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Brain : a Journal of Neurology Oct 2022Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the... (Review)
Review
Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of 'network-guided neuromodulation' for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key 'propagation points' in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points - including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients' individual epileptogenic networks.
Topics: Adult; Child; Humans; Deep Brain Stimulation; Anticonvulsants; Epilepsy; Subthalamic Nucleus; Thalamus; Epilepsies, Partial
PubMed: 35771657
DOI: 10.1093/brain/awac234 -
Neurobiology of Disease Apr 2023Neuromodulation (neurostimulation) is a relatively new and rapidly growing treatment for refractory epilepsy. Three varieties are approved in the US: vagus nerve... (Review)
Review
Neuromodulation (neurostimulation) is a relatively new and rapidly growing treatment for refractory epilepsy. Three varieties are approved in the US: vagus nerve stimulation (VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS). This article reviews thalamic DBS for epilepsy. Among many thalamic sub-nuclei, DBS for epilepsy has been targeted to the anterior nucleus (ANT), centromedian nucleus (CM), dorsomedial nucleus (DM) and pulvinar (PULV). Only ANT is FDA-approved, based upon a controlled clinical trial. Bilateral stimulation of ANT reduced seizures by 40.5% at three months in the controlled phase (p = .038) and 75% by 5 years in the uncontrolled phase. Side effects related to paresthesias, acute hemorrhage, infection, occasional increased seizures, and usually transient effects on mood and memory. Efficacy was best documented for focal onset seizures in temporal or frontal lobe. CM stimulation may be useful for generalized or multifocal seizures and PULV for posterior limbic seizures. Mechanisms of DBS for epilepsy are largely unknown, but animal work points to changes in receptors, channels, neurotransmitters, synapses, network connectivity and neurogenesis. Personalization of therapies, in terms of connectivity of the seizure onset zone to the thalamic sub- nucleus and individual characteristics of the seizures, might lead to improved efficacy. Many questions remain about DBS, including the best candidates for different types of neuromodulation, the best targets, the best stimulation parameters, how to minimize side effects and how to deliver current noninvasively. Despite the questions, neuromodulation provides useful new opportunities to treat people with refractory seizures not responding to medicines and not amenable to resective surgery.
Topics: Animals; Deep Brain Stimulation; Epilepsy; Thalamus; Seizures; Drug Resistant Epilepsy
PubMed: 36809846
DOI: 10.1016/j.nbd.2023.106045 -
Advances in Experimental Medicine and... 2020Fear is defined as a fundamental emotion promptly arising in the context of threat and when danger is perceived. Fear can be innate or learned. Examples of innate fear... (Review)
Review
Fear is defined as a fundamental emotion promptly arising in the context of threat and when danger is perceived. Fear can be innate or learned. Examples of innate fear include fears that are triggered by predators, pain, heights, rapidly approaching objects, and ancestral threats such as snakes and spiders. Animals and humans detect and respond more rapidly to threatening stimuli than to nonthreatening stimuli in the natural world. The threatening stimuli for most animals are predators, and most predators are themselves prey to other animals. Predatory avoidance is of crucial importance for survival of animals. Although humans are rarely affected by predators, we are constantly challenged by social threats such as a fearful or angry facial expression. This chapter will summarize the current knowledge on brain circuits processing innate fear responses to visual stimuli derived from studies conducted in mice and humans.
Topics: Anger; Animals; Brain; Facial Expression; Fear; Humans; Snakes; Spiders
PubMed: 32852735
DOI: 10.1007/978-981-15-7086-5_1 -
World Neurosurgery May 2020The thalamus is a deep cerebral structure that is crucial for proper neurological functioning as it transmits signals from nearly all pathways in the body. Insult to the... (Review)
Review
The thalamus is a deep cerebral structure that is crucial for proper neurological functioning as it transmits signals from nearly all pathways in the body. Insult to the thalamus can, therefore, result in complex syndromes involving sensation, cognition, executive function, fine motor control, emotion, and arousal, to name a few. Specific territories in the thalamus that are supplied by deep cerebral arteries have been shown to correlate with clinical symptoms. The aim of this review is to enhance our understanding of the arterial anatomy of the thalamus and the complications that can arise from lesions to it by considering the functions of known thalamic nuclei supplied by each vascular territory.
Topics: Anterior Thalamic Nuclei; Basilar Artery; Brain Infarction; Circle of Willis; Geniculate Bodies; Humans; Lateral Thalamic Nuclei; Mediodorsal Thalamic Nucleus; Posterior Cerebral Artery; Pulvinar; Thalamus; Ventral Thalamic Nuclei
PubMed: 32036065
DOI: 10.1016/j.wneu.2020.01.237 -
Brain : a Journal of Neurology Jul 2023Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important...
Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation. We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions. Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs. Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome.
Topics: Humans; Seizures; Brain; Epilepsy, Temporal Lobe; Electroencephalography; Drug Resistant Epilepsy; Anterior Thalamic Nuclei; Electrodes, Implanted
PubMed: 37137813
DOI: 10.1093/brain/awad121 -
Current Neurology and Neuroscience... Nov 2021Subcortical structures have long been thought to play a role in language processing. Increasingly spirited debates on language studies, arising from as early as the... (Review)
Review
PURPOSE OF REVIEW
Subcortical structures have long been thought to play a role in language processing. Increasingly spirited debates on language studies, arising from as early as the nineteenth century, grew remarkably sophisticated as the years pass. In the context of non-thalamic aphasia, a few theoretical frameworks have been laid out. The disconnection hypothesis postulates that basal ganglia insults result in aphasia due to a rupture of connectivity between Broca and Wernicke's areas. A second viewpoint conjectures that the basal ganglia would more directly partake in language processing, and a third stream proclaims that aphasia would stem from cortical deafferentation. On the other hand, thalamic aphasia is more predominantly deemed as a resultant of diaschisis. This article reviews the above topics with recent findings on deep brain stimulation, neurophysiology, and aphasiology.
RECENT FINDINGS
The more recent approach conceptualizes non-thalamic aphasias as the offspring of unpredictable cortical hypoperfusion. Regarding the thalamus, there is mounting evidence now pointing to leading contributions of the pulvinar/lateral posterior nucleus and the anterior/ventral anterior thalamus to language disturbances. While the former appears to relate to lexical-semantic indiscrimination, the latter seems to bring about a severe breakdown in word selection and/or spontaneous top-down lexical-semantic operations. The characterization of subcortical aphasias and the role of the basal ganglia and thalamus in language processing continues to pose a challenge. Neuroimaging studies have pointed a path forward, and we believe that more recent methods such as tractography and connectivity studies will significantly expand our knowledge in this particular area of aphasiology.
Topics: Aphasia; Basal Ganglia; Diaschisis; Humans; Semantics; Thalamus
PubMed: 34817710
DOI: 10.1007/s11910-021-01156-5 -
Neuroscience and Biobehavioral Reviews Sep 2019There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a...
There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.
Topics: Addiction Medicine; Humans; Outcome Assessment, Health Care; Practice Guidelines as Topic; Substance-Related Disorders; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 31271802
DOI: 10.1016/j.neubiorev.2019.06.007 -
Current Opinion in Neurology Apr 2023Neurostimulation is a quickly growing treatment approach for epilepsy patients. We summarize recent approaches to provide a perspective on the future of neurostimulation. (Review)
Review
PURPOSE OF REVIEW
Neurostimulation is a quickly growing treatment approach for epilepsy patients. We summarize recent approaches to provide a perspective on the future of neurostimulation.
RECENT FINDINGS
Invasive stimulation for treatment of focal epilepsy includes vagus nerve stimulation, responsive neurostimulation of the cortex and deep brain stimulation of the anterior nucleus of the thalamus. A wide range of other targets have been considered, including centromedian, central lateral and pulvinar thalamic nuclei; medial septum, nucleus accumbens, subthalamic nucleus, cerebellum, fornicodorsocommissure and piriform cortex. Stimulation for generalized onset seizures and mixed epilepsies as well as increased efforts focusing on paediatric populations have emerged. Hardware with more permanently implanted lead options and sensing capabilities is emerging. A wider variety of programming approaches than typically used may improve patient outcomes. Finally, noninvasive brain stimulation with its favourable risk profile offers the potential to treat increasingly diverse epilepsy patients.
SUMMARY
Neurostimulation for the treatment of epilepsy is surprisingly varied. Flexibility and reversibility of neurostimulation allows for rapid innovation. There remains a continued need for excitability biomarkers to guide treatment and innovation. Neurostimulation, a part of bioelectronic medicine, offers distinctive benefits as well as unique challenges.
Topics: Child; Humans; Deep Brain Stimulation; Epilepsy; Seizures; Cerebral Cortex; Thalamus
PubMed: 36762660
DOI: 10.1097/WCO.0000000000001138 -
Neurobiology of Disease Feb 2020Sleep and circadian rhythms are among the most powerful but least understood contributors to cognitive performance and brain health. Here we capitalize on the circadian... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized, double-blind, placebo-controlled trial of blue wavelength light exposure on sleep and recovery of brain structure, function, and cognition following mild traumatic brain injury.
Sleep and circadian rhythms are among the most powerful but least understood contributors to cognitive performance and brain health. Here we capitalize on the circadian resetting effect of blue-wavelength light to phase shift the sleep patterns of adult patients (aged 18-48 years) recovering from mild traumatic brain injury (mTBI), with the aim of facilitating recovery of brain structure, connectivity, and cognitive performance. During a randomized, double-blind, placebo-controlled trial of 32 adults with a recent mTBI, we compared 6-weeks of daily 30-min pulses of blue light (peak λ = 469 nm) each morning versus amber placebo light (peak λ = 578 nm) on neurocognitive and neuroimaging outcomes, including gray matter volume (GMV), resting-state functional connectivity, directed connectivity using Granger causality, and white matter integrity using diffusion tensor imaging (DTI). Relative to placebo, morning blue light led to phase-advanced sleep timing, reduced daytime sleepiness, and improved executive functioning, and was associated with increased volume of the posterior thalamus (i.e., pulvinar), greater thalamo-cortical functional connectivity, and increased axonal integrity of these pathways. These findings provide insight into the contributions of the circadian and sleep systems in brain repair and lay the groundwork for interventions targeting the retinohypothalamic system to facilitate injury recovery.
Topics: Actigraphy; Adolescent; Adult; Brain; Brain Concussion; Brain Mapping; Cognition; Double-Blind Method; Female; Humans; Light; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Phototherapy; Sleep; Treatment Outcome; Young Adult
PubMed: 31751607
DOI: 10.1016/j.nbd.2019.104679 -
Annual Review of Psychology Jan 2020Spatial attention is comprised of neural mechanisms that boost sensory processing at a behaviorally relevant location while filtering out competing information. The... (Review)
Review
Spatial attention is comprised of neural mechanisms that boost sensory processing at a behaviorally relevant location while filtering out competing information. The present review examines functional specialization in the network of brain regions that directs such preferential processing. This attention network includes both cortical (e.g., frontal and parietal cortices) and subcortical (e.g., the superior colliculus and the pulvinar nucleus of the thalamus) structures. Here, we piece together existing evidence that these various nodes of the attention network have dissociable functional roles by synthesizing results from electrophysiology and neuroimaging studies. We describe functional specialization across several dimensions (e.g., at different processing stages and within different behavioral contexts), while focusing on spatial attention as a dynamic process that unfolds over time. Functional contributions from each node of the attention network can change on a moment-to-moment timescale, providing the necessary cognitive flexibility for sampling from highly dynamic environments.
Topics: Attention; Cerebral Cortex; Humans; Nerve Net; Pulvinar; Space Perception; Superior Colliculi
PubMed: 31514578
DOI: 10.1146/annurev-psych-010418-103429