Stability of infraslow correlation structure in time-shifted intracranial EEG signals.

It is increasingly understood that the epilepsies are characterized by network pathology that can span multiple spatial and temporal scales. Recent work indicates that infraslow (<0.2 Hz) envelope correlations may form a basis for distant spatial coupling in the brain.

The Functional Connectome and Long-Term Symptom Presentation Associated With Mild Traumatic Brain Injury and Blast Exposure in Combat Veterans.

Mild traumatic brain injury (TBI) sustained in a deployment environment (deployment TBI) can be associated with increased severity of long-term symptom presentation, despite the general expectation of full recovery from a single mild TBI. The heterogeneity in the effects of deployment TBI on the brain can be difficult for a case-control design to capture. The functional connectome of the brain is an approach robust to heterogeneity that allows global measurement of effects using a common set of outcomes.

Protein kinase C epsilon-mediated modulation of T-type calcium channels underlies alcohol withdrawal hyperexcitability in the midline thalamus.

Background: Millions of people struggle with alcohol use disorder (AUD). Abrupt abstinence after a period of chronic alcohol use can precipitate the alcohol withdrawal syndrome (AWS), which includes hyperexcitability and, potentially, seizures. We have shown that T-type Ca channels are novel, sensitive targets of alcohol, an effect that is dependent upon protein kinase C (PKC).

Use of magnetic source imaging to assess recovery after severe traumatic brain injury-an MEG pilot study.

Rationale: Severe TBI (sTBI) is a devastating neurological injury that comprises a significant global trauma burden. Early comprehensive neurocritical care and rehabilitation improve outcomes for such patients, although better diagnostic and prognostic tools are necessary to guide personalized treatment plans.

Methods: In this study, we explored the feasibility of conducting resting state magnetoencephalography (MEG) in a case series of sTBI patients acutely after injury (~7 days), and then about 1.

Alcohol withdrawal produces changes in excitability, population discharge probability, and seizure threshold.

Background: Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death.

Contextual Effects of Traumatic Brain Injury on the Connectome: Differential Effects of Deployment- and Non-Deployment-Acquired Injuries.

Objective: To identify differential effects of mild traumatic brain injury (TBI) occurring in a deployment or nondeployment setting on the functional brain connectome.

Setting: Veterans Affairs Medical Center.

Participants: In total, 181 combat-exposed veterans of the wars in Iraq and Afghanistan ( n = 74 with deployment-related mild TBI, average time since injury = 11.

Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T-T continuum to advance the care of hospitalized patients who experience SAWS.

MEG source imaging detects optogenetically-induced activity in cortical and subcortical networks.

Magnetoencephalography measures neuromagnetic activity with high temporal, and theoretically, high spatial resolution. We developed an experimental platform combining MEG-compatible optogenetic techniques in nonhuman primates for use as a functional brain-mapping platform. Here we show localization of optogenetically evoked signals to known sources in the superficial arcuate sulcus of cortex and in CA3 of hippocampus at a resolution of 750 µm.

Alterations in the Topology of Functional Connectomes Are Associated with Post-Traumatic Stress Disorder and Blast-Related Mild Traumatic Brain Injury in Combat Veterans.

Post-traumatic stress disorder (PTSD) is a common condition in post-deployment service members (SM). SMs of the conflicts in Iraq and Afghanistan also frequently experience traumatic brain injury (TBI) and exposure to blasts during deployments. This study evaluated the effect of these conditions and experiences on functional brain connectomes in post-deployment, combat-exposed veterans.

Rich Club Characteristics of Alcohol-Naïve Functional Brain Networks Predict Future Drinking Phenotypes in Rhesus Macaques.

: A fundamental question for Alcohol use disorder (AUD) is how and when naïve brain networks are reorganized in response to alcohol consumption. The current study aimed to determine the progression of alcohol's effect on functional brain networks during transition from the naïve state to chronic consumption. : Resting-state brain networks of six female rhesus macaque ( monkeys were acquired using magnetoencephalography (MEG) prior to alcohol exposure and after free-access to alcohol using a well-established model of chronic heavy alcohol consumption.

Tumour-specific amplitude-modulated radiofrequency electromagnetic fields induce differentiation of hepatocellular carcinoma via targeting Ca3.2 T-type voltage-gated calcium channels and Ca influx.

Background: Administration of amplitude modulated 27·12 MHz radiofrequency electromagnetic fields (AM RF EMF) by means of a spoon-shaped applicator placed on the patient's tongue is a newly approved treatment for advanced hepatocellular carcinoma (HCC). The mechanism of action of tumour-specific AM RF EMF is largely unknown.

Methods: Whole body and organ-specific human dosimetry analyses were performed.

Seizure susceptibility and infraslow modulatory activity in the intracranial electroencephalogram.

Objective: Studies of infraslow amplitude modulations (<0.15 Hz) of band power time series suggest that these envelope correlations may form a basis for distant spatial coupling in the brain. In this study, we sought to determine how infraslow relationships are affected by antiepileptic drug (AED) taper, time of day, and seizure.

Magnetoencephalography: Clinical and Research Practices.

Magnetoencephalography (MEG) is a neurophysiological technique that detects the magnetic fields associated with brain activity. Synthetic aperture magnetometry (SAM), a MEG magnetic source imaging technique, can be used to construct both detailed maps of global brain activity as well as virtual electrode signals, which provide information that is similar to invasive electrode recordings. This innovative approach has demonstrated utility in both clinical and research settings.

Selective Blockade of T-Type Ca2+ Channels is Protective Against Alcohol-Withdrawal Induced Seizure and Mortality.

Aims: We have previously demonstrated that blockade of T-type calcium channels by the non-selective antagonist, ethosuximide (ETX), is effective at reducing electrographical and behavioral correlates of alcohol-withdrawal (WD) seizure. Here, we investigated whether blockade of these calcium channels with the selective antagonist TTA-P2 also reduces alcohol-WD seizure.

Short Summary: The non-specific T-type calcium channel antagonist, ETX, is protective against alcohol-WD seizure.

Increased Small-World Network Topology Following Deployment-Acquired Traumatic Brain Injury Associated with the Development of Post-Traumatic Stress Disorder.

Cross-sectional and longitudinal studies in active duty and veteran cohorts have both demonstrated that deployment-acquired traumatic brain injury (TBI) is an independent risk factor for developing post-traumatic stress disorder (PTSD), beyond confounds such as combat exposure, physical injury, predeployment TBI, and pre-deployment psychiatric symptoms. This study investigated how resting-state brain networks differ between individuals who developed PTSD and those who did not following deployment-acquired TBI. Participants included postdeployment veterans with deployment-acquired TBI history both with and without current PTSD diagnosis.

Expression of channelrhodopsin-2 localized within the deep CA1 hippocampal sublayer in the Thy1 line 18 mouse.

Optogenetic proteins are powerful tools for advancing our understanding of neural circuitry. However, the precision of optogenetics is dependent in part on the extent to which expression is limited to cells of interest. The Thy1-ChR2 transgenic mouse is commonly used in optogenetic experiments.

Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals.

Introduction: Chronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys.

Contrasting Effects of Posttraumatic Stress Disorder and Mild Traumatic Brain Injury on the Whole-Brain Resting-State Network: A Magnetoencephalography Study.

The aim of this study was to evaluate alterations in whole-brain resting-state networks associated with posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI). Networks were constructed from locations of peak statistical power on an individual basis from magnetoencephalography (MEG) source series data by applying the weighted phase lag index and surrogate data thresholding procedures. Networks representing activity in the alpha bandwidth as well as wideband activity (DC-80 Hz) were created.

Ethosuximide Reduces Mortality and Seizure Severity in Response to Pentylenetetrazole Treatment During Ethanol Withdrawal.

Aims: We recently demonstrated that T-type calcium channels are affected by alcohol abuse and withdrawal. Treatment with ethosuximide, an antiepileptic drug that blocks T-type calcium channels, reduces seizure activity induced by intermittent ethanol exposures and withdrawals. Here, we expand on these findings to test whether ethosuximide can reduce the sensitivity to pentylenetetrazole-induced seizures during ethanol withdrawal.

Localization of interictal epileptiform activity using magnetoencephalography with synthetic aperture magnetometry in patients with a vagus nerve stimulator.

Magnetoencephalography (MEG) provides useful and non-redundant information in the evaluation of patients with epilepsy, and in particular, during the pre-surgical evaluation of pharmaco-resistant epilepsy. Vagus nerve stimulation (VNS) is a common treatment for pharmaco-resistant epilepsy. However, interpretation of MEG recordings from patients with a VNS is challenging due to the severe magnetic artifacts produced by the VNS.

Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice.

Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound hyperexcitability can result in withdrawal seizure. Withdrawal symptoms, including seizures, may drive individuals to relapse, thus representing a significant barrier to recovery. Our lab previously identified an upregulation of the thalamic T-type calcium (T channel) isoform CaV3.

Functional dynamics of primate cortico-striatal networks during volitional movements.

The motor cortex and dorsal striatum (caudate nucleus and putamen) are key regions in motor processing but the interface between the cortex and striatum is not well understood. While dorsal striatum integrates information from multiple brain regions to shape motor learning and habit formation, the disruption of cortico-striatal circuits compromises the functionality of these circuits resulting in a multitude of neurologic disorders, including Parkinson's disease. To better understand the modulation of the cortico-striatal circuits we recorded simultaneously single neuron activity from four brain regions, primary motor, and sensory cortices, together with the rostral and caudal segments of the putamen in rhesus monkeys performing a visual motor task.

A magnetic rotary optical fiber connector for optogenetic experiments in freely moving animals.

Background: Performing optogenetic experiments in a behaving animal presents a unique technical challenge. In order to provide an optical path between a fixed light source and a chronically implanted fiber in a freely moving animal, a typical experimental setup includes a detachable connection between the light source and the head of the animal, as well as a rotary joint to relieve torsional stress during movement.

New Method: We have combined the functionality of the head mounted connector and the rotary joint into a single integrated device that is inexpensive, simple to build, and easy to use.

Activation of group 2 metabotropic glutamate receptors reduces behavioral and electrographic correlates of pilocarpine induced status epilepticus.

Novel treatments for epilepsy are necessary because many epilepsy patients are resistant to medication. Metabotropic glutamate receptors (mGluRs), specifically mGluR 2 and 3, may serve as antiepileptic drug targets because of their role in controlling synaptic release. In this study, we administered a Group 2 mGluR agonist, LY379268, one of two mGluR2-specific positive allosteric modulators, BINA or CBiPES, or a cocktail of both BINA and LY379268 in a series of experiments using the pilocarpine model of SE.

Ethanol inhibition of a T-type Ca²+ channel through activity of protein kinase C.

Background: T-type calcium channels (T-channels) are widely distributed in the central and peripheral nervous system, where they mediate calcium entry and regulate the intrinsic excitability of neurons. T-channels are dysregulated in response to alcohol administration and withdrawal. We therefore investigated acute ethanol (EtOH) effects and the underlying mechanism of action in human embryonic kidney (HEK) 293 cell lines, as well as effects on native currents recorded from dorsal root ganglion (DRG) neurons cultured from Long-Evans rats.