Neuroingegneria

1. FUNCTIONAL NEUROANATOMY AND NEUROPHYSIOLOGY

1. Nervous system
   • CNS: brain & spinal cord
     • receives info and gives orders for the muscles and glands to act.
   • PNS: sensory + motor nerves
     • bring the messages into and out of the CNS

Anatomy and functional areas of the brain

• 2 cerebral hemisphere
  • 4 lobes (frontal, parietal, occipital, temporal)
• primary motor cortex (lies along the anterior wall of cs)
• primary somatosensory cortex (in the posterior wall of cs)
• Hippocampus: one in each temporal lobe. It plays a very important role in memory

1.2 Cerebral cortex

• Each hemisphere is covered with cortex:
  • outer layer of gray matter. It's convoluted into hundreds of folds made of gyri and sulci to optimize space. It contains neuronal soma (cell body) and unmyelinated axons
• White matter: it is composed of myelinated axons (long-range nerve fibers) that interconnect the various cortical areas and that connect the cortex to subcortical area.

1.3 BRAIN CONNECTIVITY

• Structural connectivity: neurons are physically connected
  • stable within short time scale (sec. to minute)
  • variable within longer time scale due to plasticity

4. Functional connectivity:

There is some synchronicity in time and a correlation between areas.

5. Effective connectivity:

The pre-neuronal influences the post-neuronal.

Neocortex:

Is the largest part of the cerebral cortex. It is made up of 6 layers:

1. Molecular layer: Each layer contains a characteristic distribution of neuronal cell types. Few neurons and its composed by axons and dendrites connect axon and subcortical regions.
2. External granular layer: Small pyramidal cells.
3. External pyramidal layer: It is the primary source of fibers that interconnect the areas of the cortex.
4. Internal granular layer: Contains non-pyramidal neurons. (afferent fibers)
5. Internal pyramidal layer: Largest pyramidal cells (efferent fibers)
6. Polymorphic layer: + cells

The 6th layer is in contact with white matter. Motor cortex sends information to the CNS.

Subcortical areas:

The cortex is made up of other deeper gray matter structures:

• Thalamus: Receives information from sensory inputs and sends it to the cortex for processing.
• Brain stem: It contains nerve fibers descending to and ascending from the spinal cord and a number of motor and sensory nuclei.
• Basal ganglia: Collection of interconnected nuclei strongly connected with cerebral cortex. It plays a critical role in motor functions.

L2.2 Simple cell AF detection

The current through each ion channel depends on:

• driving force (Vm-Eion), size of resistance
• conductance g (measure of ion channel permeability)

I_Na = g_Na(Vm-E_Na)

I = g(Vm-E_k)

Vm = membrane potential

E_ion = equilibrium potential of specific ion

Resting potential → equilibrium I=I_Na + I_K = 0

They are changing over time and they change with voltage

Analysis could be much easier if one of these elements (voltage or time), could be controlled.

The voltage clamp technique does just that, it controls or clamps the voltage across the membrane to whatever value the investigator chooses so that the changes in g_Na and g_K that occur with time can be studied.

Method used to measure the ion current through the membrane of excitable cells while holding the membrane voltage at a set level.

Steps:

1. Vm is measured by an amplifier using an internal recording electrode insert into the cell and an external reference, or bath, electrode.
2. Vc (command voltage) is the desired membrane voltage. The diff. between Vm & Vc is determined by a comparator. If Vm ≠ Vc the comparator generates a difference signal.
3. The diff. signal is used to generate a I that is injected into the axon to make Vm=Vc. (The I injected can be measured and recorded)
4. a) As X-gated ion channels open and close over time in response to changes in Vm - the current generated by these channels can be recorded and analyzed.

Microelectrode Array (MEAs)

→ extracellular recording

• In vitro

  • developed to characterize cultured neural networks (ex: synaptogenesis, how synapses are created, neural plasticity, mechanisms of neural information processing)
  • neurons are directly grown on top of the electrodes
  • very good accessibility
  • controlled environment
• Biological tissue analyzed

• Disassociated neural cultures

  • Extract brain → dissect brain region → mechanically or enzymatically dispersion within liquid suspension to separate individual cells → the neurons are then removed from the suspension and plated onto a substrate on which the cells can attach and grow.

  • Their properties are similar to the mature neurons (axons, dendrites...) → slow producing spontaneous electrical activity.

• Slice cultures

  • Extract brain → section brain (with vibratome) → kept alive in slice culture

  • 3D environment of neurons, where the brain architecture is preserved.
  • Acute slices: are used immediately (for short term, electrophysiological experiments)
  • Organotypic slice cultures: are maintained over multiple days and used to observe structural and morphological changes

If there are 2 chromophores:

ΔA_λ1 = d₁·B^HbO₂·Δc + d₂·B^HHb·Δc

ΔA_λ2 = d₃·B^HbO₂·Δc + d₄·B^HHb·Δc

To obtain Δc^HbO₂ Δc^HHb it is necessary to solve a system of linear equations.

3.0 fNIRS (functional near infrared spectroscopy):

• non invasive optical technology
• monitoring hemodynamic responses, in the cerebral cortex, to a wide range of stimuli
• it uses at least 2 wavelengths in the NIR spectrum of light
• local measurement of oxyhemoglobin (O₂Hb) and deoxyhemoglobin (HHb) concentration changes in cortical brain areas

The changes in the oxy/deoxy total can be detected because the absorption spectra at NIR wavelengths differ for O₂Hb and deoxyHb.

• Techniques:
• continuous wave (CW)
• frequency domain (FD)
• time domain (TD)

Continuous wave (CW)

It only measures the changes in the intensity of the NIR light that passes through the tissue. It can quantify changes in O₂Hb and HHb but not their absolute value.

Frequency domain (FD)

It measures both intensity and phase shift. It can measure the absolute value.

Time domain (TD)

It measures the arrival times of the photons that emerge from the tissue. It yields the highest amount of information, but it is the most complex technology.