cognitive control, impulsivity, motivation and attention