Week 10 ELM 21: Neurotechniques

Past Neurotechniques

• Neurosurgery: The oldest medical specialty, dating back to 10,000 BC, practiced by ancient civilizations like the Maya, Inca, Egyptians, and Chinese.

Cranial Trepanation

• Trepanation: Involves boring holes in the skull.
• Evidence suggests it was practiced as early as 7000 years ago.
• Purpose: Possibly for healing and/or ritualistic reasons.
• Some individuals underwent multiple trepanation procedures and survived.
• Ancient Egyptian Perspective: The heart, not the brain, was considered the seat of the soul and memory repository.

Experimental Ablation

• Experimental Ablation: Involves lesioning/destroying specific brain areas to study their function.
• Example: Study of shoaling behavior in goldfish.

Lesion Studies

• Fish with ablated telencephalon did not swim with the group and remained isolated.

Producing Brain Lesions: Stereotaxic Atlas

• Stereotaxic atlas is used to locate specific brain regions for lesioning, with coordinates (e.g., Interaural 1.74 mm, Bregma -2.06 mm) to target areas like AuV, AND, Te.A, Cpu, etc.

Producing Brain Lesions: Stereotaxic Surgery

• Procedure: Involves adjusting knobs, securing the skull, and using an electrode/cannula holder.
• A hole is drilled above the target lesion site.

Producing Brain Lesions: Stereotaxic Surgery Tools

• Electrode: Delivers electrical current to create lesions.
• Cannula: Delivers excitatory amino acids (e.g., kainic acid) to cause lesions.
• Sham Lesion: A control procedure mimicking lesion production steps without causing actual brain damage.

Stereotaxic Apparatus in Humans

• Stereotaxic apparatus is also used in humans for precise targeting during neurosurgical procedures.

Histological Methods

• Histological Methods: Procedures to observe the lesion's location, including fixing, slicing, staining, and examining the brain.
• Example: Lesioned SCN (suprachiasmatic nucleus).

Accidents – Phineas Gage

• Phineas Gage: A railroad construction foreman known for efficiency and capability.
• Accident: While preparing an explosive charge, a tamping iron was propelled through his head.

Impact of the Accident

• The tamping iron penetrated his left cheek, went through his brain, and exited via the skull.
• Survival: Gage survived and remained conscious.
• Personality Changes: He exhibited profanity, disrespect, violence, and became uncontrollable.
• Significance: Gage's case was the first to link brain trauma and personality change.

Wilder Penfield (1891-1976)

• Wilder Penfield: Used electrical brain stimulation on awake patients during epilepsy treatment.
• Method: Recorded patient reactions when stimulating specific areas of the brain.
• Outcome: Created functional maps of the cortex based on gathered information.

Wilder Penfield Experiments

• Penfield developed a complete map of the motor cortex, known as the “motor homunculus”.

Present Neurotechniques

Electrical Recording/Stimulation

• Electrophysiology: Studies single or multiple cells.
• Electroencephalogram (EEG): Measures brain electrical activity.
• Deep Brain Stimulation (DBS): Involves implanting electrodes in the brain.

Brain Imaging

• Computerised Tomography (CT): Uses X-rays to create cross-sectional images.
• Positron Emission Tomography (PET): Uses radioactivity to show brain activity.
• Magnetic Resonance Imaging (MRI): Uses magnetic fields to create detailed images of the brain.

Deep Brain Stimulation (DBS)

• Method: Electrodes are implanted within specific brain areas.
• Control: Stimulation amount is regulated by a pacemaker-like device under the skin in the upper chest, connected to the electrodes via a wire.
• Mechanism: Produces electrical impulses that regulate abnormal impulses or affect certain brain cells and chemicals; specific mechanisms are still under investigation.

Approved DBS Treatments

• Dystonia
• Essential tremor
• Parkinson's disease
• Obsessive-compulsive disorder
• Epilepsy

Potential DBS Treatments (Under Study)

• Addiction
• Chronic pain
• Cluster headache
• Dementia
• Major depression
• Huntington's disease
• Multiple sclerosis
• Stroke recovery
• Tourette syndrome
• Traumatic brain injury

Computerised Tomography (CT)

• Technique: Combines a series of X-ray images taken from different angles and uses computer processing to create cross-sectional images.
• Use: Quickly examine individuals with internal injuries from accidents or trauma.

Uses of CT Scans

• Pinpoint the location of a tumor, infection, or blood clot.
• Guide procedures such as surgery, biopsy, and radiation therapy.
• Detect and monitor diseases such as cancer.
• Monitor treatment effectiveness.
• Examples: Detecting haematoma, brain tumours.

Positron Emission Tomography (PET)

• Method: Uses a radioactive drug (tracer) to show brain activity.
• Use: Useful in revealing or evaluating tumors and other brain disorders such as Alzheimer's disease (AD) and seizures.
• Can be combined with CT and MRI.
• Example: Demonstrates decreased metabolic activity in Alzheimer's disease through blue and green colors.

Magnetic Resonance Imaging (MRI)

• Technique: Uses a magnetic field and radio waves to create detailed images of the brain.
• Use: Most frequently used imaging test of the brain and spinal cord.
• Diagnoses: aneurysms, disorders of the eye and inner ear, multiple sclerosis, spinal cord injuries, stroke, tumours, brain injury from trauma.

Functional MRI (fMRI)

• Method: Measures metabolic changes within the brain.
• Applications: Examine brain anatomy in people being considered for brain surgery and assess damage from head injury or disorders like AD.
• Example: MRI scans showing that parts of the visual cortex are recruited in language processing in blind people.

Future Neural Therapies

Gene Therapy

• Gene Therapy: Involves altering genes inside the body’s cells to treat or stop disease, instead of using drugs or surgery.
• Approaches:
  • Replacing a mutated gene that causes disease with a healthy copy.
  • Inactivating or “knocking out” a mutated gene that is functioning improperly.
  • Introducing a new gene into the body to help fight a disease.

Gene Therapy Techniques

• Ex vivo gene transfer: Insertion of genetically modified cells.
• Direct in vivo injection: Viral vectors are directly injected into the target tissue.

Commonly Used Viral Vectors

• Retroviral and lentiviral (Lv)
• Adenovirus (AdV) and adeno-associated virus (AAV)
• Herpes simplex virus (HSV)

Gene Therapy Steps

• Step 1: New gene is inserted into a vector.
• Step 2: Vector enters target cells.
• Step 3: New gene is delivered into the nucleus.

Gene Therapy Example

• Progression of thalamic infusion for Parkinson’s disease using adeno-associated virus gene therapy via intraparenchymal administration.
• Before (A) and after (B) aromatic-l-amino-acid decarboxylase (AADC) gene transfer.
• Images use PET as a measure of AADC enzyme activity. Deverman et al., 2018.

Stem Cells

• Stem Cells: Provide new cells for the body as it grows and replace specialized cells that are damaged or lost.
  • Bone marrow produces different types of blood cells.
  • Embryonic stem cells originate from an early-stage embryo.
• Unique Properties:
  • Self-renewal
  • Differentiation into other cell types
• Types:
  • Embryonic stem cells
  • Adult stem cells
  • Induced pluripotent stem cells
• Pluripotent stem cells can differentiate into many cell types, while multipotent stem cells are more restricted and specialised cells have a specific function.

Neural Stem Cells

• Neural Stem Cells: Self-renewing population that generates neurons and glia in the developing brain.
• Potential: Can be isolated, proliferated, genetically manipulated, differentiated in vitro, and reintroduced into a developing, adult, or pathologically altered CNS.
• Therapy Consideration: Considered for use in cell replacement therapies in neurodegenerative diseases (e.g., AD, PD).

Neural Stem Cell Therapy

Studies show stem cells delivered intranasally can engraft to produce olfactory neurons, project to the brain olfactory bulb, and recover sense of smell in mice with hyposmia. Kurtenbach et al., Stem Cell Reports, 2019.

Summary

• Neurosurgery has dramatically developed from the Egyptian periods to the 21st century in parallel with technical advances.
• Current functional neuroimaging provides new insights into complex functional anatomy of the human brain and how it changes in the presence of disease.
• Novel neural therapies have a promising future in research as well as in disease treatment.