Long-term brain network reorganization predicts responsive neurostimulation outcomes for focal epilepsy

2021 ◽  
Vol 13 (608) ◽  
pp. eabf6588
Author(s):  
Ankit N. Khambhati ◽  
Alia Shafi ◽  
Vikram R. Rao ◽  
Edward F. Chang
Keyword(s):  
Therapeutic Response ◽  
Focal Epilepsy ◽  
Therapeutic Benefit ◽  
Brain Network ◽  
First Year ◽  
Seizure Reduction ◽  
Neural Recordings ◽  
Brain Network Reorganization ◽  
The Brain

Responsive neurostimulation (RNS) devices, able to detect imminent seizures and to rapidly deliver electrical stimulation to the brain, are effective in reducing seizures in some patients with focal epilepsy. However, therapeutic response to RNS is often slow, is highly variable, and defies prognostication based on clinical factors. A prevailing view holds that RNS efficacy is primarily mediated by acute seizure termination; yet, stimulations greatly outnumber seizures and occur mostly in the interictal state, suggesting chronic modulation of brain networks that generate seizures. Here, using years-long intracranial neural recordings collected during RNS therapy, we found that patients with the greatest therapeutic benefit undergo progressive, frequency-dependent reorganization of interictal functional connectivity. The extent of this reorganization scales directly with seizure reduction and emerges within the first year of RNS treatment, enabling potential early prediction of therapeutic response. Our findings reveal a mechanism for RNS that involves network plasticity and may inform development of next-generation devices for epilepsy.

scholarly journals Association Between Trait Empathy and Resting Brain Activity in Women With Primary Dysmenorrhea During the Pain and Pain-Free Phases

2020 ◽  
Vol 11 ◽  
Author(s):  
Wanghuan Dun ◽  
Tongtong Fan ◽  
Qiming Wang ◽  
Ke Wang ◽  
Jing Yang ◽  
...  
Keyword(s):  
Brain Activity ◽  
Inferior Frontal Gyrus ◽  
Brain Network ◽  
Primary Dysmenorrhea ◽  
Pain Experience ◽  
Current State ◽  
The Neural Network ◽  
The Right ◽  
The Brain

Empathy refers to the ability to understand someone else's emotions and fluctuates with the current state in healthy individuals. However, little is known about the neural network of empathy in clinical populations at different pain states. The current study aimed to examine the effects of long-term pain on empathy-related networks and whether empathy varied at different pain states by studying primary dysmenorrhea (PDM) patients. Multivariate partial least squares was employed in 46 PDM women and 46 healthy controls (HC) during periovulatory, luteal, and menstruation phases. We identified neural networks associated with different aspects of empathy in both groups. Part of the obtained empathy-related network in PDM exhibited a similar activity compared with HC, including the right anterior insula and other regions, whereas others have an opposite activity in PDM, including the inferior frontal gyrus and right inferior parietal lobule. These results indicated an abnormal regulation to empathy in PDM. Furthermore, there was no difference in empathy association patterns in PDM between the pain and pain-free states. This study suggested that long-term pain experience may lead to an abnormal function of the brain network for empathy processing that did not vary with the pain or pain-free state across the menstrual cycle.

scholarly journals Drug-resistant focal epilepsy in children is associated with increased modal controllability of the whole brain and epileptogenic regions

2021 ◽  
Author(s):  
Kiran Seunarine ◽  
Xiaosong He ◽  
Martin Tisdall ◽  
Christopher Clark ◽  
Danielle S Bassett ◽  
...  
Keyword(s):  
Diffusion Mri ◽  
Focal Epilepsy ◽  
Brain Network ◽  
Structure And Function ◽  
Network Control ◽  
Drug Resistant ◽  
Drug Resistant Epilepsy ◽  
And Function ◽  
The Brain ◽  
Disease Understanding

Network control theory provides a framework by which neurophysiological dynamics of the brain can be modelled as a function of the structural connectome constructed from diffusion MRI. Average controllability describes the ability of a region to drive the brain to easy-to-reach neurophysiological states whilst modal controllability describes the ability of a region to drive the brain to difficult-to-reach states. In this study, we identify increases in mean average and modal controllability in children with drug-resistant epilepsy compared to healthy controls. Using simulations, we purport that these changes may be a result of increased thalamocortical connectivity. At the node level, we demonstrate decreased modal controllability in the thalamus and posterior cingulate regions. In those undergoing resective surgery, we also demonstrate increased modal controllability of the resected parcels, a finding specific to patients who were rendered seizure free following surgery. Changes in controllability are a manifestation of brain network dysfunction in epilepsy and may be a useful construct to understand the pathophysiology of this archetypical network disease. Understanding the mechanisms underlying these controllability changes may also facilitate the design of network-focussed interventions that seek to normalise network structure and function.

scholarly journals Critical slowing as a biomarker for seizure susceptibility

2019 ◽  
Author(s):  
Matias I. Maturana ◽  
Christian Meisel ◽  
Katrina Dell ◽  
Philippa J. Karoly ◽  
Wendyl D’Souza ◽  
...  
Keyword(s):  
Focal Epilepsy ◽  
Warning Signal ◽  
Theoretical Models ◽  
Critical Transitions ◽  
Epileptiform Discharges ◽  
Brain Signals ◽  
Change State ◽  
Intracranial Electroencephalography ◽  
The Brain

AbstractThe human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system would suggest that prior to a seizure recorded brain signals may exhibit critical slowing, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we found key signatures of critical slowing prior to seizures. Signals related to a critically slowing process fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing is a reliable indicator that could be used in seizure forecasting algorithms.

scholarly journals Prolonged Beneficial Effect of Brief Erythropoietin Peptide JM4 Therapy on Chronic Relapsing EAE

2020 ◽  
Author(s):  
Deeya Gaindh ◽  
Yun-Beom Choi ◽  
Michelle Marchese ◽  
Peter Dowling ◽  
Stuart Cook ◽  
...  
Keyword(s):  
Neurovascular Unit ◽  
Therapeutic Benefit ◽  
Term Treatment ◽  
Demyelinating Diseases ◽  
Neuroprotective Activity ◽  
Clinical Effects ◽  
Long Term Treatment ◽  
Chronic Relapsing Eae ◽  
The Brain

Abstract Potent beneficial immunomodulatory and anti-inflammatory effects of whole-molecule erythropoietin have been demonstrated in a variety of animal disease models including experimental autoimmune encephalomyelitis (EAE); however, excessive hematopoiesis limits its use in clinical applications. Our group previously generated an Epo-derived small peptide JM4 that is side-effect free and has strong neuroprotective activity without hematologic effects. Here, we investigated the long-term clinical effects of brief treatment with JM4 in chronic relapsing EAE using bioluminescence imaging (BLI) in transgenic mice containing the luciferase gene driven by the murine GFAP promoter. EAE mice treated with JM4 exhibited marked improvement in clinical scores and showed fewer disease flareups than control animals. JM4 therapy concomitantly led to markedly decreased GFAP bioluminescence in the brain and spinal cord in both acute and chronic relapsing EAE mouse models. We found a marker for toxic A1 astrocytes, complement component C3, that is upregulated in the brain and cord of EAE mice and sharply reduced in JM4-treated animals. In addition, an abnormally leaky neurovascular unit permeability was rapidly normalized within 5 days by JM4 therapy. The prolonged therapeutic benefit seen following brief JM4 treatment in EAE mice closely resemble that recently described in humans receiving pulsed immune reconstitution therapy with the disease-modifying compounds, alemtuzumab and cladribine. Our study suggests that JM4 therapy may have widespread clinical applicability for long-term treatment of inflammatory demyelinating diseases and that BLI is a useful noninvasive means of monitoring murine disease activity of the central nervous system.

scholarly journals DIFFICULTIES OF EARLY INFANTILE EPILEPTIC ENCEPHALOPATHY-9 DIAGNOSTIC

2019 ◽  
pp. 24-30
Author(s):  
A. G. Malov ◽  
M. I. Vshivkov ◽  
M. A. Mamunts
Keyword(s):  
Structural Changes ◽  
Focal Epilepsy ◽  
Correct Diagnosis ◽  
Hereditary Disease ◽  
Epileptic Activity ◽  
Epileptic Encephalopathy ◽  
Genetic Examination ◽  
Convulsive Seizures ◽  
The Brain

Introduction: Early infantile epileptic encephalopathy (EIEE) is a group of monogenic epilepsies which are caused by mutations in more than 70 genes. Material and methods: The data of a long-term dynamic EEG observation of a girl with EIEE9 (OMIM 300088) caused by a mutation in the PCDH19 gene (OMIM 300460) are presented. Results: Correct etiological diagnosis of the hereditary disease was established only at the age of 14 years. Epilepsy debuted at the age of 8 months as a series of one minute long generalized tonic convulsions with myoclonia in the left arm. After further examination the symptoms were mistakenly regarded as viral encephalitis. Subsequently, clusters of convulsive seizures provoked by febrile states periodically were occurring several times per year irrespective of the type and amount of anticonvulsants taken. Despite the fact, that no significant structural changes in the brain we found during neuroimaging, pharmacoresistant focal epilepsy gradually developed. At the age of 14 years, as part of a pre-surgical examination for two days, the complete abolition of anticonvulsants and the implantation of subdural electrodes were performed. Focal motor seizures with a transition to bilateral tonic-clonic seizures were recorded, during which the primary generation of epileptic activity was localized in the left temporal lobe. А thorough examination with a clarification of the monogenic origin of the disease made it possible to avoid undue surgery on the brain. Discussion: The presented observation is a clear example of why a timely genetic examination is important for establishing correct diagnosis, adequate selection of anticonvulsants and a making a right decision on the possibility of surgical treatment.

scholarly journals Making the Invisible Visible: Advanced Neuroimaging Techniques in Focal Epilepsy

2021 ◽  
Vol 15 ◽  
Author(s):  
Daichi Sone
Keyword(s):  
Focal Epilepsy ◽  
Seizure Reduction ◽  
Intensive Intervention ◽  
Conventional Mri ◽  
Mri Sequences ◽  
Applications Of Machine Learning ◽  
Non Gaussian ◽  
Focus Detection ◽  
The Brain ◽  
Neuroimaging Techniques

It has been a clinically important, long-standing challenge to accurately localize epileptogenic focus in drug-resistant focal epilepsy because more intensive intervention to the detected focus, including resection neurosurgery, can provide significant seizure reduction. In addition to neurophysiological examinations, neuroimaging plays a crucial role in the detection of focus by providing morphological and neuroanatomical information. On the other hand, epileptogenic lesions in the brain may sometimes show only subtle or even invisible abnormalities on conventional MRI sequences, and thus, efforts have been made for better visualization and improved detection of the focus lesions. Recent advance in neuroimaging has been attracting attention because of the potentials to better visualize the epileptogenic lesions as well as provide novel information about the pathophysiology of epilepsy. While the progress of newer neuroimaging techniques, including the non-Gaussian diffusion model and arterial spin labeling, could non-invasively detect decreased neurite parameters or hypoperfusion within the focus lesions, advances in analytic technology may also provide usefulness for both focus detection and understanding of epilepsy. There has been an increasing number of clinical and experimental applications of machine learning and network analysis in the field of epilepsy. This review article will shed light on recent advances in neuroimaging for focal epilepsy, including both technical progress of images and newer analytical methodologies and discuss about the potential usefulness in clinical practice.

scholarly journals Levodopa-induced plasticity: a double-edged sword in Parkinson's disease?

2015 ◽  
Vol 370 (1672) ◽  
pp. 20140184 ◽  
Author(s):  
Paolo Calabresi ◽  
Veronica Ghiglieri ◽  
Petra Mazzocchetti ◽  
Ilenia Corbelli ◽  
Barbara Picconi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuropsychiatric Symptoms ◽  
Dorsal Striatum ◽  
Long Term Potentiation ◽  
Therapeutic Benefit ◽  
Neurodegenerative Process ◽  
Advanced Phase ◽  
The Brain

The long-term replacement therapy with the dopamine (DA) precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) is a milestone in the treatment of Parkinson's disease (PD). Although this drug precursor can be metabolized into the active neurotransmitter DA throughout the brain, its therapeutic benefit is due to restoring extracellular DA levels within the dorsal striatum, which lacks endogenous DA as a consequence of the neurodegenerative process induced by the disease. In the early phases of PD, L-DOPA treatment is able to restore both long-term depression (LTD) and long-term potentiation (LTP), two major forms of corticostriatal synaptic plasticity that are altered by dopaminergic denervation. However, unlike physiological DA transmission, this therapeutic approach in the advanced phase of the disease leads to abnormal peaks of DA, non-synaptically released, which are supposed to trigger behavioural sensitization, namely L-DOPA-induced dyskinesia. This condition is characterized by a loss of synaptic depotentiation, an inability to reverse previously induced LTP. In the advanced stages of PD, L-DOPA can also induce non-motor fluctuations with cognitive dysfunction and neuropsychiatric symptoms such as compulsive behaviours and impulse control disorders. Although the mechanisms underlying the role of L-DOPA in both motor and behavioural symptoms are still incompletely understood, recent data from electrophysiological and imaging studies have increased our understanding of the function of the brain areas involved and of the mechanisms implicated in both therapeutic and adverse actions of L-DOPA in PD patients.

The Acute Effect of Alcohol on Various Memory Processes

2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Acute Effect ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processes ◽  
Different Types ◽  
The Brain ◽  
Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

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