Michael R. Trimble’s research while affiliated with UCL Eastman Dental Institute and other places

In this paper, we review in brief the development of ideas that over time have tried to explain why some individuals are more creative than others and what may be the neurobiological links underlying artistic creativity. We note associations with another unique human idea, that of genius. In particular, we discuss frontotemporal dementia and bipolar, cyclothymic mood disorder as clinical conditions that are helping to unravel the underlying neuroanatomy and neurochemistry of human creativity. This article is part of a Special Issue entitled Epilepsy, Art, and Creativity.

We report data from two patients, followed over 3 years after electrodermal biofeedback treatment. Patients were trained three times each week for four weeks to increase their sympathetic arousal using electrodermal biofeedback. This treatment was directed at enabling the patients to change their psychophysiological state as a countermeasure to prevent seizures. Both patients voluntarily kept a record of seizure frequency over the year preceding the treatment and continued to record their seizures for up to 3 years after the termination of biofeedback treatment. Both patients showed a marked reduction in seizure frequency (54.9% and 59.8%) during the month of biofeedback treatment. This improvement was maintained over the subsequent years. We highlight the therapeutic potential of biofeedback interventions that enable patients to volitionally control their state of physiological arousal in the management of drug-resistant epilepsy.

Introduction: Chronic intractable temporal lobe epilepsy (TLE) is associated with certain comorbidities including cognitive impairment. A less common condition among patients with TLE is intermittent explosive disorder (IED), a specific form of aggressive behavior that has been linked to low intelligence and structural pathology in the amygdala. We aimed to identify other neuroanatomical substrates of both cognitive dysfunction and IED in patients with TLE, with special focus on the cerebellum, a brain region known to participate in functional networks involved in neuropsychological and affective processes. Methods: Magnetic resonance imaging-based volumetric data from 60 patients with temporal lobe epilepsy (36 with and 24 without IED) were evaluated. Cerebellar, hippocampal, and total brain volumes were processed separately. In a total of 50 patients, the relationship between volumetric measurements and clinical and neuropsychological data (full-scale, verbal, and performance intelligence quotients) was analyzed. Results: Intermittent explosive disorder in patients with TLE was not significantly linked to any of the regional volumes analyzed. However, cognitive performance showed a significant association both with total brain volume and cerebellar volume measurements, whereby the left cerebellar volume showed the strongest association. A deviation from normal cerebellar volumes was related to lower intelligence. Of note, left cerebellar volume was influenced by age and duration of epilepsy. Hippocampal volumes had a minor influence on cognitive parameters. Conclusion: Our findings suggest that cerebellar volume is not linked to IED in patients with TLE but is significantly associated with cognitive dysfunction. Our findings support recent hypotheses proposing that the cerebellum has a relevant functional topography.

The neurobiological basis of psychogenic movement disorders remains poorly understood and the management of these conditions difficult. Functional neuroimaging studies have provided some insight into the pathophysiology of disorders implicating particularly the prefrontal cortex, but there are no studies on psychogenic dystonia, and comparisons with findings in organic counterparts are rare. To understand the pathophysiology of these disorders better, we compared the similarities and differences in functional neuroimaging of patients with psychogenic dystonia and genetically determined dystonia, and tested hypotheses on the role of the prefrontal cortex in functional neurological disorders. Patients with psychogenic (n = 6) or organic (n = 5, DYT1 gene mutation positive) dystonia of the right leg, and matched healthy control subjects (n = 6) underwent positron emission tomography of regional cerebral blood flow. Participants were studied during rest, during fixed posturing of the right leg and during paced ankle movements. Continuous surface electromyography and footplate manometry monitored task performance. Averaging regional cerebral blood flow across all tasks, the organic dystonia group showed abnormal increases in the primary motor cortex and thalamus compared with controls, with decreases in the cerebellum. In contrast, the psychogenic dystonia group showed the opposite pattern, with abnormally increased blood flow in the cerebellum and basal ganglia, with decreases in the primary motor cortex. Comparing organic dystonia with psychogenic dystonia revealed significantly greater regional blood flow in the primary motor cortex, whereas psychogenic dystonia was associated with significantly greater blood flow in the cerebellum and basal ganglia (all P < 0.05, family-wise whole-brain corrected). Group × task interactions were also examined. During movement, compared with rest, there was abnormal activation in the right dorsolateral prefrontal cortex that was common to both organic and psychogenic dystonia groups (compared with control subjects, P < 0.05, family-wise small-volume correction). These data show a cortical-subcortical differentiation between organic and psychogenic dystonia in terms of regional blood flow, both at rest and during active motor tasks. The pathological prefrontal cortical activation was confirmed in, but was not specific to, psychogenic dystonia. This suggests that psychogenic and organic dystonia have different cortical and subcortical pathophysiology, while a derangement in mechanisms of motor attention may be a feature of both conditions.

Introduction On the 23rd May 2008, the American Food and Drug Administration released its analysis on the relationship between anticonvulsant drugs (AEDs) and suicidal behaviors. This was an analysis of data following a request sent to manufacturers of AEDs for data from randomized parallel-arm placebo, low-dose placebo, and active control arm clinical trials. They analyzed data for 11 compounds, the endpoints being a range of behaviors from self-injurious behavior, suicidal ideation, and suicide attempt through to completed suicide. In total 199 placebo-controlled trials consisting of 27 863 patients were collated, and the drugs involved and the key forest plot are shown in Figure 14.1. There were four completed suicides; 0.37% of the drug-treated patients and 0.24% of placebo patients had a suicidal behavior. As a result of this research, the FDA concluded that AEDs were associated with a risk of suicidality, that this was effectively a class effect, and from that point insisted that manufacturers included a warning in their data and information sheets on the potential for suicidality. Epilepsy and suicide There is an association between epilepsy and suicide which had been reviewed in previous communications, including the first edition of this book (Blumer 2004). It is accepted that the risk of suicide is increased in epilepsy, and that in some studies, patients with a temporal lobe focus have the highest risk (Barraclough 1981).

We adapted a generic, individualised, patient-centred quality of life (QOL) assessment technique, the Quality of Life Assessment Schedule (QOLAS) for use with patients with dementia. The QOLAS was administered to a group of patients with mild to moderate dementia alongside a number of other measures of well-being to assess its psychometric properties. Each patient's main carer also completed the QOLAS, giving a proxy rating of the QOL of the patient. The patients understood the interview and were able to describe their quality of life both qualitatively and quantitatively. In this preliminary study the QOLAS was demonstrated to have good validity (content, construct, and criterion) and good internal reliability. The carers rated the patients as having a worse QOL than did the patients themselves on all subdomains of the QOLAS. The results suggest that patients with mild to moderate dementia can rate their own QOL and that the QOLAS is a promising method for assessing QOL in this patient group. The discrepancy between the patients' own views and the views of their carers raises important issues about whether the patient or a proxy is the best judge of QOL in patients with dementia.