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Article ; Online: Electrophysiological correlates of abused drugs: relation to natural rewards.

Deadwyler, Sam A

Annals of the New York Academy of Sciences

2010 Volume 1187, Page(s) 140–147

Abstract: The addictive consequences of abused substances depend upon activation of neurons in reward centers of the brain. Investigations aimed at determining the underlying basis for substance abuse have resulted in breakthroughs related to drug actions on ... ...

Abstract	The addictive consequences of abused substances depend upon activation of neurons in reward centers of the brain. Investigations aimed at determining the underlying basis for substance abuse have resulted in breakthroughs related to drug actions on normal neural processes; for example, the singular role of dopamine as the basis for drug addiction has been revised to include effects that, with other transmitter systems, produce changes in target neuronal firing that are different from those previously assumed, including "reward value" at the neuronal and systems levels and changes in the significance of pursued stimuli as a function of motivational state, context, effort, salience, and cognitive demand. Studies comparing these factors directly show differences between the actions of abused substances and less potent food-related rewards. Characterization of the change in reward-encoding processes for drug and natural rewards has provided insight into how abused substances gain control over behavior. This report explores how abused drugs alter neuron firing in reward-sensitive brain regions and how those alterations effect drug-seeking activity in animals and humans.
MeSH term(s)	Animals ; Brain/drug effects ; Brain/physiopathology ; Cocaine/toxicity ; Cocaine-Related Disorders/physiopathology ; Cocaine-Related Disorders/psychology ; Dopamine/physiology ; Electrophysiological Phenomena ; Humans ; Neurons/drug effects ; Neurons/physiology ; Reward ; Street Drugs/toxicity ; Substance-Related Disorders/physiopathology ; Substance-Related Disorders/psychology
Chemical Substances	Street Drugs ; Cocaine (I5Y540LHVR) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2010-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1111/j.1749-6632.2009.05155.x
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Article ; Online: (with research data) Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

Sandler, Roman A / Fetterhoff, Dustin / Hampson, Robert E / Deadwyler, Sam A / Marmarelis, Vasilis Z

PLoS computational biology

2017 Volume 13, Issue 7, Page(s) e1005624

Abstract: Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on ... ...

Abstract	Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.
MeSH term(s)	Animals ; Behavior, Animal/drug effects ; CA1 Region, Hippocampal/drug effects ; CA3 Region, Hippocampal/drug effects ; Cannabinoids/pharmacology ; Computational Biology ; Male ; Memory, Short-Term/drug effects ; Models, Neurological ; Rats ; Rats, Long-Evans ; Task Performance and Analysis
Chemical Substances	Cannabinoids
Language	English
Publishing date	2017-07-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1005624
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Article: The endocannabinoid system: a modulator of brain-behavioral processes.

Deadwyler, Sam A

Psychopharmacology

2008 Volume 198, Issue 4, Page(s) 447–448

MeSH term(s)	Animals ; Behavior/physiology ; Behavior, Animal/physiology ; Brain/physiology ; Cannabinoid Receptor Modulators/physiology ; Endocannabinoids ; Humans
Chemical Substances	Cannabinoid Receptor Modulators ; Endocannabinoids
Language	English
Publishing date	2008-05-07
Publishing country	Germany
Document type	Editorial ; Introductory Journal Article
ZDB-ID	130601-7
ISSN	1432-2072 ; 0033-3158
ISSN (online)	1432-2072
ISSN	0033-3158
DOI	10.1007/s00213-008-1153-4
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Article ; Online: Designing Patient-Specific Optimal Neurostimulation Patterns for Seizure Suppression.

Sandler, Roman A / Geng, Kunling / Song, Dong / Hampson, Robert E / Witcher, Mark R / Deadwyler, Sam A / Berger, Theodore W / Marmarelis, Vasilis Z

Neural computation

2018 Volume 30, Issue 5, Page(s) 1180–1208

Abstract: Neurostimulation is a promising therapy for abating epileptic seizures. However, it is extremely difficult to identify optimal stimulation patterns experimentally. In this study, human recordings are used to develop a functional 24 neuron network ... ...

Abstract	Neurostimulation is a promising therapy for abating epileptic seizures. However, it is extremely difficult to identify optimal stimulation patterns experimentally. In this study, human recordings are used to develop a functional 24 neuron network statistical model of hippocampal connectivity and dynamics. Spontaneous seizure-like activity is induced in silico in this reconstructed neuronal network. The network is then used as a testbed to design and validate a wide range of neurostimulation patterns. Commonly used periodic trains were not able to permanently abate seizures at any frequency. A simulated annealing global optimization algorithm was then used to identify an optimal stimulation pattern, which successfully abated 92% of seizures. Finally, in a fully responsive, or closed-loop, neurostimulation paradigm, the optimal stimulation successfully prevented the network from entering the seizure state. We propose that the framework presented here for algorithmically identifying patient-specific neurostimulation patterns can greatly increase the efficacy of neurostimulation devices for seizures.
MeSH term(s)	Algorithms ; Brain/physiology ; Computer Simulation ; Electric Stimulation Therapy/methods ; Electroencephalography ; Hippocampus/pathology ; Hippocampus/physiopathology ; Humans ; Models, Neurological ; Neurons/physiology ; Nonlinear Dynamics ; Seizures/diagnostic imaging ; Seizures/pathology ; Seizures/physiopathology ; Seizures/therapy
Language	English
Publishing date	2018-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1025692-1
ISSN	1530-888X ; 0899-7667
ISSN (online)	1530-888X
ISSN	0899-7667
DOI	10.1162/NECO_a_01075
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Article ; Online: Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

Roman A Sandler / Dustin Fetterhoff / Robert E Hampson / Sam A Deadwyler / Vasilis Z Marmarelis

PLoS Computational Biology, Vol 13, Iss 7, p e

2017 Volume 1005624

Abstract	Much of the research on cannabinoids (CBs) has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC), the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.
Keywords	Biology (General) ; QH301-705.5
Subject code	150
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article: Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall of stimulus features and categories.

Frontiers in computational neuroscience

2024 Volume 18, Page(s) 1263311

Abstract: Objective: Here, we demonstrate the first successful use of static neural stimulation patterns for specific information content. These static patterns were derived by a model that was applied to a subject's own hippocampal spatiotemporal neural codes ... ...

Abstract	Objective: Here, we demonstrate the first successful use of static neural stimulation patterns for specific information content. These static patterns were derived by a model that was applied to a subject's own hippocampal spatiotemporal neural codes for memory. Approach: We constructed a new model of processes by which the hippocampus encodes specific memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of targeted content into short-term memory. A memory decoding model (MDM) of hippocampal CA3 and CA1 neural firing was computed which derives a stimulation pattern for CA1 and CA3 neurons to be applied during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. Main results: MDM electrical stimulation delivered to the CA1 and CA3 locations in the hippocampus during the sample phase of DMS trials facilitated memory of images from the DMS task during a delayed recognition (DR) task that also included control images that were not from the DMS task. Across all subjects, the stimulated trials exhibited significant changes in performance in 22.4% of patient and category combinations. Changes in performance were a combination of both increased memory performance and decreased memory performance, with increases in performance occurring at almost 2 to 1 relative to decreases in performance. Across patients with impaired memory that received bilateral stimulation, significant changes in over 37.9% of patient and category combinations was seen with the changes in memory performance show a ratio of increased to decreased performance of over 4 to 1. Modification of memory performance was dependent on whether memory function was intact or impaired, and if stimulation was applied bilaterally or unilaterally, with nearly all increase in performance seen in subjects with impaired memory receiving bilateral stimulation. Significance: These results demonstrate that memory encoding in patients with impaired memory function can be facilitated for specific memory content, which offers a stimulation method for a future implantable neural prosthetic to improve human memory.
Language	English
Publishing date	2024-02-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452964-3
ISSN	1662-5188
ISSN	1662-5188
DOI	10.3389/fncom.2024.1263311
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Article ; Online: Multifractal analysis of information processing in hippocampal neural ensembles during working memory under Δ⁹-tetrahydrocannabinol administration.

Fetterhoff, Dustin / Opris, Ioan / Simpson, Sean L / Deadwyler, Sam A / Hampson, Robert E / Kraft, Robert A

Journal of neuroscience methods

2014 Volume 244, Page(s) 136–153

Abstract: Background: Multifractal analysis quantifies the time-scale-invariant properties in data by describing the structure of variability over time. By applying this analysis to hippocampal interspike interval sequences recorded during performance of a ... ...

Abstract	Background: Multifractal analysis quantifies the time-scale-invariant properties in data by describing the structure of variability over time. By applying this analysis to hippocampal interspike interval sequences recorded during performance of a working memory task, a measure of long-range temporal correlations and multifractal dynamics can reveal single neuron correlates of information processing. New method: Wavelet leaders-based multifractal analysis (WLMA) was applied to hippocampal interspike intervals recorded during a working memory task. WLMA can be used to identify neurons likely to exhibit information processing relevant to operation of brain-computer interfaces and nonlinear neuronal models. Results: Neurons involved in memory processing ("Functional Cell Types" or FCTs) showed a greater degree of multifractal firing properties than neurons without task-relevant firing characteristics. In addition, previously unidentified FCTs were revealed because multifractal analysis suggested further functional classification. The cannabinoid type-1 receptor (CB1R) partial agonist, tetrahydrocannabinol (THC), selectively reduced multifractal dynamics in FCT neurons compared to non-FCT neurons. Comparison with existing methods: WLMA is an objective tool for quantifying the memory-correlated complexity represented by FCTs that reveals additional information compared to classification of FCTs using traditional z-scores to identify neuronal correlates of behavioral events. Conclusion: z-Score-based FCT classification provides limited information about the dynamical range of neuronal activity characterized by WLMA. Increased complexity, as measured with multifractal analysis, may be a marker of functional involvement in memory processing. The level of multifractal attributes can be used to differentially emphasize neural signals to improve computational models and algorithms underlying brain-computer interfaces.
MeSH term(s)	Action Potentials/drug effects ; Algorithms ; Analysis of Variance ; Animals ; Computer Simulation ; Dose-Response Relationship, Drug ; Dronabinol/administration & dosage ; Electronic Data Processing ; Hippocampus/cytology ; Memory, Short-Term/drug effects ; Models, Neurological ; Neurons/cytology ; Neurons/drug effects ; Nonlinear Dynamics ; Psychotropic Drugs/administration & dosage ; Rats ; Rats, Long-Evans
Chemical Substances	Psychotropic Drugs ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2014-07-30
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	282721-9
ISSN	1872-678X ; 0165-0270
ISSN (online)	1872-678X
ISSN	0165-0270
DOI	10.1016/j.jneumeth.2014.07.013
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Article: Disruption of columnar and laminar cognitive processing in primate prefrontal cortex following cocaine exposure.

Opris, Ioan / Gerhardt, Greg A / Hampson, Robert E / Deadwyler, Sam A

Frontiers in systems neuroscience

2015 Volume 9, Page(s) 79

Abstract: Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns ... ...

Abstract	Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs) were trained in a visual delayed match-to-sample (DMS) task while the activity of prefrontal cortical neurons (areas 46, 8 and 6) was recorded simultaneously with a custom multielectrode array in cell layers 2/3 and 5. Animals were reinforced with juice for correct responses. The first half of the recording session (control) was conducted following saline injection and in the second half of the same session cocaine was administered. Prefrontal neuron activity with respect to inter- and intra-laminar firing in layers 2/3 and 5 was assessed in the DMS task before and after the injection of cocaine. Results showed that firing rates of both pyramidal cells and interneurons increased on Match phase presentation and the Match Response (MR) in both control and cocaine halves of the session. Differential firing under cocaine vs. control in the Match phase was increased for interneurons but decreased for pyramidal cells. In addition, functional' interactions between prefrontal pyramidal cells in layer 2/3 and 5 decreased while intra-laminar cross-correlations in both layers increased. These neural recordings demonstrate that prefrontal neurons differentially encode and process information within and between cortical cell layers via cortical columns which is disrupted in a differential manner by cocaine: administration.
Language	English
Publishing date	2015-05-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2453005-0
ISSN	1662-5137
ISSN	1662-5137
DOI	10.3389/fnsys.2015.00079
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Article: Distinguishing cognitive state with multifractal complexity of hippocampal interspike interval sequences.

Fetterhoff, Dustin / Kraft, Robert A / Sandler, Roman A / Opris, Ioan / Sexton, Cheryl A / Marmarelis, Vasilis Z / Hampson, Robert E / Deadwyler, Sam A

Frontiers in systems neuroscience

2015 Volume 9, Page(s) 130

Abstract: Fractality, represented as self-similar repeating patterns, is ubiquitous in nature and the brain. Dynamic patterns of hippocampal spike trains are known to exhibit multifractal properties during working memory processing; however, it is unclear whether ... ...

Abstract	Fractality, represented as self-similar repeating patterns, is ubiquitous in nature and the brain. Dynamic patterns of hippocampal spike trains are known to exhibit multifractal properties during working memory processing; however, it is unclear whether the multifractal properties inherent to hippocampal spike trains reflect active cognitive processing. To examine this possibility, hippocampal neuronal ensembles were recorded from rats before, during and after a spatial working memory task following administration of tetrahydrocannabinol (THC), a memory-impairing component of cannabis. Multifractal detrended fluctuation analysis was performed on hippocampal interspike interval sequences to determine characteristics of monofractal long-range temporal correlations (LRTCs), quantified by the Hurst exponent, and the degree/magnitude of multifractal complexity, quantified by the width of the singularity spectrum. Our results demonstrate that multifractal firing patterns of hippocampal spike trains are a marker of functional memory processing, as they are more complex during the working memory task and significantly reduced following administration of memory impairing THC doses. Conversely, LRTCs are largest during resting state recordings, therefore reflecting different information compared to multifractality. In order to deepen conceptual understanding of multifractal complexity and LRTCs, these measures were compared to classical methods using hippocampal frequency content and firing variability measures. These results showed that LRTCs, multifractality, and theta rhythm represent independent processes, while delta rhythm correlated with multifractality. Taken together, these results provide a novel perspective on memory function by demonstrating that the multifractal nature of spike trains reflects hippocampal microcircuit activity that can be used to detect and quantify cognitive, physiological, and pathological states.
Language	English
Publishing date	2015-09-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2453005-0
ISSN	1662-5137
ISSN	1662-5137
DOI	10.3389/fnsys.2015.00130
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Article ; Online: Functional connectivity between Layer 2/3 and Layer 5 neurons in prefrontal cortex of nonhuman primates during a delayed match-to-sample task.

Song, Dong / Opris, Ioan / Chan, Rosa H M / Marmarelis, Vasilis Z / Hampson, Robert E / Deadwyler, Sam A / Berger, Theodore W

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2019 Volume 2012, Page(s) 2555–2558

Abstract: The prefrontal cortex (PFC) has been postulated to play critical roles in cognitive control and the formation of long-term memories. To gain insights into the neurobiological mechanism of such high-order cognitive functions, it is important to understand ...

Abstract	The prefrontal cortex (PFC) has been postulated to play critical roles in cognitive control and the formation of long-term memories. To gain insights into the neurobiological mechanism of such high-order cognitive functions, it is important to understand the input-output transformational properties of the PFC micro-circuitry. In this study, we identify the functional connectivity between the Layer 2/3 (input) neurons and the Layer 5 (output) neurons using a previously developed generalized Volterra model (GVM). Input-output spike trains are recorded from the PFCs of nonhuman primates performing a memory-dependent delayed match-to-sample task with a customized conformal ceramic multi-electrode array. The GVM describes how the input spike trains are transformed into the output spike trains by the PFC micro-circuitry and represents the transformation in the form of Volterra kernels. Results show that Layer 2/3 neurons have strong and transient facilitatory effects on the firings of Layer 5 neurons. The magnitude and temporal range of the input-output nonlinear dynamics are strikingly different from those of the hippocampal CA3-CA1. This form of functional connectivity may have important implications to understanding the computational principle of the PFC.
MeSH term(s)	Animals ; Macaca mulatta ; Models, Theoretical ; Neurons/cytology ; Neurons/physiology ; Nonlinear Dynamics ; Prefrontal Cortex/cytology ; Primates
Language	English
Publishing date	2019-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC.2012.6346485
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