GBM8320 Dispositifs Médicaux Intelligents. Introduction

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1 GBM8320 Dispositifs Médicaux Intelligents Introduction Part 2: Mohamad Sawan et al. Laboratoire de neurotechnologies Polystim!! Chargé de cours: Responsable: M5031! 15 January 2012 Division of the nervous system 1. Central Nervous system (CNS) Brain and spinal cord 2. Peripheral Nervous system (PNS) Neural tissue outside CNS Afferent division brings sensory information from receptors Efferent division carries motor commands to effectors Efferent division includes somatic nervous system and autonomic nervous system. GBM Dispositifs Médicaux Intelligents 2 1

2 Functional overview of the nervous system GBM Dispositifs Médicaux Intelligents 3 The Central nervous system Composed of the brain and the spinal cord The brain is organized in functional systems Each functional systems involve several brain regions that carry out different types of processing Identifiable pathways link the component of a functional system Each part of the brain projects in an orderly fashion onto the next, creating topographical maps Hierarchical organization of functional systems Contra lateral organization (one side of the brain control the other side of the body). GBM Dispositifs Médicaux Intelligents 4 2

3 The cerebral cortex (Concerned with cognitive functioning) Divided into 4 lobes and separated in 3 internal structures (Fore, Mid & Hindbrain) Frontal lobe (Language and emotional processing) Temporal lobe (somatosensory cortex and the dorsal stream of the visual system) Parietal lobe (primary auditory cortex) Occipital lobe (primary visual cortex). Kandel et al., «Principles of Neural Science», McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 5 Cortical layers (The cortex is organized in cell layers) Layer I : Molecular Layer II : Outer Granular (Small pyramidal cells) Layer III : Outer Pyramidal (Medium pyramidal cells) Layer IV : Inner Granular Layer V : Inner Pyramidal (Large pyramidal cells) Layer VI : Fusiform. These layers organize in/out and projection interneurons. Kandel et al., «Principles of Neural Science», McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 6 3

4 The peripheral nervous system The PNS supplies the sensory information about the environment to the brain The brain sends signals to specific parts of the body through peripheral nerves Divided into somatic and autonomic divisions. Somatic division - Includes the sensory neurons that innervate the skin, muscles and joints Autonomic division - Mediates visceral sensation as well as motor control of the viscera, smooth muscles, and exocrine glands. ACh = Acétylcholine ions chlorure Cl GBM Dispositifs Médicaux Intelligents 7 The spinal cord and peripheral nerves GBM Dispositifs Médicaux Intelligents 8 4

5 The neuron (main signaling units in the nervous system) A neuron fires by transmitting electrical signals along its axon. When signals reach the end of the axon, they trigger the release of neurotransmitters that are stored in pouches called vesicles. Neurotransmitters bind to receptor molecules that are present on the surfaces of adjacent neurons. The point of virtual contact is known as Synapse. GBM Dispositifs Médicaux Intelligents 9 Neuron signaling The released neurotransmitter causes a potential in the postsynaptic cell. Whether the synaptic potential has an excitatory or inhibitory effect depends on the type of receptors in the postsynaptic cell. Kandel et al, Principles of Neural Science, McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 10 5

6 Types of neurons and functional classification Sensory neurons Deliver information from exteroceptors, interoceptors, or proprioceptors Motor neurons Form the efferent division of the PNS Interneurons Located entirely within the CNS Distribute sensory input and coordinate motor output. GBM Dispositifs Médicaux Intelligents 11 Neural membrane and ion channels Neural membrane : the resting potential The resting potential is determined by the relative proportion of different types of ion channels that are open, together with the value of their equilibrium potential. Kandel et al, Principles of Neural Science, McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 12 6

7 Neural membrane and ion channels The resting potential A B The membrane is selective. It is permeable to Na+, K+, and Cl- At rest, the flux of K+ and Na+ is balanced by active pumping of ions. The resting membrane potential is mostly determined by the efflux of K+ outside of the cell, leaving an excess of negative charge on the inside, because there is a lot more resting K+ channels. The flux of ion across the membrane is determined by both the concentration gradient and the electrical potential. This charge build up leads to a potential difference across the membrane (K+ equilibrium potential). Kandel et al, Principles of Neural Science, McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 13 Neural membrane and ion channels The resting potential The equilibrium potential for any ion can be calculated from the Nernst equation where R is the gas constant, T the temperature, z the valence of ion, F the Faraday constant, and [X] o and [X] i the concentrations of the ion outside and inside the cell. Example: Give the ionic potentials for the potassium and sodium across the membrane at rest for [K+] o = 20 mm, [K+] i = 400 mm, [Na+] o = 440 mm, [Na+] i = 50 mm, with RT/F = 25 mv at 25 C (the constant for converting the natural log to base 10 log is 2.3) GBM Dispositifs Médicaux Intelligents 14 7

8 Neural membrane and ion channels Contributions of the different ions When the membrane potential V m is determined by two or more species of ions, the influence of each is determined not only by the concentration of ions inside and outside the cell but also by the ease the ion crosses the membrane. The permeability (P) of the membrane to a specific ions is measured in units of velocity (cm/s). The dependence of membrane potential on ionic permeability and concentration is given by the Goldman equation. For example, if P K >> P Cl and P NA, the equation becomes : GBM Dispositifs Médicaux Intelligents 15 Equivalent circuit (Hodgkin & Huxley model) at rest The transient behavior of the membrane in response to changes in its permeability needs to be modeled by an equivalent electrical circuit (Hodgkin & Huxley). Equivalent circuit modeling the passive current flow in a neuron. This current is balanced by active Na+ and K+ fluxes driven by ionic pumps. C m is the membrane capacitance associated with the lipid layer. The membrane potential is given by : GBM Dispositifs Médicaux Intelligents 16 8

9 Equivalent circuit (con t) I ext In terms of ionic current: I ext = I Na + I k + I L + I C where Ohm's Law: V m -E Na = I Na R Na I Na = g Na (V m E Na ) I k = g k (V m E k ) I L = g L (V m E L ) I C = C dv dt I ext = g Na (V m E Na ) + g K (V m E K ) + g L (V m E L ) + C dv m dt GBM Dispositifs Médicaux Intelligents 17 The action potential: detailed steps a. Resting potential: Na+ and K+ channels closed. A resting potential is measured across the membrane (V m -70 mv). a b c d Absolute refractory period Refractory period e b. Depolarization: Activation gates cause Na+ channels to open (g Na increases rapidly). K+ channels also open, but Na+ inflow >> K+ outflow, resulting in an inward current. GBM Dispositifs Médicaux Intelligents 18 9

10 The action potential: detailed steps (continued) This current discharges the membrane and gives rise to a regenerative process that drives the membrane towards E Na, causing the rising phase of the AP. c. Repolarization: Na+ channels are closed gradually (g Na decreases), and K+ channels open (K+ outflow is greater). An outward K+ current tends to repolarizes the membrane (g K increases). d. Hyperpolarization: some K+ outflow continues after V m has returned to its resting potential. e. Resting potential re-established after K+ channels close. Absolute refractory period Refractory period a b c d e ~10 msec GBM Dispositifs Médicaux Intelligents 19 Action potentials g Na increases quickly, but then inactivation kicks in and it decreases again. g K increases more slowly, and only decreases once the voltage has decreased. Hence, the threshold for action potential initiation is where the inward Na + current exactly balances the outward K + current. There is a refractory period immediately after the action potential where no depolarization can occur. Absolute refractory period Refractory period a b c d e Kandel et al, Principles of Neural Science, McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 20 10

11 Nerve conduction (a) Charge distribution in the vicinity of the active region of an ummyelinated fiber conducting an impulse. External medium Local closed ( solenoidal ) lines of current flow Active region Axon Resting Repolarized membrane membrane Direction of Depolarized propagation membrane (a) (b) Local circuit current flow in the myelinated nerve fiber. Periaxonal space Active node Axon + Myelin sheath Cell (b) Webster (ed.), Medical instrumentation: application and design. 3 rd ed., Wiley Node of Ranvier GBM Dispositifs Médicaux Intelligents 21 Nerve parameters GBM Dispositifs Médicaux Intelligents 22 11

12 Hearing: the auditory system Sound waves are funnelled through the pinna (or external ear) and the external auditory canal, to the tympanic membrane, which vibrates at different speeds. The malleus transmits the vibrations to the incus which passes them onto the stapes, which delivers them to the inner ear. The cochlea contain 16,000 hair cells, whose microscopic, hairlike projections respond to the vibrations produced by sound. GBM Dispositifs Médicaux Intelligents 23 GBM Dispositifs Médicaux Intelligents 24 The auditory system : Middle ear The hair cells, in turn, excite the 28,000 fibers of the auditory nerve, which terminate in the medulla of the brain. Auditory information flows via the thalamus to the temporal gyrus, the part of the cerebral cortex involved in receiving and perceiving sound. 12

13 The auditory system Motion of the basilar membrane in the cochlea. Kandel et al, Principles of Neural Science, McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 25 The auditory system Organ of corti (along the inside of the basilar membrane) and hair cells Kandel et al, Principles of Neural Science, McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 26 13

14 The vision system (the visual pathway) The left halves of both retinas project to the left visual cortex and the right halves project to the right visual cortex. The left half of the scene you are watching registers in your right hemisphere whereas the right half registers in your left hemisphere. A similar arrangement applies to movement and touch. Much is known about the way cells encode visual information in the retina, the lateral geniculate nucleus (LGN) and the visual cortex. However, it is not the case for the brain analyzes/processes of the information. GBM Dispositifs Médicaux Intelligents 27 GBM Dispositifs Médicaux Intelligents 28 The vision system The cornea does the focusing and the lens varies the focus. They produce a clear image on the retina (photoreceptors), and neurons lining the back of the eye. The image on the retina is reversed. Visual receptors are neurons specialized to turn light into electrical signals. Rods are most sensitive to dim light and do not convey color. Cones work in bright light and are responsible for acute detail, black&white and color visions. Visual signals pass from each eye the optic nerve to the optic chiasm, in the lateral geniculate nucleus, where some nerve fibers cross over. 14

15 Visual processing by neurons (retina and central visual pathway) The retina contains 3 stages of neurons: the rods and cones layer sends its signals to the middle layer, which relays signals to a third layer. Nerve fibers (ganglion cells) from the third layer assemble to form the optic nerve. Each cell in the middle or third layer receives input from many cells in the previous layer, but the number of inputs varies across the retina. Each cell in the third layer receives signals from a cluster of rods and cones. Whether large or small, this region of visual space is called the receptive field of the third-layer cell.. GBM Dispositifs Médicaux Intelligents 29 Visual processing by neurons (retina and central visual pathway) The primary visual cortex (densely packed with cells in many layers in the occipital lobe) receives messages from the lateral geniculate. Scientists found patterns of cells responsiveness similar to those observed in the retina and lateral geniculate cells. Cells above and below this layer responded differently. They preferred stimuli in the shape of bars or edges. Further studies showed that different cells preferred edges at particular angles, edges that moved, or edges moving in a particular direction. Receptive field of such a cell is activated when light hits a tiny region in its center and is inhibited when light hits the surrounding part of its center. If light covers the entire receptive field, the cell reacts only weakly and perhaps not at all. GBM Dispositifs Médicaux Intelligents 30 15

16 Visual processing (receptive fields) Retinal ganglion cells respond optimally to contrast in their receptive fields. Ganglion cells have circular receptive fields, with specialized center (pink) and surround (gray) regions. On-center cells are excited when stimulated by light in the center and inhibited when stimulated in the surround; off-center cells have the opposite responses. The figure shows the responses of both types of cells to five different light stimuli (the stimulated portion of the receptive field is shown in yellow). The pattern of action potentials fired by the ganglion cell in response to each stimulus is also shown in extracellular recordings. Duration of illumination is indicated by a bar above each record. Kandel et al, Principles of Neural Science, McGraw-Hill Medical, GBM Dispositifs Médicaux Intelligents 31 The cardiovascular system Anterior view of the human heart showing the four chambers, the inlet and outlet valves, the inlet and outlet major blood vessels, the wall separating the right side from the left side, and the two cardiac pacing centers -the sinoatrial node and the atrio -ventricular node. GBM Dispositifs Médicaux Intelligents 32 16

17 The cardiovascular system Representative electric activity from various regions of the heart. The bottom trace is a scalar ECG, which has a typical QRS amplitude of 1-3 mv. Webster, Medical instrumentation: application and design. 3 rd ed, Wiley, GBM Dispositifs Médicaux Intelligents 33 The gastrointestinal system The primary function of the gastrointestinal system is to supply the body with nutrients and water. The ingested food is moved along the alimentary canal at an appropriate rate for digestion, absorption, storage, and expulsion. The main organs are The esophagus: it s the passage to the stomach. The stomach: trituration and mixing of food. The small intestine: digestion and absorption processes. The colon: Emptying, absorbs water and electrolytes Bronzino, The Biomedical Engineering Handbook, 3dEd. - 3 Vols, CRC, GBM Dispositifs Médicaux Intelligents 34 17

18 Gastrointestinal Electrical Oscillations Gastrointestinal motility is governed by myogenic, neural, and chemical control systems. This control system is manifest by periodic depolarizations of the smooth muscle cells of the gastrointestinal wall. There is autonomous electrical oscillations called the electrical control activity (ECA) or slow waves and rapid electrical oscillations, called the electrical response activity (ERA) or spike bursts. The layers of the gastrointestinal wall The properties of this myogenic system and its electrical oscillations dictate to a large extent the contraction patterns in the gastrointestinal tract. Bronzino, The Biomedical Engineering Handbook, 3dEd. - 3 Vols, CRC, GBM Dispositifs Médicaux Intelligents 35 The endocrine system The body possesses mechanisms for sensing and responding appropriately to numerous biologic cues and signals in order to control and maintain its internal environment. This complex role is effected by the integrative action of the endocrine and neural systems. The endocrine contribution is achieved through a highly sophisticated set of communication and control systems involving signal generation, propagation, recognition, transduction, and response. The signal entities are chemical messengers or hormones that are distributed through the body by the blood circulatory system to their respective target organs to modify their activity in some fashion. 1 brain, 2 thyroid, 3 lung, 4 adrenals, 5 kidney, 6 uterus, 7 testes, 8 ovaries, 9 pancreas, 10 parathyroids, 11 pituitary. GBM Dispositifs Médicaux Intelligents 36 18

19 The endocrine system Hormones are chemically diverse, physiologically potent molecules that are the primary vehicle for intercellular communication with the capacity to override the intrinsic mechanisms of normal cellular control. Regulation and Control: negative & positive feedbacks, rhythmic and endocrine control. Main endocrine glands and the hormones they produce and release. Bronzino, The Biomedical Engineering Handbook, 3ed, 3Vols, CRC, GBM Dispositifs Médicaux Intelligents 37 The respiratory system Function: gas exchange with blood (O2, CO2) The respiratory system includes the lungs, conducting airways, pulmonary vasculature, respiratory muscles, and surrounding tissues and structures. Partial pressure of one constituent: Volume of one constituent: Bronzino, The Biomedical Engineering Handbook, 3ed, 3Vols, CRC, GBM Dispositifs Médicaux Intelligents 38 19

20 The respiratory system Proprioceptors Irritation Pulmonary mechanics Cerebral Cortex, Limbic System, Hypothalamus Medullary & Pons Respiratory centers Respiratory muscles Arterial blood Cnemoreceptors Inflation receptors Baroreceptors Bronzino, The Biomedical Engineering Handbook, 3ed, 3Vols, CRC, GBM Dispositifs Médicaux Intelligents 39 Movements Example 1 Activation of a skeletal muscles open or close joints depending upon whether it is a joint flexor (closer) or extensor (opener). Each skeletal muscle is made up of thousands of individual muscle fibers, and each of these is controlled by one alpha motor neuron in either the brain or the spinal cord. Each single alpha motor neuron controls many muscle fibers (ranging from a few to a hundred or more), forming a functional unit referred to as a motor unit. These motor units are the critical link between the brain and muscles. Reflexes are relatively fixed, automatic muscle responses to particular stimuli. The brain control the actions of motor neurons and muscles. GBM Dispositifs Médicaux Intelligents 40 20

21 Movements (Continued) Example 2 It also controls the nature of the feedback that it receives from sensory receptors in the muscles as movements occur. For example, the sensitivity of the muscle spindle organs is controlled by the brain through a separate set of gamma motor neurons that control the specialized muscle fibers and allow the brain to fine-tune the system for different movement tasks. On right, a sensory input sends a barrage of impulses into the spinal cord along muscle spindle sensory fibers and activates motor neurons to the stretched muscle to cause contraction (stretch reflex). The same stimulus causes inactivation, or inhibition, of the motor neurons to the antagonist muscles through connection neurons, called inhibitory neurons, within the spinal cord. GBM Dispositifs Médicaux Intelligents 41 21

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