The Descent of Preferences

[A slightly revised version of this paper has been accepted by the BJPS] More attention has been devoted to providing evolutionary scenarios accounting for the development of beliefs, or belief-like states, than for desires or preferences. Here I articulate and defend an evolutionary rationale for the development of psychologically real preference states. Preferences token or represent the expected values of discriminated states, available actions, or action-state pairings. The argument is an application the ‘environmental complexity thesis’ found in Godfrey-Smith and Sterelny, although my conclusions differ from Sterelny’s. I argue that tokening expected utilities can, under specified general conditions, be a powerful design solution to the problem of allocating the capacities of an agent in an efficient way. Preferences are for efficient action selection, and are a ‘fuel for success’ in the sense urged by Godfrey-Smith for true beliefs. They will tend to be favoured by selection when environments are complex in ways that matter to an organism, and when organisms have rich behavioural repertoires with heterogenous returns and costs.   The rationale suggested here is conditional, especially on contingencies in what design options are available to selection and on trade-offs associated with the costs of generating and processing representations of value. The unqualified efficiency rationale for preferences suggests that organisms should represent expected utilities in a comprehensive and consistent way, but none of them do. In the final stages of the paper I consider some of the ways in which design trade-offs compromise the implementation of preferences in organisms that have them

The Evolution of ADHD: A Disorder of Communication?

Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed psychiatric condition. Many believe that the central disability is impaired inhibition, which leads to reduced abilities in social skills, self-control, organization and time management. The behaviors identified by clinicians as problematic-inattention, hyperactivity and impulsivity-have been incorporated into several evolutionary models as selectively adaptive cognitive skills for surviving the challenges of a variable Pleistocene environment. We propose that the disabilities exhibited by individuals with ADHD are maladaptive, and we concur with Barkley that there is a central impairment in the behavioral inhibition system. The underlying neural anatomy and physiology support the possibility that neurotransmitter pathology may have an impact on other interlinked systems (including language), and may also account for the frequent comorbidity of aggression, anxiety, depression, and learning disabilities (many of which are language-related). Language skills compete with other cognitive activities for the attentional system, and thus the evolution of language could not in fact be independent of the evolution of attention. If language represents the ultimate expression of the attentional system, and some individuals with ADHD are seriously impaired in the coordination of interlinked neural systems (including language), then ADHD fits Jerome Wakefield\u27s definition of harmful dysfunction, and communication impairments should be investigated more thoroughly by clinicians

Rhodopsin-mediated light-off-induced protein kinase A activation in mouse rod photoreceptor cells

網膜の知られざる光応答を顕微鏡観察で発見 --光センサー細胞が暗黒に反応した--. 京都大学プレスリリース. 2020-10-14.Detect with PKAchu. 京都大学プレスリリース. 2020-10-30.Light-induced extrasynaptic dopamine release in the retina reduces adenosine 3′, 5′-cyclic monophosphate (cAMP) in rod photoreceptor cells, which is thought to mediate light-dependent desensitization. However, the fine time course of the cAMP dynamics in rods remains elusive due to technical difficulty. Here, we visualized the spatiotemporal regulation of cAMP-dependent protein kinase (PKA) in mouse rods by two-photon live imaging of retinal explants of PKAchu mice, which express a fluorescent biosensor for PKA. Unexpectedly, in addition to the light-on-induced suppression, we observed prominent light-off-induced PKA activation. This activation required photopic light intensity and was confined to the illuminated rods. The estimated maximum spectral sensitivity of 489 nm and loss of the light-off-induced PKA activation in rod-transducin-knockout retinas strongly suggest the involvement of rhodopsin. In support of this notion, rhodopsin-deficient retinal explants showed only the light-on-induced PKA suppression. Taken together, these results suggest that, upon photopic light stimulation, rhodopsin and dopamine signals are integrated to shape the light-off-induced cAMP production and following PKA activation. This may support the dark adaptation of rods

Use of functional neuroimaging and optogenetics to explore deep brain stimulation targets for the treatment of Parkinson's disease and epilepsy

Deep brain stimulation (DBS) is a neurosurgical therapy for Parkinson’s disease and epilepsy. In DBS, an electrode is stereotactically implanted in a specific region of the brain and electrical pulses are delivered using a subcutaneous pacemaker-like stimulator. DBS-therapy has proven to effectively suppress tremor or seizures in pharmaco-resistant Parkinson’s disease and epilepsy patients respectively. It is most commonly applied in the subthalamic nucleus for Parkinson’s disease, or in the anterior thalamic nucleus for epilepsy. Despite the rapidly growing use of DBS at these classic brain structures, there are still non-responders to the treatment. This creates a need to explore other brain structures as potential DBS-targets. However, research in patients is restricted mainly because of ethical reasons. Therefore, in order to search for potential new DBS targets, animal research is indispensable. Previous animal studies of DBS-relevant circuitry largely relied on electrophysiological recordings at predefined brain areas with assumed relevance to DBS therapy. Due to their inherent regional biases, such experimental techniques prevent the identification of less recognized brain structures that might be suitable DBS targets. Therefore, functional neuroimaging techniques, such as functional Magnetic Resonance Imaging and Positron Emission Tomography, were used in this thesis because they allow to visualize and to analyze the whole brain during DBS. Additionally, optogenetics, a new technique that uses light instead of electricity, was employed to manipulate brain cells with unprecedented selectivity

Spatio-temporal Dynamics of the Wnt/beta-catenin Signaling Pathway: A Computational Systems Biology Approach

The Wnt/β-catenin signaling pathway is involved in human neural progenitor cell differentiation. This dissertation employs the cyclic workflow of computational systems biology to investigate the pathway spatio-temporal dynamics during differentiation. Quantitative in vitro analyses show biphasic kinetics of the pathway proteins. A computational model is developed to investigate in silico these kinetics in correlation with cell cycle and self-induced signaling. We show the importance of stochastic approach and suggest further experiments, hence closing the computational systems biology loop

The role of cortical oscillations in a spiking neural network model of the basal ganglia.

Although brain oscillations involving the basal ganglia (BG) have been the target of extensive research, the main focus lies disproportionally on oscillations generated within the BG circuit rather than other sources, such as cortical areas. We remedy this here by investigating the influence of various cortical frequency bands on the intrinsic effective connectivity of the BG, as well as the role of the latter in regulating cortical behaviour. To do this, we construct a detailed neural model of the complete BG circuit based on fine-tuned spiking neurons, with both electrical and chemical synapses as well as short-term plasticity between structures. As a measure of effective connectivity, we estimate information transfer between nuclei by means of transfer entropy. Our model successfully reproduces firing and oscillatory behaviour found in both the healthy and Parkinsonian BG. We found that, indeed, effective connectivity changes dramatically for different cortical frequency bands and phase offsets, which are able to modulate (or even block) information flow in the three major BG pathways. In particular, alpha (8-12Hz) and beta (13-30Hz) oscillations activate the direct BG pathway, and favour the modulation of the indirect and hyper-direct pathways via the subthalamic nucleus-globus pallidus loop. In contrast, gamma (30-90Hz) frequencies block the information flow from the cortex completely through activation of the indirect pathway. Finally, below alpha, all pathways decay gradually and the system gives rise to spontaneous activity generated in the globus pallidus. Our results indicate the existence of a multimodal gating mechanism at the level of the BG that can be entirely controlled by cortical oscillations, and provide evidence for the hypothesis of cortically-entrained but locally-generated subthalamic beta activity. These two findings suggest new insights into the pathophysiology of specific BG disorders

Pharmacogenetics of Non-Motor Symptoms in Parkinson\u27s Disease

Memory deficits are recognized in Parkinson’s disease (PD). The nature of these memory deficits is unclear because few studies have both isolated memory encoding and retrieval processes while testing patients on and off their dopamine replacement medication. Previous work suggests encoding depends upon regions innervated by the ventral tegmental area, which is relatively spared in PD, while retrieval depends upon dorsal striatum, which is dopamine deficient even early in PD. We investigated the impact of a dopamine transporter (DAT1), a dopamine reuptake protein, polymorphism (a 40-base-pair variable repeat affecting expression) on encoding and retrieval in healthy, elderly controls as well as in patients on and off medication. We only found encoding deficits in PD patients who carry a DAT1 polymorphism when on, relative to off, medication, suggesting interactive effects of medication and genotype. We found improvements in memory retrieval in patients who were on, relative to off, medication, but this effect may be independent of DAT1 genotype. This work demonstrates the need for further investigation of interactive effects of medication and genetic profile in PD