David M Devilbiss - Academia.edu (original) (raw)
Papers by David M Devilbiss
<p><b>A</b>) Schematic of the T-Maze. On each trial, animals were placed in the... more <p><b>A</b>) Schematic of the T-Maze. On each trial, animals were placed in the start box (red) by the experimenter for a delay interval. The retaining gate was removed and the animal traveled to the branch point and revealed the choice to enter either arm (grey). Reward was then offered by the experimenter within the reward zone (cyan) if the arm opposite to the spatial location of last arm entered was chosen. Following reward or an incorrect choice, the animal was picked up by the experimenter and returned to the start box for a subsequent trial. <b>Inset</b> illustrates the video tracked path of a rat during one recording session. NOTE: paths crossing the T-maze from Pickup to Start Box reflect relocating the animal by the experimenter (right handed). <b>B</b>) Bar graph quantifying performance in the T-maze task during baseline and acute noise stress (93 db) conditions. n = 5; **p<0.01. <b>C</b>) 40× photomicrograph illustrating the final placement of one of eight microwires in layer V of the <sub>pl</sub>PFC (Arrow Tip; CC, corpus callosum; <sub>pl</sub>PFC, prelimbic PFC). <b>D</b>) Action potential waveforms of 5 discriminated and validated <sub>pl</sub>PFC neurons. Waveform width = 450 µs. Waveforms from these units exhibited separable clusters when plotted in principal component space (inset). Sorted spiking activity with unsorted activity is presented in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002681#pcbi.1002681.s001" target="_blank">Fig. S1</a>. The cyan colored neuron represents the characteristic WS-type neuron. <b>E</b>) Timeline of behavioral training and testing. Details of a single testing day are shown beginning at 8:00 AM.</p
<p>Plot of 80 seconds of spike train data, spanning three trials and fit with a GLM using (... more <p>Plot of 80 seconds of spike train data, spanning three trials and fit with a GLM using (<b>A</b>) a homogeneous Poisson model, (<b>B</b>) an inhomogeneous Poisson model, and (<b>C</b>) an a conditional intensity model (Model 1b, during baseline conditions only). Spike counts of the original spike train are plotted with black dots against lambda (<i>λ</i>; green line with red confidence intervals). X-axis = experimental time. <b>D</b>) Kolmogorov–Smirnov (K-S) goodness-of-fit plot demonstrates that incorporation of spike history improves performance of the CI-GLM (blue vs. green line). The K-S plot of the final model (blue line; model from panel C) falls within equivalency confidence intervals of the K-S test (diagonal solid and dotted lines) for all quantiles, indicating that inclusion of spike history with behavioral intervals in the CI-GLM is critical to appropriately model <sub>pl</sub>PFC spiking activity. Inhomogeneous Poisson models using solely the behavioral states of the task overestimate neuron interspike intervals (green line; model from panel B). Models of neuronal activity (1–3; main text) also passed K-S goodness-of-fit tests (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002681#pcbi.1002681.s003" target="_blank">Fig. S3</a>).</p
<p><b>A</b>) Spiking gain (rate-ratio exp<i><sup>α,η</sup><... more <p><b>A</b>) Spiking gain (rate-ratio exp<i><sup>α,η</sup></i>) measures of the contribution of spike history at different points back in time for a small (n = 50) ensemble of neurons. The SHPD gain of one exemplar neuron is highlighted. <b>B</b>) SHPD gain at different points back in time decay exponentially under baseline and stress conditions (Model 1a). Described in the main text, stress produced an overall reduction in SHPD gains (inset; *p<0.005), but did not significantly alter the decay of gains at any spike history time bin. <b>C</b>) Schematic of recurrent pathways within the PFC of connectivity within layers II/III or V as well as connectivity between II/III and V represents one putative mechanism supporting SHPD. Adopted from: <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002681#pcbi.1002681-Gabbott1" target="_blank">[72]</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002681#pcbi.1002681-Zhang1" target="_blank">[74]</a>.</p
ADHD attention deficit hyperactivity disorder A, L, V anterior, lateral, ventral
Neurology, 2016
Objective: Evaluate the predictive accuracy of the Borealis neurodiagnostic platform in its abili... more Objective: Evaluate the predictive accuracy of the Borealis neurodiagnostic platform in its ability to detect sports concussion in collegiate athletes. Background: Non-invasive biomarkers are emerging as essential tools as diagnostic aids to primary care physicians and neurologists. Static imaging (MRI/PET/SPECT) and fluid based (blood and CSF) biomarkers are limited in their ability to capture the inherent dynamics of brain physiology. The present study evaluates a telemetric EEG during a series of cognitive tasks to assess test-retest reliability of this approach, classify injured athletes, and collect longitudinal data during recovery. Methods: Recent advances in wireless EEG hardware have enabled Cerora to develop a novel activated EEG system (Cerora BorealisTM) to focus the physiological assessment of brain health while activating various neural circuits during cognitive tasks. In a 3 year study, baselines scans consisting of 16 tasks were conducted on N=274 varsity athletes. L...
Neurology, 2016
Objective: Determine the degree to which acute moderate exercise impacts performance in several c... more Objective: Determine the degree to which acute moderate exercise impacts performance in several concussion assessment tools and electrocortical measures of cognitive function used in the detection of concussion. Background: The effects of acute exercise on cognitive function are dependent on a number of factors, including the assessment type, exercise intensity, and recovery time before testing. Recently, emphasis is being placed on using cognitive assessment tools before and after injury in athletes, however little empirical evidence exists on the influence of exercise on these measures. Methods: A gender-balanced cohort (N=8 /gender) was assessed with a single channel telemetric EEG recording device and cognitive test battery (Cerora Borealis, Cerora Inc.) immediately before and after moderate exercise (1-mile run). Heart rate and arterial oxygen levels were collected to control for the level of exertion. Results: We provide novel evidence that moderate exercise modestly improves ...
Journal of Healthcare Engineering, 2019
A variety of cognitive assessment tools are used to determine the functional status of the brain ... more A variety of cognitive assessment tools are used to determine the functional status of the brain before and after injury in athletes. Questionnaires, neuropsychological tests, and electroencephalographic (EEG) measures have been recently used to directly assess brain function on and near the playing field. However, exercise can affect cognitive performance and EEG measures of cortical activity. To date, little empirical evidence exists on the effects of acute exercise on these measures of neurological function. We therefore quantified athlete performance on a standardized battery of concussion assessment tools and EEG measurements immediately before and after acute exercise to simulate conditions of athletic competition. Heart rate and arterial oxygen levels were collected before and after the exercise challenge consisting of a 1-mile run. Together these data, from a gender-balanced cohort of collegiate athletes, demonstrated that moderate to hard levels of acute exercise improved p...
Brain Research, 2019
Flexible and adaptive behaviors have evolved with increasing complexity and numbers of neuromodul... more Flexible and adaptive behaviors have evolved with increasing complexity and numbers of neuromodulator systems. The neuromodulatory locus coeruleus-norepinephrine (LC-NE) system is central to regulating cognitive function in a behaviorally-relevant and arousal-dependent manner. Through its nearly ubiquitous efferent projections, the LC-NE system acts to modulate neuron function on a cell-by-cell basis and exert a spectrum of actions across different brain regions to optimize target circuit function. As LC neuron activity, NE signaling, and arousal level increases, cognitive performance improves over an inverted-U shaped curve. Additionally, LC neurons burst phasically in relation to novel or salient sensory stimuli and top-down decision-or response-related processes. Together, the variety of LC activity patterns and complex actions of the LC-NE system indicate that the LC-NE system may dynamically regulate function of target neural circuits. The manner in which neural networks encode, represent, and perform neurocomputations continue to be revealed. This has improved our ability to understand the optimization of neural circuits by NE and generate flexible and adaptive goal-directed behaviors. In this review, the rat vibrissa somatosensory system is explored as a model neural circuit to bridge known modulatory actions of NE and changes in cognitive function. It is argued that fluid transitions between neural computational states, reflect the ability of this sensory system to shift between two principal functions: detection of novel or salient sensory information and detailed descriptions of sensory information. Such flexibility in circuit function is likely critical for producing context-appropriate sensory signal processing. Nonetheless, many challenges remain including providing a causal link between NE mediated changes in sensory neural coding and perceptual changes, as well as extending these principles to higher cognitive functions including behavioral flexibility and decision making.
The Journal of Neuroscience, 2019
The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-... more The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRFdependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction.
Medicine & Science in Sports & Exercise, 2015
Cerebral cortex (New York, N.Y. : 1991), May 25, 2016
Stress, pervasive in modern society, impairs prefrontal cortex (PFC)-dependent cognitive processe... more Stress, pervasive in modern society, impairs prefrontal cortex (PFC)-dependent cognitive processes, an action implicated in multiple psychopathologies and estimated to contribute to nearly half of all work place accidents. However, the neurophysiological bases for stress-related impairment of PFC-dependent function remain poorly understood. The current studies examined the effects of stress on PFC neural coding during a working memory task in rats. Stress suppressed responses of medial PFC (mPFC) neurons strongly tuned to a diversity of task events, including delay and outcome (reward, error). Stress-related impairment of task-related neuronal activity included multidimensional coding by PFC neurons, an action that significantly predicted cognitive impairment. Importantly, the effects of stress on PFC neuronal signaling were highly conditional on tuning strength: stress increased task-related activity in the larger population of PFC neurons weakly tuned to task events. Combined, str...
Technometrics, 2016
Identifying the network structure of a neuron ensemble beyond the standard measure of pairwise co... more Identifying the network structure of a neuron ensemble beyond the standard measure of pairwise correlations is critical for understanding how information is transferred within such a neural population. However, the spike train data pose significant challenges to conventional statistical methods due to not only the complexity, massive size, and large scale, but also high dimensionality. In this article, we propose a novel "structural information enhanced" (SIE) regularization method for estimating the conditional intensities under the generalized linear model (GLM) framework to better capture the functional connectivity among neurons. We study the consistency of parameter estimation of the proposed method. A new "accelerated full gradient update" algorithm is developed to efficiently handle the complex penalty in the SIE-GLM for large sparse datasets applicable to spike train data. Simulation results indicate that our proposed method outperforms existing approaches. An application of the proposed method to a real spike train dataset, obtained from the prelimbic region of the prefrontal cortex of adult male rats when performing a T-maze based delayed-alternation task of working memory, provides some insight into the neuronal network in that region.
Catecholamine Research in the 21st Century, 2014
Frontiers in Neuroscience, 2002
Current Opinion in Neurobiology, 2004
Although the presence of neuromodulators in mammalian sensory systems has been noted for some tim... more Although the presence of neuromodulators in mammalian sensory systems has been noted for some time, a groundswell of evidence has now begun to document the scope of these regulatory mechanisms in several sensory systems, highlighting the importance of neuromodulation in shaping feature extraction at all levels of neural processing. The emergence of more sophisticated models of sensory encoding and of the interaction between sensory and regulatory regions of the brain will challenge sensory neurobiologists to further incorporate a concept of sensory network function that is contingent on neuromodulatory and behavioral state.
Biochemical Pharmacology, 2011
Electroencephalography (EEG) and related methodologies offer the promise of predicting the likeli... more Electroencephalography (EEG) and related methodologies offer the promise of predicting the likelihood that novel therapies and compounds will exhibit clinical efficacy early in preclinical development. These analyses, including quantitative EEG (e.g. brain mapping) and evoked/event-related potentials (EP/ERP), can provide a physiological endpoint that may be used to facilitate drug discovery, optimize lead or candidate compound selection, as well as afford patient stratification and Go/No-Go decisions in clinical trials. Currently, the degree to which these different methodologies hold promise for translatability between preclinical models and the clinic have not been well summarized. To address this need, we review well-established and emerging EEG analytic approaches that are currently being integrated into drug discovery programs throughout preclinical development and clinical research. Furthermore, we present the use of EEG in the drug development process in the context of a number of major central nervous system disorders including Alzheimer's disease, schizophrenia, depression, attention deficit hyperactivity disorder, and pain. Lastly, we discuss the requirements necessary to consider EEG technologies as a biomarker. Many of these analyses show considerable translatability between species and are used to predict clinical efficacy from preclinical data. Nonetheless, the next challenge faced is the selection and validation of EEG endpoints that provide a set of robust and translatable biomarkers bridging preclinical and clinical programs.
Alzheimer's & Dementia, 2013
and might be due to increased vulnerability of their memory networks. Conclusions: The higher abs... more and might be due to increased vulnerability of their memory networks. Conclusions: The higher absolute power of upper alpha in resting EEG and the increased upper alpha desynchronization during cognitive task in non-demented older individuals carrying AD risk variant CLU CC implies unfavorable effect of this genotype on brain cholinergic pathways and hippocampus long before the presumable dementia. The results suggest that the neurophysiological markers may be important in monitoring disease progression in at-risk elderly.
<p><b>A</b>) Schematic of the T-Maze. On each trial, animals were placed in the... more <p><b>A</b>) Schematic of the T-Maze. On each trial, animals were placed in the start box (red) by the experimenter for a delay interval. The retaining gate was removed and the animal traveled to the branch point and revealed the choice to enter either arm (grey). Reward was then offered by the experimenter within the reward zone (cyan) if the arm opposite to the spatial location of last arm entered was chosen. Following reward or an incorrect choice, the animal was picked up by the experimenter and returned to the start box for a subsequent trial. <b>Inset</b> illustrates the video tracked path of a rat during one recording session. NOTE: paths crossing the T-maze from Pickup to Start Box reflect relocating the animal by the experimenter (right handed). <b>B</b>) Bar graph quantifying performance in the T-maze task during baseline and acute noise stress (93 db) conditions. n = 5; **p<0.01. <b>C</b>) 40× photomicrograph illustrating the final placement of one of eight microwires in layer V of the <sub>pl</sub>PFC (Arrow Tip; CC, corpus callosum; <sub>pl</sub>PFC, prelimbic PFC). <b>D</b>) Action potential waveforms of 5 discriminated and validated <sub>pl</sub>PFC neurons. Waveform width = 450 µs. Waveforms from these units exhibited separable clusters when plotted in principal component space (inset). Sorted spiking activity with unsorted activity is presented in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002681#pcbi.1002681.s001" target="_blank">Fig. S1</a>. The cyan colored neuron represents the characteristic WS-type neuron. <b>E</b>) Timeline of behavioral training and testing. Details of a single testing day are shown beginning at 8:00 AM.</p
<p>Plot of 80 seconds of spike train data, spanning three trials and fit with a GLM using (... more <p>Plot of 80 seconds of spike train data, spanning three trials and fit with a GLM using (<b>A</b>) a homogeneous Poisson model, (<b>B</b>) an inhomogeneous Poisson model, and (<b>C</b>) an a conditional intensity model (Model 1b, during baseline conditions only). Spike counts of the original spike train are plotted with black dots against lambda (<i>λ</i>; green line with red confidence intervals). X-axis = experimental time. <b>D</b>) Kolmogorov–Smirnov (K-S) goodness-of-fit plot demonstrates that incorporation of spike history improves performance of the CI-GLM (blue vs. green line). The K-S plot of the final model (blue line; model from panel C) falls within equivalency confidence intervals of the K-S test (diagonal solid and dotted lines) for all quantiles, indicating that inclusion of spike history with behavioral intervals in the CI-GLM is critical to appropriately model <sub>pl</sub>PFC spiking activity. Inhomogeneous Poisson models using solely the behavioral states of the task overestimate neuron interspike intervals (green line; model from panel B). Models of neuronal activity (1–3; main text) also passed K-S goodness-of-fit tests (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002681#pcbi.1002681.s003" target="_blank">Fig. S3</a>).</p
<p><b>A</b>) Spiking gain (rate-ratio exp<i><sup>α,η</sup><... more <p><b>A</b>) Spiking gain (rate-ratio exp<i><sup>α,η</sup></i>) measures of the contribution of spike history at different points back in time for a small (n = 50) ensemble of neurons. The SHPD gain of one exemplar neuron is highlighted. <b>B</b>) SHPD gain at different points back in time decay exponentially under baseline and stress conditions (Model 1a). Described in the main text, stress produced an overall reduction in SHPD gains (inset; *p<0.005), but did not significantly alter the decay of gains at any spike history time bin. <b>C</b>) Schematic of recurrent pathways within the PFC of connectivity within layers II/III or V as well as connectivity between II/III and V represents one putative mechanism supporting SHPD. Adopted from: <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002681#pcbi.1002681-Gabbott1" target="_blank">[72]</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002681#pcbi.1002681-Zhang1" target="_blank">[74]</a>.</p
ADHD attention deficit hyperactivity disorder A, L, V anterior, lateral, ventral
Neurology, 2016
Objective: Evaluate the predictive accuracy of the Borealis neurodiagnostic platform in its abili... more Objective: Evaluate the predictive accuracy of the Borealis neurodiagnostic platform in its ability to detect sports concussion in collegiate athletes. Background: Non-invasive biomarkers are emerging as essential tools as diagnostic aids to primary care physicians and neurologists. Static imaging (MRI/PET/SPECT) and fluid based (blood and CSF) biomarkers are limited in their ability to capture the inherent dynamics of brain physiology. The present study evaluates a telemetric EEG during a series of cognitive tasks to assess test-retest reliability of this approach, classify injured athletes, and collect longitudinal data during recovery. Methods: Recent advances in wireless EEG hardware have enabled Cerora to develop a novel activated EEG system (Cerora BorealisTM) to focus the physiological assessment of brain health while activating various neural circuits during cognitive tasks. In a 3 year study, baselines scans consisting of 16 tasks were conducted on N=274 varsity athletes. L...
Neurology, 2016
Objective: Determine the degree to which acute moderate exercise impacts performance in several c... more Objective: Determine the degree to which acute moderate exercise impacts performance in several concussion assessment tools and electrocortical measures of cognitive function used in the detection of concussion. Background: The effects of acute exercise on cognitive function are dependent on a number of factors, including the assessment type, exercise intensity, and recovery time before testing. Recently, emphasis is being placed on using cognitive assessment tools before and after injury in athletes, however little empirical evidence exists on the influence of exercise on these measures. Methods: A gender-balanced cohort (N=8 /gender) was assessed with a single channel telemetric EEG recording device and cognitive test battery (Cerora Borealis, Cerora Inc.) immediately before and after moderate exercise (1-mile run). Heart rate and arterial oxygen levels were collected to control for the level of exertion. Results: We provide novel evidence that moderate exercise modestly improves ...
Journal of Healthcare Engineering, 2019
A variety of cognitive assessment tools are used to determine the functional status of the brain ... more A variety of cognitive assessment tools are used to determine the functional status of the brain before and after injury in athletes. Questionnaires, neuropsychological tests, and electroencephalographic (EEG) measures have been recently used to directly assess brain function on and near the playing field. However, exercise can affect cognitive performance and EEG measures of cortical activity. To date, little empirical evidence exists on the effects of acute exercise on these measures of neurological function. We therefore quantified athlete performance on a standardized battery of concussion assessment tools and EEG measurements immediately before and after acute exercise to simulate conditions of athletic competition. Heart rate and arterial oxygen levels were collected before and after the exercise challenge consisting of a 1-mile run. Together these data, from a gender-balanced cohort of collegiate athletes, demonstrated that moderate to hard levels of acute exercise improved p...
Brain Research, 2019
Flexible and adaptive behaviors have evolved with increasing complexity and numbers of neuromodul... more Flexible and adaptive behaviors have evolved with increasing complexity and numbers of neuromodulator systems. The neuromodulatory locus coeruleus-norepinephrine (LC-NE) system is central to regulating cognitive function in a behaviorally-relevant and arousal-dependent manner. Through its nearly ubiquitous efferent projections, the LC-NE system acts to modulate neuron function on a cell-by-cell basis and exert a spectrum of actions across different brain regions to optimize target circuit function. As LC neuron activity, NE signaling, and arousal level increases, cognitive performance improves over an inverted-U shaped curve. Additionally, LC neurons burst phasically in relation to novel or salient sensory stimuli and top-down decision-or response-related processes. Together, the variety of LC activity patterns and complex actions of the LC-NE system indicate that the LC-NE system may dynamically regulate function of target neural circuits. The manner in which neural networks encode, represent, and perform neurocomputations continue to be revealed. This has improved our ability to understand the optimization of neural circuits by NE and generate flexible and adaptive goal-directed behaviors. In this review, the rat vibrissa somatosensory system is explored as a model neural circuit to bridge known modulatory actions of NE and changes in cognitive function. It is argued that fluid transitions between neural computational states, reflect the ability of this sensory system to shift between two principal functions: detection of novel or salient sensory information and detailed descriptions of sensory information. Such flexibility in circuit function is likely critical for producing context-appropriate sensory signal processing. Nonetheless, many challenges remain including providing a causal link between NE mediated changes in sensory neural coding and perceptual changes, as well as extending these principles to higher cognitive functions including behavioral flexibility and decision making.
The Journal of Neuroscience, 2019
The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-... more The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRFdependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction.
Medicine & Science in Sports & Exercise, 2015
Cerebral cortex (New York, N.Y. : 1991), May 25, 2016
Stress, pervasive in modern society, impairs prefrontal cortex (PFC)-dependent cognitive processe... more Stress, pervasive in modern society, impairs prefrontal cortex (PFC)-dependent cognitive processes, an action implicated in multiple psychopathologies and estimated to contribute to nearly half of all work place accidents. However, the neurophysiological bases for stress-related impairment of PFC-dependent function remain poorly understood. The current studies examined the effects of stress on PFC neural coding during a working memory task in rats. Stress suppressed responses of medial PFC (mPFC) neurons strongly tuned to a diversity of task events, including delay and outcome (reward, error). Stress-related impairment of task-related neuronal activity included multidimensional coding by PFC neurons, an action that significantly predicted cognitive impairment. Importantly, the effects of stress on PFC neuronal signaling were highly conditional on tuning strength: stress increased task-related activity in the larger population of PFC neurons weakly tuned to task events. Combined, str...
Technometrics, 2016
Identifying the network structure of a neuron ensemble beyond the standard measure of pairwise co... more Identifying the network structure of a neuron ensemble beyond the standard measure of pairwise correlations is critical for understanding how information is transferred within such a neural population. However, the spike train data pose significant challenges to conventional statistical methods due to not only the complexity, massive size, and large scale, but also high dimensionality. In this article, we propose a novel "structural information enhanced" (SIE) regularization method for estimating the conditional intensities under the generalized linear model (GLM) framework to better capture the functional connectivity among neurons. We study the consistency of parameter estimation of the proposed method. A new "accelerated full gradient update" algorithm is developed to efficiently handle the complex penalty in the SIE-GLM for large sparse datasets applicable to spike train data. Simulation results indicate that our proposed method outperforms existing approaches. An application of the proposed method to a real spike train dataset, obtained from the prelimbic region of the prefrontal cortex of adult male rats when performing a T-maze based delayed-alternation task of working memory, provides some insight into the neuronal network in that region.
Catecholamine Research in the 21st Century, 2014
Frontiers in Neuroscience, 2002
Current Opinion in Neurobiology, 2004
Although the presence of neuromodulators in mammalian sensory systems has been noted for some tim... more Although the presence of neuromodulators in mammalian sensory systems has been noted for some time, a groundswell of evidence has now begun to document the scope of these regulatory mechanisms in several sensory systems, highlighting the importance of neuromodulation in shaping feature extraction at all levels of neural processing. The emergence of more sophisticated models of sensory encoding and of the interaction between sensory and regulatory regions of the brain will challenge sensory neurobiologists to further incorporate a concept of sensory network function that is contingent on neuromodulatory and behavioral state.
Biochemical Pharmacology, 2011
Electroencephalography (EEG) and related methodologies offer the promise of predicting the likeli... more Electroencephalography (EEG) and related methodologies offer the promise of predicting the likelihood that novel therapies and compounds will exhibit clinical efficacy early in preclinical development. These analyses, including quantitative EEG (e.g. brain mapping) and evoked/event-related potentials (EP/ERP), can provide a physiological endpoint that may be used to facilitate drug discovery, optimize lead or candidate compound selection, as well as afford patient stratification and Go/No-Go decisions in clinical trials. Currently, the degree to which these different methodologies hold promise for translatability between preclinical models and the clinic have not been well summarized. To address this need, we review well-established and emerging EEG analytic approaches that are currently being integrated into drug discovery programs throughout preclinical development and clinical research. Furthermore, we present the use of EEG in the drug development process in the context of a number of major central nervous system disorders including Alzheimer's disease, schizophrenia, depression, attention deficit hyperactivity disorder, and pain. Lastly, we discuss the requirements necessary to consider EEG technologies as a biomarker. Many of these analyses show considerable translatability between species and are used to predict clinical efficacy from preclinical data. Nonetheless, the next challenge faced is the selection and validation of EEG endpoints that provide a set of robust and translatable biomarkers bridging preclinical and clinical programs.
Alzheimer's & Dementia, 2013
and might be due to increased vulnerability of their memory networks. Conclusions: The higher abs... more and might be due to increased vulnerability of their memory networks. Conclusions: The higher absolute power of upper alpha in resting EEG and the increased upper alpha desynchronization during cognitive task in non-demented older individuals carrying AD risk variant CLU CC implies unfavorable effect of this genotype on brain cholinergic pathways and hippocampus long before the presumable dementia. The results suggest that the neurophysiological markers may be important in monitoring disease progression in at-risk elderly.