Evaluations of artificial intelligence and machine learning algorithms in neurodiagnostics.

This article evaluates the ethical implications of utilizing artificial intelligence (AI) algorithms in neurological diagnostic examinations. Applications of AI technology have been utilized to aid in the determination of pharmacological dosages of gadolinium for brain lesion detection, localization of seizure foci, and the characterization of large vessel occlusion in ischemic stroke patients. Multiple subtypes of AI/machine learning (ML) algorithms are analyzed, as AI-assisted neurology utilizes supervised, unsupervised, artificial neural network (ANN), and deep neural network (DNN) learning models. As ANN and DNN analyses can be applied to data with an unknown clinical diagnosis, these algorithms are evaluated according to Bayesian statistical analyses. Bayesian neural network analyses are incorporated, as these algorithms indicate that the predictive accuracy and model performance are dependent upon accurate configurations of the model's hyperparameters and neural inputs. Thus, mathematical evaluations of AI algorithms are comprehensively explored to examine their clinical utility, as underperformance of AI/ML models may have deleterious consequences that affect patient outcomes due to misdiagnosis and false-negative test results.

Aptamer Technologies in Neuroscience, Neuro-Diagnostics and Neuro-Medicine Development.

Aptamers developed using in vitro Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology are single-stranded nucleic acids 10-100 nucleotides in length. Their targets, often with specificity and high affinity, range from ions and small molecules to proteins and other biological molecules as well as larger systems, including cells, tissues, and animals. Aptamers often rival conventional antibodies with improved performance, due to aptamers' unique biophysical and biochemical properties, including small size, synthetic accessibility, facile modification, low production cost, and low immunogenicity. Therefore, there is sustained interest in engineering and adapting aptamers for many applications, including diagnostics and therapeutics. Recently, aptamers have shown promise as early diagnostic biomarkers and in precision medicine for neurodegenerative and neurological diseases. Here, we critically review neuro-targeting aptamers and their potential applications in neuroscience research, neuro-diagnostics, and neuro-medicine. We also discuss challenges that must be overcome, including delivery across the blood-brain barrier, increased affinity, and improved in vivo stability and in vivo pharmacokinetic properties.

Family caregivers' sense-making of the results of functional neurodiagnostics for patients with Prolonged Disorders of Consciousness.

Functional neuroimaging and electrophysiological assessments can identify evidence of residual consciousness and cognition in patients with prolonged disorders of consciousness (PDOC) who are otherwise behaviourally unresponsive. These functional neurodiagnostics are increasingly available in clinical settings and are recommended by international clinical guidelines to reduce diagnostic and prognostic uncertainty, and thereby assist family caregivers in their best-interests decision-making. Nevertheless, little is known about how family caregivers make sense of the results of these state-of-the-art functional neurodiagnostics. By applying Interpretative Phenomenological Analysis (IPA) to interviews with family caregivers of patients with diagnoses of PDOC who had received a functional neurodiagnostic assessment, we identify three primary themes of sense-making: The special significance of "brain scans"; A dynamic sense-making process; Holding on to hope and holding on to the person. These themes highlight the challenges of helping family caregivers to balance the relative importance of functional neurodiagnostic results with other clinical assessments and identify an ability of family caregivers to hold a contradiction in which they hope for recovery but simultaneously express a rational understanding of evidence to the contrary. We offer several recommendations for the ways in which family caregivers can be better supported to make sense of the results of functional neurodiagnostics.

Raman Spectroscopy Spectral Fingerprints of Biomarkers of Traumatic Brain Injury.

Traumatic brain injury (TBI) affects millions of people of all ages around the globe. TBI is notoriously hard to diagnose at the point of care, resulting in incorrect patient management, avoidable death and disability, long-term neurodegenerative complications, and increased costs. It is vital to develop timely, alternative diagnostics for TBI to assist triage and clinical decision-making, complementary to current techniques such as neuroimaging and cognitive assessment. These could deliver rapid, quantitative TBI detection, by obtaining information on biochemical changes from patient's biofluids. If available, this would reduce mis-triage, save healthcare providers costs (both over- and under-triage are expensive) and improve outcomes by guiding early management. Herein, we utilize Raman spectroscopy-based detection to profile a panel of 18 raw (human, animal, and synthetically derived) TBI-indicative biomarkers (N-acetyl-aspartic acid (NAA), Ganglioside, Glutathione (GSH), Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase L1 (UCHL1), Cholesterol, D-Serine, Sphingomyelin, Sulfatides, Cardiolipin, Interleukin-6 (IL-6), S100B, Galactocerebroside, Beta-D-(+)-Glucose, Myo-Inositol, Interleukin-18 (IL-18), Neurofilament Light Chain (NFL)) and their aqueous solution. The subsequently derived unique spectral reference library, exploiting four excitation lasers of 514, 633, 785, and 830 nm, will aid the development of rapid, non-destructive, and label-free spectroscopy-based neuro-diagnostic technologies. These biomolecules, released during cellular damage, provide additional means of diagnosing TBI and assessing the severity of injury. The spectroscopic temporal profiles of the studied biofluid neuro-markers are classed according to their acute, sub-acute, and chronic temporal injury phases and we have further generated detailed peak assignment tables for each brain-specific biomolecule within each injury phase. The intensity ratios of significant peaks, yielding the combined unique spectroscopic barcode for each brain-injury marker, are compared to assess variance between lasers, with the smallest variance found for UCHL1 (σ2 = 0.000164) and the highest for sulfatide (σ2 = 0.158). Overall, this work paves the way for defining and setting the most appropriate diagnostic time window for detection following brain injury. Further rapid and specific detection of these biomarkers, from easily accessible biofluids, would not only enable the triage of TBI, predict outcomes, indicate the progress of recovery, and save healthcare providers costs, but also cement the potential of Raman-based spectroscopy as a powerful tool for neurodiagnostics.

Design and Validation of a Low-Cost Mobile EEG-Based Brain-Computer Interface.

Objective: We designed and validated a wireless, low-cost, easy-to-use, mobile, dry-electrode headset for scalp electroencephalography (EEG) recordings for closed-loop brain-computer (BCI) interface and internet-of-things (IoT) applications. Approach: The EEG-based BCI headset was designed from commercial off-the-shelf (COTS) components using a multi-pronged approach that balanced interoperability, cost, portability, usability, form factor, reliability, and closed-loop operation. Main Results: The adjustable headset was designed to accommodate 90% of the population. A patent-pending self-positioning dry electrode bracket allowed for vertical self-positioning while parting the user's hair to ensure contact of the electrode with the scalp. In the current prototype, five EEG electrodes were incorporated in the electrode bracket spanning the sensorimotor cortices bilaterally, and three skin sensors were included to measure eye movement and blinks. An inertial measurement unit (IMU) provides monitoring of head movements. The EEG amplifier operates with 24-bit resolution up to 500 Hz sampling frequency and can communicate with other devices using 802.11 b/g/n WiFi. It has high signal-to-noise ratio (SNR) and common-mode rejection ratio (CMRR) (121 dB and 110 dB, respectively) and low input noise. In closed-loop BCI mode, the system can operate at 40 Hz, including real-time adaptive noise cancellation and 512 MB of processor memory. It supports LabVIEW as a backend coding language and JavaScript (JS), Cascading Style Sheets (CSS), and HyperText Markup Language (HTML) as front-end coding languages and includes training and optimization of support vector machine (SVM) neural classifiers. Extensive bench testing supports the technical specifications and human-subject pilot testing of a closed-loop BCI application to support upper-limb rehabilitation and provides proof-of-concept validation for the device's use at both the clinic and at home. Significance: The usability, interoperability, portability, reliability, and programmability of the proposed wireless closed-loop BCI system provides a low-cost solution for BCI and neurorehabilitation research and IoT applications.

Guidelines for Qualifications of Neurodiagnostic Personnel: A Joint Position Statement of the American Clinical Neurophysiology Society, the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Society of Neurophysiological Monitoring, and ASET The Neurodiagnostic Society.

The Guidelines for Qualifications of Neurodiagnostic Personnel (QNP) document has been created through the collaboration of the American Clinical Neurophysiology Society (ACNS), the American Society of Neurophysiological Monitoring (ASNM), the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), and ASET The Neurodiagnostic Society (ASET). The quality of patient care is optimized when neurophysiological procedures are performed and interpreted by appropriately trained and qualified practitioners at every level. These societies recognize that neurodiagnostics is a large field with practitioners who have entered the field through a variety of training paths. This document suggests job titles, associated job responsibilities, and the recommended levels of education, certification, experience, and ongoing education appropriate for each job. This is important because of the growth and development of standardized training programs, board certifications, and continuing education in recent years. This document matches training, education, and credentials to the various tasks required for performing and interpreting neurodiagnostic procedures. This document does not intend to restrict the practice of those already working in neurodiagnostics. It represents recommendations of these societies with the understanding that federal, state, and local regulations, as well as individual hospital bylaws, supersede these recommendations. Because neurodiagnostics is a growing and dynamic field, the authors fully intend this document to change over time.

Ellen R. Grass Lecture: The Future of Neurodiagnostics and Emergence of a New Science.

Electroencepholography (EEG) is the oldest and original brain measurement technology. Since EEG was first used in clinical settings, the role of neurodiagnostic professionals has focused on two principal tasks that require specialized training. These include collecting the EEG recording, performed primarily by EEG Technologists, and interpreting the recording, generally done by physicians with proper specialization. Emerging technology appears to enable non-specialists to contribute to these tasks. Neurotechnologists may feel vulnerable to being displaced by new technology. A similar shift occurred in the last century when human "computers," employed to perform repetitive calculations needed to solve complex mathematics for the Manhattan and Apollo Projects, were displaced by new electronic computing machines. Many human "computers" seized on the opportunity created by the new computing technology to become the first computer programmers and create the new field of computer science. That transition offers insights for the future of neurodiagnostics. From its inception, neurodiagnostics has been an information processing discipline. Advances in dynamical systems theory, cognitive neuroscience, and biomedical informatics have created an opportunity for neurodiagnostic professionals to help create a new science of functional brain monitoring. A new generation of advanced neurodiagnostic professionals that bring together knowledge and skills in clinical neuroscience and biomedical informatics will benefit psychiatry, neurology, and precision healthcare, lead to preventive brain health through the lifespan, and lead the establishment of a new science of clinical neuroinformatics.

Guidelines for Qualifications of Neurodiagnostic Personnel: A Joint Position Statement of the American Clinical Neurophysiology Society, the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Society of Neurophysiological Monitoring, and ASET - The Neurodiagnostic Society.

The Guidelines for Qualifications of Neurodiagnostic Personnel (QNP) document has been created through the collaboration of the American Clinical Neurophysiology Society (ACNS), the American Society of Neurophysiological Monitoring (ASNM), the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), and ASET - The Neurodiagnostic Society (ASET). The quality of patient care is optimized when neurophysiological procedures are performed and interpreted by appropriately trained and qualified practitioners at every level. These Societies recognize that Neurodiagnostics is a large field with practitioners who have entered the field through a variety of training paths. This document suggests job titles, associated job responsibilities, and the recommended levels of education, certification, experience, and ongoing education appropriate for each job. This is important because of the growth and development of standardized training programs, board certifications, and continuing education in recent years. This document matches training, education, and credentials to the various tasks required for performing and interpreting Neurodiagnostic procedures. This document does not intend to restrict the practice of those already working in Neurodiagnostics. It represents recommendations of these Societies with the understanding that federal, state, and local regulations, as well as individual hospital bylaws, supersede these recommendations. As Neurodiagnostics is a growing and dynamic field, we fully intend this document to change over time.

Technical Tips: Advocacy: A Cornerstone of Advancing the Interests of the Profession.

Advocacy should be thought of as a permanent part of recognition efforts during Neurodiagnostic Week (April 16-22, 2023) for Neurodiagnostic professionals. It is the perfect opportunity to engage in advocacy and educate others on the importance of using well qualified Neurodiagnostic Technologists to perform neurodiagnostic procedures. Why is advocacy important? Because there is strength in numbers and constituent voices matter. If Neurodiagnostic Technologists do not advocate for the profession and educate decision makers, legislators, and the public about the importance of professional competency in Neurodiagnostics, no one else will. Advocacy works and is a critical part of moving the profession forward to ensure that lawmakers and policy understand that those performing the procedures should be the best qualified professionals to do so.

Informal Caregivers of Patients with Disorders of Consciousness: a Qualitative Study of Communication Experiences and Information Needs with Physicians.

Due to improvements in medicine, the figures of patients with disorders of consciousness (DoC) are increasing. Diagnostics of DoC and prognostication of rehabilitation outcome is challenging but necessary to evaluate recovery potential and to decide on treatment options. Such decisions should be made by doctors and patients' surrogates based on medico-ethical principles. Meeting information needs and communicating effectively with caregivers as the patients´ most common surrogate-decision makers is crucial, and challenging when novel tech-nologies are introduced. This qualitative study aims to explore information needs of informal DoC caregivers, how they manage the obtained information and their perceptions and experiences with caregiver-physician communication in facilities that implemented innovative neurodiagnostics studies. In 2021, we conducted semi-structured interviews with nine caregivers of clinically stable DoC patients in two rehabilitation centers in Italy and Germany. Participants were selected based on consecutive purposeful sampling. Caregivers were recruited at the facilities after written informed consent. All interviews were recorded, transcribed verbatim and translated. For analysis, we used reflexive thematic analysis according to Braun & Clarke (2006). Caregivers experienced the conversations emotionally, generally based on the value of the information provided. They reported to seek positive information, comfort and empathy with-in the communication of results of examinations. They needed detailed information to gain a deep understanding and a clear picture of their loved-one's condition. The results suggest a mismatch between the perspectives of caregivers and the perspectives of medical profession-als, and stress the need for more elaborate approaches to the communication of results of neu-rodiagnostics studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12152-022-09503-0.

GFAP and S100B: What You Always Wanted to Know and Never Dared to Ask.

Traumatic brain injury (TBI) is a major global health issue, with outcomes spanning from intracranial bleeding, debilitating sequelae, and invalidity with consequences for individuals, families, and healthcare systems. Early diagnosis of TBI by testing peripheral fluids such as blood or saliva has been the focus of many research efforts, leading to FDA approval for a bench-top assay for blood GFAP and UCH-L1 and a plasma point-of-care test for GFAP. The biomarker S100B has been included in clinical guidelines for mTBI (mTBI) in Europe. Despite these successes, several unresolved issues have been recognized, including the robustness of prior data, the presence of biomarkers in tissues beyond the central nervous system, and the time course of biomarkers in peripheral body fluids. In this review article, we present some of these issues and provide a viewpoint derived from an analysis of existing literature. We focus on two astrocytic proteins, S100B and GFAP, the most commonly employed biomarkers used in mTBI. We also offer recommendations that may translate into a broader acceptance of these clinical tools.

Evaluation and Utility of Submaximal Stimulation Intensity in Transcranial Magnetic Stimulation in the Standing Horse☆.

Transcranial magnetic stimulation (TMS) has been successfully used in horses to evaluate function and integrity of descending motor pathways in patients affected by neurological gait abnormalities. In preceding studies, lengthening latency times (LT) of cranially evoked limb muscle potentials have been considered a reliable diagnostic parameter. Standardized settings use device output signal intensities of 100%. The aim of this study was to determine the effect of submaximal stimulation intensities (SI) and to determine the minimum coil output necessary to evoke motor unit potentials. As an additional effect, lower stimulation intensities are supposed to decrease sensory irritation of the equine patient. Altogether, 36 neurologically healthy horses underwent TMS under sedation with a dome coil at stimulation intensities varying from 40% to 100% of device output intensity. Motor potentials were recorded by surface electrodes from all four limbs and LT was calculated in milliseconds. To further refine the stimulation settings, cortical motor thresholds (CMT) were assessed in triplets, using IFCN recommendations. The electromyographic recordings were evaluated in 30 horses. Increasing stimulation intensities resulted in significant (P < .05) LT shortening until application of 80% of maximal output intensity. Further increase to maximal SI of 100%, brought up no significant differences (P > .05). Gating effects were excluded as there was no difference of LT upon ascending and descending SI changes (P > .05). CMT revealed a large inter-individual variability amongst horses independent of their body size. There was a strong linearity in between CMT and LT even within submaximal SI ranges (P < .001). The inverse impact of SI on LT may be explained by deeper penetration of the magnetic field, circumvention of interposed neurons and subsequent activation of fast acting motor pathways. However, in warmblood horses a stimulation intensity of 80% coil output already appeared sufficient for reproducible activation of lower motor neurons in all limbs. Furthermore, due to the strong linear correlation of CMT and LT, the tested CMT algorithms may be used to estimate the normal LT on submaximal stimulation for equine myelopathy patients in future.

Central nervous system (CNS) enterovirus infections: A single center retrospective study on clinical features, diagnostic studies, and outcome.

Enteroviruses (EV) are responsible for a large number of meningoencephalitis cases, especially in children. The objective of this study was to identify modes of diagnosis including the significance of respiratory and cerebrospinal fluid samples, associated clinical characteristics, inpatient management, and outcome of individuals with EV infections of the central nervous system (CNS). Electronic medical records of individuals with enterovirus infections of the CNS who presented to the Columbia University Irving Medical Center and Children's Hospital of New York between January 1, 2012 and December 31, 2017 were reviewed retrospectively for demographic, epidemiological, and clinical data. The median age overall was 1.7 months (interquartile range 14 years) and most (62.4%) were male. The majority of CNS infections presented as meningitis (95.7%) and occurred in the summer (45.2%) and fall seasons (37.6%). Eighty-five cases (91.4%) demonstrated EV positivity in cerebrospinal fluid, thirty cases (32.3%) exhibited both cerebrospinal fluid and respiratory positivity, and eight cases (8.6%) exhibited respiratory positivity with coinciding neurological findings. Eighty-nine individuals overall (95.7%) received antibiotics and 37 (39.8%) received antiviral treatment. All surviving individuals had favorable Modified Rankin Scores (MRS) within the zero to two ranges upon discharge. Testing respiratory samples in addition to cerebrospinal fluid was found to be an important diagnostic tool in EV-associated cases. While clinical outcomes were favorable for an overwhelming majority of cases, etiological understanding of CNS infections is essential for identifying ongoing and changing epidemiological patterns and aid in improving the diagnosis and treatment.

Proband-Only Clinical Exome Sequencing for Neurodevelopmental Disabilities.

BACKGROUND: Whole exome sequencing on family trios gives the highest diagnostic yield, but high cost limits its application. Here, we performed proband-only clinical exome sequencing in a population of patients with neurodevelopmental disabilities and tested the diagnostic yield. METHODS: This observational, retrospective study included 108 unrelated patients with neurodevelopmental disabilities who underwent clinical exome sequencing at the outpatient clinics of the Severance Children's Hospital, Seoul, South Korea, between March 2017 and May 2018. Clinical exome sequencing targeted 4503 disease-causing genes. RESULTS: The overall diagnostic rate was 38.0% (41 of 108) when proband-only clinical exome sequencing was performed without additional parental testing. Four sequence variants were reclassified as likely pathogenic after parental testing, representing an additional 3.7% of the diagnostic yield. The final diagnostic rate was 41.7% (45 of 108). Of 45 patients with genetic abnormalities, a total of 38 sequence variations were detected in 33 (30.6%) patients with five homozygous cases, and 13 chromosomal copy number variants were detected in 12 (11.1%) patients. Novel variants of known causal genes for neurodevelopmental disabilities were detected in 18 (16.7%) patients. These were variants that could be reclassified as likely pathogenic if the de novo nature of the mutation was confirmed after testing of parental samples. CONCLUSIONS: Proband-only clinical exome sequencing is a practical diagnostic tool that may be implemented in the clinical setting for patients with neurodevelopmental disabilities. A cost-effective approach to neurodevelopmental disabilities would be a proband-only clinical exome sequencing followed by parental testing of selective candidate variants.

Electrodiagnostic consultations in Zambia: Referral characteristics and neuromuscular disorders.

INTRODUCTION: Research on neuromuscular disorders in sub-Saharan Africa is scarce. We aimed to delineate referral characteristics and the neuromuscular disorders observed among electrodiagnostic (EDX) consultations in a tertiary care setting in Zambia. METHODS: EDX records were reviewed for all specialist-performed studies after the establishment of the laboratory. The frequency of demographic, medical characteristics, and final EDX impressions are presented. RESULTS: Among 108 referrals, 52% were male, 84% were adults (mean age 44 years). Referrals were predominantly outpatients (85%) and sent by neurologists (68%). HIV infection was common (12%). Diabetes was rare (3%). Overall, 77% of studies were abnormal. Polyneuropathy was the most common abnormal EDX finding, followed by motor neuron disease. DISCUSSION: A diverse range of neuromuscular diseases was evaluated among EDX referrals in Zambia. Though labor and expertise intensive, access to EDX consultation can enhance clinical care and facilitate research and surveillance of neuromuscular disorders in the region.

The Emerging Role of Neurodiagnostic Informatics in Integrated Neurological and Mental Health Care.

Mental, neurological, and neurodevelopmental (MNN) disorders impose an enormous burden of disease globally. Many MNN disorders follow a developmental trajectory. Thus, defining symptoms of MNN disorders may be conceived as the end product of a long developmental process. Many pharmaceutical therapies are aimed at the end symptoms, essentially attempting to reverse pathological brain function that has developed over a long time. A new paradigm is needed to leverage the developmental trajectory of MNN disorders, based on measuring brain function through the life span. Electroencephalography (EEG) is ideally suited for this task. New developments in several fields, including consumer EEG hardware, ubiquitous access to the Internet and electronic health records, and nonlinear mathematics to extract information from physiological signals have converged to enable new approaches to integrating EEG into routine health care. Research continues to demonstrate that EEG analysis can be used to discover digital biomarkers for a wide range of MNN disorders, including autism, attention-deficit/hyperactivity disorder (ADHD), schizophrenia and dementias, and likely many others. When EEG-derived information about brain function is stored with an electronic health record, clinical decision support software may use these data to detect atypical brain development in the earliest stages, thus opening a potential window for early intervention. These developments create an opportunity for neurodiagnostics to merge with biomedical informatics to create clinical tools for monitoring brain function through the life span. Advanced professionals with neurodiagnostics and biomedical informatics skills and training are needed to lead the way in this emerging field.