scholarly journals Full-bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene microtransistor depth neural probes

Author(s):  
Andrea Bonaccini Calia ◽  
Eduard Masvidal-Codina ◽  
Trevor M. Smith ◽  
Nathan Schäfer ◽  
Daman Rathore ◽  
...  
2021 ◽  
Author(s):  
Andrea Bonaccini Calia ◽  
Eduard Masvidal-Codina ◽  
Trevor M. Smith ◽  
Nathan Schäfer ◽  
Daman Rathore ◽  
...  

ABSTRACTMapping the entire frequency bandwidth of neuronal oscillations in the brain is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously infraslow activity (<0.1 Hz) and higher frequencies (0.1-600 Hz) using the same recording electrode would particularly benefit epilepsy research. However, commonly used metal microelectrode technology is not well suited for recording infraslow activity. Here we use flexible graphene depth neural probes (gDNP), consisting of a linear array of graphene microtransistors, to concurrently record infraslow and high frequency neuronal activity in awake rodents. We show that gDNPs can reliably record and map with high spatial resolution seizures, post-ictal spreading depolarisation, and high frequency epileptic activity through cortical laminae to the CA1 layer of the hippocampus in a mouse model of chemically-induced seizures. We demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow activity in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, in particular, to examine the contributions of infraslow activity to seizure initiation and termination.


2020 ◽  
Vol 1 (2) ◽  
pp. 38-44
Author(s):  
Irina V. Vakhlova ◽  
Anastasia D. Kazachina ◽  
Olga A. Beglyanina

Background. In the international clinical practice there have been occasional reports of phenylketonuria (PKU) and cystic fibrosis (CF) found simultaneously in the same patient. Both PKU and CF are the inherited disorders characterized by autosomal recessive type of inheritance. Currently the combination of two or more inherited disorders in one patient is considered to be a clinical rarity.Case description. This is a clinical case of two genetic disorders, CF and PKU, combined in a 5-year old patient who had been followed up since birth. Owing to implementation of neonatal screening for inherited and congenital diseases into clinical practice, during the first month of life the infant was diagnosed with CF (diagnostically significant elevation of immunoreactive trypsin [IRT] at the initial [163.2 ng/mL] and repeat testing on day 21 of life [138.7 ng/mL]) and PKU (phenylalanine [PA] level 15.9 mg/dL). Both disorders have been confirmed by genetic tests, i.e., homozygous DelF508 mutation was found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and P281L mutation in the phenylalanine hydroxylase (PAH) gene was also present in homozygous state. Child’s parents strictly adhered to dietary and treatment recommendations. By the age of 5 years the child developed symptoms of neurological disorder and disorder of the respiratory system, cognitive impairment and delay in speech development, subclinical epileptiform activity with high risk of epilepsy, and chronic inflammation of the respiratory tract.Conclusion. This case report demonstrates the important role of neonatal screening in early diagnosis and timely start of therapy, and underscores the importance of continuous medication in such genetic disorders as CF and PKU. On the whole, such approach brings about a relative preservation of functioning of the most affected organs and systems. By the age of 5 years the child does not form bronchiectases, shows no signs of chronic hypoxia, nutritional deficiency or pronounced neurologic deficit, and is at low risk for the development of autism spectrum disorder. At the same time, the larger scale and longer-term observations are required in order to make the unequivocal conclusions about the prognosis of these diseases under conditions of modern-day medical follow-up.


2021 ◽  
pp. 088307382098126
Author(s):  
Phillip L. Pearl ◽  
Melissa L. DiBacco ◽  
Christos Papadelis ◽  
Thomas Opladen ◽  
Ellen Hanson ◽  
...  

Objective: The SSADHD Natural History Study was initiated in 2019 to define the natural course and identify biomarkers correlating with severity. Methods: The study is conducted by 4 institutions: BCH (US clinical), WSU (bioanalytical core), USF (biostatistical core), and Heidelberg (iNTD), with support from the family advocacy group (SSADH Association). Recruitment goals were to study 20 patients on-site at BCH, 10 with iNTD, and 25 as a standard-of care cohort. Results: At this half-way point of this longitudinal study, 28 subjects have been recruited (57% female, mean 9 years, range 18 months–40 years). Epilepsy is present in half and increases in incidence and severity, as do psychiatric symptoms, in adolescence and adulthood. The average Full Scale IQ (FSIQ) was 53 (Verbal score of 56, Non Verbal score of 49), and half scored as having ASD. Although there was no correlation between gene variant and phenotypic severity, there were extreme cases of lowest functioning in one individual and highest in another that may have genotype-phenotype correlation. The most common EEG finding was mild background slowing with rare epileptiform activity, whereas high-density EEG and magnetoencephalography showed reduction in the gamma frequency band consistent with GABAergic dysfunction. MR spectroscopy showed elevations in the GABA/NAA ratio in all regions studied with no crossover between subjects and controls. Conclusions: The SSADH Natural History Study is providing a unique opportunity to study the complex pathophysiology longitudinally and derive electrophysiologic, neuroimaging, and laboratory data for correlation and to serve as biomarkers for clinical trials and prognostic assessments in this ultra-rare inherited disorder of GABA metabolism.


2021 ◽  
Vol 22 (12) ◽  
pp. 6593
Author(s):  
Kenta H.T. Cho ◽  
Mhoyra Fraser ◽  
Bing Xu ◽  
Justin M. Dean ◽  
Alistair J. Gunn ◽  
...  

Background: Toll-like receptor (TLR) agonists are key immunomodulatory factors that can markedly ameliorate or exacerbate hypoxic–ischemic brain injury. We recently demonstrated that central infusion of the TLR7 agonist Gardiquimod (GDQ) following asphyxia was highly neuroprotective after 3 days but not 7 days of recovery. We hypothesize that this apparent transient neuroprotection is associated with modulation of seizure-genic processes and hemodynamic control. Methods: Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion (20.9 ± 0.5 min) and were monitored continuously for 7 days. GDQ 3.34 mg or vehicle were infused intracerebroventricularly from 1 to 4 h after asphyxia. Results: GDQ infusion was associated with sustained moderate hypertension that resolved after 72 h recovery. Electrophysiologically, GDQ infusion was associated with reduced number and burden of postasphyxial seizures in the first 18 h of recovery (p < 0.05). Subsequently, GDQ was associated with induction of slow rhythmic epileptiform discharges (EDs) from 72 to 96 h of recovery (p < 0.05 vs asphyxia + vehicle). The total burden of EDs was associated with reduced numbers of neurons in the caudate nucleus (r2 = 0.61, p < 0.05) and CA1/2 hippocampal region (r2 = 0.66, p < 0.05). Conclusion: These data demonstrate that TLR7 activation by GDQ modulated blood pressure and suppressed seizures in the early phase of postasphyxial recovery, with subsequent prolonged induction of epileptiform activity. Speculatively, this may reflect delayed loss of early protection or contribute to differential neuronal survival in subcortical regions.


2021 ◽  
Author(s):  
Mauricio Mandel ◽  
Layton Lamsam ◽  
Pue Farooque ◽  
Dennis Spencer ◽  
Eyiyemisi Damisah

Abstract The insula is well established as an epileptogenic area.1 Insular epilepsy surgery demands precise anatomic knowledge2-4 and tailored removal of the epileptic zone with careful neuromonitoring.5 We present an operative video illustrating an intracranial electroencephalogram (EEG) depth electrode guided anterior insulectomy.  We report a 17-yr-old right-handed woman with a 4-yr history of medically refractory epilepsy. The patient reported daily nocturnal ictal vocalization preceded by an indescribable feeling. Preoperative evaluation was suggestive of a right frontal-temporal onset, but the noninvasive results were discordant. She underwent a combined intracranial EEG study with a frontal-parietal grid, with strips and depth electrodes covering the entire right hemisphere. Epileptiform activity was observed in contact 6 of the anterior insula electrode. The patient consented to the procedure and to the publication of her images.  A right anterior insulectomy was performed. First, a portion of the frontal operculum was resected and neuronavigation was used for the initial insula localization. However, due to unreliable neuronavigation (ie, brain shift), the medial and anterior borders of the insular resection were guided by the depth electrode reference. The patient was discharged 3 d after surgery with no neurological deficits and remains seizure free.  We demonstrate that depth electrode guided insular surgery is a safe and precise technique, leading to an optimal outcome.


2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Howaida E. Mansour ◽  
Reem A. Habeeb ◽  
Noran O. El-Azizi ◽  
Heba H. Afeefy ◽  
Marwa A. Nassef ◽  
...  

Abstract Background Neuropsychiatric manifestations are frequently reported in systemic lupus erythematosus (SLE) patients. This study was done to describe electroencephalographic (EEG) findings in SLE patients with neuropsychiatric manifestation (NPSLE). Results Among 60 SLE patients, there were 50 females (83.3%) and 10 males (16.7%). EEG abnormalities were reported in 12 patients out of 30 (40%) with NPSLE, while all patients with non-NPSLE (n = 30) had no EEG abnormalities; diffuse slowing (20%) was the most common abnormalities, followed by generalized epileptiform activity (13.3%), and lastly temporal epileptiform activity (6.7%). Seizure was the most reported neuropsychiatric disorder in 13 patients (43.3%); 8 of them had abnormal EEG (61.5%). Periventricular white matter lesion (23.3%) followed by infarction (13.3%) were the most common MRI brain findings among 53.3% of NPSLE group. Half of the cases with EEG abnormality had normal brain MRI. SLEDAI score and ACL IgM positivity were higher in the NPSLE group than the non-NPSLE group. EEG is not a sensitive or specific test for detecting NPSLE with sensitivity (37.5%) and specificity (57.1%). Conclusion Not all patients with NPSLE must have abnormal brain MRI or EEG. EEG is a useful assistant tool in the assessment of different manifestations of NPSLE, but it cannot be used as a screening test alone and must be supplemented by neuroimaging studies.


Sensors ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 2605
Author(s):  
Ashley Novais ◽  
Carlos Calaza ◽  
José Fernandes ◽  
Helder Fonseca ◽  
Patricia Monteiro ◽  
...  

Multisite neural probes are a fundamental tool to study brain function. Hybrid silicon/polymer neural probes combine rigid silicon and flexible polymer parts into one single device and allow, for example, the precise integration of complex probe geometries, such as multishank designs, with flexible biocompatible cabling. Despite these advantages and benefiting from highly reproducible fabrication methods on both silicon and polymer substrates, they have not been widely available. This paper presents the development, fabrication, characterization, and in vivo electrophysiological assessment of a hybrid multisite multishank silicon probe with a monolithically integrated polyimide flexible interconnect cable. The fabrication process was optimized at wafer level, and several neural probes with 64 gold electrode sites equally distributed along 8 shanks with an integrated 8 µm thick highly flexible polyimide interconnect cable were produced. The monolithic integration of the polyimide cable in the same fabrication process removed the necessity of the postfabrication bonding of the cable to the probe. This is the highest electrode site density and thinnest flexible cable ever reported for a hybrid silicon/polymer probe. Additionally, to avoid the time-consuming bonding of the probe to definitive packaging, the flexible cable was designed to terminate in a connector pad that can mate with commercial zero-insertion force (ZIF) connectors for electronics interfacing. This allows great experimental flexibility because interchangeable packaging can be used according to experimental demands. High-density distributed in vivo electrophysiological recordings were obtained from the hybrid neural probes with low intrinsic noise and high signal-to-noise ratio (SNR).


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