Bradykinesia models of Parkinson’s disease

This entry describes a plethora of experimental observations from PD bradykinesia in humans and animals ranging across neuronal, electromyographic and behavioral levels and discusses related theoretical and computational models developed to reproduce and explain these findings. Some computational models of bradykinesia have focused entirely on the effects of dopamine depletion in the basal ganglio-thalamo-cortical relations, whereas others emphasize dopamine depletion in cortico-spino-muscular interactions. Future models will have to produce a more comprehensive and detailed neural model of basal ganglia-thalamo-cortico-spino-muscular interactions, in order to study more systematically the effects of dopamine depletion in these nuclei and integrate into a ‘unified theory’ all the known neurophysiological, EMG and behavioral observations associated with parkinsonism

Bradykinesia models of Parkinson’s disease

This entry describes a plethora of experimental observations from PD bradykinesia in humans and animals ranging across neuronal, electromyographic and behavioral levels and discusses related theoretical and computational models developed to reproduce and explain these findings. Some computational models of bradykinesia have focused entirely on the effects of dopamine depletion in the basal ganglio-thalamo-cortical relations, whereas others emphasize dopamine depletion in cortico-spino-muscular interactions. Future models will have to produce a more comprehensive and detailed neural model of basal ganglia-thalamo-cortico-spino-muscular interactions, in order to study more systematically the effects of dopamine depletion in these nuclei and integrate into a ‘unified theory’ all the known neurophysiological, EMG and behavioral observations associated with parkinsonism

Memory processes in medial temporal lobe: experimental, theoretical and computational approaches

The medial temporal lobe (MTL) includes the hippocampus, amygdala and parahippocampal regions, and is crucial for episodic and spatial memory. MTL memory function consists of distinct processes such as encoding, consolidation and retrieval. Encoding is the process by which perceived information is transformed into a memory trace. After encoding, memory traces are stabilized by consolidation. Memory retrieval (recall) refers to the process by which memory traces are reactivated to access information previously encoded and stored in the brain. Although underlying neural mechanisms supporting these distinct functional stages remain largely unknown, recent studies have indicated that distinct oscillatory dynamics, specific neuron types, synaptic plasticity and neuromodulation, play a central role. The theta rhythm is believed to be crucial in the encoding and retrieval of memories. Experimental and computational studies indicate that precise timing of principal cell firing in the hippocampus, relative to the theta rhythm, underlies encoding and retrieval processes. On the other hand, sharp-wave ripples have been implicated in the consolidation through the “replay” of memories in compressed time scales. The neural circuits and cell types supporting memory processes in the MTL areas have only recently been delineated using experimental approaches such as optogenetics, juxtacellular recordings, and optical imaging. Principal (excitatory) cells are crucial for encoding, storing and retrieving memories at the cellular level, whereas inhibitory interneurons provide the temporal structures for orchestrating the activities of neuronal populations of principal cells by regulating synaptic integration and timing of action potential generation of principal cells as well as the generation and maintenance of network oscillations (rhythms). In addition, neuromodulators such as acetylcholine alter dynamical properties of neurons and synapses, and modulate oscillatory state and rules of synaptic plasticity and their levels might tune MTL to specific memory processes. The research topic offers a snapshot of the current state of-the-art on how memories are encoded, consolidated, stored and retrieved in MTL structures. Accepted papers to the research topic include studies (experimental or computational) focusing on the structure and function of neural circuits, their cellular components (principal cell and inhibitory interneurons) and their properties, synaptic plasticity rules involved in these memory processes, network oscillations such as theta, gamma and sharp-wave ripples, and the role of neuromodulators in health and in disease (Alzheimer's disease and schizophrenia)

A Neural Accumulator Model of Antisaccade Performance of Healthy Controls and Obsessive-Compulsive Disorder Patients

Antisaccade performance in obsessive-compulsive disorder (OCD) is related to a dysfunctional network of brain structures including the (pre)frontal and posterior parietal cortices, basal ganglia, and superior colliculus. Previously recorded antisaccade performance of healthy and OCD subjects is re-analyzed to show greater variability in mean latency and variance of corrected antisaccades as well as in shape of antisaccade and corrected antisaccade latency distributions and increased error rates of OCD patients relative to healthy participants. Then a well-established neural accumulator model of antisaccade performance is employed to uncover the mechanisms giving rise to these observed OCD deficits. The model shows: i) increased variability in latency distributions of OCD patients is due to a more noisy accumulation of information by both correct and erroneous decision signals; (ii) OCD patients are almost as confident about their decisions as healthy controls; iii) competition via local lateral inhibition between the correct and erroneous decision processes, and not a third top-down STOP signal of the erroneous response, accounts for both the antisaccade performance of healthy controls and OCD patients

Neural competition via lateral inhibition between decision processes and not a STOP signal accounts for the antisaccade performance in healthy and schizophrenia subjects

A commentary on Re-starting a neural race: anti-saccade correction by Noorani, I., and Carpenter, R. H. S. (2014). Eur. J. Neurosci. 39, 159–164. doi: 10.1111/ejn.12396 Decision making is the process of accumulating evidence about the world and the utility of possible outcomes (Cutsuridis, 2010). A paradigm often used by behavioral neuroscientists to investigate decision processes is the antisaccade paradigm (see Figure 1A; Hallett, 1978). In the antisaccade paradigm subjects are required to suppress an erroneous saccade (error prosaccade) toward a peripheral stimulus and instead make an eye movement to a position in the opposite hemifield (antisaccade). The response repertoire of a subject performing the antisaccade task has been reported to be: (1) the subject makes an erroneous response (i.e., looking toward the peripheral stimulus), (2) the subject makes the antisaccade (i.e., looking in the opposite direction of the peripheral stimulus, and (3) the subject makes an erroneous response followed by a corrected antisaccade (Evdokimidis et al., 2002)

Action Potential Bursts Modulate the NMDA-R Mediated Spike Timing Dependent Plasticity in a Biophysical Model

Spike timing dependent plasticity (STDP) requires the temporal association of presynaptic and postsynaptic action potentials (APs). However, some synapses in the CA1 region of the hippocampus are suprisingle unreliable at signaling the arrival of single spikes to the postsynaptic neuron [4]. In such unreliable synapses pairing of excitatory postsynaptic potentials (EPSPs) and single APs at low frequencies is ineffective at generating plasticity [2], [3]. A recent computational study [7] has shown that the shape of the STDP curve strongly depends on the burst interspike interval in the presence/absence of inhibition when a presynaptic dendritic burst and a postsynaptic somatic spike were paired together. In this study, we investigate via computer simulations the conditions under which STDP is affected when now a high frequency somatic burst instead of a single spike is paired with another dendritic spike. We show that during such pairing conditions in the absence of inhibition a symmetric STDP profile with a distinct positive LTP region is evident at 10-30ms interstimulus interval and flat LTD tails at all other interstimulus intervals. The symmetry is preserved at all burst interspike intervals. When inhibition is present, the STDP profile shape into a Mexican hat shaped one or an inverted symmetrical one with flat LTP tails

Cognitive Models of the Perception-Action Cycle: A View from the Brain

Perception-action cycle is the circular flow of information that takes place between an organism and its environment in the course of a sensory-guided sequence of actions towards a goal. Each action causes changes in the environment which are processed by the organism’s sensory hierarchy and lead to the generation of further action by its motor effectors. These actions cause new changes that are sensory analyzed and lead to a new action, and so the cycle continues. The efficient and timely coordination of the sensory and motor structures involved will ensure the organism’s survival in a dynamic environment. Two brain inspired cognitive models of the perception-action cycle are presented in this paper: (1) A cognitive model of visual saliency, overt attention and active visual search, and (2) A cognitive model of visuo-motor coordination of reaching and grasping. Both models are multi-modular. They share a number of features (visual saliency, focus of attention, recognition, expectation, resonance, value attribution), while at the same time have distinct properties

Demonstration of a Literature Based Discovery System based on Ontologies, Semantic Filters and Word Embeddings for the Raynaud Disease-Fish Oil Rediscovery

A novel literature-based discovery system based on UMLS Ontologies, Semantic Filters, Statistics, and Word Embeddings was developed and validated against the well-established Raynaud’s disease – Fish Oil discovery by mining different size and specificity corpora of Pubmed titles and abstracts. Results show an ‘inverse effect’ between open versus closed discovery search modes. In open discovery, a more general and bigger corpus (Vascular disease or Perivascular disease) produces better results than a more specific and smaller in size corpus (Raynaud disease), whereas in closed discovery, the exact opposite is true

Dynamics and function of a CA1 model of the hippocampus during theta and ripples

The hippocampus is known to be involved in spatial learning in rats. Spatial learning involves the encoding and replay of temporally sequenced spatial information. Temporally sequenced spatial memories are encoded and replayed by the firing rate and phase of pyramidal cells and inhibitory interneurons with respect to ongoing network oscillations (theta and ripples). Understanding how the different hippocampal neuronal classes interact during these encoding and replay processes is of great importance. A computational model of the CA1 microcircuit [3], [4], [5] that uses biophysical representations of the major cell types, including pyramidal cells and four types of inhibitory interneurons is extended to address: (1) How are the encoding and replay (forward and reverse) of behavioural place sequences controlled in the CA1 microcircuit during theta and ripples? and (2) What roles do the various types of inhibitory interneurons play in these processes