Brain Interventions

For basic science - having understanding of brain function
Medicine - developing treatments for brain diseases
Society/personal - improving performance/changing how we feel

Correlation does not mean cuasation

Physical/structural connectivity
Electrial signalling
Neurochemical signalling
Genetic engineering

Phineas Gage
HM

Bilateral medial temporal lobectomy to cure epilepsy
Damaged hippocampus and amygdala
Profound anterograde amnesia (memory loss for events after surgery)
Graded retrograde amnesia (memory loss for events before surgery worse closer to surgery date)

Radio frequency
Excitotoxic

Electrodes inserted into brain
Alternating, high frequency current
Produces heat, killing surrounding cells
Non-specific

Excitatory aa injected into brain
Overstimulates neuron, causing cell death
Only kills target neuron cell bodies
Specific

Deep brain stimulation (DBS)
Transcranial magnetic stimulation (TMS)
Electroconvulsive therapy (ECT)
Direct current stimulation (DCS)

Electrode surgically implanted deep into brain
Delivers electrical impulses to specific target brain regions
Thought that these regions are overactive
DBS may reduce their activity, leading to more normal function

+ Used to treat Parkinson's disease, essential tremor, OCD
+ Potential treatment for depression and Tourette's syndrome
- Surgical risks
- Not fully understood

Produces temporary inactivation of specific brain regions
Electromagnetic stimulation induces electrcial activity in brain

+ Non invasive
+ Localised to small regions of cortex
+ Approved for treatment of depression
+ Relatively safe with few side effects
+ Terraneo 2016 - TMS treatment applied to dorsolateral PFC for 29 days reduced cocaine use and craving in humans
- Cannot penetrate deep into brain, limited to cortex / grey-white matter junction
- Not fully understood, adding noise

General anaesthetic
Electric current applied to precise locations on scalp
Causes short lasting seizure

+ Used as last resort treatment for severe depression, SCZ, mania and severe OCD
- Side effects, headaches and memory loss
- Not fully understood, may change brain chemistry and brain activity

Uses direct electrical currents to stimulate specific parts of brain
Constant, low intensity current passed through 2 electrodes
Anodal stimulation excites neuronal activity
Cathodal stimulation inhibits neuronal activity

+ Non invasive
+ Painless
- Not FDA approved (+ but may be useful in treating depression, anxiety, chronic pain)

Decrease conc. of NET released into synapse
Increase conc. of NET in synapse by blocking reuptake
Change balance of action of NET at different types of receptor

Serotonin (5-HT)
Dopamine (DA)
Noradrenaline (NA)

Metabotropic (G-protein coupled) receptors

Block presynaptic transporter
Increased stimulation of synapse, AP more likely
Eg. SSRIs

By blocking its production
Eg. acute tryptophan depletion procedure

Reduces serotonin
Tryptophan (TRP) = essential aa needed to produce serotonin
Rapid and substantial decrease in TRP produced by injesting large no. of other large neutral aa (LNAA)
Stimulates liver to synthesise protein, removing aa (including TRP) from blood
Additional LNAA also introduces direct competition to protein carriers to reducing transportation of TRP across blood-brain barrier to allow for serotonin production in the brain

Ingest aa not containing tyrosine or phenylalanine

Proteins used to transport NET overflow back into pre-synaptic neuron from synaptic cleft
Located in pre-synaptic neuron membrane
(Reuptake protein)

Designer receptors exclusively activated by designer drugs (DREADDs)
Optogenetics

Method by which engineered GPCRs are activated by otherwise small, inert, drug-like molecules (designer drugs)

Protein that receives chemical signals via the binding of another molecule (ligand)

Type of DREADD
Based on human M3 muscarinic receptor (hM3)
2 point mutations result in hM3Dq:
- Potency for CNO (clozapine-N-oxide)
- Insensitivity to acetylcholine (ACh)
- Low constitutive activity

Biological technique that involves using genetic engineering techniques to enable expression of light-sensitive proteins in neurons

Channelrhodopsins (ChR)
Harlorhodopsins (NpHR)

In the presence of blue light:
Undergoes conformational change
Permits influx of cations, activating cell

Presence of yellow light
Hyperpolarises cell - inactivating it

Dopamine release in striatum

Chronic = high impulsivity and compulsivity, executive function impairements
Recreational = low impulsivity and compulsivity