High-frequency oscillations (HFO) are brain waves of the frequency faster than ~80 Hz, generated by

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

al cell population. High-frequency oscillations can be recorded during an electroencephalagram (EEG),

local field potential Local field potentials (LFP) are transient electrical signals generated in nerves and other tissues by the summed and synchronous electrical activity of the individual cells (e.g. neurons) in that tissue. LFP are "extracellular" signals, meaning t ...

(LFP) or electrocorticogram (ECoG)

electrophysiology Electrophysiology (from ee the Electron#Etymology, etymology of "electron" ; and ) is the branch of physiology that studies the electrical properties of biological cell (biology), cells and tissues. It involves measurements of voltage change ...

recordings. They are present in physiological state during sharp waves and ripples - oscillatory patterns involved in

memory consolidation Memory consolidation is a category of processes that stabilize a memory trace after its initial acquisition. A memory trace is a change in the nervous system caused by memorizing something. Consolidation is distinguished into two specific processe ...

processes. HFOs are associated with pathophysiology of the brain like

epileptic seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

and are often recorded during seizure onset. It makes a promising biomarker for the identification of the epileptogenic zone. Other studies points to the HFO role in

psychiatric disorders A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...

and possible implications to psychotic episodes in

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

Background and history

Traditional classification of the frequency bands, that are associated to different functions/states of the brain and consist of

delta Delta commonly refers to: * Delta (letter) (Δ or δ), the fourth letter of the Greek alphabet * D (NATO phonetic alphabet: "Delta"), the fourth letter in the Latin alphabet * River delta, at a river mouth * Delta Air Lines, a major US carrier ...

theta Theta (, ) uppercase Θ or ; lowercase θ or ; ''thē̂ta'' ; Modern: ''thī́ta'' ) is the eighth letter of the Greek alphabet, derived from the Phoenician letter Teth 𐤈. In the system of Greek numerals, it has a value of 9. Gree ...

alpha Alpha (uppercase , lowercase ) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter ''aleph'' , whose name comes from the West Semitic word for ' ...

beta Beta (, ; uppercase , lowercase , or cursive ; or ) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Ancient Greek, beta represented the voiced bilabial plosive . In Modern Greek, it represe ...

and

gamma Gamma (; uppercase , lowercase ; ) is the third letter of the Greek alphabet. In the system of Greek numerals it has a value of 3. In Ancient Greek, the letter gamma represented a voiced velar stop . In Modern Greek, this letter normally repr ...

bands. Due to the limited capabilities of the early experimental/medical setup to record fast frequencies, for historical reason, all oscillations above 30 Hz were considered as high frequency and were difficult to investigate. Recent advance in manufacturing electrophysiological setups enables to record

electric potential Electric potential (also called the ''electric field potential'', potential drop, the electrostatic potential) is defined as electric potential energy per unit of electric charge. More precisely, electric potential is the amount of work (physic ...

with high temporal and space resolution, and to "catch" dynamics of single cell

action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

. In neuroscience nomenclature, there is still a reaming gap between ~100 Hz and multi unit activity (>500 Hz), so these oscillations are often called high gamma or HFO.

Neurophysiological features

HFO are generated by different cellular mechanisms and can be detected in many brain areas. In

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

, this fast neuronal activity is effect of the population synchronous spiking of

pyramidal cells Pyramidal cells, or pyramidal neurons, are a type of multipolar neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal cells are the primary excitation units of the mammalian prefrontal cort ...

in the CA3 region and

dendritic Dendrite derives from the Greek word "dendron" meaning ( "tree-like"), and may refer to: Biology *Dendrite, a branched projection of a neuron *Dendrite (non-neuronal), branching projections of certain skin cells and immune cells Physical *Dendri ...

layer of the CA1, which give rise to a characteristic oscillation pattern (see more in sharp waves and ripples). The HFO occurrence during memory task (encoding and recalling images) was also reported in human patients from intracranial recordings in primary visual,

limbic The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''P ...

and higher order cortical areas. Another example of physiological HFO of around 300 Hz, was found in subthalamic nucleus, the brain region which is the main target for high-frequency (130 Hz)

deep brain stimulation Deep brain stimulation (DBS) is a type of neurostimulation therapy in which an implantable pulse generator is stereotactic surgery, surgically implanted subcutaneous tissue, below the skin of the chest and connected by Lead (electronics), leads ...

treatment for patients with

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

Somatosensory evoked high-frequency oscillations

ECoG recordings from human

somatosensory cortex The somatosensory system, or somatic sensory system is a subset of the sensory nervous system. The main functions of the somatosensory system are the perception of external stimuli, the perception of internal stimuli, and the regulation of bod ...

, has shown HFO (reaching even 600 Hz) presence during sensory evoked potentials and somatosensory evoked magnetic field after

median nerve The median nerve is a nerve in humans and other animals in the upper limb. It is one of the five main nerves originating from the brachial plexus. The median nerve originates from the lateral and medial cords of the brachial plexus, and has cont ...

stimulation. These bursts of activity are generated by thalamocortical loop and driven by highly synchronized spiking of the thalamocortical fibres, and are thought to play a role in information processing. Somatosensory evoked HFO amplitude changes may be potentially used as biomarker for neurologic disorders, which can help in diagnosis in certain clinical contexts. Some oncology patients with

brain tumor A brain tumor (sometimes referred to as brain cancer) occurs when a group of cells within the Human brain, brain turn cancerous and grow out of control, creating a mass. There are two main types of tumors: malignant (cancerous) tumors and benign ...

s showed higher HFOs amplitude on the same side, where the tumor was. Authors of this study also suggest contribution from the thalamocortical pathways to the fast oscillations. Interestingly, higher HFO amplitudes (between 400 and 800 Hz) after nerve stimulation were also reported in the EEG signal of healthy

football Football is a family of team sports that involve, to varying degrees, kick (football), kicking a football (ball), ball to score a goal (sports), goal. Unqualified, football (word), the word ''football'' generally means the form of football t ...

and racquet sports players.

Pathological HFO

There are many studies, that reports pathophysiological types of HFO in human patients and animal models of disease, which are related to different psychiatric or neurological disorders: * Amplitude aberrations of the sensory evoked HFOs (600 Hz) was reported in mild demyelination in

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

patients. * HFO (>80 Hz) occur during epileptic seizure onset. * Disruption in the HFO (200–500 Hz) synchronization in subthalamic nucleus is related to

symptoms. * HFOs are visible in different brain regions just after cardiac-arrest and are linked to near-death states. * High amplitude HFOs (80–200 Hz) bursts correlates with psychotic-like state evoked with PCP or subanesthetic dose of

ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...

(and other

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

blockers).

NMDA receptor hypofunction HFO

There are increasing number of studies indicating that HFO rhythms (130–180 Hz) may arise due to the local NMDA receptor blockage, which is also a pharmacological model of schizophrenia. These NMDA receptor dependent fast oscillations were detected in different brain areas including

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...

and

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

regions. Despite the fact that this type of HFO was not yet confirmed in human patients, second generation

antipsychotic drugs Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizoph ...

, widely used to treat schizophrenia and schizoaffective disorders (i.e.

Clozapine Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is used primarily to treat people with schizophrenia and schizoaffective disorder who have ...

Risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as aggressive and self-injurious behaviors associated with autism spectrum disorder. It is t ...

), were shown to reduce HFO frequency. Recent studies, reports on the new source of HFO in the olfactory bulb structures, which is surprisingly stronger than any other previously seen in the mammalian brain. HFO in the bulb is generated by local excitatory-inhibitory circuits modulated by breathing rhythm and may be also recorded under ketamine-xylazine anesthesia. This findings may aid understanding early symptoms of schizophrenia patients and their relatives, that can suffer from olfactory system impairments.

References

{{EEG Neuroscience Neural coding Neural circuitry Neurophysiology Electrophysiology Computational neuroscience