Medical hypotheses
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Among the basal ganglia nuclei, the subthalamic nucleus has a major function in the motor cortico-basal ganglia-thalamo-cortical circuit and is a target site for neurosurgical treatment such as parkinsonian patients with long-term motor fluctuations and dyskinesia. According to animal and human studies, the motor functions of the subthalamic nucleus have been well documented whereas its implication on limbic functions is still less well understood and is only partially explained by anatomical and functional theories of basal ganglia organisation. After chronic subthalamic nucleus stimulation in patients with Parkinson's disease, many studies showed executive impairments, apathy, depression, hypomania, and impairment of recognition of negative facial emotions. ⋯ We propose a new function scheme of the limbic system, establishing connections between limbic cortical structures (medial prefrontal cortex, amygdala and hippocampus) and the limbic part of the basal ganglia. This new circuit could be composed of a minor part based on the model of cortico-basal ganglia-thalamo-cortical loop, and of a major part linking the subthalamic nucleus with the mesolimbic dopaminergic pathway via the ventral tegmental area and the nucleus accumbens, and with limbic cortical structures. This scheme could explain limbic impairments after subthalamic nucleus stimulation by disruption of limbic information inside the subthalamic nucleus and the ventral tegmental area.
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I have come to believe that science depends for its long-term success on an explicit and pervasive pursuit of the ideal of transcendental truth. 'Transcendental' implies that a value is ideal and ultimate - it is aimed-at but can only imperfectly be known, achieved or measured. So, transcendental truth is located outside of science; beyond scientific methods, processes and peer consensus. Although the ultimate scientific authority of a transcendental value of truth was a view held almost universally by the greatest scientists throughout recorded history, modern science has all-but banished references to truth from professional scientific discourse - these being regarded as wishful, mystical and embarrassing at best, and hypocritical or manipulative at worst. ⋯ Ultimately, science should be conducted at every level, from top to bottom, on the basis of what Bronowski termed the 'habit of truth'. Such a situation currently seems remote and fanciful. But within living memory, routine truthfulness and truth-seeking were simply facts of scientific life - taken for granted among real scientists.
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Comment Letter Historical Article
Comment on Malloy (2008) "James Watson tells the inconvenient truth: faces the consequences".
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why are so many leading modern scientists so dull and lacking in scientific ambition? ⋯ because the science selection process ruthlessly weeds-out interesting and imaginative people. At each level in education, training and career progression there is a tendency to exclude smart and creative people by preferring Conscientious and Agreeable people. The progressive lengthening of scientific training and the reduced independence of career scientists have tended to deter vocational 'revolutionary' scientists in favour of industrious and socially adept individuals better suited to incremental 'normal' science. High general intelligence (IQ) is required for revolutionary science. But educational attainment depends on a combination of intelligence and the personality trait of Conscientiousness; and these attributes do not correlate closely. Therefore elite scientific institutions seeking potential revolutionary scientists need to use IQ tests as well as examination results to pick-out high IQ 'under-achievers'. As well as high IQ, revolutionary science requires high creativity. Creativity is probably associated with moderately high levels of Eysenck's personality trait of 'Psychoticism'. Psychoticism combines qualities such as selfishness, independence from group norms, impulsivity and sensation-seeking; with a style of cognition that involves fluent, associative and rapid production of many ideas. But modern science selects for high Conscientiousness and high Agreeableness; therefore it enforces low Psychoticism and low creativity. Yet my counter-proposal to select elite revolutionary scientists on the basis of high IQ and moderately high Psychoticism may sound like a recipe for disaster, since resembles a formula for choosing gifted charlatans and confidence tricksters. A further vital ingredient is therefore necessary: devotion to the transcendental value of Truth. Elite revolutionary science should therefore be a place that welcomes brilliant, impulsive, inspired, antisocial oddballs - so long as they are also dedicated truth-seekers.
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Medical management and drug development for epilepsy emphasizes increasing pharmacological specificity to improve efficacy while minimizing side effects. However, growing evidence supports potential benefits of "magic shotgun" over "magic bullet" approaches to treatment of complex disease processes. We discuss experimental and theoretical evidence suggesting that seizures may be more amenable to a multi-target rather than a high-specificity approach, including evidence that individual anticonvulsants directly modulate a variety ion channel targets, the most direct determinants of neuronal excitability. Although the relevance of this promiscuity remains untested, it may contribute to anticonvulsant efficacy and should therefore be considered in drug development strategies and in therapeutic decision making.