Behavioural Effects
behavioural effects
Ebselen: a lithium-mimetic without lithium side-effects?
Development of new medications for mental health conditions is a pressing need given the high proportion of people not responding to available treatments. We hope that presenting ebselen to a wider audience will inspire further studies on this promising agent with a benign side-effects profile. Laboratory research, animal research and human studies suggest that ebselen shares many features with the mood stabilising drug lithium, creating a promise of a drug that would have a similar clinical effect but without lithium’s troublesome side-effect profile and toxicity. Both drugs have a common biological target, inositol monophosphatase, whose inhibition is thought key to lithium’s therapeutic effect. Both drugs have neuroprotective action and reduce oxidative stress. In animal studies, ebselen affected neurotransmitters involved in the development of mental health symptoms, and in particular, produced effects of serotonin function very similar to lithium. Both ebselen and lithium share behavioural effects: antidepressant-like effects in rodent models of depression and decrease in behavioural impulsivity, a property associated with lithium's anti-suicidal action. Human neuropsychological studies support an antidepressant profile for ebselen based on its positive impact on emotional processing and reward seeking. Our group currently is exploring ebselen’s effects in patients with mood disorders. A completed ‘add-on’ clinical trial in mania showed ebselen’s superiority over placebo after three weeks of treatment. Our ongoing experimental research explores ebselen’s antidepressant profile in patients with treatment resistant depression. If successful, this will lead to a clinical trial of ebselen as an antidepressant augmentation agent, similar to lithium.
Time as a continuous dimension in natural and artificial networks
Neural representations of time are central to our understanding of the world around us. I review cognitive, neurophysiological and theoretical work that converges on three simple ideas. First, the time of past events is remembered via populations of neurons with a continuum of functional time constants. Second, these time constants evenly tile the log time axis. This results in a neural Weber-Fechner scale for time which can support behavioral Weber-Fechner laws and characteristic behavioral effects in memory experiments. Third, these populations appear as dual pairs---one type of population contains cells that change firing rate monotonically over time and a second type of population that has circumscribed temporal receptive fields. These ideas can be used to build artificial neural networks that have novel properties. Of particular interest, a convolutional neural network built using these principles can generalize to arbitrary rescaling of its inputs. That is, after learning to perform a classification task on a time series presented at one speed, it successfully classifies stimuli presented slowed down or sped up. This result illustrates the point that this confluence of ideas originating in cognitive psychology and measured in the mammalian brain could have wide-reaching impacts on AI research.