The impairment of the prefrontal cortex due to high levels of dopamine and norepinephrine in relation to ADHD

Abstract only availableAttention- Deficit/ Hyperactivity Disorder (ADHD) affects many people from various backgrounds; however, not much is known about the disorder aside from clinical symptoms. Researchers are just beginning to dissect ADHD and its effects on the brain, specifically in the prefrontal cortex (PFC) region. The PFC controls attention, motivation, planning, and most importantly working memory. Working memory is temporary storage for short-term memory; it is essential for sequencing tasks and assists with internalized language. The working hypothesis implicates increased levels of Dopamine (DA) and Norepinephrine (NE) in the impairment of PFC cells, leading to inhibition of working memory, and the development of disorder. The interaction of pyramidal neurons in the various layers of the PFC is studied in order to discover the impact of the network level plasticity on the disorder. This interdisciplinary research examines the relative impact of DA and NE, and the relevant pathway interactions on affected cells. Relevant neurophysiological experimentation data is used to examine mechanisms of ADHD in rat PFC, and to develop a computational model of the pyramidal neurons located in the six layers of the PFC. An analysis of the cognitive effects of ADHD via computational modeling may predict brain function, uncover emergent properties, and assist in the development of treatment. Reliable computational modeling will help save money and time as well as avoid the frequent use of human trial subjects.NSF-REU Program in Biosystems Modeling and Analysi

State based model of long-term potentiation and synaptic tagging and capture

Recent data indicate that plasticity protocols have not only synapse-specific but also more widespread effects. In particular, in synaptic tagging and capture (STC), tagged synapses can capture plasticity-related proteins, synthesized in response to strong stimulation of other synapses. This leads to long-lasting modification of only weakly stimulated synapses. Here we present a biophysical model of synaptic plasticity in the hippocampus that incorporates several key results from experiments on STC. The model specifies a set of physical states in which a synapse can exist, together with transition rates that are affected by high- and low-frequency stimulation protocols. In contrast to most standard plasticity models, the model exhibits both early- and late-phase LTP/D, de-potentiation, and STC. As such, it provides a useful starting point for further theoretical work on the role of STC in learning and memory

Searching for plasticity in dissociated cortical cultures on multi-electrode arrays

We attempted to induce functional plasticity in dense cultures of cortical cells using stimulation through extracellular electrodes embedded in the culture dish substrate (multi-electrode arrays, or MEAs). We looked for plasticity expressed in changes in spontaneous burst patterns, and in array-wide response patterns to electrical stimuli, following several induction protocols related to those used in the literature, as well as some novel ones. Experiments were performed with spontaneous culture-wide bursting suppressed by either distributed electrical stimulation or by elevated extracellular magnesium concentrations as well as with spontaneous bursting untreated. Changes concomitant with induction were no larger in magnitude than changes that occurred spontaneously, except in one novel protocol in which spontaneous bursts were quieted using distributed electrical stimulation

Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface

Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). What are the neuronal mechanisms responsible for these changes and how does targeted stimulation by a BBCI shape population-level synaptic connectivity? The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites are strengthened for spike-stimulus delays consistent with experimentally derived spike time dependent plasticity (STDP) rules. However, the relationship between STDP mechanisms at the level of networks, and their modification with neural implants remains poorly understood. Using our model, we successfully reproduces key experimental results and use analytical derivations, along with novel experimental data. We then derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered stimulation in different regimes of cortical activity.Comment: 35 pages, 9 figure

Neuroticism and conscientiousness respectively constrain and facilitate short-term plasticity within the working memory neural network

Individual differences in cognitive efficiency, particularly in relation to working memory (WM), have been associated both with personality dimensions that reflect enduring regularities in brain configuration, and with short-term neural plasticity, that reflects task-related changes in brain connectivity. To elucidate the relationship of these two divergent mechanisms, we tested the hypothesis that personality dimensions, which reflect enduring aspects of brain configuration, inform about the neurobiological framework within which short-term, task-related plasticity, as measured by effective connectivity, can be facilitated or constrained. As WM consistently engages the dorsolateral prefrontal (DLPFC), parietal (PAR), and anterior cingulate cortex (ACC), we specified a WM network model with bidirectional, ipsilateral, and contralateral connections between these regions from a functional magnetic resonance imaging dataset obtained from 40 healthy adults while performing the 3-back WM task. Task-related effective connectivity changes within this network were estimated using Dynamic Causal Modelling. Personality was evaluated along the major dimensions of Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness. Only two dimensions were relevant to task-dependent effective connectivity. Neuroticism and Conscientiousness respectively constrained and facilitated neuroplastic responses within the WM network. These results suggest individual differences in cognitive efficiency arise from the interplay between enduring and short-term plasticity in brain configuration