Clinical Neurophysiology Basics PDF

Clinical Neurophysiology Part I Basics Karsten Schwerdtfeger Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes. Studiengang: Neural Engineering Master WS 2024/2025  Basics: Neurophysiology - Definiti...

Clinical Neurophysiology Part I Basics Karsten Schwerdtfeger Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes. Studiengang: Neural Engineering Master WS 2024/2025  Basics: Neurophysiology - Definition Karsten Schwerdtfeger Neurosurgeon at the Neurosurgical Clinic, Saarland University Medical Center, Homburg/Saar Clinical Neurophysiology Evidence based Medicine Email: [email protected] Last Name First Name Email  Basics: Neurophysiology - Definition www.uks.eu/fileadmin/uks/patienten-besucher/anfahrt-parken- klinikbus-und-infozentrum/UKS_Campus_Map_English.pdf 512 511  Basics: Neurophysiology - Definition Neurophysiology is a branch of physiology and neuroscience that studies the function rather than the architecture of the central, peripheral and autonomous nervous system. However, to understand or interpret neurophysiological findings the knowledge of the nervous system architecture is often mandatory.  Basics: Neurophysiology - Definition Historically, neurophysiology has been dominated by the analysis of the electrical activity of neurons. The techniques range from superficial recordings of neuron conglomerates as the brain (for example the electroencephalogram - EEG) up to high sophisticated analysis of single neurons (intracellular microelectrode recordings, patch clamp, voltage- clamp, extracellular single-unit recording and recording of local field potentials). Usually, the electrical activity of at least voluntarily innervated muscle cells (electromyogram – EMG) is considered to be a part of neurophysiology. The delimitation is sometimes arbitrarily as for example the electrocardiogram (ECG) is usually excluded, however, the assessment of the heart-rate variability extracted from ECG-recordings is a typical example of analyzing the autonomous nervous system.  Basics: Neurophysiology - Definition Spontaneous activity: the EEG is an example of spontaneous electrical activity of the nervous system. Evoked responses: as neurons can be stimulated artificially, the evoked response after a stimulus is another way to analyze the nervous system, especially to assess the connections of neurons (neural pathways). – The simplest example is the (percutaneous) electrical stimulation of a peripheral nerve yielding to a contraction of the muscles innervated by this nerve. – Beside electrical current a broad variety of other stimulation techniques are in use like visual, acoustic, mechanical and magnetic stimulation to check sensory and motor pathways.  Basics: Neurophysiology - Definition Electrical recordings are not the only way to measure the activity of neurons and muscle cells. For example, the contractions of muscle cells can also be assessed by mechanical transducers. Today, this is more or less restricted to special examinations like the measurement of bladder or rectal pressure. The electrical phenomena of neurons and muscle cells are related to metabolic and molecular processes. Thus, neurophysiologists currently utilize also tools from chemistry (calcium imaging), physics (functional magnetic resonance imaging, fMRI), and others to examine brain activity.  Basics: Clinical Neurophysiology - Definition Clinical Neurophysiology means the application of the neurophysiological techniques mentioned above in humans. This is done for diagnostic reasons, i.e. to assess and differentiate diseases of the central, peripheral and autonomous nerve system… as well as for therapeutic use in suited neurological diseases or functional disturbances.  Basics: Excitable cells Cellular level All phenomena in (clinical) neurophysiology are based upon the ability of certain cells like neurons, muscle cells (and some secretory cells) to delineate information by a change of their membrane potential. They are called excitable cells. The information signal usually propagates along the cell, may cause some action like a muscle twitch or can be transmitted to other excitable cells establishing more or less complex forms of information processing. The baseline membrane potential is called resting (membrane) potential (RMP). The membrane change associated with signal propagation is called action potential (AP). Basics – resting (membrane) potential (RMP) = the difference in electrical potential between the interior and the exterior of a biological cell. Typical values range from –40 mV to –80 mV. Semipermeable membrane Potassium ions will flow across a membrane from the higher concentration to the lower concentration. However, this creates an increasing voltage across the membrane that opposes the ions' motion until the flow of ions stops. Basics – action potential (AP) A typical action potential caused by electrical stimulation of a nerve cell has various phases when measured with an intracellular microelectrode against an extracellular reference. The membrane potential starts at the RMP (approximately −70 mV at time zero). A stimulus is applied at time = 1 ms, which yields to a depolarization of the membrane. Basics – action potential (AP) If the depolarization exceeds a threshold of about −55 mV, the membrane potential rapidly rises to a peak of +40 mV at 2 ms. Just as quickly, the potential then drops and overshoots up to −90 mV at 3 ms. Finally the resting potential is reestablished at 5 ms. Depicted is an typical AP of a nerve cell. The time course may vary in other excitable cells. Basics – action potential During the AP, the permeability of the membrane of the excitable cell changes. The following description is somewhat simplified: 1. At the RMP, mainly potassium and to a much lesser extent sodium ions have limited ability to pass through the membrane. The membrane parts which allows the passing of ions are called ion channels 2. Once the AP is triggered, the depolarization activates sodium channels, allowing sodium to enter the cell, resulting in a net positive charge in the excitable cell relative to the extracellular fluid. Basics – action potential 3. After the AP-peak is reached, the excitable cell begins repolarization: the sodium channels close and potassium channels further open, returning the membrane potential to a negative value. 4. Finally, there is a refractory period during which the voltage-dependent ion channels are inactivated while the Na+ and K+ ions return to their resting state distributions by the activity of the Na+/K+ - ATPase (sodium-potassium-pump) which is energy consumptive. During the absolute refractory period the membrane is not able to generate a further AP, during the relative refractory period the depolarization threshold is increased. Therefore the refractory period determines the maximal AP repetition rate. Basics – action potential (AP) Remarks: The duration of an AP differs in the various excitable cells. In nerve cells an AP lasts usually 1 ms, in muscle cells 10 ms and in heart muscle cells up to 500 ms. An AP only triggers when the depolarization threshold is exceeded. Its cell specific shape (amplitude, duration) does not differ in physiological conditions and in case of electrical stimulation is independent of the stimulus current – all or none principle. The ion channels and the Na+/K+ - ATPase can be affected by various drugs which may be used for clinical purposes. For example local anesthetics reversibly block the sodium channel. Basics – action potential (AP) Remarks: For a long time, extracellular Ca++ was thought to stabilize the membrane of excitable cells by increasing the depolarization threshold Meanwhile several voltage-gated Ca++ - channels have been shown yielding to Ca++ - based activity lasting 100 ms or longer. In heart muscles they are related to the so called plateau phase of the action potential. In some types of CNS-neurons, slow calcium spikes provide the driving force for a long burst of rapidly emitted sodium spikes. In general, they are mediators of the cellular activity following the AP as we will see in muscle cells. Basics – neuron anatomy To understand signal propagation and signal transmission from cell to cell, the typical anatomy of a neuron has to be recapitulated. The depicted cell is a typical CNS neuron. It consists of Soma Axon Axon hillock Dendrites Basics – AP propagation To transmit signals the AP has to propagate along the membrane of the axon. In the peripheral nervous system the processes may have a length up to 1 meter. Propagation occurs by local transmembrane currents which yield to a depolarization around the excited area and trigger an AP in adjacent membrane segments. Propagation occurs in each direction. Propagation is much slower than the current in electric cables. Basics – AP propagation Propagation in “naked” axons is rather slow. It depends upon the diameter of the axon and the temperature. In humans it is about 8 -10 m/s. An acceleration is achieved by covering the cell processes with a myelin sheath. Myelin is a multilamellar membrane that enwraps the axon in segments separated by intervals known as nodes of Ranvier. It is produced by specialized cells: Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. Myelin reduces membrane capacitance and increases membrane resistance in the inter- node intervals, resulting in a fast, saltatory movement of action potentials from node to node. Beside temperature and diameter the nerve conduction velocity depends upon the length of the inter-node distance. Maximal values in humans are up to 120 m/s. Basics – neuron anatomy The axon typically divides in several branches establishing contact to other neurons or muscle cells at the terminals. Usually two neurons are not connected electrically! Basics – Synapses The usual signal transfer from neuron to neuron occurs chemically at the synapses: The axon terminal contains vesicles with a so-called neurotransmitter. When an action potential arrives at the end of the pre-synaptic axon (top), it causes the release of neurotransmitter by means of opening Ca++ - channels. The neurotransmitter molecules diffuse through the synaptic cleft and bind to receptors of the subsynaptic membrane. In consequence ion channels in the post-synaptic neuron (bottom) will open. The effect differs, as we will see. Transmission is unidirectional Basics – postsynaptic potentials A neurotransmitter may open sodium channels thus causing a depolarization (excitatory postsynaptic potential – EPSP) Or it may open a potassium channel causing hyperpolarization (inhibitory postsynaptic potential – IPSP). EPSPs and IPSPs last longer than an AP and they may add or subtract. Basics – postsynaptic potentials In fact all the dendrites and the soma consists of subsynaptic membranes The axon hillock is the first sector that is able to generate APs. The effect at the axon hillock depends upon the distance of a given synapse to the axon hillock The result is a complex but dynamic information processing which is able to adopt to changing requirements. Basics – neural network (example) For example, the afferent sensory pathway, for example the somatosensory pathway from the skin to the brain usually has three synaptic relays from the periphery to the neurons of the primary sensory cortex. Basics – neural network (example) For example, the afferent sensory pathways usually have three synaptic relays from the periphery to the neurons of the primary sensory cortex. Each afferent presynaptic axon establish excitatory synaptic contacts to a lot of postsynaptic neurons (divergence) Basics – neural network (example) For example, the afferent sensory pathways usually have three synaptic relays from the periphery to the neurons of the primary sensory cortex. Each afferent presynaptic axon establish excitatory synaptic contacts to a lot of postsynaptic neurons (divergence) Each postsynaptic neuron get input from a lot of excitatory presynaptic axons (convergence). Basics – neural network (example) In the case of a new sensory input, for example a pain stimulus, the convergence- divergence circuitry works like an amplifier. Thus, a fast orientation reaction to a potentially harmful stimulus is enabled. Basics – neural network (example) In the case of a new sensory input, for example a pain stimulus, the convergence-divergence circuitry works like an amplifier. Thus, a fast orientation reaction to a potentially harmful stimulus is enabled. But… Basics – neural network (example) At each relay level there are small interneurons establishing inhibitory contacts – the lateral inhibition. A precise localization of the damaging event is only possible after the lateral inhibition enhances the contrast: impulse propagation is limited to the afferences from the damaged site.  Basics – electrophysiological recording Clinical neurophysiology Extracellular recording of time-dependent voltage changes related to the activity of excitable cells Amplifier AD- Potential difference of Converter two electrodes (per Loudspeaker channel) Rather small signals compared to intra- vs. extracellular recordings Printer Large distance between excitable cells and recording electrodes Stimulator Bad signal-to-noise ratio Computer Complex relationship between the extracellular field and the cellular processes Setting of the recording electrodes.  Basics Amplifier AD converter – Differential amplifier Quantization – Common mode Time resolution rejection Aliasing Impedance converter Nyquist frequency Amplification Filter Signal-to-noise ratio – High-pass – Low-pass – Bandpass – notch Basics  ENG - Stimulation and recording Direct stimulating of a nerve – Usually nerves are stimulated with bipolar electrodes and a square-wave current creating an anode and a cathode. – Depolarization occurs under the cathode so it should be placed to the direction you want to analyze nerve conduction. – The anodal block is a fiction. An increased latency of the recorded responses is possible when changing the polarity. To be continued  Clinical Neurophysiology Part II Electroneurography Karsten Schwerdtfeger Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes. Studiengang: Neural Engineering Master WS 2024/2025  Intro Whats the similarity?  Definitions Electrode: An electrode is a solid electric conductor that carries electric current into non-metallic solids, or liquids, or gases, or plasmas, or vacuums. Electrodes are typically good electric conductors, but they need not be metals. Electrolyte: A substance that breaks up into ions (particles with electrical charges) when it is dissolved in water or body fluids. Some examples of ions are sodium(Na+), potassium(K+), calcium(Ca2+), chloride(Cl-), and phosphate(P3-).  Electrode-electrolyte reaction Example Example Electrode- IHP - Inner Helmholtz plane Electrolyte: Material: AgCl OHP - Outer Helmholtz plane KCl dispersed in Water (Saline) Model describing the electrode-skin interface Circuit Model Electrode Electrolyte interface Circuit Model Electrolyte Skin interface Electroneurography - Mixed nerve Most of our nerves are mixed nerves: – The efferent motor fibers are the axons of the montoneurons in the brain stem or the spinal cord extending to the voluntary muscles of the body. – The afferent sensory fibers carry the information from free nerve endings or specialized receptors to the CNS. – The somata of afferent somatosensory nerves are located in the spinal ganglions just outside the spinal column or within the foramen intervertebrale. Formally, only the part proximal to the ganglion is an axon and the distal part is a dendrite which however generates APs and directly pass into the axon so bypassing the soma (pseudounipolar ganglion cells) – Proximal to the spinal ganglion the fibers form the spinal roots with efferents in the ventral root and afferents in the dorsal root. – Distal to the spinal ganglion the fibers form the spinal nerve – Mixed nerves also contain vegetative fibers which in clinical practice, however, are not assessed electrophysiologically. Electroneurography - Muscle innervation Muscle innervation is a bit more complex: – Two different efferent fibers Aα-fibers from α-motoneurons to the main contractile muscle cells Aγ-fibers from γ-motoneurons to the contractile elements of the muscle spindles, a special receptor within muscles measuring the length of the muscle – Two afferent sensory fibers from the muscle spindle Ia – fibers carrying information of the velocity of length change II – fibers carrying information about the absolute length – From receptors in the tendons Ib – fibers carry information about the tension in the tendons. – The afferent fibers establish synaptic contacts either directly or via interneurons with the α-motoneurons Afferents from the spindle form the circuit for the deep tendon reflexes tested during a neurological examination. Neurology Exam: Reflexes (youtube.com) Afferents from the tendons inhibit the motoneurons thus protecting the muscle for damage like rupture. Electroneurography - Muscle innervation Muscle spindles – The contractile elements within the spindles (intrafusal muscle cells) are located at both ends of the cells. The center of the cells is elastic – The contraction of the ends may compensate length changes due to contraction of the outer (extrafusal) muscle cells and thus preserves the sensitivity of the receptor – Or may be used to modify the reflex circuit as part of a particular voluntary initiated movement. – A way to demonstrate the modification via the spinal Eigenapparat is the Jendrassik maneuver (https://www.youtube.com/watch?v= MyQ23ZlL8Iw) Electroneurography - Muscle innervation Neuromuscular junction – Each motoric nerve fiber has a terminal branching thus innervating several muscle cells. – As the diameter of the branches decreases AP propagation velocity decreases correspondingly – Signal transmission occurs via a synapse the motor end plate. Synaptic transmission is causing a delay of 0.5 ms Motor unit – A motoneuron and the entirety of muscle fibers innervated by one nerve fiber is called motor unit. – In the big tonic muscles for example the gastrocnemial muscle up to 2,000 muscle cells were innervated by one motoneuron. – In muscles showing well-graded force development the motor units are much smaller (a few hundred muscle cells) – Motor pool is the entirety of all motor units of one muscle. ENG - Stimulation and recording Direct stimulating of a nerve – Usually nerves are stimulated with bipolar electrodes and a square-wave current creating an anode and a cathode. – Depolarization occurs under the cathode so it should be placed to the direction you want to analyze nerve conduction. – The anodal block is a fiction. An increased latency of the recorded responses is possible when changing the polarity. Direct recording from a nerve – When recording from a nerve with many fibers, the response differs from the biphasic or triphasic shape. – There are several peaks which disperse with increasing distance to the stimulation site – They correspond to fiber groups of different diameters and myelinisation and therefore different AP propagation velocities which can be associated to distinct functions as we have already seen with the muscle innervation  ENG – fiber classifiction 100 m/s 50 m/s Erlanger/ 20 m/s Gasser 15 m/s 7 m/s 1 m/s 75 m/s 75 m/s Lloyd/Hunt 55 m/s 11 m/s 1 m/s ENG – Motor nerve conduction Stimulation of the nerve under study. Recording from a (distal) muscle innervated by the nerve under study. Usually no surgical exposure of the nerve occurs. Stimulation and recording is done with surface electrodes Motor fibers are identified by recording the response from a muscle innervated by the nerve under study The evoked response is called compound muscle action potential CMAP Due to the terminal slowing and synaptic delay at the end-plate the calculation of the nerve conduction velocity between stimulation and recording site is not reasonable ENG – Motor nerve conduction Instead the latency between stimulation and the onset of the response, the distal motor latency is noticed. Stimulation at different sites along a nerve allows to calculate conduction velocities by dividing the distance between two stimulation sites through the latency difference. Ensure that the cathode always shows in the same direction. Stimulation should occur with supramaximal stimuli activating the whole motor pool – Increase stimulus strength until no further increase in response can be recorded – Add 2 mA to the intensity As latency is measured to the onset of the muscle response, only the velocity of the fastest fibers is assessed. ENG – Motor nerve conduction Pitfalls – Difficulties with stimulation due to thick subcutaneous tissue or deep, intramuscular course of the nerve – Irradiation of the stimulus to neighboring nerves, especially at the wrist – Different or rather low temperature of the extremities ENG – Motor nerve conduction - assessment distal motor latency – Side differences – Absolute values Amplitude – Side differences – Differences between stimulation sites – Absolute – difficult due to the variability Velocity – Side differences – Differences between stimulation sites ENG – Motor nerve conduction - Age  ENG – peripheral nerve lesion types Acute (injury) – Neurapraxia – segmental degeneration of the myelin sheath Regeneration with shorter distances of Ranvier nodes – NCV decreases – Axonotmesis – disruption of the axons with intact connective tissue sheaths Partial block – amplitude decreases initially Wallerian degeneration Regeneration (1mm/day) with shorter internodal distances – NCV decreases – Neurotmesis – complete disruption of the entire nerve Total block Neuroma/retrograde degeneration with neuron loss Indication for surgical reconstruction Chronic (nerve entrapment syndromes, nerve compression syndromes) – Repetitive degeneration/regeneration of the myelin sheath – Axonal damage due to reduced blood perfusion ENG – Peripheral nerval lesion types Left: normal findings Middle: chronic damage due to an ulnar entrapment syndrome at the elbow Right: acute injury to the elbow with partial nerve block ENG – Sensory nerve conduction Usually not successful with skin stimulation Tests of nerves which are pure sensory either at stimulation or at recording site. Recording of the nerve response – Antidrome or orthodrome – Small amplitudes (up to 20 uV) – Large stimulus artifact Suited – Digital nerves – Suralis nerve https://www.youtube.com/watch?v=E6 DSRKdrqxw Clinical applications – carpal tunnel syndrome Most frequent peripheral nerve compression syndrome Incidence: 345/100.000/year main symptoms are pain, numbness and tingling in the thumb, index finger, middle finger and the thumb side of the ring finger. Symptoms typically start during the night and at rest. They are improved by “shaking” of the hand. In advanced cases permanent numbness and muscle atrophy of the thenar occur. Clinical applications – carpal tunnel syndrome Distal chronic compression syndrome with complaints on the right side Clinical applications – carpal tunnel syndrome Distal chronic compression syndrome with complaints on the right side Motor nerve conduction: the distal motor latency is increased on the right side. Clinical applications – carpal tunnel syndrome Distal chronic compression syndrome with complaints on the right side Motor nerve conduction: the distal motor latency is increased on the right side. Sensory nerve conduction: – As the fourth finger is innervated on the radial side by the median nerve and on the ulnar side by the ulnar nerve which is not affected in CTS the nerve conduction velocities should be compared Clinical applications – carpal tunnel syndrome Distal chronic compression syndrome with complaints on the right side Motor nerve conduction: the distal motor latency is increased on the right side. Sensory nerve conduction: – As the fourth finger is innervated on the radial side by the median nerve and on the ulnar side by the ulnar nerve which is not affected in CTS the nerve conduction velocities should be compared – There is a marked difference with slowing of the median sensory nerve conduction especially on the right side Clinical applications – carpal tunnel syndrome Especially in the beginning nerve conduction may appear normal. Pathological nerve conduction values without symptoms are irrelevant. In dubious cases a sonography or a MRI-scan of the wrist should occur Therapy: – With minor symptoms – splinting during the night – With major symptoms or refractory to splinting …. Clinical applications – carpal tunnel syndrome Surgical decompression – Open – Endoscopically Monoportal Biportal (Esmarch ischaemia - Tourniquet) Clinical applications – Cubital tunnel syndrome The second most frequent nerve compression syndrome Weakness of the hand Numbness D4 (ulnar), D5, over the hypothenar Muscle atrophy Clinical applications – Cubital tunnel syndrome Endoscopically assisted decompression. Clinical applications – Cubital tunnel syndrome ENG – Loge de Guyon - Syndrome Symptoms similar to the cubital tunnel syndrome Nerve conduction tests – Prolonging of the distal motor latency – Slowing of the distal sensory nerve conduction – Normal values at the elbow. ENG – Meralgia paresthetica Compression of the lateral femoral cutaneous nerve under the inguinal ligament Pain, Numbness on the lateral aspect of the thigh Unfortunately no reliable sensory nerve conduction test could be established Assessment with somatosensory evoked potentials may be helpful  ENG – Polyneuropathy Polyneuropathy is damage or Inherited causes are disease affecting peripheral hereditary motor neuropathies, nerves in roughly the same Charcot-Marie-Tooth disease, areas on both sides of the body, featuring weakness, and hereditary neuropathy with numbness, and burning pain. liability to pressure palsy. It usually begins in the hands Acquired causes are diabetes and feet and may progress to mellitus, vascular neuropathy, the arms and legs and sometimes to other parts of the alcohol abuse, and vitamin body where it may affect the B12 deficiency. autonomic nervous system. CIDP is regarded as an It may be acute or chronic. autoimmune disease  ENG – Polyneuropathy Classification – Distal axonopathy is the result of interrupted function of the peripheral nerves. It is the most common response of neurons to metabolic or toxic disturbances. – Myelinopathy, is due to a loss of myelin. – Neuronopathy is the result of issues in the peripheral nervous system neurons cell bodies. ENG – F-waves and H-reflex – F-waves are evoked by strong electrical stimuli (supramaximal) applied to the skin surface above the distal portion of a nerve. – The impulse travels in an orthodromic (towards the muscle) as well as antidromic fashion (towards the cell body in the spinal cord) – As the orthodromic impulse reaches innervated muscle fibers, a strong direct motor response (M) is evoked. – As the antidromic impulse reaches the cell bodies within the spinal cord, a part of the alpha motor neurons, (roughly 5-10%) generate a second AP after the refractory period due to persistend depolarization of the dendrites ('backfire‘). – This 'backfiring' elicits an orthodromic impulse, towards innervated muscle fibers (F-response) ENG – F-waves and H-reflex – The H-reflex (or Hoffman’s reflex) is a reflecting the monosynaptic reflex circuit of spinal stretch reflexes. – The H-reflex test is performed using an electric stimulator, which gives usually a square-wave current of short duration and small amplitude. – The response is usually a clear wave, called H- wave, 28-35 ms after the stimulus when applied to the tibial nerve at the poplitea. – The gastrocnemial muscle is the best-suited muscle to elicit a H-reflex. – With increasing stimulation strength the H-wave decreases, and at supramaximal stimulus, the H-wave will disappear. – This is the main difference to the F-wave, as the F-wave slightly increase with strengthening the stimulus. ENG – F-waves and H-reflex – A prolonged or absent F- wave/H-reflex may be caused anywhere in the depicted pathway. – Together with normal distal conduction tests a pathological F-wave/H-reflex points to a proximal lesion, either of the nerve roots or the brachial/lumbosacral plexus – Further elucidation can be done by clinical investigation and motor evoked potentials. To be continued  Clinical Neurophysiology Part IV Electroencephalography Karsten Schwerdtfeger Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes. Studiengang: Neural Engineering Master WS 2024/2025 Electroencephalography Electroencephalography is the technique to record the electrical activity of the brain usually with several electrodes from the scalp over the brain. The electroencephalogram is the recorded electrical activity of the brain. A living brain always shows a continuous electrical activity. EEG = electroencephalography or electroencephalogram The first human EEG was recorded in 1924 by Hans Berger in Jena during a neurosurgical operation with opening of the skull. Electrode placement Electrodes - The International 10-20-system  Electroencephalogram (EEG) https://www.youtube.com/watch?v=XMizSSOejg0 EEG - The International 10-20-system Based upon the distances between four anatomically defined points of the head: Nasion Inion Left ear Right ear. Nomenclature of the electrode positions: Region where the electrode is placed Fp – frontoparietal F – frontal C – central P – parietal O – occipital T – temporal A – auricular (ears) Side Z – midline Odd – left Even - right EEG – what do we record? The electrical activity under the electrodes? EEG – what do we record? The electrical activity under the electrodes Potential differences between pairs of two electrodes. EEG – what do we record? The electrical activity under the electrodes Potential differences between pairs of two electrodes. What we will see depends upon the way we connect the electrodes to the amplifiers (channels) EEG – what do we record? Montages Bipolar Longitudinal Transversal Reference Ipsilateral ear Cz ……. Average reference Laplacian montage EEG – Phase reversal in bipolar montages  EEG Each montage has its advantages and disadvantages Reference montages are a bit more sensitive especially if the distance between the active electrode and the reference is larger than in bipolar montages. The source of a concrete signal is better localized in bipolar montages. Especially if the source is more widespread and affects the reference electrode the localisation becomes very difficult. EEG - frequency bands The brain shows a permanent electric activity In the records from the scalp it is made up of a more or less rhythmic activity within distinct frequency bands – (Gamma > 31 Hz) – Beta 13 – 30 Hz – Alpha 8 – 12 Hz – Theta 4 – 7 Hz – Delta < 4 Hz Note: The limits of the alpha- and beta bands may differ in the literature EEG - normal findings The normal EEG depends upon – Indivdual factors – Normal variants – The region it is derived from – External stimuli – The degree of attention Awake Sleep (five distinct sleep stages – four ones without and one stage with rapid eye movements - REM- sleep) – Age EEG - normal findings Alpha - EEG – Very regular not differing by more than 1 Hz – Individual specific frequency – Accentuated over the occipital and temporal lobe – Side differences in amplitude of less than 50% are normal. – Often modulated in form of a spindle – Blocked by eye opening – Restored after eye closing  EEG - normal findings Alpha - EEG – Blocked by eye opening – Restored after eye closing Eye closing EEG - normal findings Alpha - EEG – My - rhythm (central region) EEG - normal findings Beta-EEG – Only beta-activity in all channels – Alpha –activity sometimes seen for a short period after eye closing – Individual factors – Subject is drowsy or sleeping – Subject is strained (EMG artifacts!) – Pharmacologically induced EEG - abnormal findings Pathologically slowed EEG – Dominated by Theta- and/or Delta-activity – Elevated intracranial pressure – Pathologically impaired consciousness – Cave: Theta- or Delta is increased during some sleep stages – Cave: alpha-coma  EEG - abnormal findings Burst – suppression EEG EEG - abnormal findings Electrocerebral silence – Amplification – Filter settings – Without ECG – artifacts not valid – May be used to shorten waiting time in the diagnosis of brain death EEG - abnormal findings Focal abnormalities – Circumscribed slowing or epileptic activity – Tumors – Small Bleedings – Infarction – ……. EEG - abnormal findings Focal abnormalities – Circumscribed slowing or epileptic activity – Tumors – Small Bleedings – Infarction – ……. EEG - abnormal findings Epileptic activity - interictal – Spikes/sharp waves – Spike waves EEG - abnormal findings Epileptic activity - ictal EEG  EEG - generators Cortical afferents – Sensory input – Specific thalamic nuclei – second relay station – Primary cortex  EEG - generators Cortical afferents – Sensory input – Specific thalamic nuclei – second relay station – Primary cortex – Association cortex  EEG - generators Cortical afferents – Sensory input – Specific thalamic nuclei – second relay station – Primary cortex – Association cortex – Unspecific thalamic nuclei – Widespread cortical projections – Relation to the ascending reticular activating system (ARAS) – Cortical inhibition  EEG - generators Relation to cell potentials – Layer I has a dense population of synapses on peripheral dendrites of the cortical pyramid cells.  EEG - generators Relation to cell potentials + - - + – Layer I has a dense population - of synapses on peripheral dendrites of the cortical pyramid cells. – EPSPs induce a greater + current than IPSPs or APs thus inducing the biggest dipole with surface negativity perpendicular to the surface and smaller dipoles to adjacent regions after activation of the unspecific thalamo-cortical projections – Potential differences at the scalp are determined by the geometric relation of the dipoles and the recording electrodes  EEG - generators And the anatomy of the cortex Dipole orientation differs between the tip of a gyrus and the slopes of a sulcus and even between the slopes of the sulcus.  EEG - generators The EEG we record is mainly generated by subsynaptic potentials in the uppermost layer (layer I) of the cortex. Afferents in this layer are part of the ARAS which regulates consciousness and attention.  EEG - generators The EEG we record is mainly generated by subsynaptic potentials in the uppermost layer (layer I) of the cortex. Afferents in this layer are part of the ARAS which regulates consciousness and attention. The frequency bands of the EEG are modulation of the synaptic activity in layer I. The rhythms in the alpha band or with even still lower frequencies express cortical inhibition due to cortical interneurons or subcortical modulators  EEG - generators The EEG we record is mainly generated by subsynaptic potentials in the uppermost layer (layer I) of the cortex. Afferents in this layer are part of the ARAS which regulates consciousness and attention. The frequency bands of the EEG are modulation of the synaptic activity in layer I. The rhythms in the alpha band or with even still lower frequencies express cortical inhibition due to cortical interneurons or subcortical modulators Beta activity indicates a cortical activation via the unspecific afferents focussing attention to the registration and processing of cortical input. To be continued  Clinical Neurophysiology Part V Evoked Potentials Karsten Schwerdtfeger Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes. Studiengang: Neural Engineering Master WS 2024/2025  Technical notes Signal-to-noise ratio SNR = Psignal/Pnoise Noise Technical noise Line frequency (50/60Hz) 100 Hz noise from electronic devices Amplifier Electrode Operating room: high frequency coagulators Biological noise Depends what we want to record Meaningful versus Unmeaningful signals  Technical notes Typical SNRs ENG CMAP >100:1 Sensory potentials 1:2 – 10:1 EMG Spontaneous activity 5:1 -10:1 MUPs > 100:1 Interference pattern > 100:1 EEG Normal subject 10:1 – 50:1 With EMG – artefacts < 1:10 Electrocerebral silence 3:1 Evoked Potentials SEP/VEP 1:2 – 1:20 FAEP 1 msec) – not selective Only used for studies  Afferent pathway Descending modulation – Mainly inhibitory – Downwards to spinal levels (spinothalamic tract) – Sensitivity control of peripheral receptors?  Afferent pathway information processing Alertness Amplification - convergence/divergence LCCS/ARAS-activation via the unspecific thalamus Cortico-thalamo-cortical loops Processing Spatial and temporal resolution in primary and secondary cortex Integration of different inputs in tertiary cortex Comparison with memory contents Response Preparation of complex motor programs (flight, attack, grip, speech….) Modulation Habituation (with the exception of pain) Lateral inhibition at various levels Descending input control Motor Systems Motor cortex – Association cortex Complex information processing in order to prepare complex movements for example speech – Supplementary motor area Preparing and designing movements – Premotor cortex Preparing and designing movements – Primary motor cortex Execution of movements (Homunculus) Motor Pathways Corticospinal (pyramidal) tract – one of several motor systems – Fast execution of movement programs – Homunculus represents movements, no individual muscles – In primates monosynaptic connection to α- motoneurons – No 1:1 transmission Motor Pathways Extrapyramidal system – Historical definition: all neuclei and tracts except the pyramidal system – Polysynaptic cortco- spinal projections – Cerebellum – Basal ganglia – Modulates spinal reflex arcs Usually inhibition Motor Pathways Upper motor neuron lesion – Paresis of movements – Minor atrophy – Initially flaccid (spinal shock) – Spasticity after some weeks – Increased reflexes – Pathological reflexes Lower motor neuron lesion – Paresis of muscles – Atrophy – Flaccid muscle tone – Loss of reflexes Motor Pathways Electrophysiological assessment – Bereitschaftspotenzial – Transcranial MEPs Electric stimulation Magnetic stimulation – Spinal magnetic stimulation – Motor nerve conduction – F-Waves – H-Reflex – EMG To be continued  Clinical Neurophysiology Part VIII Intraoperative Monitoring Karsten Schwerdtfeger Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes. Studiengang: Neural Engineering Master WS 2024/2025  Intraoperative Monitoring Methods to check functional integrity clinical electrophysiological hemodynamic metabolic  Intraoperative Monitoring Modalities Electroneurography CMAP-recording – latency/amplitude Cranial nerve stimulation Brainstem stimulation Peripheral nerve stimulation Nerve conduction velocity EMG Spontaneous activity with acoustic feedback Mimic muscles Eye muscles Laryngeal muscles EEG Spontaneous activity Processed – for example power spectra depicted as Compressed Spectral Arrays (CSA)  Intraoperative Monitoring Modalities Evoked Potentials SSEP Phase reversal SEP BAEP Electrocochleography Middle latency SEP and/or AEP VEP (?) Motor evoked potentials Magnetic TMS Electric TMS Cortical stimulation White matter stimulation D-waves Intraoperative Monitoring Intraoperative Monitoring  Intraoperative Monitoring Signal-to-noise ratio in the OR SNR = Psignal/Pnoise Noise Technical noise Line frequency (50/60Hz) 100 Hz noise from electronic devices Amplifier Electrode Operating room: high frequency coagulators Biological noise Depends what we want to record Meaningful versus Unmeaningful signals  Intraoperative Monitoring A B Kunststoffüberzug Intraoperative Monitoring  Intraoperative Monitoring Ce2 C3‘ 10:20 10:25 10:30 10:35 10:40 10:45 10:50 10:55 A B P40 P40 ? ? 2 uV 10 ms Reizung links Reizung rechts  Intraoperative Monitoring I V A B 100 nV 1 ms N20 C 1 uV D 5 ms  Intraoperative Monitoring Monitoring of skull base processes Intraoperative Monitoring N. oculomotorius N. abducens Intraoperative Monitoring N. vagus  Intraoperative Monitoring N.VII EMG  Intraoperative Monitoring A B 2 1 N.VII EMG  Intraoperative Monitoring A B 2 1 C D N.VII EMG Intraoperative Monitoring (MEP Monitoring) A B C 100 uV 20 ms To be continued with  Clinical Neurophysiology Part IX Basal ganglia and deep brain stimulation Karsten Schwerdtfeger Klinik für Neurochirurgie, Universitätsklinikum des Saarlandes. Studiengang: Neural Engineering Master WS 2024/2025 Motor Pathways Extrapyramidal system – Historical definition: all neuclei and tracts except the pyramidal system – Polysynaptic cortco- spinal projections – Cerebellum – Basal ganglia – Modulates spinal reflex arcs Usually inhibition Basal ganglia A group of subcortical nuclei at the base of the forebrain and the top of the midbrain They are associated with a variety of functions – Control of voluntary movements – Procedural learning – Habit learning – Conditional learning – Eye movements – Cognition – emotion  Basal ganglia A group of subcortical nuclei next to the thalamus Embedded in complex motor loops Tasks: – Initiation and termination of movements – Stabilization of movements – Stabilizing muscles at rest.  Basal ganglia Input from the cortex to basal ganglia: – Striatum Output to thalamus – Globus pallidus interna – Substantia nigra pars reticularis Direct pathway – Str -> SNret/GPi -> Thalamus – „- x - = +“ disinhibition = facilitation of thalamocortical projections Indirect pathway – Str -> GPe -> STN->Snret/Gpi Caution: this diagram depicts the functional -> Thalamus connections. Anatomical connections are different! – Results in an inhibition of thalamocortical projections  Basal ganglia Substantia nigra pars compacta: – Dopaminergic projections to the striatum as complex modulators – D1 receptors in the striatum yield to excitation – D2 receptors in the striatum yield to inhibition – By differences in the following pathways both projections result in a facilitation of thalamocortical impulse transmission  Basal ganglia Cortical stimulation cortical stimulation – Yields to a triphasic response in the basal ganglia output nuclei (SNret/GPi) recorded by means of an extracellular microelektrode – After a delay there is increased activity resulting in an inhibition of thalamocortical projections – This is followed by a decrease of activity resulting in a disinhibition and commonly thought to be associated with movement release – The third phase finally shows increased activity with inhibition of the thalamocortical projections stopping movement release.  Basal ganglia Cortical stimulation Motoric tasks – Initiation and termination of movements – Stabilization of movements – Stabilizing muscles at rest.  Basal ganglia diseases Parkinsons disease Parkinson's Disease, Animation – YouTube  Basal ganglia disease Cortical stimulation Parkinsons Disease – Loss of dopaminergic neurons in the substantia nigra pars compacta – Cortical activation yields to a hyperactivity of SNret and an inhibition of thalamocortical projections required for initation of movements. – Cardinal signs: Akinesia/Bradykinesia – Start/Stop – disturbance – Impaired facial expression – Micrography – Parkinsonian gait Tremor Rigidity postural instability – Other symptoms Neuropsychiatric vegetative  Basal ganglia diseases Parkinsons disease - Therapy – First line: drugs (L-Dopa, Dopaminagonists, ….) – In case of drug resistance – Deep brain stimulation (DBS) STN  Basal ganglia diseases PD_DBS.mpg  Basal ganglia diseases Parkinsons disease - DBS – Neurophysiological Biomarkers Recorded via extracellular microelectrodes (or the inserted DBS electrodes) Extracellular recording of a circumscibed neuron population - > raw data – High-pass filter –> neuronal firing action potentials of local neurons (Output?)  Basal ganglia diseases Parkinsons disease – Targeting the optimal DBS location by analysis of neuron firing – Microelectrodes record only from a limited number of neurons around the tip when compared to DBS electrodes  Basal ganglia diseases Parkinsons disease – DBS optimization with neuronal firing  Basal ganglia diseases Parkinsons disease - DBS – Neurophysiological Biomarkers Recorded via (extracellular microelectrodes or) the inserted DBS electrodes Extracellular recording of the surrounding neuron population -> raw data – Low-pass filter –> local field potential Pre- and postsynaptic potentials (Input?) Often transferred in the frequency domain and Labeled according the EEG frequency bands  Basal ganglia diseases Parkinsons disease – DBS optimization with local field potentials E0 is the common electrode showing a peak in the lower beta frequency band and is chosen for DBS In modern systems with more electrodes the channels not in use for stimulation may be used to record LFP which were evaluated for an adaptation of DBS (aDBS – closed loop stimulation)  Basal ganglia diseases Parkinsons disease – DBS effect upon local field potentials PAC – phase amplitude coupling  Basal ganglia diseases Parkinsons disease – DBS - Segmented stimulation  Basal ganglia diseases Parkinsons disease - DBS – Adverse effects Infections Hemorrhage Speech arrest Apathy Hallucinations Hypersexuality Cognitive dysfunction Depression Euphoria – Strategies to avoid adverse effects Single shot antibiotics Electrophysiologically optimized placement of the DBS-electrodes Closed loop stimulation Electrode optimization (directional stimulation) Cerebellum Vestibulocerebellum – Maintenance of posture and equilibrium – Maintenance of muscle tone Spinocerebellum – Error correction, adjust posture – Smoothness and coordination of movements Cerebrocerebellum – Planning and programming – Coordination of complex movements – Sequence and precision of movements – Timing of movements Thank you for your attention