Biology:Non-invasive cerebellar stimulation

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Non-invasive cerebellar stimulation is the application of non-invasive neurostimulation techniques on the cerebellum to modify its electrical activity. Techniques such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) can be used.[1] The cerebellum is a high potential target for neuromodulation of neurological and psychiatric 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, cognitive, and emotional functions.[2] Cerebellar TMS is a relatively new field that is undergoing experimental research. There is not yet sufficient evidence of the therapeutic effects of cerebellar TMS,[3] although some successful results have been reported in other clinical studies of TMS used to treat the frontal lobe.[4]

NICS is a neural modulation technique, showing capability to rehabilitate the brain functions of patients undergoing a plethora of neurological or psychiatric diseases.[5] 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).[1] NICS targets the cerebellum, due to the high density of neurons at its superficial layer (the cerebellar cortex), the electrical properties, and network to neural circuits (involved in motor, cognitive, and emotional functions).[2] Due to the success of clinical trials in response to rehabilitating sensorimotor functions and cognition, more NICS research is being invested into.[6] NICS has the potential to attack multiple neurological and psychiatric disorders, although NICS are still not included and heavily advocated in clinical treatment. This is due to contingent conclusions regarding NICS effects.[7] Further research is still required to confirm and identify the optimal parameters to target these regions.

Existing NICS methods

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.[8] 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.[9] 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.[10] 3) NICS induces selectivity of the activation and/or inhibition of specific neural circuits within the cerebellum.[1]

Transcranial magnetic stimulation (TMS)

Figure 1: Image derived from psych scene hub displaying the general mechanism of TMS. A small coil is placed near the scalp, whereby a magnetic field is applied to induce an electrical field within the brains outer cortex. The coil is generally directed above the motor cortex (region which primarily generates neural impulses).[11]
Figure 2: Image of Dr. Oscar Morales (medical director of TMS service at McLean Hospital) displaying how the TMS coil is positioned. This equipment was directed for the treatment of OCD.[12]

TMS utilises a magnetic field to induce a brief electrical impulse which stimulates neurons within the cerebral cortex.[13] 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.[14] TMS itself has variations in terms of magnet strength, pulse frequency, pulse patterns (rTMS), magnetic coil type and stimulation target.[15] Depending on its target use, these factors can be manipulated specific to the target disease.[16] This is a method which is FDA approved and primarily utilized for mental illnesses such as depression.[16]

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.[17] When directed on the cerebellum, tDCs can increase or suppress the excitability of neurons.[18] This is the dependent on the current; an anode is placed on the target region and a cathode on the reference region, I.e. excitability of neurons is enhanced in the target region and alternatively suppressed in the reference region.[19]

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.[20]

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.[21] Results of this study indicated the ability of electrical stimulation in the cerebellum to induce chances in muscle tone and movement.[21] 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.[22] 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.[23]

Medical Use

Currently NICS treatments are not being heavily advocated by medical practitioners due to the insufficient research surrounding their mechanisms.[7] However, there are multiple clinical trials which have deduced that using such techniques have in fact benefited patients with neurological and psychiatric disorders.[7]

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).[24] Clinical trials additionally concluded positive results in relation to improving Obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and schizophrenia.[25] TMS has also been investigated for its potential use in the treatment of chronic pain and stroke rehabilitation.[26]

tDCS likewise have produced positive results in the treatment of disorders such as depression, anxiety, chronic pain and stroke rehabilitation.[27] 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.[28]

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.[29]

Neurological disorders

Cerebellar ataxia

Cerebellar Ataxia are a complex group of degenerative disorders which impair voluntary movements and are associated with the cerebellum.[7] The cerebellum plays a significant role in motor coordination, balance and posture, and its dysfunction is what results in Cerebellar Ataxia.[7] Currently, there are no effective disease-modifying therapies for this condition.[7] However, NICS has demonstrated potential as a therapeutic approach to address the clinical symptoms of patients with these debilitating disorders.[7] 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.[7]

Dystonia

Dystonia is a multifaceted disorder that stems from cerebellar dysfunction, and it is marked by the development of uncontrollable muscle contractions.[30] 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.[30] The approach of TMS and tDCS provides a novel treatment target, however, the efficacy of using NICS within these parameters are undetermined.[30]

Psychiatric disorders

Schizophrenia

Schizophrenia is a psychotic disorder resulting from the impairment of the cerebellum, and it is characterised by hallucinations, distorted thinking and delusions.[31] The NICS technique of tDCS is commonly applied to Schizophrenia to alleviate symptoms and enhance cognitive, social, behavioural and emotional functions.[31] However, clinical trials are needed in order to examine the possible therapeutic potential of tDCS in Schizophrenia.[31]

Benefits

NICS are a safer treatment option unlike invasive procedures and treatment options which require incisions and anaesthesia.[7] 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.[7] 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.[28]

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, hearing loss, transient impairment of working memory etc.[32]

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.[33] 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.[7] This information is still inconclusive and requires further research on how to optimally determine this.

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.[9] 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.[7]

See also

References

  1. ↑ 1.0 1.1 1.2 "Non-invasive cerebellar stimulation--a consensus paper". Cerebellum 13 (1): 121–138. February 2014. doi:10.1007/s12311-013-0514-7. PMID 23943521. http://pure-oai.bham.ac.uk/ws/files/24292821/Non_invasive_cerebellar_stimulation_A_Consensus_Paper_REVISION_1.0.pdf. 
  2. ↑ 2.0 2.1 "Non-invasive Cerebellar Stimulation: Moving Towards Clinical Applications for Cerebellar and Extra-Cerebellar Disorders". Cerebellum 17 (3): 259–263. June 2018. doi:10.1007/s12311-017-0908-z. PMID 29282616. 
  3. ↑ "Transcranial magnetic stimulation of the cerebellum". Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia 154 (2): 133–139. June 2010. doi:10.5507/bp.2010.020. PMID 20668494. 
  4. ↑ "Transcranial magnetic stimulation for major depressive disorder: a pragmatic approach to implementing TMS in a clinical practice". Annals of Clinical Psychiatry 22 (4 Suppl): S4-11. November 2010. PMID 21180663. 
  5. ↑ "Bibliometric and visualised analysis on non-invasive cerebellar stimulation from 1995 to 2021". Frontiers in Neuroscience 17: 1047238. 2023. doi:10.3389/fnins.2023.1047238. PMID 37065918. 
  6. ↑ "Non-invasive Brain Stimulation for the Rehabilitation of Children and Adolescents With Neurodevelopmental Disorders: A Systematic Review". Frontiers in Psychology 10: 135. 2019. doi:10.3389/fpsyg.2019.00135. PMID 30787895. 
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 "Non-Invasive Cerebellar Stimulation in Neurodegenerative Ataxia: A Literature Review". International Journal of Molecular Sciences 21 (6): 1948. March 2020. doi:10.3390/ijms21061948. PMID 32178459. 
  8. ↑ "Does noninvasive cerebellar stimulation improve the balance and walking function of patients with stroke: A meta-analysis of randomized controlled trials" (in en-US). Medicine 101 (36): e30302. September 2022. doi:10.1097/MD.0000000000030302. PMID 36086722. 
  9. ↑ 9.0 9.1 "Transcranial direct current stimulation improves recognition memory in Alzheimer disease". Neurology 71 (7): 493–498. August 2008. doi:10.1212/01.wnl.0000317060.43722.a3. PMID 18525028. 
  10. ↑ "Non-invasive Cerebellar Stimulation in Cerebellar Disorders". CNS & Neurological Disorders Drug Targets 17 (3): 193–198. 2018. doi:10.2174/1871527317666180404113444. PMID 29623859. 
  11. ↑ "Transcranial Magnetic Stimulation for Depression - Review of the Evidence" (in en-US). 21 March 2023. https://psychscenehub.com/psychinsights/transcranial-magnetic-stimulation-for-depression/. 
  12. ↑ "International OCD Foundation | Transcranial Magnetic Stimulation (TMS) for OCD" (in en-US). https://iocdf.org/about-ocd/ocd-treatment/tms/. 
  13. ↑ "How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior 45 (9): 1035–1042. October 2009. doi:10.1016/j.cortex.2009.02.007. PMID 19371866. 
  14. ↑ "How Does TMS Work?" (in en-US). https://www.med.unc.edu/psych/patient-care/interventional-psychiatry/tms/how-tms-works/. 
  15. ↑ "TMS (Transcranial Magnetic Stimulation): What It Is" (in en). https://my.clevelandclinic.org/health/treatments/17827-transcranial-magnetic-stimulation-tms. 
  16. ↑ 16.0 16.1 "Transcranial Magnetic Stimulation (TMS) to Treat Symptoms of Depression: Americas TMS Center: TMS Specialists" (in en). https://www.americastms.com/blog/transcranial-magnetic-stimulation-tms-to-treat-symptoms-of-depression. 
  17. ↑ "Transcranial Direct Current Stimulation (tDCS): A Beginner's Guide for Design and Implementation". Frontiers in Neuroscience 11: 641. 2017. doi:10.3389/fnins.2017.00641. PMID 29213226. 
  18. ↑ "Transcranial direct current stimulation for hyperactivity and noncompliance in autistic disorder". The World Journal of Biological Psychiatry 16 (5): 361–366. 2015. doi:10.3109/15622975.2015.1014411. PMID 25800799. 
  19. ↑ "Transcranial direct current stimulation--update 2011". Restorative Neurology and Neuroscience 29 (6): 463–492. 2011. doi:10.3233/RNN-2011-0618. PMID 22085959. 
  20. ↑ "Topography of cerebellar deficits in humans". Cerebellum 11 (2): 336–351. June 2012. doi:10.1007/s12311-011-0247-4. PMID 21240580. 
  21. ↑ 21.0 21.1 "Cécile & Oskar Vogt: The significance of their contributions in modern neuroscience". Brain Edema XII. 86. Vienna: Springer Vienna. 2003. pp. 29–32. doi:10.1007/978-3-7091-0651-8_6. ISBN 978-3-7091-7220-9. http://link.springer.com/10.1007/978-3-7091-0651-8_6. Retrieved 2023-03-28. 
  22. ↑ "Applications of transcranial magnetic stimulation and magnetic seizure therapy in the study and treatment of disorders related to cerebral aging". Dialogues in Clinical Neuroscience 15 (1): 87–98. March 2013. doi:10.31887/DCNS.2013.15.1/bluber. PMID 23576892. 
  23. ↑ "The Effect of Repetitive Transcranial Magnetic Stimulation of Cerebellar Swallowing Cortex on Brain Neural Activities: A Resting-State fMRI Study". Frontiers in Human Neuroscience 16: 802996. 2022-04-27. doi:10.3389/fnhum.2022.802996. PMID 35572005. 
  24. ↑ Center for Devices and Radiological Health (2021-03-25). "Repetitive Transcranial Magnetic Stimulation (rTMS) Systems - Class II Special Controls Guidance for Industry and FDA Staff" (in en). FDA. https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/repetitive-transcranial-magnetic-stimulation-rtms-systems-class-ii-special-controls-guidance. 
  25. ↑ "Use of repetitive transcranial magnetic stimulation for treatment in psychiatry". Clinical Psychopharmacology and Neuroscience 11 (2): 53–59. August 2013. doi:10.9758/cpn.2013.11.2.53. PMID 24023548. 
  26. ↑ "Transcranial magnetic stimulation: applications in neuropsychiatry". Archives of General Psychiatry 56 (4): 300–311. April 1999. doi:10.1001/archpsyc.56.4.300. PMID 10197824. 
  27. ↑ "Transcranial direct current stimulation for the treatment of post-stroke depression: A systematic review". Frontiers in Neurology 13: 955209. 2023-01-18. doi:10.3389/fneur.2022.955209. PMID 36742053. 
  28. ↑ 28.0 28.1 "Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016". Brain Stimulation 9 (5): 641–661. 2016-06-14. doi:10.1016/j.brs.2016.06.004. PMID 27372845. 
  29. ↑ "Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes". Frontiers in Human Neuroscience 7: 279. 2013. doi:10.3389/fnhum.2013.00279. PMID 23785325. 
  30. ↑ 30.0 30.1 30.2 "Non-invasive cerebellar stimulation in dystonia" (in en). Translational Neuroscience 4 (4): 458–465. 2013-12-01. doi:10.2478/s13380-013-0143-0. ISSN 2081-6936. 
  31. ↑ 31.0 31.1 31.2 "Cognitive Impact of Cerebellar Non-invasive Stimulation in a Patient With Schizophrenia". Frontiers in Psychiatry 11: 174. 2020-03-17. doi:10.3389/fpsyt.2020.00174. PMID 32256404. 
  32. ↑ "Veljko Dubljevic" (in en-US). https://chass.ncsu.edu/people/vdublje/. 
  33. ↑ "Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction". Methods 44 (4): 329–337. April 2008. doi:10.1016/j.ymeth.2007.02.001. PMID 18374276. 



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