Neurophysiological Profiles Research Articles

Calcium/calmodulin-dependent protein kinase IIα heterozygous knockout mice show electroencephalogram and behavioral changes characteristic of a subpopulation of schizophrenia and intellectual impairment

Cognitive deficit remains an intractable symptom of schizophrenia, accounting for substantial disability. Despite this, little is known about the cause of cognitive dysfunction in schizophrenia. Recent studies suggest that schizophrenia patients show several changes in dentate gyrus structure and functional characteristic of immaturity. The immature dentate gyrus (iDG) has been replicated in several mouse models, most notably the CaMKIIα heterozygous mouse (CaMKIIα-hKO). The current study characterizes behavioral phenotypes of CaMKIIα-hKO mice and determines their neurophysiological profile using electroencephalogram (EEG) recording from hippocampus. CaMKIIα-hKO mice were hypoactive in home-cage environment; however, they displayed less anxiety-like phenotype, suggestive of impulsivity-like behavior. In addition, severe cognitive dysfunction was evident in CaMKIIα-hKO mice as examined by novel object recognition and contextual fear conditioning. Several EEG phenomena established in both patients and relevant animal models indicate key pathological changes associated with the disease, include auditory event-related potentials and time–frequency EEG oscillations. CaMKIIα-hKO mice showed altered event-related potentials characterized by an increase in amplitude of the N40 and P80, as well as increased P80 latency. These mice also showed increased power in theta range time–frequency measures. Additionally, CaMKIIα-hKO mice showed spontaneous bursts of spike wave activity, possibly indicating absence seizures. The GABAB agonist baclofen increased, while the GABAB antagonist CGP35348 and the T-Type Ca2+ channel blocker Ethosuximide decreased spike wave burst frequency. None of these changes in event-related potentials or EEG oscillations are characteristic of those observed in general population of patients with schizophrenia; yet, CaMKIIα-hKO mice likely model a subpopulation of patients with schizophrenia.

Cerebral Oxygenation and Metabolism After Hypoxia-Ischemia.

Perinatal hypoxia-ischemia (HI) is still a significant contributor to mortality and adverse neurodevelopmental outcomes in term and preterm infants. HI brain injury evolves over hours to days, and involves complex interactions between the endogenous protective and pathological processes. Understanding the timing of evolution of injury is vital to guide treatment. Post-HI recovery is associated with a typical neurophysiological profile, with stereotypic changes in cerebral perfusion and oxygenation. After the initial recovery, there is a delayed, prolonged reduction in cerebral perfusion related to metabolic suppression, followed by secondary deterioration with hyperperfusion and increased cerebral oxygenation, associated with altered neurovascular coupling and impaired cerebral autoregulation. These changes in cerebral perfusion are associated with the stages of evolution of injury and injury severity. Further, iatrogenic factors can also affect cerebral oxygenation during the early period of deranged metabolism, and improving clinical management may improve neuroprotection. We will review recent evidence that changes in cerebral oxygenation and metabolism after HI may be useful biomarkers of prognosis.

High-frequency rTMS in the treatment of depressive symptoms in schizophrenia: a neurophysiological profile of respondents and nonresponders

IntroductionDepressive symptoms in schizophrenia have a high prevalence – up to 20-60 %, at the different illness stages. Non-pharmacological treatment, namely rTMS, seems like a promising approach that lacks side-effects typical for antidepressants. RTMS is widely applied in the treatment of depression, however the studies within schizophrenia domain are still rather fewObjectivesThe aim was to examine a potential of neurophysiological data for prediction of the effects of rTMS in the treatment of patients with schizophrenia with depressive symptomsMethods20 male patients with schizophrenia (F20.004, F20.014, F20.414, ICD–10) were examined at the stage of incomplete remission with predominance of prolonged (more than 6 months) treatment resistant depressive symptoms. An examination (clinical and neurophysiological (oddball ERP and EEG) fragments)) was repeated twice - before and after a course of 10 Hz rTMS (left DLPC, 2000 pulses per session, 15 sessions).ResultsPoor outcome was associated with initially higher coherence in alpha and lower - in beta1 EEG bands. The amplitudes of non-target N100 and mismatch negativity didn’t differ the groups of responders and nonrespondersConclusionsThe disturbances within brain networks of beta1 and alpha generators merit attention as potential neurophysiological markers with predictive value in rTMS treatment of patients with schizophrenia with depressive symptoms.DisclosureNo significant relationships.

The relationship between acoustic and musical pitch processing in adolescents.

Amusia is defined as a difficulty processing the tonal pitch structure of music such that an individual cannot tell the difference between notes that are in-key and out-of-key. A fine-grained pitch discrimination deficit is often observed in people with amusia. It is possible that an intervention, early in development, could mitigate amusia; however, one challenge identifying amusia early in development is that identifying in- and out-of-key notes is a metacognitive task. Given the common co-occurrence of difficulties with pitch discrimination, it would be easier to identify amusia in developing children by using a pitch change detection task. The goal of this study was to explore the behavioural and neurophysiological profiles of adolescents with poor pitch processing (Poor PP) abilities compared with those with normal pitch processing (Normal PP) abilities. Neurophysiologically, the Poor PPs exhibited a similar event-related potential (ERP) profile to adult amusics during both acoustic and musical pitch discrimination tasks. That is, early ERPs (ERAN, MMN) were similar in Poor PPs compared with Normal PPs, whereas late positivities (P300, P600) were absent in Poor PPs, but present in Normal PPs. At the same time, behavioural data revealed a double dissociation between the abilities to detect a pitch deviant in acoustic and musical context, suggesting that about a third of the children would be missed by selecting a fine-grained acoustic pitch discrimination task to identify the presence of amusia in early childhood.

High Dream Recall Frequency is Associated with Increased Creativity and Default Mode Network Connectivity.

IntroductionSeveral results suggest that the frequency of dream recall is positively correlated with personality traits such as creativity and openness to experience. In addition, neuroimaging results have evidenced different neurophysiological profiles in high dream recallers (HR) and low dream recallers (LR) during both sleep and wakefulness, specifically within regions of the default mode network (DMN). These findings are consistent with the emerging view that dreaming and mind wandering pertain to the same family of spontaneous mental processes, subserved by the DMN.MethodsTo further test this hypothesis, we measured the DMN functional connectivity during resting wakefulness, together with personality and cognitive abilities (including creativity) in 28 HR and 27 LR.ResultsAs expected, HR demonstrated a greater DMN connectivity than LR, higher scores of creativity, and no significant difference in memory abilities. However, there was no significant correlation between creativity scores and DMN connectivity.DiscussionThese results further demonstrate that there are trait neurophysiological and psychological differences between individuals who frequently recall their dreams and those who do not. They support the forebrain and the DMN hypotheses of dreaming and leave open the possibility that increased activity in the DMN promotes creative-thinking during both wakefulness and sleep. Further work is needed to test whether activity in the DMN is causally associated with creative-thinking.

Neurophysiological profiles of responders and nonresponders to hypoglossal nerve stimulation: a single-institution study.

Hypoglossal nerve stimulation (HGNS) is an effective alternative treatment for obstructive sleep apnea that acts by opening the airway via selective stimulation of nerve fibers that innervate tongue muscles that protrude (genioglossus) and stiffen the tongue (transverse and vertical) while avoiding nerve fibers that innervate tongue muscles that retract the tongue (styloglossus and hyoglossus). There remains a subset of postoperative patients who fail to adequately respond to HGNS, in some cases due to mixed activation of muscles that simultaneously protrude and retract the tongue. This study aims to characterize the relationship between neurophysiological data from individual tongue muscle activation during intraoperative electromyographic recordings and postoperative apnea-hypopnea index responses to HGNS. A single-institution review of 46 patients undergoing unilateral HGNS implantation for obstructive sleep apnea. Patients were separated into responders and nonresponders through comparison of pre and postoperative apnea-hypopnea index. Neurophysiological data included electromyographic responses of the genioglossus, styloglossus/hyoglossus, intrinsic/vertical, and hyoglossus (neck) muscles to intraoperative stimulation using unipolar (- to - and o to o) and bipolar (+ to +) settings. The overall treatment success rate was 61% as determined by a postoperative apnea-hypopnea index < 20 events/h with a greater than 50% AHI reduction. We observed no statistically significant relationships between treatment response and individual muscle responses. However, we did note that increasing body mass index was correlated with worse postoperative responses. Although we noted a significant subgroup of clinical nonresponders to HGNS postoperatively, these patients were not found to exhibit significant inclusion of tongue retractors intraoperatively on neurophysiological analysis. Further research is needed to delineate additional phenotypic factors that may contribute to HGNS treatment responses. Wang D, Modik O, Sturm JJ, etal. Neurophysiological profiles of responders and nonresponders to hypoglossal nerve stimulation: a single-institution study. J Clin Sleep Med. 2022;18(5):1327-1333.

Resting-state EEG reveals four subphenotypes of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a devastating disease characterized primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. Amyotrophic lateral sclerosis is both clinically and biologically heterogeneous. Subgrouping is currently undertaken using clinical parameters, such as site of symptom onset (bulbar or spinal), burden of disease (based on the modified El Escorial Research Criteria) and genomics in those with familial disease. However, with the exception of genomics, these subcategories do not take into account underlying disease pathobiology, and are not fully predictive of disease course or prognosis.Recently, we have shown that resting-state EEG can reliably and quantitatively capture abnormal patterns of motor and cognitive network disruption in amyotrophic lateral sclerosis. These network disruptions have been identified across multiple frequency bands, and using measures of neural activity (spectral power) and connectivity (comodulation of activity by amplitude envelope correlation and synchrony by imaginary coherence) on source-localized brain oscillations from high-density EEG. Using data-driven methods (similarity network fusion and spectral clustering), we have now undertaken a clustering analysis to identify disease subphenotypes and to determine whether different patterns of disruption are predictive of disease outcome.We show that amyotrophic lateral sclerosis patients (n = 95) can be subgrouped into four phenotypes with distinct neurophysiological profiles. These clusters are characterized by varying degrees of disruption in the somatomotor (α-band synchrony), frontotemporal (β-band neural activity and γl-band synchrony) and frontoparietal (γl-band comodulation) networks, which reliably correlate with distinct clinical profiles and different disease trajectories. Using an in-depth stability analysis, we show that these clusters are statistically reproducible and robust, remain stable after reassessment using a follow-up EEG session, and continue to predict the clinical trajectory and disease outcome.Our data demonstrate that novel phenotyping using neuroelectric signal analysis can distinguish disease subtypes based exclusively on different patterns of network disturbances. These patterns may reflect underlying disease neurobiology. The identification of amyotrophic lateral sclerosis subtypes based on profiles of differential impairment in neuronal networks has clear potential in future stratification for clinical trials. Advanced network profiling in amyotrophic lateral sclerosis can also underpin new therapeutic strategies that are based on principles of neurobiology and designed to modulate network disruption.

Clinical Pattern and Associated Comorbidities of Corpus Callosum Agenesis- A Tertiary Hospital Study

Background: The corpus callosum is the main commissural bundle of fibers interconnecting the two cerebral hemispheres. Defective embryogenesis during 8 and 20 weeks of gestation can lead to partial or complete agenesis of the corpus callosum.&#x0D; Objective: To see the patient’s clinical, neurophysiological profile, and comorbidities with corpus callosum agenesis presented in tertiary care hospital.&#x0D; Materials &amp;Methods: This descriptive cross-sectional study was conducted in the department of Paediatric Neurology, BSMMU, Dhaka, from January to December 2018. Patients who were diagnosed clinically and neuro-radiologically as corpus callosum agenesis were included in this study.&#x0D; Results:Out of 20 patients, 45% were in 13-24 months and 30% were in the 0-12 months’ age group. Female patients (55%) were predominant.Forty percent of patients had microcephaly and 30% facial dysmorphism. The majority of patients presented with developmental delay (90%), followed by epilepsy, speech impairment, and mental retardation. About one-fourth (25%) of patients were diagnosed as quadriplegic cerebral palsy and one-third (30%) dyskinetic cerebral palsy. Abnormal ophthalmological findings were found in 40% of cases. EEG showed hypsarrhythmia in 30%, partial seizure with secondary generalization in 15%, and myoclonic epilepsy in 15% of patients.&#x0D; Conclusion: In this study, common clinical features of patients with corpus callosal agenesis were developmental delay, facial dysmorphism, and microcephaly. About half of the patients had epilepsy, speech impairment, and mental retardation. About two-thirds of the patients had EEG changes and the most common EEG change was hypsarrhythmia.&#x0D; BANGLADESH J CHILD HEALTH 2021; VOL 45 (1) : 10-14

Exploring Clinical and Neurophysiological Factors Associated with Response to Constraint Therapy and Brain Stimulation in Children with Hemiparetic Cerebral Palsy

ABSTRACT Background Perinatal stroke causes hemiparetic cerebral palsy (HCP) and lifelong disability. Constraint-induced movement therapy (CIMT) and neurostimulation may enhance motor function, but the individual factors associated with responsiveness are undetermined. Objective We explored the clinical and neurophysiological factors associated with responsiveness to CIMT and/or brain stimulation within a clinical trial. Methods PLASTIC CHAMPS was a randomized, blinded, sham-controlled trial (n = 45) of CIMT and neurostimulation paired with intensive, goal-directed therapy. Primary outcome was the Assisting Hand Assessment (AHA). Classification trees created through recursive partitioning suggested clinical and neurophysiological profiles associated with improvement at 6-months. Results Both clinical (stroke side (left) and age >14 years) and neurophysiological (intracortical inhibition/facilitation and motor threshold) were associated with responsiveness across treatment groups with positive predictive values (PPV) approaching 80%. Conclusion This preliminary analysis suggested sets of variables that may be associated with response to intensive therapies in HCP. Further modeling in larger trials is required.

Psycho-affective health, cognition, and neurophysiological functioning following sports-related concussion in symptomatic and asymptomatic athletes, and control athletes

Little is known about the neuropsychiatric and neurophysiological differences that characterize abnormal recovery following a concussion. The present study aimed to investigate the psycho-affective, cognitive, and neurophysiological profiles of symptomatic, slow-to-recover, concussed athletes, asymptomatic concussed athletes, and control athletes. Seventy-eight athletes (26 symptomatic, 26 asymptomatic, 26 control) completed the Beck Depression Inventory-II, Profile of Mood States, and 2-Back task. Additionally, event-related brain potentials were recorded during an experimental three-stimulus visual Oddball paradigm. Compared to asymptomatic and control groups, the symptomatic group reported greater depression symptoms and negatively altered mood states. Symptomatic athletes also exhibited poorer cognitive performance on the 2-Back task, indicated by more errors and slower reaction time. ERP analyses indicated prolonged P3b latency for both symptomatic and asymptomatic groups, but symptomatic athletes also exhibited reduced P3b amplitude compared to both asymptomatic and control groups. For the asymptomatic group, correlations were observed between time since last concussion and functioning, but no relations were observed within the symptomatic group for any measure. The current findings provide valuable information regarding the psycho-affective, cognitive, and neurophysiological profiles of athletes with and without persistent symptoms following a concussion and highlight the need to assess and treat symptomatic, slow-to-recover athletes from a multidimensional and integrative perspective.

Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort

BackgroundAla97Ser transthyretin amyloidosis-associated polyneuropathy (ATTRA97S-PN) is a rare form of inherited polyneuropathy, usually manifesting with late-onset (> 50) progressive polyneuropathy. This mutation is mostly prevalent in Taiwanese and Han-Chinese individuals. The aim of this study was to describe the clinical and comprehensive neurophysiological profiles of ATTRA97S-PN in Thai patients.MethodsThe clinical profiles and serial neurophysiologic studies (nerve conduction study (NCS), quantitative sensory test (QST), and comprehensive autonomic function test (AFT)) of symptomatic ATTRA97S-PN patients who had been followed-up at King Chulalongkorn Memorial Hospital during 2010–2020 were retrospectively reviewed.ResultsNine symptomatic patients (55.6 % were male) from four unrelated families were included. All were Thais of mixed Thai Chinese descent. The mean age of onset was 48.3 (32–60) years. The mean age at diagnosis was 54.8 (33–66) years. Three patients developed early-onset (< 40y) polyneuropathy. The mean Neuropathy Impairment Score was 41.33 (10–92) at diagnosis. Sensory (9/9) and autonomic (9/9) neuropathies were more frequent than motor neuropathy (5/9), which appeared in the late stage of disease. Hypoesthesia in the feet, and gastrointestinal autonomic symptoms were frequently reported as the initial symptoms. The course of neuropathy progressed over years to decades. The worsening of neuropathy tended to progress faster once motor nerves were affected in both clinical and neurophysiological aspects. Concurrent cardiac amyloidosis was found in 6/9 patients. NCS showed length-dependent sensorimotor axonal polyneuropathy in 5/9 patients, and median neuropathy at the wrist (mostly bilateral) in 7/9 patients. QST showed abnormalities in the vibratory detection threshold, the cold detection threshold and the heat pain sensation in 8/9, 8/9 and 7/7 tested patients, respectively. AFT results were abnormal in all. The mean composite autonomic severity score was 5 (3–9).ConclusionsThis clinical study is the first of ATTRA97S-PN in Thai patients. The mixed polyneuropathy-cardiopathy phenotype was the most common manifestation. In this cohort, the age of onset was lower, and the course of neuropathy was relatively longer, than that in previous studies. Some patients may develop early-onset polyneuropathy. This mutation has not yet been documented in any population other than Han Chinese-related populations, probably suggesting a founder effect. Further studies are warranted.

Whole-brain modelling of resting state fMRI differentiates ADHD subtypes and facilitates stratified neuro-stimulation therapy

Recent advances in non-linear computational and dynamical modelling have opened up the possibility to parametrize dynamic neural mechanisms that drive complex behavior. Importantly, building models of neuronal processes is of key importance to fully understand disorders of the brain as it may provide a quantitative platform that is capable of binding multiple neurophysiological processes to phenotype profiles. In this study, we apply a newly developed adaptive frequency-based model of whole-brain oscillations to resting-state fMRI data acquired from healthy controls and a cohort of attention deficit hyperactivity disorder (ADHD) subjects. As expected, we found that healthy control subjects differed from ADHD in terms of attractor dynamics. However, we also found a marked dichotomy in neural dynamics within the ADHD cohort. Next, we classified the ADHD group according to the level of distance of each individual's empirical network from the two model-based simulated networks. Critically, the model was mirrored in the empirical behavior data with the two ADHD subgroups displaying distinct behavioral phenotypes related to emotional instability (i.e., depression and hypomanic personality traits). Finally, we investigated the applicability and feasibility of our whole-brain model in a therapeutic setting by conducting in silico excitatory stimulations to parsimoniously mimic clinical neuro-stimulation paradigms in ADHD. We tested the effect of stimulating any individual brain region on the key network measures derived from the simulated brain network and its contribution in rectifying the brain dynamics to that of the healthy brain, separately for each ADHD subgroup. This showed that this was indeed possible for both subgroups. However, the current effect sizes were small suggesting that the stimulation protocol needs to be tailored at the individual level. These findings demonstrate the potential of this new modelling framework to unveil hidden neurophysiological profiles and establish tailored clinical interventions.

Desflurane and sevoflurane differentially affect activity of the subthalamic nucleus in Parkinson's disease

BackgroundDesflurane and sevoflurane are commonly used during inhalational anaesthesia, but few studies have investigated their effects on deep cerebral neuronal activity. In addition, the association between subthalamic nucleus (STN) neurophysiology and general anaesthesia induced by volatile anaesthetics are not yet identified. This study aimed to identify differences in neurophysiological characteristics of the STN during comparable minimal alveolar concentration (MAC) desflurane and sevoflurane anaesthesia for deep brain stimulation (DBS) in patients with Parkinson's disease. MethodsTwelve patients with similar Parkinson's disease severity received desflurane (n=6) or sevoflurane (n=6) during DBS surgery. We obtained STN spike firing using microelectrode recording at 0.5–0.6 MAC and compared firing rate, power spectral density, and coherence. ResultsNeuronal firing rate was lower with desflurane (47.4 [26.7] Hz) than with sevoflurane (63.9 [36.5] Hz) anaesthesia (P<0.001). Sevoflurane entrained greater gamma oscillation power than desflurane (62.9% [0.9%] vs 57.0% [1.5%], respectively; P=0.002). There was greater coherence in the theta band of the desflurane group compared with the sevoflurane group (13% vs 6%, respectively). Anaesthetic choice did not differentially influence STN mapping accuracy or the clinical outcome of DBS electrode implantation. ConclusionsDesflurane and sevoflurane produced distinct neurophysiological profiles in humans that may be associated with their analgesic and hypnotic actions.

Cortical neurophysiology of primary isolated dystonia and non-dystonic adults: A meta-analysis.

Transcranial magnetic stimulation (TMS) is a non-invasive method to assess neurophysiology of the primary motor cortex in humans. Dystonia is a poorly understood neurological movement disorder, often presenting in an idiopathic, isolated form across different parts of the body. The neurophysiological profile of isolated dystonia compared to healthy adults remains unclear. We conducted a systematic review with meta-analysis of neurophysiologic TMS measures in people with isolated dystonia to provide a synthesized understanding of cortical neurophysiology associated with isolated dystonia. We performed a systematic database search and data were extracted independently by the two authors. Separate meta-analyses were performed for TMS measures of: motor threshold, corticomotor excitability, short interval intracortical inhibition, cortical silent period, intracortical facilitation and afferent-induced inhibition. Standardized mean differences were calculated using a random effects model to determine overall effect sizes and confidence intervals. Heterogeneity was explored using dystonia type subgroup analysis. The search resulted in 78 studies meeting inclusion criteria, of these 57 studies reported data in participants with focal hand dystonia, cervical dystonia, blepharospasm or spasmodic dysphonia, and were included in at least one meta-analysis. The cortical silent period, short-interval intracortical inhibition and afferent-induced inhibition was found to be reduced in isolated dystonia compared to controls. Reduced GABAergic-mediated inhibition in the primary motor cortex in idiopathic isolated dystonia's suggest interventions targeted to aberrant cortical disinhibition could provide a novel treatment. Future meta-analyses require neurophysiology studies to use homogeneous cohorts of isolated dystonia participants, publish raw data values, and record electromyographic responses from dystonic musculature where possible.

Off-line effects of alpha-frequency transcranial alternating current stimulation on a visuomotor learning task.

IntroductionIt has been suggested that transcranial alternating current stimulation (tACS) at both alpha and beta frequencies promotes motor function as well as motor learning. However, limited information exists on the aftereffects of tACS on motor learning and neurophysiological profiles such as entrainment and neural plasticity in parallel. Therefore, in the present study, we examined the effect of tACS on motor learning and neurophysiological profiles using an off‐line tACS condition.MethodsThirty‐three healthy participants were randomly assigned to 10 Hz, 20 Hz, or the sham group. Participants performed visuomotor learning tasks consisting of a baseline task (preadaptation task) and training task (adaptation task) to reach a target with a lever‐type controller. Electroencephalography was recorded from eight locations during the learning tasks. tACS was performed between the preadaptation task and adaptation task over the left primary motor cortex for 10 min at 1 mA.ResultsAs a result, 10 Hz tACS was shown to be effective for initial angular error correction in the visuomotor learning tasks. However, there were no significant differences in neural oscillatory activities among the three groups.ConclusionThese results suggest that initial motor learning can be facilitated even when 10 Hz tACS is applied under off‐line conditions. However, neurophysiological aftereffects were recently demonstrated to be induced by tACS at individual alpha frequencies rather than fixed alpha tACS, which suggests that the neurophysiological aftereffects by fixed frequency stimulation in the present study may have been insufficient to generate changes in oscillatory neural activity.

Pupillary Dynamics Link Spontaneous and Task-Evoked Activations Recorded Directly from Human Insula.

Spontaneous activations within neuronal populations can emerge similarly to "task-evoked" activations elicited during cognitive performance or sensory stimulation. We hypothesized that spontaneous activations within a given brain region have comparable functional and physiological properties to task-evoked activations. Using human intracranial EEG with concurrent pupillometry in 3 subjects (2 males, 1 female), we localized neuronal populations in the dorsal anterior insular cortex that showed task-evoked activations correlating positively with the magnitude of pupil dilation during a continuous performance task. The pupillary response peaks lagged behind insular activations by several hundreds of milliseconds. We then detected spontaneous activations, within the same neuronal populations of insular cortex, that emerged intermittently during a wakeful "resting state" and that had comparable electrophysiological properties (magnitude, duration, and spectral signature) to task-evoked activations. Critically, similar to task-evoked activations, spontaneous activations systematically preceded phasic pupil dilations with a strikingly similar temporal profile. Our findings suggest similar neurophysiological profiles between spontaneous and task-evoked activations in the human insula and support a clear link between these activations and autonomic functions measured by dynamics of pupillary dilation.SIGNIFICANCE STATEMENT Most of our knowledge about activations in the human brain is derived from studies of responses to external events and experimental conditions (i.e., "task-evoked" activations). We obtained direct neural recordings from electrodes implanted in human subjects and showed that activations emerge spontaneously and have strong similarities to task-evoked activations(e.g., magnitude, temporal profile) within the same populations of neurons. Within the dorsal anterior insula, a brain region implicated in salience processing and alertness, activations that are either spontaneous or task-evoked are coupled with brief dilations of the pupil. Our findings underscore how spontaneous brain activity, a major current focus of human neuroimaging studies aimed at developing biomarkers of disease, is relevant to ongoing physiological and possibly self-generated mental processes.

Attenuation of Motor Evoked Potentials Following Prone

Background and Importance: Of utmost importance for successful neurosurgical operations is proper patient positioning. This is particularly the case for operations conducted in the prone position, which is associated with several potential complications. Case Presentation: Here we report the case of a 52-year-old male patient who underwent endoscopic discectomy for L5-S1 herniated disc. Following placement in the prone position, Motor Evoked Potentials (MEP) were significantly asymmetric, with those from the left side being disproportionately low considering his clinical presentation. MEP recordings were ameliorated when the patient was placed in the supine position. Considering the nervous and vascular anatomy of the area, a peripheral insult is highly unlikely to be the cause of the neurophysiological profile of this patient. Instead, compression of the dural sac due to biomechanical alterations of the contents of the spinal canal is the most possible pathogenetic mechanism. Conclusion: Proper patient positioning is of paramount importance for the success of a neurosurgical operation. Still, even if all precautions are taken, it is possible that insults to neuronal structures can be due to biomechanical alterations of the contents of the spinal canal, secondary to prone positioning.

Neural Stem Cell Transplantation Improves Locomotor Function in Spinal Cord Transection Rats Associated with Nerve Regeneration and IGF-1 R Expression

Transplantation of neural stem cells (NSCs) is a potential strategy for the treatment of spinal cord transection (SCT). Here we investigated whether transplanted NSCs would improve motor function of rats with SCT and explored the underlying mechanism. First, the rats were divided into sham, SCT, and NSC groups. Rats in the SCT and NSC groups were all subjected to SCT in T10, and were administered with media and NSC transplantation into the lesion site, respectively. Immunohistochemistry was used to label Nestin-, TUNEL-, and NeuN-positive cells and reveal the expression and location of type I insulin-like growth factor receptor (IGF-1 R). Locomotor function of hind limbs was assessed by Basso, Beattie, Bresnahan (BBB) score and inclined plane test. The conduction velocity and amplitude of spinal nerve fibers were measured by electrophysiology and the anatomical changes were measured using magnetic resonance imaging. Moreover, expression of IGF-1 R was determined by real-time polymerase chain reaction and Western blotting. The results showed that NSCs could survive and differentiate into neurons in vitro and in vivo. SCT-induced deficits were reduced by NSC transplantation, including increase in NeuN-positive cells and decrease in apoptotic cells. Moreover, neurophysiological profiles indicated that the latent period was decreased and the peak-to-peak amplitude of spinal nerve fibers conduction was increased in transplanted rats, while morphological measures indicated that fractional anisotropy and the number of nerve fibers in the site of spinal cord injury were increased after NSC transplantation. In addition, mRNA and protein level of IGF-1 R were increased in the rostral segment in the NSC group, especially in neurons. Therefore, we concluded that NSC transplantation promotes motor function improvement of SCT, which might be associated with activated IGF-1 R, especially in the rostral site. All of the above suggests that this approach has potential for clinical treatment of spinal cord injury.

Ayres Theories of Autism and Sensory Integration Revisited: What Contemporary Neuroscience Has to Say.

Abnormal sensory-based behaviors are a defining feature of autism spectrum disorders (ASD). Dr. A. Jean Ayres was the first occupational therapist to conceptualize Sensory Integration (SI) theories and therapies to address these deficits. Her work was based on neurological knowledge of the 1970’s. Since then, advancements in neuroimaging techniques make it possible to better understand the brain areas that may underlie sensory processing deficits in ASD. In this article, we explore the postulates proposed by Ayres (i.e., registration, modulation, motivation) through current neuroimaging literature. To this end, we review the neural underpinnings of sensory processing and integration in ASD by examining the literature on neurophysiological responses to sensory stimuli in individuals with ASD as well as structural and network organization using a variety of neuroimaging techniques. Many aspects of Ayres’ hypotheses about the nature of the disorder were found to be highly consistent with current literature on sensory processing in children with ASD but there are some discrepancies across various methodological techniques and ASD development. With additional characterization, neurophysiological profiles of sensory processing in ASD may serve as valuable biomarkers for diagnosis and monitoring of therapeutic interventions, such as SI therapy.

The KCNH3 inhibitor ASP2905 shows potential in the treatment of attention deficit/hyperactivity disorder.

N-(4-fluorophenyl)-N'-phenyl-N"-(pyrimidin-2-ylmethyl)-1,3,5-triazine-2,4,6-triamine [ASP2905] is a potent and selective inhibitor of the potassium voltage-gated channel subfamily H member 3 (KCNH3) that was originally identified in our laboratory. KCNH3 is concentrated in the forebrain, and its overexpression in mice leads to cognitive deficits. In contrast, Kcnh3 knockout mice exhibit enhanced performance in cognitive tasks such as attention. These data suggest that KCNH3 plays important roles in cognition. Here we investigated the neurochemical and neurophysiological profiles of ASP2905 as well as its effects on cognitive function, focusing on attention. ASP2905 (0.0313 and 0.0625 mg/kg, po) improved the latent learning ability of mice, which reflects attention. Microdialysis assays in rats revealed that ASP2905 increased the efflux of dopamine and acetylcholine in the medial prefrontal cortex (0.03, 0.1 mg/kg, po; 0.1, 1 mg/kg, po, respectively). The activities of these neurotransmitters are closely associated with attention. We used a multiple-trial passive avoidance task to investigate the effects of ASP2905 on inattention and impulsivity in juvenile stroke-prone spontaneously hypertensive rats. ASP2905 (0.1 and 0.3 mg/kg, po) significantly prolonged cumulative latency as effectively as methylphenidate (0.1 and 0.3 mg/kg, sc), which is the gold standard for treating ADHD. Further, ASP2905, amphetamine, and methylphenidate significantly increased the alpha-band power of rats, suggesting that ASP2905 increases arousal, which is a pharmacologically important activity for treating ADHD. In contrast, atomoxetine and guanfacine did not significantly affect power. Together, these findings suggest that ASP2905, which acts through a novel mechanism, is as effective for treating ADHD as currently available drugs such as methylphenidate.