The hierarchical organisation of cortical and basal-ganglia systems: a computationally-informed review and integrated hypothesis

To suitably adapt to the challenges posed by reproduction and survival, animals need to learn to select when to perform different behaviours, to have internal criteria for guiding these learning processes, and to perform behaviours efficiently once selected. To implement these processes, their brain must be organised in a suitable hierarchical fashion. Here we briefly review two types of neural/behavioural/computational literatures, focussed respectively on cortex and on sub-cortical areas, and highlight their important limitations. Then we review two computational modelling works of the authors that exemplify the problems, brain areas, experiments, main concepts and limitations of the two research threads. Finally we propose a theoretical integration of the two views, showing how this allows to solve most of the problems found by the two accounts if taken in isolation. The overall picture that emerges is that the cortical and the basal ganglia systems form two highly-organised hierarchical systems working in close synergy and jointly solving all the challenges of choice, selection, and implementation needed to acquire and express adaptive behaviour

Different Dopaminergic Dysfunctions Underlying Parkinsonian Akinesia and Tremor

Although the occurrence of Parkinsonian akinesia and tremor is traditionally associated to dopaminergic degeneration, the multifaceted neural processes that cause these impairments are not fully understood. As a consequence, current dopamine medications cannot be tailored to the specific dysfunctions of patients with the result that generic drug therapies produce different effects on akinesia and tremor. This article proposes a computational model focusing on the role of dopamine impairments in the occurrence of akinesia and resting tremor. The model has three key features, to date never integrated in a single computational system: (a) an architecture constrained on the basis of the relevant known system-level anatomy of the basal ganglia-thalamo-cortical loops; (b) spiking neurons with physiologically-constrained parameters; (c) a detailed simulation of the effects of both phasic and tonic dopamine release. The model exhibits a neural dynamics compatible with that recorded in the brain of primates and humans. Moreover, it suggests that akinesia might involve both tonic and phasic dopamine dysregulations whereas resting tremor might be primarily caused by impairments involving tonic dopamine release and the responsiveness of dopamine receptors. These results could lead to develop new therapies based on a system-level view of the Parkinson's disease and targeting phasic and tonic dopamine in differential ways

Action Observation With Dual Task for Improving Cognitive Abilities in Parkinson's Disease: A Pilot Study

Action observation therapy (AOT) has been recently proposed as a new rehabilitation approach for treatment of motor deficits in Parkinson's disease. To date, this approach has never been used to deal with cognitive deficits (e.g., deficits in working memory, attention), which are impairments that are increasingly recognized in Parkinsonian patients. Typically, patients affected by these dysfunctions have difficulty filtering out irrelevant information and tend to lose track of the task goal. In this paper, we propose that AOT may also be used to improve cognitive abilities of Parkinsonian patients if it is used within a dual task framework. We articulate our hypothesis by pivoting on recent findings and on preliminary results that were obtained through a pilot study that was designed to test the efficacy of a long-term rehabilitation program that, for the first time, uses AOT within a dual task framework for treating cognitive deficits in patients with Parkinson's disease. Ten Parkinson's disease patients underwent a 45-min treatment that consisted in watching a video of an actor performing a daily-life activity and then executing it while performing distractive tasks (AOT with dual task). The treatment was repeated three times per week for a total of 4 weeks. Patients' cognitive/motor features were evaluated through standard tests four times: 1 month before treatment, the first and the last day of treatment and 1 month after treatment. The results show that this approach may provide relevant improvements in cognitive aspects related to working memory (verbal and visuospatial memory) and attention. We discuss these results by pivoting on literature on action observation and recent literature demonstrating that the dual task method can be used to stimulate cognition and concentration. In particular, we propose that using AOT together with a dual task may train the brain systems supporting executive functions through two mechanisms: (i) stimulation of goal setting within the mirror neuron system through action observation and (ii) working memory and persistent goal maintenance through dual task stimuli

Chapter Environmental training of the Italian Coast Guard between tradition and innovation

The Coast Guard is an organization committed to safeguarding the marine environment, that requires specialized personnel. Therefore, it is necessary to integrate the "basic" preparation, with "specialist" training in compliance with the high standards of a Q.M.S. of training, which uses teaching methods advanced, classroom and lessons, case studies, but also practice in the field. The latter methodology plays an important role since learning by doing, even more than theory, guarantees the effectiveness of learning, emotional involvement and the formation of experiential memory of learners

Action Observation With Dual Task for Improving Cognitive Abilities in Parkinson’s Disease: A Pilot Study

Action observation therapy (AOT) has been recently proposed as a new rehabilitation approach for treatment of motor deficits in Parkinson’s disease. To date, this approach has never been used to deal with cognitive deficits (e.g., deficits in working memory, attention), which are impairments that are increasingly recognized in Parkinsonian patients. Typically, patients affected by these dysfunctions have difficulty filtering out irrelevant information and tend to lose track of the task goal. In this paper, we propose that AOT may also be used to improve cognitive abilities of Parkinsonian patients if it is used within a dual task framework. We articulate our hypothesis by pivoting on recent findings and on preliminary results that were obtained through a pilot study that was designed to test the efficacy of a long-term rehabilitation program that, for the first time, uses AOT within a dual task framework for treating cognitive deficits in patients with Parkinson’s disease. Ten Parkinson’s disease patients underwent a 45-min treatment that consisted in watching a video of an actor performing a daily-life activity and then executing it while performing distractive tasks (AOT with dual task). The treatment was repeated three times per week for a total of 4 weeks. Patients’ cognitive/motor features were evaluated through standard tests four times: 1 month before treatment, the first and the last day of treatment and 1 month after treatment. The results show that this approach may provide relevant improvements in cognitive aspects related to working memory (verbal and visuospatial memory) and attention. We discuss these results by pivoting on literature on action observation and recent literature demonstrating that the dual task method can be used to stimulate cognition and concentration. In particular, we propose that using AOT together with a dual task may train the brain systems supporting executive functions through two mechanisms: (i) stimulation of goal setting within the mirror neuron system through action observation and (ii) working memory and persistent goal maintenance through dual task stimuli

Active Inference, homeostatic regulation and adaptive behavioural control

We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference

The promiscuous binding pocket of SLC35A1 ensures redundant transport of CDP-ribitol to the Golgi.

The glycoprotein α-dystroglycan helps to link the intracellular cytoskeleton to the extracellular matrix. A unique glycan structure attached to this protein is required for its interaction with extracellular matrix proteins such as laminin. Up to now, this is the only mammalian glycan known to contain ribitol phosphate groups. Enzymes in the Golgi apparatus use CDP-ribitol to incorporate ribitol phosphate into the glycan chain of α-dystroglycan. Since CDP-ribitol is synthesized in the cytoplasm, we hypothesized that an unknown transporter must be required for its import into the Golgi apparatus. We discovered that CDP-ribitol transport relies on the CMP-sialic acid transporter SLC35A1 and the transporter SLC35A4 in a redundant manner. These two transporters are closely related, but bulky residues in the predicted binding pocket of SLC35A4 limit its size. We hypothesized that the large binding pocket SLC35A1 might accommodate the bulky CMP-sialic acid and the smaller CDP-ribitol, whereas SLC35A4 might only accept CDP-ribitol. To test this, we expressed SLC35A1 with mutations in its binding pocket in SLC35A1 KO cell lines. When we restricted the binding site of SLC35A1 by introducing the bulky residues present in SLC35A4, the mutant transporter was unable to support sialylation of proteins in cells but still supported ribitol phosphorylation. This demonstrates that the size of the binding pocket determines the substrate specificity of SLC35A1, allowing a variety of cytosine nucleotide conjugates to be transported. The redundancy with SLC35A4 also explains why patients with SLC35A1 mutations do not show symptoms of α-dystroglycan deficiency