Non-invasive Cerebellar Stimulation
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Non-invasive cerebellar stimulation (NICS) is the application of non-invasive
neurostimulation Neurostimulation is the purposeful modulation of the nervous system's activity using invasive (e.g. microelectrodes) or Non-invasive procedure, non-invasive means (e.g. transcranial magnetic stimulation, transcranial electric stimulation such as ...
techniques on the
cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...
to modify its electrical activity. Techniques such as
transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation technique in which a changing magnetic field is used to induce an electric current in a targeted area of the brain through electromagnetic induction. A device called a st ...
(TMS) or transcranial direct current stimulation (tDCS) can be used. The cerebellum is a high potential target for neuromodulation of
neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
and
psychiatric Psychiatry is the medical specialty devoted to the diagnosis, treatment, and prevention of deleterious mental conditions. These include matters related to cognition, perceptions, mood, emotion, and behavior. Initial psychiatric assessment of ...
disorders due to the high density of neurons in its superficial layer, its electrical properties, and its participation in numerous closed-loop circuits involved in
motor An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy. Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power gene ...
,
cognitive Cognition is the "mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...
, and emotional functions. Cerebellar TMS is a relatively new field that is undergoing experimental research. A review of scientific literature (2024) has identified hypotheses of underlying processes of different non-invasive neurostimulation techniques. Val Danilov I (2024). "The Origin of Natural Neurostimulation: A Narrative Review of Noninvasive Brain Stimulation Techniques." ''OBM Neurobiology'' 2024; 8(4): 260; https://doi:10.21926/obm.neurobiol.2404260. Data analysis revealed that mitochondrial activity plays a central role in all of them. This insight and findings from an analysis of the mother-fetus neurocognitive model constituted the hypothesis of natural brain stimulation. According to this hypothesis, the interactions within the mother-fetus bio-system of acoustic waves, electromagnetic fields, and chemical interactions synchronize their brain oscillations, affecting neuroplasticity in the fetus. At the same time, ecological dynamics during the mother's intentional acts provide a clue to the fetus's nervous system, linking synaptic activity with appropriate stimuli. These processes enable the child's nervous system to evolve with adequate biological sentience. During pregnancy, the mother's body produces this set of physical interactions that provide natural neurostimulation to form the balanced nervous system in the child. Therefore, the balanced architecture of the child's nervous system appears with specific cognitive functions, contributing to the beginning of cognition. It is thought that existing neurostimulation techniques are just exceptional cases of this universal natural sequence of actions, a part of a natural flow of physical interactions in nervous system development during pregnancy. However, there is not yet sufficient evidence of the therapeutic effects of cerebellar TMS, although some successful results have been reported in other clinical studies of TMS used to treat the
frontal lobe The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a Sulcus (neur ...
. NICS is a neural modulation technique, showing capability to rehabilitate the brain functions of patients undergoing a plethora of neurological or psychiatric diseases. There are 3 forms of NICS which are primarily used; transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). NICS targets the
cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...
, due to the high density of
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 ...
s at its superficial layer (the
cerebellar cortex The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or e ...
), the electrical properties, and network to neural circuits (involved in motor, cognitive, and emotional functions). Due to the success of clinical trials in response to rehabilitating sensorimotor functions and cognition, more money is being invested in NICS research. NICS has the potential to attack multiple neurological and psychiatric disorders, although NICS is still not included and heavily advocated in clinical treatment. This is due to contingent conclusions regarding NICS effects. Further research is still required to confirm and identify the optimal parameters to target these regions.


Existing NICS methods

The non-invasive electroceutical neurostimulation encompasses five approaches: * Photonic neurostimulation through the image-forming vision pathways and skin irradiation. This technique is known as
Light therapy Light therapy, also called phototherapy or bright light therapy is the exposure to direct sunlight or artificial light at controlled wavelengths in order to treat a variety of medical disorders, including seasonal affective disorder (SAD), circ ...
, and also known as Phototherapy or Luxtherapy. It refers to the body's exposure to intensive electrical light at managed wavelengths to treat different diseases. * Transcranial laser radiation refers to directional low-power and high-fluence monochromatic or quasimonochromatic light radiation, also known as
photobiomodulation Low-level laser therapy (LLLT), cold laser therapy or photobiomodulation (PBM) is a medical treatment approach that applies low-level (low- power) lasers or light-emitting diodes (LEDs) to the surface of the body. Whereas high-power lasers are ...
(PBM). * Transcranial electric current and magnetic field stimulations; * Low-frequency sound stimulations, including vibroacoustic therapy (VAT) and rhythmic auditory stimulation (RAS). * Acoustic photonic intellectual neurostimulation (APIN). It applies features of natural neurostimulation during pregnancy scaled on specific patients. Three therapeutic agents cause oxygenation of neuronal tissues, release of adenosine-5′-triphosphate proteins, and neuronal plasticity. This method shows significant results in chronic pain management in various conditions. The three most distinguished NICS methods include transcranial magnetic stimulation (TMS), transcranial direct-current stimulation (tDCS) and transcranial alternating current stimulation (tACS). All methods involve the targeting to the cerebellar region of interest. However collectively the effects of these treatments are not fully disclosed. Multiple theories have been suggested; 1) NICS influences the excitability of cerebellar neurons and in the connectivity between cerebellar and other brain regions, which henceforth alters the cerebellums motor and cognitive functions. 2) NICS can induce variations in plasticity (ability of nervous system to adapt its activity in response to stimuli), which create long-lasting effects behaviour and cognition. 3) NICS induces selectivity of the activation and/or inhibition of specific neural circuits within the cerebellum.


Transcranial magnetic stimulation (TMS)

TMS utilises a magnetic field to induce a brief electrical impulse which stimulates neurons within the
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...
. This targets the cerebral cortex through electromagnetic induction. Its general mechanism is applying a magnetic field in the form of coil to the scalp which then influences your
motor cortex The motor cortex is the region of the cerebral cortex involved in the planning, motor control, control, and execution of voluntary movements. The motor cortex is an area of the frontal lobe located in the posterior precentral gyrus immediately ...
. TMS itself has variations in terms of magnet strength, pulse frequency, pulse patterns (rTMS), magnetic coil type and stimulation target. Depending on its target use, these factors can be manipulated specific to the target disease. This is a method which is FDA approved and primarily utilized for mental illnesses such as depression.


Transcranial direct current stimulation (tDCS)

tDCS involves the application of a weak direct electrical current to the scalp which flows through underlying brain tissue and modulates the activity of the neurons within the targeted region. When directed on the cerebellum, tDCs can increase or suppress the excitability of neurons. This is the dependent on the current; an
anode An anode usually is an electrode of a polarized electrical device through which conventional current enters the device. This contrasts with a cathode, which is usually an electrode of the device through which conventional current leaves the devic ...
is placed on the target region and a
cathode A cathode is the electrode from which a conventional current leaves a polarized electrical device such as a lead-acid battery. This definition can be recalled by using the mnemonic ''CCD'' for ''Cathode Current Departs''. Conventional curren ...
on the reference region, I.e. excitability of neurons is enhanced in the target region and alternatively suppressed in the reference region.


Transcranial alternating current stimulation (tACS)

tACS involves the utilisation of an alternating current on the target region which is stated to modulate activity of brain regions through entraining neuronal oscillations and hence enhance cerebellar function.


History

The first reports of NICS date back to the early 1960s, when German neurologist Oskar Vogt first used electrical stimulation to stimulate the cerebellum. Results of this study indicated the ability of
electrical stimulation Functional electrical stimulation (FES) is a technique that uses low-energy electrical pulses to artificially generate body movements in individuals who have been paralyzed due to injury to the central nervous system. More specifically, FES ca ...
in the cerebellum to induce chances in muscle tone and movement. However, the use of an invasive procedure limited the clinical application and relevance of the study. The development of transcranial magnetic stimulation (TMS) in the 1980s opened new possibilities for the application NICS, and brain imaging techniques developed in the latter half of the 20th century later revealed the effects of cerebellum stimulation on higher cognitive functions such as language, emotion and attention. In the 1990s, researchers began to study the effects of TMS in humans. Since then, extensive studies have been conducted exploring the impact of NICS on cerebellar function and its possibilities in clinical contexts.


Medical Use

Currently NICS treatments are not being heavily advocated by medical practitioners due to the insufficient research surrounding their mechanisms. However, there are multiple clinical trials which have deduced that using such techniques have in fact benefited patients with
neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
and
psychiatric Psychiatry is the medical specialty devoted to the diagnosis, treatment, and prevention of deleterious mental conditions. These include matters related to cognition, perceptions, mood, emotion, and behavior. Initial psychiatric assessment of ...
disorders. TMS has been approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorders who do not respond to the oral medications (antidepressants). Clinical trials additionally concluded positive results in relation to improving Obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and
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 ...
. TMS has also been investigated for its potential use in the treatment of chronic pain and stroke rehabilitation. tDCS likewise have produced positive results in the treatment of disorders such as depression, anxiety, chronic pain and stroke rehabilitation. However, such evidence is still insufficient to be fully implemented in clinical practice and hence does not have FDA approval. Such research is to be further explored. tACS are similar to this; having promising results in clinical trials but have insufficient research and understanding of mechanisms to further implement this in clinical practice.


Neurological disorders


Cerebellar ataxia

Cerebellar Ataxia Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias. Cerebellar ataxia can occur as a result of many diseases and may present with symptoms ...
are a complex group of degenerative disorders which impair voluntary movements and are associated with the cerebellum. The cerebellum plays a significant role in motor coordination, balance and posture, and its dysfunction is what results in Cerebellar Ataxia. Currently, there are no effective disease-modifying therapies for this condition. However, NICS has demonstrated potential as a therapeutic approach to address the clinical symptoms of patients with these debilitating disorders. The application of NICS techniques such as TMS and tDCS enable the alleviation of symptoms through improved motor function, although further research is needed before it can be broadly utilised within clinical context.


Dystonia

Dystonia Dystonia is a neurology, neurological Hyperkinesia, hyperkinetic Movement disorders, movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed po ...
is a multifaceted disorder that stems from cerebellar dysfunction, and it is marked by the development of uncontrollable muscle contractions. The capacity to restore functional cerebellar processing after impairments suggests NICS as a potential treatment to aid in the control of these symptoms within certain patients. The approach of TMS and tDCS provides a novel treatment target, however, the efficacy of using NICS within these parameters are undetermined.


Psychiatric disorders


Schizophrenia

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 ...
is a
psychotic disorder In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or incoher ...
resulting from the impairment of the cerebellum, and it is characterised by hallucinations, distorted thinking and delusions. The NICS technique of tDCS is commonly applied to Schizophrenia to alleviate symptoms and enhance cognitive, social, behavioural and emotional functions. However, clinical trials are needed in order to examine the possible therapeutic potential of tDCS in Schizophrenia.


Benefits

NICS are a safer treatment option unlike invasive procedures and treatment options which require incisions and anaesthesia. These characteristics make it relatively safe and uncomplicated to administer. NICS enables patients to be treated without the hassle of being hospitalised or sedated as the procedure is often done in an outpatient setting. This is in particularly useful for patients who opt for untraditional treatments (avoiding surgery or use of drugs). NICS are considered to be a cost-effective option for patients. The cost of these treatments may vary in the parameters for an individual patient, although cumulatively this is still a cost-effective option if the alternative is continuous drugs or referring to surgery. Despite the limited information and research available for this topic, NICS withhold potential in the medical field to improve a variety of neuronal and psychiatric disorders.


Limitations and adverse effects

Despite being reported as mostly safe, adverse effects still exist; which influence the patients’ decision to pursue this form of treatment. The most common side effect reported are mild and transient which include headaches, scalp discomfort and tingling sensations. However, there are more severe side-effects reported including induced seizures, pain, syncope, transient induction of
hypomania Hypomania (literally "under mania" or "less than mania") is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome characterized essentially by an apparently non-contextual elevation of Mood (psychology), mood (i.e., euphoria) th ...
, hearing loss, transient impairment of working memory etc. Such implications are due to the lack of research, particularly information regarding the effectiveness and the most optimal method of treatment. Techniques in inducing optimal parameters such as the intensity, target region of the magnetic field and current, duration of pulses, and type of treatment are still unspecified. Such methods (particularly RMS and tDCS) lack specific targeting to certain regions, which thus affects other regions of the brain which otherwise do not require intervention. Additionally, the methods included are not generalisable to all patients. There is more inter-individual variability in the response to cerebellar stimulation, thereafter it requires the calculation and determination of the specific target region for a patient. This information is still inconclusive and requires further research on how to optimally determine this. The noted above issue of an undefined dose (time and field technical parameters) for appropriate and healthy stimulation can destroy healthy cells during the treatment procedure. In many current noninvasive electrical and magnetic therapies, stimulation involves excessive exposure of the patient to an intense field that exceeds natural currents and electromagnetic fields in the brain by times and even orders of magnitude. Due to the lack of standardisation in the protocol of administering these interventions, NICS's are not currently suitable/advocated for application in clinical practice. In order for effective treatment to occur, specified protocols must be administered for each patient, which is impractical in a wide scale population. Due to the limited and mixed conclusions of studies, patients and medical practitioners alike may be hesitant to use and invest in these non-invasive methods. Instead more traditional, invasive methods are preferred; including oral medications or practical therapies.


See also

*
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 ...
*
Neuromodulation Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a sec ...
*
Neurostimulation Neurostimulation is the purposeful modulation of the nervous system's activity using invasive (e.g. microelectrodes) or Non-invasive procedure, non-invasive means (e.g. transcranial magnetic stimulation, transcranial electric stimulation such as ...
*
Neurotechnology Neurotechnology encompasses any method or electronic device which interfaces with the nervous system to monitor or modulate neural activity. Common design goals for neurotechnologies include using neural activity readings to control external devi ...
*
Neurotherapy Neurotherapy is medical treatment that implements systemic targeted delivery of an energy stimulus or chemical agents to a specific neurological zone in the body to alter neuronal activity and stimulate neuroplasticity in a way that develops (or b ...
* Transcranial alternating current stimulation (tACS) *
Transcranial random noise stimulation Transcranial random noise stimulation (tRNS) is a non-invasive brain stimulation technique and a form of transcranial electrical stimulation (tES). Terney et al from Göttingen University was the first group to apply tRNS in humans in 2008. The ...
(tRNS)


References

{{reflist Neurostimulation Cerebellum