Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC) and nucleus accumbens (NAcb) and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD) and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP) oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT), which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50–60 Hz) LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7–9 Hz) LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour.

The medial prefrontal cortex (mPFC) and ventral striatum (VS), including the nucleus accumbens, are key forebrain regions involved in regulating behaviour for future rewards. Dysfunction of these regions can result in impulsivity, characterized by actions that are mistimed and executed without due consideration of their consequences. Here we recorded the activity of single neurons in the mPFC and VS of 16 rats during performance on a five-choice serial reaction time task of sustained visual attention and impulsivity. Impulsive responses were assessed by the number of premature responses made before target stimuli were presented. We found that the majority of cells signalled trial outcome after an action was made (both rewarded and unrewarded). Positive and negative ramping activity was a feature of population activity in the mPFC and VS (49.5 and 50.4% of cells, respectively). This delay-related activity increased at the same rate and reached the same maximum (or minimum) for trials terminated by either correct or premature responses. However, on premature trials, the ramping activity started earlier and coincided with shorter latencies to begin waiting. For all trial types the pattern of ramping activity was unchanged when the pre-stimulus delay period was made variable. Thus, premature responses may result from a failure in the timing of the initiation of a waiting process, combined with a reduced reliance on external sensory cues, rather than a primary failure in delay activity. Our findings further show that the neural locus of this aberrant timing signal may emanate from structures outside the mPFC and VS.

Balance disequilibrium is a significant contributor to falls in the elderly. The most common cause of balance dysfunction is loss of sensory cells from the vestibular sensory epithelia of the inner ear. However, inaccessibility of inner ear tissue in humans severely restricts possibilities for experimental manipulation to develop therapies to ameliorate this loss. We provide a structural and functional analysis of human vestibular sensory epithelia harvested at trans-labyrinthine surgery. We demonstrate the viability of the tissue and labeling with specific markers of hair cell function and of ion homeostasis in the epithelium. Samples obtained from the oldest patients revealed a significant loss of hair cells across the tissue surface, but we found immature hair bundles present in epithelia harvested from patients >60 years of age. These results suggest that the environment of the human vestibular sensory epithelium could be responsive to stimulation of developmental pathways to enhance hair cell regeneration, as has been demonstrated successfully in the vestibular organs of adult mice.

Objective: We report our experience of functional imaging with 11 C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. Design: Twenty patients with i) de novo Cushing's disease (CD, nZ10), ii) residual or recurrent hypercortisolism following first pituitary surgery (Gradiotherapy; nZ8) or iii) ectopic Cushing's syndrome (nZ2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. Methods: All patients underwent 11 C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of 11 C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. Results: In seven of ten patients with de novo CD, asymmetric 11 C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal 11 C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, 11 C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. Conclusions:11 C-methionine PET-CT can aid the detection of ACTH-secreting tumours in Cushing's syndrome and facilitate targeted therapy.

Background and aimsEustachian tube dysfunction (ETD) is a commonly diagnosed disorder of Eustachian tube opening and closure, which may be associated with severe symptoms and middle ear disease. Currently the diagnosis of obstructive and patulous forms of ETD is primarily based on non-specific symptoms or examination findings, rather than measurement of the underlying function of the Eustachian tube. This has proved problematic when selecting patients for treatment, and when designing trial inclusion criteria and outcomes. This study aims to determine the correlation and diagnostic value of various tests of ET opening and patient reported outcome measures (PROMs), in order to generate a recommended diagnostic pathway for ETD.MethodsIndex tests included two PROMs and 14 tests of ET opening (nine for obstructive, five for patulous ETD). In the absence of an accepted reference standard two methods were adopted to establish index test accuracy: expert panel diagnosis and latent class analysis. Index test results were assessed with Pearson correlation and principle component analysis, and test accuracy was determined. Logistic regression models assessed the predictive value of grouped test results.ResultsThe expert panel diagnosis and PROMs results correlated with each other, but not with ET function measured by tests of ET opening. All index tests were found to be feasible in clinic, and acceptable to patients. PROMs had very poor specificity, and no diagnostic value. Combining the results of tests of ET function appeared beneficial. The latent class model suggested tympanometry, sonotubometry and tubomanometry have the best diagnostic performance for obstructive ETD, and these are included in a proposed diagnostic pathway.ConclusionsETD should be diagnosed on the basis of clinical assessment and tests of ET opening, as PROMs have no diagnostic value. Currently diagnostic uncertainty exists for some patients who appear to have intermittent ETD clinically, but have negative index test results.

We would recommend a full review of all histological specimens in patients with a diagnosis of temporal bone inflammatory pseudotumour or inflammatory myofibroblastic tumour. Consideration should be given to immunohistochemical analysis for anaplastic lymphoma kinase and immunoglobulin G4, with measurement of serum levels of the latter. Management of the condition is medical, with corticosteroids and immunosuppression, rather than surgical excision.

BackgroundThe purpose of this study was to estimate the prevalence of drug use, including injecting drug use, among the prisoner population in the Republic of Ireland. Drug use surveys carried out by the National Advisory Committee on Drugs and Alcohol (NACDA) provide population data, but the most recent drug prevalence data on the Irish prisoner population dated from a 1999 study on Blood Borne Viruses (BBVs) in prisons. Accurate up-to-date data for service planning and policy development were required.MethodsAn observational cross-sectional study was undertaken, with 824 prisoners randomly selected in proportion to the population in each prison. Data collection instruments included a self-completion questionnaire (based on European Monitoring Centre for Drugs and Drug Addiction guidelines), and oral fluid samples, which were tested for six drugs. Prevalence proportions and confidence intervals were calculated. T-tests and Chi2 testing were used for group comparisons.ResultsThe response rate was 50% and the sample was representative of the full prison population. Prevalence of any drug  use for individual drugs was, not unexpectedly, higher than in the general population. Results are presented as prevalence range for individual drugs (95% CI lower and upper bounds) for: lifetime, 33% (CI: 30–36%) to 87% (CI: 85–89%); last year, 12 (CI: 10–14%) to 69% (CI: 66–71%); and last month, 2% (CI: 1–3%) to 43% (CI: 40–47%). Lifetime injecting prevalence for any drug was 26% (CI: 23–28%) and lifetime individual drug injecting rates ranged from 2 (CI: 1–2%) to 19% (CI: 17–22%). Women were significantly more likely to inject drugs than men (44% vs 24%, p < 0.01).ConclusionThe findings confirmed the need for drug treatment and harm reduction services in prisons and highlighted key risk areas and groups for specific and targeted interventions. The NACDA has published recommendations for practice, policy and research based on the results.

The CETDA and ETDQ-7 are not disease-specific and cannot distinguish obstructive from patulous ETD subtypes. A relatively weak correlation between sonotubometry and tubomanometry results, PROM scores, and the clinical diagnosis suggests that a varied core set of outcome measures is required to monitor response to treatments for ETD.