I. Quantitative electroencephalographic-based assessment of the theta/beta ratio is considered investigational as a diagnostic aid for attention-deficit/hyperactivity disorder.

II. Quantitative electroencephalographic-based assessment is considered investigational as a diagnostic aid for cognitive impairment.

III. Quantitative electroencephalographic-based assessment is considered investigational as a diagnostic aid for autism spectrum disorder.

Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is common in children, adolescents, and adults, and is defined by pervasive symptoms of inattention and/or hyperactivity-impulsivity, which lead to impairment in at least 2 domains of the work, school, or home environments. Stimulant medications reduce symptoms associated with ADHD, although there are concerns about the potential for overdiagnosis and overprescribing of medication.

Diagnosis

Presently, ADHD is diagnosed clinically by assessing behavioral symptoms and impairment via interviews and standard questionnaires. Diagnosis can be challenging because the core symptoms are nonspecific. They may be present in other psychiatric disorders (eg, learning disabilities, conduct disorders, affective disorders) or result from environmental influences such as a lack of discipline. Also, ADHD is a heterogeneous disorder with multiple subtypes and frequently coexists with other psychiatric disorders.

There has been substantial research conducted over the last several decades on whether electroencephalography (EEG)-derived brain wave patterns in patients with ADHD differ from those without ADHD. EEG patterns are typically categorized into 4 frequency ranges: delta (<4 Hz), theta (4-7 Hz), alpha (8-12 Hz), and beta (13-25 Hz). The largest focus of research on brain wave patterns in ADHD has been on whether there are increased theta wave activity and an increased theta/beta ratio in ADHD patients.

The Neuropsychiatric EEG-based ADHD Assessment Aid (NEBA^®) system is a specific quantitative EEG system that measures the resting theta/beta ratio of the electroencephalogram with an electrode located at the central midline position (referred to as position CZ in the international 10-20 EEG system). Quantitative EEG uses computer analysis with the mathematical transformation from the time domain into the frequency domain (fast-Fourier transform) to determine the total power at each frequency. The relative power of the waveform can then be calculated in relation to the total power of the 4 frequency ranges. The NEBA system uses proprietary cutoffs to generate an estimate of the likelihood of ADHD based on the resting theta/beta ratio.

It is proposed that the NEBA system can be used to confirm a clinical diagnosis or support further testing in children and adolescents with ADHD. The system is not intended to evaluate patients for whom the clinician’s diagnosis of ADHD is negative, and the system does not generate an interpretive report in this situation. It is also proposed that the clinician’s diagnostic impression plus the results generated by the NEBA system may reduce the potential for overdiagnosis of ADHD, and thereby reduce the risks of administering unnecessary pharmacologic therapy in the intended-use population. Also, as a result of research on EEG brain waves in ADHD, neurofeedback has been developed as a potential treatment for ADHD. This treatment employs principles of biofeedback using EEG brain wave activity and attempts to alter the brainwave patterns in beneficial ways.

Cognitive Impairment

Dementia is characterized by the decline in cognition in one or more cognitive domains, such as learning and memory, language, executive function, complex attention, perceptual-motor, and social cognition. Alzheimer Disease (AD) is the most common form of dementia in older adults. AD is a fatal neurodegenerative disease that causes progressive loss in memory, language, and thinking, with the eventual loss of ability to perform social and functional activities in daily life. Survival after a diagnosis of dementia due to AD generally ranges between 4 and 8 years; however, life expectancy can be influenced by other factors, such as comorbid medical conditions. It is estimated that 6.2 million Americans aged 65 and older are currently living with AD dementia, and the number is projected to reach over 12 million by 2050, with an approximate lifetime risk of developing AD dementia at age 65 of 21.1% for women and 11.6% for men. The lifetime risk for dementia due to AD is approximately 20% for women and 10% for men. Per the 2018 American Academy of Neurology practice guideline update on mild cognitive impairment (MCI), the prevalence of MCI was 6.7% for ages 60 to 64, 8.4% for ages 65 to 69, 10.1% for ages 70 to 74, 14.8% for ages 75 to 79, and 25.2% for ages 80 to 84. The cumulative dementia incidence was 14.9% in individuals with MCI >65 years of age followed for 2 years.

Data from the National Institute on Aging have shown that Black Americans are approximately 1.5 to 2 times more likely to develop AD and related dementias as compared to Whites. Additionally, Black participants in AD research studies were 35% less likely to be diagnosed with AD and related dementias and were found to have more risk factors for the disease as well as greater cognitive impairment and symptom severity than White participants. Findings from 2 national surveys conducted by the Alzheimer's Association also found that people of color face discrimination when seeking health care for AD and related dementias with the highest level of discrimination in dementia health care reported by Black Americans (50%) followed by Native (42%), Asian (34%), and Hispanic (33%) Americans. Non-Hispanic White Americans reported a discrimination rate of 9%.

Diagnosis

Presently, dementia is diagnosed clinically through initial cognitive testing followed by a physical examination including neurological examination, and then subsequent laboratory testing and neuroimaging (eg, computed tomography (CT) or magnetic resonance imaging MRI). According to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), criteria for major neurocognitive disorder (eg, dementia), include the following:

• "Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition) based on:

  • Concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function; and

  • A substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment.

• The cognitive deficits interfere with independence in everyday activities (i.e., at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications).

• The cognitive deficits do not occur exclusively in the context of a delirium.

• The cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia)."

Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a biologically based neurodevelopmental disorder characterized by persistent deficits in social communication, social interaction and restricted, repetitive patterns of behavior, interests, and activities. ASD can range from mild social impairment to severely impaired functioning. As many as half of individuals with autism are non-verbal and have symptoms that may include debilitating intellectual disabilities, inability to change routines, and severe sensory reactions. The American Psychiatric Association’s DSM-5 provides standardized criteria to help diagnose ASD. Autism can co-occur with mental health diagnoses, including, but not limited to, depression, anxiety disorders (eg, social anxiety, obsessive-compulsive disorder), attention deficit hyperactivity disorder, Tourette syndrome/tic disorder, personality disorder, and/or psychosis.

Diagnosis

Diagnosis of ASD in the United States (U.S.) generally occurs in 2 steps: developmental screening followed by comprehensive diagnostic evaluation if screened positive. The American Academy of Pediatrics (AAP) recommends general developmental screening at 9, 18, and 30 months of age and ASD-specific screening at 18 and 24 months of age. Diagnosis and intervention in the first few years of life can have a strong impact on functioning since it allows for treatment during a key window of developmental plasticity.^, However, early diagnosis in the US remains an unmet need even though studies have demonstrated a temporal trend of decreasing mean age at diagnosis over time.

Regulatory Status

In 2011, the generic device Neuropsychiatric Interpretive Electroencephalograph Assessment Aid was granted a de novo 510(k) classification and cleared for marketing by the U.S. Food and Drug Administration (FDA; class II, special controls, product code: NCG). According to the FDA documentation, a neuropsychiatric interpretive EEG assessment aid is a device prescribed by a physician that uses a patient’s electroencephalogram to provide an interpretation of the patient’s neuropsychiatric condition. In addition to the general controls, approval of these devices is subject to a number of special controls, including the following:

• Clinical performance testing must demonstrate the accuracy, precision, and reproducibility of the EEG-based interpretation, including any specified equivocal ones (cutoffs).

• Clinical performance testing must demonstrate the ability of the device to function as an assessment aid for the medical condition for which the device is indicated. Performance measures must demonstrate device performance characteristics per the intended use in the intended use environment. Performance measurements must include sensitivity, specificity, positive predictive value, and negative predictive value per the device intended use. Repeatability of measurement must be demonstrated using interclass correlation coefficients and illustrated by qualitative scatterplots.

• The device design must include safeguards to prevent device use as a stand-alone diagnostic.

• The labeling must bear all information required for the safe and effective use of the device.

In 2013, the Neuropsychiatric EEG-based Assessment Aid (NEBA ; NEBA Health previously Lexicor Medical Technology) for ADHD was granted a de novo 510(k) classification and cleared for marketing by the FDA (K112711). The device is indicated to measure the theta/beta ratio of the electroencephalogram at electrode CZ on patients 6 to 17 years of age, combined with a clinician’s evaluation, to aid in the diagnosis of ADHD. NEBA should only be used by a clinician as confirmatory support for a completed clinical evaluation or as support for the clinician’s decision to pursue further testing following clinical evaluation. The device is not intended as a stand-alone tool in the evaluation or diagnosis of ADHD. FDA product code: NCG

In 2017, the eVox System (Evoke Neuroscience, Inc.) was granted 510(k) classification and cleared for marketing by the FDA (K171781; FDA Product Codes: GWQ, GWJ). In 2020, the NeuralScan System was granted 510(k) classification and cleared for marketing by the FDA (K192753; FDA Product Codes: OLT, GWJ, GWQ). Both of these devices are indicated for: "the acquisition, display, and storage, of electrical activity of a patient’s brain including electroencephalograph (EEG) and event-related potentials (ERP) obtained by placing two or more electrodes on the head to aid in diagnosis." These indications are not condition- or disease-specific.