Neurosurgery for Temporal Lobe Epilepsy: Psychiatric Outcome and Relationship to Cognitive Function

Temporal lobe epilepsy (TLE) is a chronic neurological disorder characterised by recurrent seizures arising from temporal lobe structures. Medical treatment is effective for the majority but for the remainder, seizure control remains difficult to achieve. Epilepsy surgery, however, has proved an effective treatment. Following TLE surgery psychiatric symptoms can develop for the first time (de novo), and pre-existing symptoms may worsen; having a detrimental impact on patients’ quality of life. Yet, research data on psychiatric complications following TLE surgery is limited, in sharp contrast to the continuing emphasis on neuropsychological and neurological sequelae. The central aims of this thesis were to increase our understanding of the psychiatric status of patients with intractable TLE pre- and postoperatively, and to identify risk factors associated with poorer postoperative outcomes. This thesis is divided into 2 main sections. Section 1 (Chapters 1-5) provide a literature review that demonstrates pre- and postoperative psychopathology in TLE is common, unrecognised, and under-treated. Emerging evidence suggests that pre-surgical psychiatric morbidity is associated with more widespread cerebral pathology, but striking, is the lack of attention to its relationship to cognitive variables. The central hypothesis formulated and explored here is that TLE patients with less localised cerebral dysfunction, as supported by electrophysiological, neuro-radiological and cognitive indicators will be at risk for psychiatric disturbance preoperatively and have poorer outcomes following TLE surgery. Section 2 consists of 5 interlinked studies incorporating retrospective and prospective methodologies. In Study 1 (Chapter 7), the medical records of 280 TLE surgical cases were reviewed, and more than a third presented with significant psychiatric morbidity within 4 years following surgery. Fifty-one patients (18%) developed de novo psychopathology, half within 6 months of surgery and for the majority, persisted for more than 6 months. A preoperative history of secondary generalised tonic-clonic seizures (SGTCS) was an independent predictor of de novo psychopathology, but cognitive variables were not. Patients with a history of SGTCS and those with a preoperative psychiatric diagnosis were significantly less likely to remain seizure free. Using voxel based morphometry (VBM), Study 2 (Chapter 8) explored the preoperative neural correlates of de novo depression in a sub-group of patients (n=43) presented in Study 1. Grey matter (GM) reductions in the orbitofrontal cortices (OFC), ipsilateral cingulate gyrus and ipsilateral thalamus were associated with the development of de novo depression within 4 years postoperatively. In Study 3 (Chapter 9), a sub-group of patients from Study 1, with a diagnosis of post-ictal psychosis (TLE+PIP), were compared to age-matched TLE patients without any psychiatric history (TLE-only; n=60), with respect to pre-surgical clinical and cognitive variables. TLE+PIP patients were significantly less likely to have localised ictal epileptiform activity and more likely to have a positive family psychiatric history than TLE controls. Other clinical and cognitive variables did not distinguish between the groups. Patients with two or more PIP episodes had significantly increased odds of developing de novo psychopathology within 4 years of surgery, after controlling for comorbid pre-surgical psychiatric status and a history of SGTCS. A history of PIP was not a predictor of seizure status or cognitive outcome. Study 4 (Chapter 11) investigated the relationship between executive function and concurrent depression in TLE patients undergoing surgical evaluation. Depressed mood in TLE patients was associated with clinical, cognitive and behavioural indicators of more diffuse cerebral dysfunction. Using multilevel modelling, Study 5 (Chapter 12) provides clinically relevant data confirming that psychiatric disturbance is a significant complication following TLE surgery, and is predicted by the presence of pre-surgical executive dysfunction. The final chapter provides an overall summary of the findings, their implications, methodological limitations and directions for future research. It is argued that these studies have provided clinically relevant data that will aid the surgical decision-making process, and hopefully guide and improve post-surgical care and support

Attention Deficit Hyperactivity Disorder: Is There an App for That? Suitability Assessment of Apps for Children and Young People With ADHD

Background: Attention-deficit/hyperactivity disorder (ADHD) is a complex highly comorbid disorder, which can have a huge impact on those with ADHD, their family, and the community around them. ADHD is currently managed using pharmacological and nonpharmacological interventions. However, with advances in technology and an increase in the use of mobile apps, managing ADHD can be augmented using apps specifically designed for this population. However, little is known regarding the suitability and usability of currently available apps. Objective: The aim of this study was to explore the suitability of the top 10 listed apps for children and young people with ADHD and clinicians who work with them. It is hypothesized that mobile apps designed for this population could be more suitably designed for this population. Methods: The top 10 listed apps that are specifically targeted toward children and young people with ADHD in the United Kingdom were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 5 clinicians who specialize in treating this population and 5 children and young people with ADHD themselves, to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable for this population. Results: Five themes emerged from clinician and young people interviews: the accessibility of the technology, the importance of relating to apps, addressing ADHD symptoms and related difficulties, age appropriateness, and app interaction. Three additional themes emerged from the clinician interviews alone: monitoring symptoms, side effects and app effect on relationships, and the impact of common comorbid conditions. The characteristics of the apps did not appear to match well with the views of our sample. Conclusions: These findings suggest that the apps may not be suitable in meeting the complex needs associated with this condition. Further research is required to explore the value of apps for children and young people with ADHD and their families and, in particular, any positive role for apps in the management of ADHD in this age group. A systematic review on how technology can be used to engage this population and how it can be used to help them would be a useful way forward. This could be the platform to begin exploring the use of apps further

Cannabis dampens the effects of music in brain regions sensitive to reward and emotion

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here we investigate the effects of cannabis on listening to music - a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol (CBD), which may offset cannabis-related harms. Methods: Across three sessions, sixteen cannabis users inhaled cannabis with CBD, cannabis without CBD, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging (fMRI) within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (p<0.05). Results: Compared to placebo, cannabis without CBD dampened response to music in bilateral auditory cortex (right: p=0.005, left: p=0.008), right hippocampus/parahippocampal gyrus (p=0.025), right amygdala (p=0.025) and right ventral striatum (p=0.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (p=0.002) and increased functional connectivity with auditory cortex (right: p=0.000, left: p=0.000), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by CBD (right: p=0.003, left: p=0.030), and cannabis with CBD did not differ from placebo on any fMRI measures. Both types of cannabis increased ratings of wanting to listen to music (p<0.002) and enhanced sound perception (p<0.001). Conclusions: Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol

Kerr-Newman Black Hole Thermodynamical State Space: Blockwise Coordinates

A coordinate system that blockwise-simplifies the Kerr-Newman black hole's thermodynamical state space Ruppeiner metric geometry is constructed, with discussion of the limiting cases corresponding to simpler black holes. It is deduced that one of the three conformal Killing vectors of the Reissner-Nordstrom and Kerr cases (whose thermodynamical state space metrics are 2 by 2 and conformally flat) survives generalization to the Kerr-Newman case's 3 by 3 thermodynamical state space metric.Comment: 4 pages incl 2 figs. Accepted by Gen. Rel. Grav. Replaced with Accepted version (minor corrections

The Prevalence and Characteristics of Performance-Enhancing Drug Use Among Bodybuilding Athletes in the South of Iran, Bushehr

Background: Several reports have implied progressive increase of performance-enhancing drug (PED) use among Iranian athletes. More importantly, most of the previous research in the Iranian population had mainly focused on the anabolic steroid abuse, and ignored other agents. Objectives: The aim of this study was to investigate the prevalence and characteristics of PED use among bodybuilding athletes in Bushehr, south of Iran. Methods: Four hundred and fifty three male bodybuilding athletes were recruited from Bushehr gyms between February and May of 2015. Men were eligible to participate in the survey if they had regularly participated in the strength-training exercise (minimum of 1 year and 4 hour/week). Data were collected via a face-to-face interview. The survey consisted of three separate parts including demographic data, exercise pattern and PED use. Results: According to this study, 234 (51.7%) of bodybuilding athletes had used PEDs. The PED users reported an average of 3.80 � 4.52 agents’ use in their programs and they had used PEDs for the average of 3.24 � 3.99 years. The most prevalent agents which had been abused by the athletes were anabolic steroids (used by 185 athletes (79.4% of athletes). Furthermore, 110 (47%) of athletes reported stimulant agents’ use during their routines. The most prevalent motivation for using PEDs was increasing muscle mass that was reported by 164 (70.1%) of PED users. In addition, sexual and dermatologic effects were the most prevalent adverse effects reported by the PED user athletes (114 (49.4%) and 103 (44.2%), respectively). Conclusions: This study showed the high rate of PED use among recreational and professional Iranian bodybuilding athletes that can expose them to the serious side effects of these agents

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses

Rationale: Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence. Objectives: The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning. Methods: In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state. Results: Cann-CBD reduced the likelihood of high-effort choices relative to placebo (p = 0.042) and increased sensitivity to expected value compared to both placebo (p = 0.014) and Cann + CBD (p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (p = 0.007). Conclusions: Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC

The impact of hyperhidrosis on patients' daily life and quality of life : A qualitative investigation

Background: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. Methods: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. Results: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. Conclusions: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.Peer reviewe

Lung Cancer and Cardiovascular Disease Mortality Associated with Ambient Air Pollution and Cigarette Smoke: Shape of the Exposure–Response Relationships

Background: Lung cancer and cardiovascular disease (CVD) mortality risks increase with smoking, secondhand smoke (SHS), and exposure to fine particulate matter < 2.5 μm in diameter (PM2.5) from ambient air pollution. Recent research indicates that the exposure–response relationship for CVD is nonlinear, with a steep increase in risk at low exposures and flattening out at higher exposures. Comparable estimates of the exposure–response relationship for lung cancer are required for disease burden estimates and related public health policy assessments

Microcrystals coating the wing membranes of a living insect (Psocoptera: Psyllipsocidae) from a Brazilian cave

Two specimens of Psyllipsocus yucatan with black wings were found with normal individuals of this species on guano piles produced by the common vampire bat Desmodus rotundus. These specimens have both pairs of wings dorsally and ventrally covered by a black crystalline layer. They did not exhibit any signs of reduced vitality in the field and their morphology is completely normal. This ultrathin (1.5 µm) crystalline layer, naturally deposited on a biological membrane, is documented by photographs, SEM micrographs, energy dispersive spectroscopy (EDS) and X-ray diffractometry (XRD). The crystalline deposit contains iron, carbon and oxygen, but the mineral species could not be identified. Guano probably played a role in its formation; the presence of iron may be a consequence of the excretion of iron by the common vampire bat. This enigmatic phenomenon lacks obvious biological significance but may inspire bionic applications. Nothing similar has ever been observed in terrestrial arthropods