3.1.3 Perturbing brain function

Perturbing brain function

Functional neuroimaging has evolved over the last two decades from mapping distinct cognitive, perceptual, and motor functions onto discrete brain regions to investigating functional connections across specialised modules. A statistical examination of variations in brain activity has been the major tool in this endeavour (Paus, 2005).

Perturbation has a long history as a method for exploring brain-behaviour interactions. Irreversible changes (brain lesions) revealed, that the inferior frontal cortex is required for language production and the hippocampal system for declarative memory (Broca, 1861) (Scoville, 1957). The somatotopic structure of the motor cortex was revealed by reversible disturbance of neuronal activity with direct electrical stimulation (Leyton, 1917) (Penfield, 1950).

Lesion studies:

Brain lesions refer to damage to brain tissue as a result of any injury or disease. For the diagnosis of brain lesions different scans are often used. Some brain lesions are treatable and some heal with time by themselves. However, some lesions are untreatable. Lesion studies are used to examine the damage to brain structure. Lesions to the brain can result from many factors, including vascular disorders, traumatic brain injuries, and tumours (Wilkes, K.V., 1980).

Lesion location:	Effect of brain lesion:
Fusiform gyrus	Results in prosopagnosia (inability to recognize faces).
Visual cortex	Different effects depend on the sub-area affected. Lesion to V1 can lead to blindness to of various degrees relative to the calcarine fissure.
Amygdala	Lesions would eliminate the enhanced activation seen in the occipital and fusiform visual area in response to fear. Amygdala lesions change the activation of emotional stimuli.

Electrical stimulation:

Electric stimulation is one of the best techniques to build a connection between neurons to hypothesized brain circuits. It is usually used for vision and evoking eye movements. Perturbing during the neuronal impulses stimulus process may be turned on and off frequently. It is a frequently used method to provide neuronal activity of temporary control. The weakest point of this technique is that it usually activates neurons that are less associated with regular physiological functioning (Wurtz, R.H., 2015).

Transcranial Magnetic Stimulation:

Transcranial magnetic stimulation (TMS) is a treatment method; it is as used magnetic stimulation of brain nerve cells to improve the symptoms of major depressive disorder. It is commonly used when major depressive disorder pharmacology and electroconvulsive treatments were unsuccessful. It is also used to treat obsessive-compulsive disorder and other brain-related disorders. In a repetitive TMS session, a coil of electromagnetics is attached near the patient’s forehead, against the scalp. The electromagnet stimulates the brain region or area by delivering a painless magnetic pulse. It considers that TMS activates different brain areas that are associated with mood and depression, these areas decrease activity stimulated by magnetic stimulation. There is no evidence to support the concept that TMS might cause adverse effects on brain areas (Rizvi, 2019).

Optogenetics:

Optogenetics is a modern method used by researchers and neuroscientists to handle or regulate the neuron’s activities. This method results in the expression of light-sensitive ion channels and enzyme activation. Within individual cells, the associated enzymes are activated by light and biochemical signalling pathways allowed by transcription factors. This control of genetic activity allows research studies to understand their role in decision-making, learning, fear,  memory, addiction, mating, feeding, and locomotion. Optogenetics regulates and alter the activity of the genetically labelled neurons with light (Guru, 2015).

Transcranial Direct-Current Stimulation:

Transcranial Direct-Current Stimulation (tDCS) is a type of neuromodulation that employs steady, low direct current given through electrodes placed on the head. It was first designed to aid individuals suffering from brain injuries or neuropsychiatric disorders such as severe depressive disorder. It differs from cranial electrotherapy stimulation, which employs alternating current in the same way, and transcranial magnetic stimulation. tDCS changes in the brain area are immediate and long-lasting.

tDCS is applied via direct current electrodes between 1-2 mA by using positive (anodal) and negative (cathodic) in specific brain areas. In the human brain, plasticity can allow lasting excitability changes in the response to tDCS use, namely in the treatment of chronic depression (LTD) (Fregni, F., 2015).

The National Institute for Health and Care Excellence (NICE) determined tDCS to be a safe and effective therapeutic technique for depression in 2015 (NICE, 2015).

Deep brain stimulation:

Deep brain stimulation (DBS) is a technique in which a device is placed within the brain tissue, a neurostimulator. An electrical current directly passes to your brain by this device. The human brain consists of billions of neurons, and communication occurs between these cells through chemical signals and electrical signals. In parts of the brain where there is less activity the DBS technique can find some utility.

DBS is most frequently used for the treatment of Parkinson’s disease, epilepsy and essential tremor. But recent research indicates that it has therapeutic benefits for obsessive-compulsive disorder and dystonia. DBS is utilized when medication does not give an appropriate response or results in side effects causing trouble in daily life activities. DBS does not damage any brain tissue (Lee, 2019).

In Parkinson’s disease, there are four areas of the brain that have been treated with neural stimulators. These are the globus pallidus, thalamus, subthalamic nucleus and pedunculopontine nucleus. However, most DBS surgeries in routine practice target either the globus pallidus or the subthalamic nucleus.

Vagus nerve stimulation:

Vagus Nerve stimulation (VNS) is a neuro-modulator tool used in both neurology and psychiatry frequently for the treatment of intractable epilepsy and treatment-resistant depression (Smith, 2006). The vagus nerve which is the 10th cranial nerve arises from the rootlets in the medulla.

VNS generator is implanted under the skin often of the left chest. An electrode is attached to the generator which tunnels up to the left vagus nerve near the carotid sheath where it will deliver electric impulses to the vagus nerve itself (Wheless, 2018.). There is not one clear mechanism of action for how VNS accounts for its efficacy in epilepsy or depression. In epilepsy, there is evidence that VNS leads to cortical resynchronization (Fraschini, 2013). In depression, it is thought that VNS can change the activity of several neurotransmitters or change the functional connectivity of the default mode network (Manta, 2012) (Fang, 2016).

References:

(1) Broca P. 1861, Nouvelle observation d’aphémie produite par une lésion de la moitié postérieure des deuxième et troisième circonvolution frontales gauches. Bulletin de la Société Anatomique, 1861d, tome. XXXVI, 398–407. 

(2) Fang, Jiliang; Rong, Peijing; Hong, Yang; Fan, Yangyang; Liu, Jun; Wang, Honghong; Zhang, Guolei; Chen, Xiaoyan; Shi, Shan; Wang, Liping; Liu, Rupeng; Hwang, Jiwon; Li, Zhengjie; Tao, Jing; Wang, Yang (2016-02-15). “Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder”. Biological Psychiatry. 79 (4): 266–273.

(3) Fraschini, Matteo; Puligheddu, Monica; Demuru, Matteo; Polizzi, Lorenzo; Maleci, Alberto; Tamburini, Giorgio; Congia, Socrate; Bortolato, Marco; Marrosu, Francesco (2013-03-01). “VNS induced desynchronization in gamma bands correlates with positive clinical outcome in temporal lobe pharmacoresistant epilepsy”. Neuroscience Letters. 536: 14–18.

(4) Fregni, F., Nitsche, M.A., Loo, C.K., Brunoni, A.R., Marangolo, P., Leite, J., Carvalho, S., Bolognini, N., Caumo, W., Paik, N.J. and Simis, M., 2015. Regulatory considerations for the clinical and research use of transcranial direct current stimulation (tDCS): review and recommendations from an expert panel. Clinical research and regulatory affairs, 32(1), pp.22-35.

(5) Guru, A., Post, R.J., Ho, Y.Y. and Warden, M.R., 2015. Making sense of optogenetics. International Journal of Neuropsychopharmacology, 18(11), p.pyv079.

(6) Lee, D.J., Lozano, C.S., Dallapiazza, R.F. and Lozano, A.M., 2019. Current and future directions of deep brain stimulation for neurological and psychiatric disorders: JNSPG 75th Anniversary Invited Review Article. Journal of neurosurgery, 131(2), pp.333-342.

(7) Leyton A.S.F& Sherington C.S. 1917Observations on the excitable cortex of the chimpanzee, orang-utan and gorilla. Q. J. Exp. Physiol. 11, 135–222. 

(8) Manta, Stella; El Mansari, Mostafa; Debonnel, Guy; Blier, Pierre (2012-04-17). “Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems”. International Journal of Neuropsychopharmacology. 16 (2): 459–470.

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(10) Penfield W& Rasmussen A.TThe cerebral cortex of man. 1950. New York: Macmillan. 

(11) Rizvi, S. and Khan, A.M., 2019. Use of transcranial magnetic stimulation for depression. Cureus, 11(5).

(12) Smith, D.C., Tan, A.A., Duke, A., Neese, S.L., Clough, R.W., Browning, R.A. and Jensen, R.A. (2006). Recovery of Function after Vagus Nerve Stimulation Initiated 24 Hours after Fluid Percussion Brain Injury. Journal of Neurotrauma, 23(10), pp.1549–1560. doi:10.1089/neu.2006.23.1549.

(13) Scoville W.B& Milner B. 1957Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Neurosurg. Psychiatry. 20, 11–21.

(14) www.nice.org.uk. (n.d.). Overview | Transcranial direct current stimulation (tDCS) for depression | Guidance | NICE. [online] Available at: https://www.nice.org.uk/guidance/ipg530#:~:text=Transcranial%20direct%20current%20stimulation%20(tDCS)%20is%20a%20non%2Dinvasive [Accessed 3 Jan. 2023].

(15) Wilkes, K.V. (1980). More Brain Lesions. Philosophy, 55(214), pp.455–470. doi:10.1017/s0031819100049482.

(16) Wurtz, R.H., 2015. Using perturbations to identify the brain circuits underlying active vision. Philosophical Transactions of the Royal Society B: Biological Sciences, 370(1677), p.20140205.