Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Cognitive Disorders, Depression and Anxiety in Temporal Lobe Epilepsy: An Overview

Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.

MicroRNAs as potential biomarkers in temporal lobe epilepsy and mesial temporal lobe epilepsy

Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or involving mesial temporal structures such as the hippocampus,and many of these patients being refractory to treatment with anti-epileptic drugs.Temporal lobe epilepsy is the most common childhood neurological disorder and,compared with adults,the symptoms are greatly affected by age and brain development.Diagnosis of temporal lobe epilepsy relies on clinical examination,patient history,electroencephalographic recordings,and brain imaging.Misdiagnosis or delay in diagnosis is common.A molecular biomarker that could distinguish epilepsy from healthy subjects and other neurological conditions would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Among possible biomarkers of pathological changes as well as potential therapeutic targets in the epileptic brain are micro RNAs.Most of the recent studies had performed micro RNA profiling in body fluids such as blood plasma and blood serum and brain tissues such as temporal cortex tissue and hippocampal tissue.A large number of micro RNAs were dysregulated when compared to healthy controls and with some overlap between individual studies that could serve as potential biomarkers.For example,in adults with temporal lobe epilepsy,possible biomarkers are miR-199a-3p in blood plasma and miR-142-5p in blood plasma and blood serum.In adults with mesial temporal lobe epilepsy,possible biomarkers are miR-153 in blood plasma and miR-145-3p in blood serum.However,in many of the studies involving patients who receive one or several anti-epileptic drugs,the influence of these on micro RNA expression in body fluids and brain tissues is largely unknown.Further studies are warranted with children with temporal lobe epilepsy and consideration should be given to utilizing mouse or rat and non-human primate models of temporal lobe epilepsy.The animal models could be used to confirm micro RNA findings in human patients and to test the effects of targeting specific micro RNAs on disease progression and behavior.

Activation of medial septum cholinergic neurons restores cognitive function in temporal lobe epilepsy

Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.

Molecular typing of familial temporal lobe epilepsy

The pathogenesis of temporal lobe epilepsy(TLE)was originally considered to be acquired.However,some reports showed that TLE was clustered in some families,indicating a genetic etiology.With the popularity of genetic testing technology,eleven different types of familial TLE(FTLE),including ETL1-ETL11,have been reported,of which ETL9-ETL11 had not yet been included in the OMIM database.These types of FTLE were caused by different genes/Loci and had distinct characteristics.ETL1,ETL7 and ETL10 were characterized by auditory,visual and aphasia seizures,leading to the diagnosis of familial lateral TLE.ETL2,ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities,indicating a mesial temporal origin.Febrile seizures were common in FTLEs such as ETL2,ETL5,ETL6 and ETL11.ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura.Considering the diversity and complexity of the symptoms of TLE,neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully.Most FTLE patients had a good prognosis with or without anti-seizure medication treatment,with the exception of patients with heterozygous mutations of the CPA6 gene.The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development,differentiation and synaptic signaling.In this article,we describe the research progress on eleven different types of FTLE.The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.

The brain activation pattern of the medial temporal lobe during chewing gum: a functional MRI study

The human brain is known to be influenced by environmental stimuli(Feeney et al.,1982;Kaplan,1988).Therefore,research on the brain activation pattern by external stimuli has been an important topic in neuroscience(Kaplan,1988).Chewing gum has been known to have a positive effect on cognition,including alertness,attention,cognitive processing speed,

Early Detection of Temporal Lobe Epilepsy: Identification of Novel Candidate Genes and Potential Biomarkers Using Integrative Genomics Analysis

Currently afflicting more than 50 million people worldwide, epilepsy is the spectrum disorder characterizing seizures that occur without other plausible medical explanations. Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy. Current clinical methods;including MRI scans, EEG tests, and doctor visits;can take upwards of several months to confirm a TLE diagnosis;during this time, patients may experience additional seizures and are at an increased risk for other psychiatric disorders. The purpose of this study is to identify candidate genetic biomarkers to facilitate the earlier detection and diagnosis of TLE through gene-based testing (e.g., genomic heatmap analysis or genetic and/or microarray testing). It was hypothesized that potential biomarkers could be identified by analyzing genes that are normally significantly overexpressed in the temporal lobe relative to the gray matter. Statistical and functional analysis was performed on significantly overexpressed genes (≥3.000 fold change) in the gene expression profiles of four donors without epilepsy. The experimental-evidence-based STRING protein interactions analysis showed associations between genes found in DAVID keyword search and other genes facilitating network interconnectivity. After evaluation of the genes’ STRING enriched functions, changes in the expression of the genes CAMK2A, NPY, DLG4, MEF2C, and MAPK7 were concluded to be potential biomarkers for TLE, confirming the original hypothesis. Specifically, the identification of MEF2C and MAPK7 for this purpose is relatively novel in the fields of bioinformatics and neurogenetics. Future work includes investigating the utility of the candidate genes in real-world gene-based diagnostic methods.

The Relationship between Aggressiveness and Gender in Patients with Temporal Lobe Epilepsy

Purpose: To examine the impact of gender and social gender on the level and typology of interictal aggressiveness in patients with temporal lobe epilepsy. Material and Methods: 40 adult patients with Temporal Lobe Epilepsy (TLE) and 86 healthy individuals were included. The qualitative and quantitative aggressiveness assess- ment was made with Buss-Durkee Hostility Inventory. The gender role behavior was measured with Bem Sex Role Inventory. Results: Patients with TLE didn’t differ from healthy subjects on the total scores of motor and attitudinal hostility components, but scored higher on subscales “resentment” and “guilt”. The comparative gender analysis showed there were no phenomenological differences in people with TLE. Assault dominated in healthy male subjects, resentment—in healthy female subjects. The prevalence of feminine social gender type was significantly higher in people with TLE in comparison to healthy people (55% vs. 26%, p 0.01). In patients with TLE, the number of masculine traits positively correlated with indirect hostility subscale and attitudinal hostility component scores. In healthy subjects, the masculine traits positively correlated with assault.

Research on Medial Temporal Lobe Epilepsy by Combining Structural and Functional MRI

Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. This paper focuses on the study of medial temporal lobe epilepsy with hippocampal sclerosis. The hippocampus plays an important role in short-term memory. However, little is known about the connectivity between hippocampal structures and adjacent brain regions. The functional and structural connectivity between patients and controls was investigated by using the techniques of functional magnetic resonance imaging and diffusion tensor imaging in the paper. Three pairs of ROIs related to working memory from BOLD-fMRI data were chosen. These ROIs were registrated from MNI space to individual space and the fiber bundle between two ROIs were traced in the DTI images. The results show that the number of fiber bundle of patients reduce among these ROIs, such as left hippocampus and right hippocampus, left hippocampus and left thalamus, left hippocampus and left frontal lobe and so on. And the number of fiber bundle of patients increase among these ROIs, such as left thalamus and right thalamus, right hippocampus and right thalamus. And the FA values of the fiber bundles of patients in some regions related to left hippocampus decrease. The cause of abnormal functional and structural connections due to the damage of hippocampus in medial temporal lobe epilepsy is studied from a new perspective.

Left Temporal Lobe Arachnoid Cyst Presenting with Symptoms of Psychosis

Arachnoid cysts are uncommon benign neurological tumors,and having presentation like schizophrenia,which has been reported in association with this cyst.The presence of psychiatric disturbances of arachnoid cyst has not been clearly mentioned in the literature.Even though,the appearance of some of the references that focuses on a possible link between arachnoid cysts and psychotic symptoms.Here we present a case report of a 35-year-old man,characterized by the insidious onset of psychotic symptoms of varying intensity such as multiple physical assaults on people with stone.Due to organic suspicion one cannot exclude the possibility that the lesion played a significant role in this psychiatric presentation.

Anterior temporal lobectomy improved mood status and quality of life in Chinese patients with mesial temporal lobe epilepsy:a single-arm cohort study

Background: Many studies have emphasized that selective resection of epileptic lesions in temoral lobe is associated with better preservation of cognition function;whether this applies to patients with refractory mesial temporal lobe epilepsy (MTLE) remains unknown. The objective of this study was to evaluate changes in cognitive functions, mood status, and quality of life after anterior temporal lobectomy in patients with refractory MTLE. Methods: This single-arm cohort study assessed cognitive function, mood status, and quality of life, as well as electroencephalography findings, in patients with refractory MTLE who underwent anterior temporal lobectomy at Xuanwu Hospital from January 2018 to March 2019. Pre- and post-operative characteristics were compared to evaluate the effects of surgery. Results: Anterior temporal lobectomy significantly reduced the frequencies of epileptiform discharges. The overall success rate of surgery was acceptable. Anterior temporal lobectomy did not result in significant changes in overall cognitive functions (P > 0.05), although changes in certain domains, including visuospatial ability, executive ability, and abstract thinking, were detected. Anterior temporal lobectomy resulted in improvements in anxiety and depression symptoms and quality of life. Conclusions: Anterior temporal lobectomy reduced epileptiform discharges and incidence of post-operative seizures as well as resulted in improved mood status and quality of life without causing significant changes in cognitive function.

Independent temporal lobe epilepsy in patients with tuberous sclerosis complex

Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrelated epilepsy,is particularly rare in patients with TSC.Here,we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography(EEG),postoperative pathological findings,and seizure outcome at follow-up.The patients were retrospectively enrolled at two centers;their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG.The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery.Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients.Furthermore,postoperative intelligence quotient improvement was evident in one patient,while the quality of life was improved in two patients at 12 months after surgery.

A study of medial and lateral temporal lobe epilepsy based on stereoelectroencephalography

Background:Patients with temporal lobe epilepsy(TLE)originating from different seizure onset zones had distinct electrophysiological characteristics and surgical outcomes.In this study,we aimed to investigate the relationship between the origin and prognosis of TLE,and the stereoelectroencephalography(SEEG)features.Methods:Thirty patients with TLE,who underwent surgical treatment in our functional neurosurgery department from January 2016 to December 2017,were enrolled in this study.All patients underwent anterior temporal lobectomy after an invasive preoperative evaluation with SEEG.Depending on the epileptic focus location,patients were divided into those with medial temporal lobe seizures(MTLS)and those with lateral temporal lobe seizures(LTLS).The Engel classification was used to evaluate operation effectiveness,and the Kaplan-Meier analysis was used to detect seizure-free duration.Results:The mean follow-up time was 25.7±4.8 months.Effectiveness was 63.3%for Engel I(n=19),13.3%for Engel II,3.3%for Engel III,and 20.0%for Engel IV.According to the SEEG,60.0%(n=18)had MTLS,and 40.0%(n=12)had LTLS.Compared with the MTLS group,the operation age of those with LTLS was significantly greater(26.9±6.9 vs.29.9±12.5 years,t=-0.840,P=0.009)with longer epilepsy duration(11.9±6.0 vs.17.9±12.1 years,t=-1.801,P=0.038).Patients with MTLS had a longer time interval between ictal onset to seizure(67.3±59.1 s vs.29.3±24.4 s,t=2.017,P=0.008).The most common SEEG ictal pattern was a sharp/spike-wave rhythm in the MTLS group(55.6%)and low-voltage fast activity in the LTLS group(58.3%).Compared with the LTLS group,patients with MTLS had a more favorable prognosis(41.7%vs.77.8%,P=0.049).Post-operative recurrence was more likely to occur within three months after the operation for both groups,and there appeared to be a stable longterm outcome.Conclusion:Patients with MTLS,who accounted for three-fifths of patients with TLE,showed a more favorable surgical outcome.

Machine learning for detecting mesial temporal lobe epilepsy by structural and functional neuroimaging

Mesial temporal lobe epilepsy(mTLE),the most common type of focal epilepsy,is associated with functional and structural brain alterations.Machine learning(ML)techniques have been successfully used in discriminating mTLE from healthy controls.However,either functional or structural neuroimaging data are mostly used separately as input,and the opportunity to combine both has not been exploited yet.We conducted a multimodal ML study based on functional and structural neuroimaging measures.We enrolled 37 patients with left mTLE,37 patients with right mTLE,and 74 healthy controls and trained a support vector ML model to distinguish them by using each measure and the combinations of the measures.For each single measure,we obtained a mean accuracy of 74%and 69%for discriminating left mTLE and right mTLE from controls,respectively,and 64%when all patients were combined.We achieved an accuracy of 78%by integrating functional data and 79%by integrating structural data for left mTLE,and the highest accuracy of 84%was obtained when all functional and structural measures were combined.These findings suggest that combining multimodal measures within a single model is a promising direction for improving the classification of individual patients with mTLE.

Hippocampus chronic deep brain stimulation induces reversible transcript changes in a macaque model of mesial temporal lobe epilepsy

Background:Deep brain stimulation(DBS)has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear.This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.Methods:We established a macaque model of mesial temporal lobe epilepsy(mTLE),and continuous high-frequency hippocampus DBS(hip-DBS)was applied for 3 months.The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis.Moreover,the microarray results were validated using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot analyses.Results:The results showed that chronic hip-DBS modulated the hippocampal gene expression.We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles.Series test of cluster analysis showed that profiles 5,3,and 2 were the predominant expression profiles.Moreover,profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway.Nine dysregulated genes(Arhgap5,Colla2,Itgbl^Pik3rl,Lama4,Fnl,Col3al,Itga9,and Shc4)and three genes(Colla2,Itgbl,and Flna)in these two pathways were further validated by qRT-PCR and Western blot analyses,respectively,which showed a concordance.Conclusion:Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression.Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

Systemic evidence of acute seizureassociated elevation in serum neuronal injury biomarker in patients with temporal lobe epilepsy

Background:Patients with drug refractory temporal lobe epilepsy frequently accumulate cognitive impairment over time,suggesting loss of neurons induced by seizures.Our objective was to determine whether there is a temporal association between changes in serum levels of neural injury markers and electroencephalographic(EEG)evidence of seizures and interictal spikes.Methods:We measured serum levels of neuron-specific enolase(NSE),a neuronal injury marker,relative to levels of S100β,a marker of glial injury,at 6 AM,9 AM,noon,3 PM,and 6 PM over the course of several days in 7 epilepsy patients undergoing continuous video-EEG monitoring and in 4 healthy controls.Results:All epilepsy patients exhibited significant deviations in NSE levels through time,and 4 of the epilepsy patients exhibited large sample entropy values and large signal variation metrics for NSE relative to S100β.Controls did not exhibit such changes.Correlation analysis revealed that NSE levels were significantly elevated after seizures.There was also a highly significant relationship between increased EEG spike frequency and an increase in serum NSE levels measured 24 h later.Conclusions:The detection of large but transient post-ictal increases in NSE suggests that even self-limited seizures may cause an injury to neurons that underlies cognitive decline in some patients.While this study used a small patient population,the pilot findings suggest that post-ictal assessment of serum NSE may serve as a biomarker for measuring the efficacy of future acute neuroprotective strategies in epilepsy patients.

Involvement of GluA1-AMPAR-mediated LTP in time-dependent decline of cognitive function in rats with temporal lobe epilepsy

Background:Cognitive impairment is one of the common comorbidities in patients with temporal lobe epilepsy(TLE),but the underlying mechanisms remain largely unknown.Previous studies have found significant decay of hippocampal long-term potentiation(LTP)in TLE rats with cognitive impairment.As the activation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs)is responsible for LTP formation and learning and memory,we investigated whether AMPARs are involved in the LTP inhibition and the TLE-associated cognitive impairments.Methods:TLE rat model was established by intraperitoneal injection of lithium chloride-pilocarpine on postnatal day 21(P21).Learning and memory performance,hippocampal expression of membrane GluA1-AMPARs,and hippocampal LTP were tested by behavioral tests,western blotting,and field potential recording,respectively,at 1,5 and 13 weeks after induction of status epilepticu(SE).Finally,the effects of(S)-AMPA,an agonist of AMPARs,on LTP and cognitive function were tested.Results:Results of behavioral tests revealed an time-dependent decline in the learning and memory of TLE rats when compared to the age-matched controls at week 5 and 13,rather than at week 1 after the induction of SE.Western blotting showed that the hippocampal expression of membrane GluA1 was significantly decreased in a time-dependent manner in the TLE rats when compared to the age-matched controls at weeks 5 and 13,rather than at week 1 after the induction of SE.Similarly,the hippocampal LTP was inhibited in a time-dependent manner in TLE rats at weeks 5 and 13,rather than at week 1 after the induction of SE.Moreover,intra-hippocampal injection of(S)-AMPA ameliorated the deficits in learning as well as spatial and emotional memory in a dosedependent manner,and partially reversed the inhibition of CA1 LTP in the TLE rats at week 13 after the induction of SE.Conclusions:The reduced expression of hippocampal membrane GluA1 may be involved in LTP decay in CA1 and cognition impairment in TLE rats.

Temporal lobe epilepsy associated with human herpes virus 6

Human herpes virus 6(HHV-6)is a ubiquitous and most common pathogen that affects humans.Human herpes virus 6B(HHV-6B)is a wide spread human herpesvirus that infects most people when they are children,establishes latent infections in the central nervous system(CNS),especially in the hippocampus and amygdala,and induces neurologic diseases.HHV-6 can establish a latent infection and be reactivated by various stimuli.Recently,viral genomic DNA of HHV-6B has been detected in surgically removed brain tissues of intractable epilepsy patients,suggesting the involvement of HHV-6B in the pathogenesis of epilepsy.Temporal lobe epilepsy(TLE)has been shown to be closely related with HHV-6B.TLE patients with HHV-6B in their brains suffer from reiterative attacks of febrile seizures and hippocampal sclerosis.However,the mechanisms underlying the contribution of this virus to the development of TLE remains unknown.The direct damage and immune activation caused by the virus are involved in the process of neuron damage,abnormal neural circuit formation and glial cell proliferation.In addition,some cytokines like interleukin-17A(IL-17A),nuclear factor-kappa B(NF-κb),transforming growth factor-β(TGF-β),mitogen-activated protein kinase(MAPK)and phospholipase A2 are up-regulated and involved in the pathological process of TLE.More studies are needed to clarify the mechanisms underlying the link between HHV-6B and epilepsy,and identify biomarkers to recognize different patient groups for anti-inflammatory or immunomodulatory therapies.

Lateralizing value of ictal face wiping in patients with mesial temporal lobe epilepsy

Objective To investigate the lateralizing value of ictal face wiping(FW)in patients with refractory mesial temporal lobe epilepsy(MTLE).Methods Presurgical video types were retrospectively reviewed among 96 patients who were seizure-free for at least 3 years after temporal lobectomy between 1997 and 2012.Attention

Validating New Technologies to Treat Depression, Pain and the Feeling of Sentient Beings: A Reply to “Neuroscience for the Soul”

The primary assumption of Neuroscience is that all experiences are strongly correlated with or caused by the specifics of brain structures and their particular dynamics. The profound experiences attributed to the “sensed presence” and their cultural anthropomorphisms such as deities and gods are persistent reports in human populations that are frequently associated with permanent changes in behavior, reduced depression and alleviation of pain. The majority of traditional clinical observations and modern imaging techniques have emphasized the central role of right temporal lobe structures and their directly related networks. The experimental simulation of sensed presences which can result in attributions to spiritual, deity-based or mystical sources within the clinical laboratory by the application of physiologically-patterned magnetic fields across the temporal lobes through our God Helmet requires the same precision of technology that is essential for synthesizing molecular treatments for modifying anomalous behavior, depression and pain. Despite the clinical utility of these simulated conditions within Neuroscience and Medicine, misinformation concerning the bases and efficacy of this new technology persist. Here we present detailed technical clarifications and rebuttals to refute these misconceptions. A Hegelian approach to this delay of development and impedance provides a context through which the ultimate synthesis and application of this technology may be accommodated in the near future.