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Article ; Online: Opioid-induced microglia reactivity modulates opioid reward, analgesia, and behavior.

Green, Jacob M / Sundman, Mark H / Chou, Ying-Hui

2022 Volume 135, Page(s) 104544

Abstract: Opioid-induced microglia reactivity affects opioid reward and analgesic processes in ways that may contribute to the neurocognitive impairment observed in opioid addicted individuals. Opioids elicit microglia reactivity through the actions of opioid ... ...

Abstract	Opioid-induced microglia reactivity affects opioid reward and analgesic processes in ways that may contribute to the neurocognitive impairment observed in opioid addicted individuals. Opioids elicit microglia reactivity through the actions of opioid metabolites at TLR4 receptors, that are located primarily on microglia but are also present on astrocytes. Specifically, the M3G metabolite, which has no affinity for opioid receptors, exerts off-target effects on TLR4 receptors that can trigger downstream immunologic consequences. This off-target microglial reactivity, and the subsequent increase in microglial release of TNFα, IL-1β, and BDNF, have been suggested to modulate both opioid-induced reward and opioid-induced analgesia. Despite occurring independently of each other, these neuro-immune effects could converge and result in overactivation of the insula. This would produce an imbalance between the "impulsive system" and the "executive system", such that the impulsive system's influence over behavior becomes dominant. This state, derived from changes in microglial reactivity, could contribute to impairment in a range of neurocognitive domains that are intricately involved in addiction and lead to increases in addiction-related behaviors.
MeSH term(s)	Analgesia ; Analgesics, Opioid/pharmacology ; Humans ; Microglia ; Pain/metabolism ; Reward
Chemical Substances	Analgesics, Opioid
Language	English
Publishing date	2022-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2022.104544
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Article ; Online: Exploring the potential of combining transcranial magnetic stimulation and electroencephalography to investigate mild cognitive impairment and Alzheimer's disease: a systematic review.

Hall, J D / Green, Jacob M / Chen, Yu-Chin A / Liu, Yilin / Zhang, Hangbin / Sundman, Mark H / Chou, Ying-Hui

GeroScience

2024

Abstract: Transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are non-invasive techniques used for neuromodulation and recording brain electrical activity, respectively. The integration of TMS-EEG has emerged as a valuable tool for ... ...

Abstract	Transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are non-invasive techniques used for neuromodulation and recording brain electrical activity, respectively. The integration of TMS-EEG has emerged as a valuable tool for investigating the complex mechanisms involved in age-related disorders, such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). By systematically synthesizing TMS-EEG studies, this review aims to shed light on the neurophysiological mechanisms underlying MCI and AD, while also exploring the practical applications of TMS-EEG in clinical settings. PubMed, ScienceDirect, and PsychInfo were selected as the databases for this review. The 22 eligible studies included a total of 592 individuals with MCI or AD as well as 301 cognitively normal adults. TMS-EEG assessments unveiled specific patterns of corticospinal excitability, plasticity, and brain connectivity that distinguished individuals on the AD spectrum from cognitively normal older adults. Moreover, the TMS-induced EEG features were observed to be correlated with cognitive performance and the presence of AD pathological biomarkers. The comprehensive examination of the existing studies demonstrates that the combination of TMS and EEG has yielded valuable insights into the neurophysiology of MCI and AD. This integration shows great potential for early detection, monitoring disease progression, and anticipating response to treatment. Future research is of paramount importance to delve into the potential utilization of TMS-EEG for treatment optimization in individuals with MCI and AD.
Language	English
Publishing date	2024-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-024-01075-6
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Zs.A 1502: Show issues

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Article ; Online: The (hyper)excitable brain: what can a ubiquitous TMS measure reveal about cognitive aging?

Sundman, Mark H / Avila De Vault, Bernadette Elise / Chen, Allison Yu-Chin / Madhavan, Lalitha / Fuglevand, Andrew J / Chou, Ying-Hui

Neurobiology of aging

2023 Volume 132, Page(s) 250–252

MeSH term(s)	Cognitive Aging ; Brain ; Transcranial Magnetic Stimulation ; Brain Mapping
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Letter
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2023.09.007
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Zs.A 1685: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Differential impacts of healthy cognitive aging on directed and random exploration.

Mizell, Jack-Morgan / Wang, Siyu / Frisvold, Alec / Alvarado, Lily / Farrell-Skupny, Alex / Keung, Waitsang / Phelps, Caroline E / Sundman, Mark H / Franchetti, Mary-Kathryn / Chou, Ying-Hui / Alexander, Gene E / Wilson, Robert C

Psychology and aging

2024 Volume 39, Issue 1, Page(s) 88–101

Abstract: Deciding whether to explore unknown opportunities or exploit well-known options is a ubiquitous part of our everyday lives. Extensive work in college students suggests that young people make explore-exploit decisions using a mixture of information ... ...

Abstract	Deciding whether to explore unknown opportunities or exploit well-known options is a ubiquitous part of our everyday lives. Extensive work in college students suggests that young people make explore-exploit decisions using a mixture of information seeking and random behavioral variability. Whether, and to what extent, older adults use the same strategies is unknown. To address this question, 51 older adults (ages 65-74) and 32 younger adults (ages 18-25) completed the Horizon Task, a gambling task that quantifies information seeking and behavioral variability as well as how these strategies are controlled for the purposes of exploration. Qualitatively, we found that older adults performed similar to younger adults on this task, increasing both their information seeking and behavioral variability when it was adaptive to explore. Quantitively, however, there were substantial differences between the age groups, with older adults showing less information seeking overall and less reliance on variability as a means to explore. In addition, we found a subset of approximately 26% of older adults whose information seeking was close to zero, avoiding informative options even when they were clearly the better choice. Unsurprisingly, these "information avoiders" performed worse on the task. In contrast, task performance in the remaining "information seeking" older adults was comparable to that of younger adults suggesting that age-related differences in explore-exploit decision making may be adaptive except when they are taken to extremes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
MeSH term(s)	Humans ; Aged ; Adolescent ; Young Adult ; Adult ; Cognitive Aging ; Aging ; Gambling ; Healthy Aging ; Students
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	635596-1
ISSN	1939-1498 ; 0882-7974
ISSN (online)	1939-1498
ISSN	0882-7974
DOI	10.1037/pag0000791
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Article ; Online: Association Between Responsiveness to Transcranial Magnetic Stimulation and Interhemispheric Functional Connectivity of Sensorimotor Cortex in Older Adults.

Liu, Yilin / Lim, Koeun / Sundman, Mark H / Ugonna, Chidi / Ton That, Viet / Cowen, Stephen / Chou, Ying-Hui

Brain connectivity

2022 Volume 13, Issue 1, Page(s) 39–50

Abstract: Introduction: ...

Abstract	Introduction:
MeSH term(s)	Humans ; Aged ; Transcranial Magnetic Stimulation/methods ; Brain ; Magnetic Resonance Imaging ; Motor Cortex/physiology ; Evoked Potentials, Motor/physiology
Language	English
Publishing date	2022-06-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2609017-X
ISSN	2158-0022 ; 2158-0014
ISSN (online)	2158-0022
ISSN	2158-0014
DOI	10.1089/brain.2021.0180
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Article: Baseline Neurocognitive Performance and Symptoms in Those With Attention Deficit Hyperactivity Disorders and History of Concussion With Previous Loss of Consciousness.

Kaye, Sarah / Sundman, Mark H / Hall, Eric E / Williams, Ethan / Patel, Kirtida / Ketcham, Caroline J

Frontiers in neurology

2019 Volume 10, Page(s) 396

Abstract: Previous consensus statements on sports concussion have highlighted the importance of Attention Deficit Hyperactivity Disorder (ADHD) and loss of consciousness (LOC) as risk factors related to concussion management. The present study investigated how ... ...

Abstract	Previous consensus statements on sports concussion have highlighted the importance of Attention Deficit Hyperactivity Disorder (ADHD) and loss of consciousness (LOC) as risk factors related to concussion management. The present study investigated how self-reported history of either ADHD diagnosis or history of previous concussion resulting in LOC influence baseline neurocognitive performance and self-reported symptoms. This analysis was performed retrospectively on data collected primarily from student-athletes, both Division 1 and club sports athletes. The dataset (
Language	English
Publishing date	2019-04-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2019.00396
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Article ; Online: The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease.

Sundman, Mark H / Chen, Nan-Kuei / Subbian, Vignesh / Chou, Ying-Hui

Brain, behavior, and immunity

2017 Volume 66, Page(s) 31–44

Abstract: As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the ... ...

Abstract	As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.
Language	English
Publishing date	2017-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2017.05.009
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 327: Show issues

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Article: Examining the relationship between head trauma and neurodegenerative disease: A review of epidemiology, pathology and neuroimaging techniques.

Sundman, Mark H / Hall, Eric E / Chen, Nan-Kuei

Journal of Alzheimer's disease & Parkinsonism

2014 Volume 4

Abstract: Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma ... ...

Abstract	Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern.
Language	English
Publishing date	2014-09-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2711981-6
ISSN	2161-0460
ISSN	2161-0460
DOI	10.4172/2161-0460.1000137
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Article ; Online: Neuroimaging of Parkinson's disease: Expanding views.

Weingarten, Carol P / Sundman, Mark H / Hickey, Patrick / Chen, Nan-kuei

Neuroscience and biobehavioral reviews

2015 Volume 59, Page(s) 16–52

Abstract: Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson's disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for ... ...

Abstract	Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson's disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD.
MeSH term(s)	Animals ; Brain/metabolism ; Brain/pathology ; Humans ; Magnetoencephalography/methods ; Nerve Net/pathology ; Neuroimaging/methods ; Neurotransmitter Agents/metabolism ; Parkinson Disease/diagnosis ; Parkinson Disease/pathology ; Parkinson Disease/prevention & control
Chemical Substances	Neurotransmitter Agents
Language	English
Publishing date	2015-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	282464-4
ISSN	1873-7528 ; 0149-7634
ISSN (online)	1873-7528
ISSN	0149-7634
DOI	10.1016/j.neubiorev.2015.09.007
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Article ; Online: Transcranial magnetic stimulation reveals diminished homoeostatic metaplasticity in cognitively impaired adults.

Sundman, Mark H / Lim, Koeun / Ton That, Viet / Mizell, Jack-Morgan / Ugonna, Chidi / Rodriguez, Rudolph / Chen, Nan-Kuei / Fuglevand, Andrew J / Liu, Yilin / Wilson, Robert C / Fellous, Jean-Marc / Rapcsak, Steven / Chou, Ying-Hui

Brain communications

2020 Volume 2, Issue 2, Page(s) fcaa203

Abstract: Homoeostatic metaplasticity is a neuroprotective physiological feature that counterbalances Hebbian forms of plasticity to prevent network destabilization and hyperexcitability. Recent animal models highlight dysfunctional homoeostatic metaplasticity in ... ...

Abstract	Homoeostatic metaplasticity is a neuroprotective physiological feature that counterbalances Hebbian forms of plasticity to prevent network destabilization and hyperexcitability. Recent animal models highlight dysfunctional homoeostatic metaplasticity in the pathogenesis of Alzheimer's disease. However, the association between homoeostatic metaplasticity and cognitive status has not been systematically characterized in either demented or non-demented human populations, and the potential value of homoeostatic metaplasticity as an early biomarker of cognitive impairment has not been explored in humans. Here, we report that, through pre-conditioning the synaptic activity prior to non-invasive brain stimulation, the association between homoeostatic metaplasticity and cognitive status could be established in a population of non-demented human subjects (older adults across cognitive spectrums; all within the non-demented range). All participants (
Language	English
Publishing date	2020-11-27
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcaa203
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