Neuromodulation

Introduction to Neuromodulation

Neuromodulation encompasses, according to the “International Neuromodulation Society”, as the alternation of various nerve activity through directed stimuli delivery (Garcia); in this case, electrical stimulation or chemical signals directed to specific neurological pathways associated with psychosis as a means of treatment. They work by either facilitating or inhibiting the release of neurotransmitters themselves (chemical signals used by neurons to communicate), or the effect of receptors for these neurotransmitters. The various actions of these neurotransmitters are called neuromodulators.

The brain hosts many different neuromodulators, and each has a specific receptor(s) that carry out different cellular functions. Each receptor has varying effects on other neurons either within range or through interconnected networks of communicating neurons in the brain. Here we will focus on three main neuromodulators and their involvement in schizophrenia: Dopamine, Serotonin, and Glutamate.  

" Breakthroughs in neuromodulation could create more effective alternatives to prescription painkillers, according to Dr. Konstantin V. Slavin, professor of neurosurgery at the University of Illinois at Chicago...

...Neuromodulation is a form of non-destructive and minimally invasive surgical treatment that uses electrical, chemical, or mechanical stimulation to the brain or nervous system."

                                                                       -Dr. Konstantin V. Slavin, professor of neurosurgery at the University of Illinois at Chicago 

How does this work?

By actively stimulating the nerves to produce either a biological response or by the artificial application of targeted pharmaceuticals to the intended area.


Region of interest?

The midbrain region (area of the medulla and pons) is most indicative of neuromodulation systems. They are roughly separated into a rostral region (stimulation) and caudal region (motor control and function). The thalamus cortex is also heavily involved in this process.

The rostral area is specifically involved with particular neurotransmitters that target the thalamus. This process attributes to arousal. Many of the associated neurotransmitters have overlapping projection regions (mainly the forebrain) and include the central cortex, hypothalamus, hippocampus, and of course the thalamus. The spinal cord region is also included.


Effects of neuromodulators?

These central areas then process information transmitted from the projections received from neuromodulators. Projections of these varying structures indicate different effects. Examples include the regulation of emotions and memory in limbic sites and sympathetic control for projections traveling through the hypothalamus to the spinal cord.


Some neuromodulatory pathways:

The image above represents some of the main neuromodulatory pathways:

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Potentially new antipsychotic treatment:  


A recent study published the potential of a series of a new generation of antipsychotic medication that focuses on specific neuromodulatory effects/ pathways in varying brain regions. One example of such is as followed:

The effects of CBD (cannabidiol) and SNP (sodium nitroprusside) in schizophrenia patients actively stimulate the NDMA-nitric oxide-cGMP process that improves both positive and negative symptoms. These effects are even faster than the current antipsychotic processes. Prior research confirms the influence of increased nitric oxide (NO) levels in individuals with schizophrenia (Oliveira et al., 2008). Past data also suggested the antipsychotic effects of CBD on the inhibition of reuptake and metabolism of anandamide. Anandamide concentrations in the CSF of schizophrenic patients is known to be notably higher than in unaffected individuals (Giuffrida et.al 2004). This data suggests an apparent feedback mechanism of anandamide levels and psychosis symptoms.

Neuromodulatory signaling of this substance can potentially positively affect schizophrenic symptoms. Specific drugs that can effectively inhibit reuptake and metabolism of anandamide (CBD) or increase the NO concentration within the brain (sodium nitroprusside) can potentially serve as successful antipsychotics. Therefore, future comparative studies should be completed to fully understand their effects under differing settings (Crippa et al. 2015).



References:
Garcia, N. (n.d.). Neuromodulation Defined. Retrieved from https://www.neuromodulation.com/neuromodulation-defined
Kravcik, Justin. “Neuromodulation, a Weapon in the Fight against Opioid Addiction ~ Drug Addiction Now.” Addiction Now | Substance Abuse, Drug Addiction and Recovery News Source, Drug Addiction Now, 13 June 2018, www.drugaddictionnow.com/2016/12/30/neuromodulation-weapon-fight-opioid-addiction/.
Purves, Dale, et al. Neuroscience. Oxford University Press, 2019.
Araneda, R. (2020). Modulation of Neural Circuits [PowerPoint slides]. Retrieved from file:///C:/Users/emida/Downloads/Lecture-16%20(1).pdf

Oliveira JP, Zuardi AW, Hallak JE. Role of nitric oxide in patients with schizophrenia - a systematic review of the literature. Curr Psychiatry Rev 2008; 4: 219-27. 

Giuffrida A, Leweke FM, Gerth CW, et al. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology 2004; 29: 2108-14. 

Crippa, Jose, et al. “Cannabidiol and Sodium Nitroprusside: Two Novel Neuromodulatory Pharmacological Interventions to Treat and Prevent Psychosis.” CNS & Neurological Disorders - Drug Targets, vol. 14, no. 8, July 2015, pp. 970–978., doi:10.2174/1871527314666150909113930. http://pdfs.semanticscholar.org/1650/73afe4063c7874ccf7a432cb286c85f9c200.pdf