ELECTROPHYSIOLOGY

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ELECTROPHYSIOLOGY

• Single Neuron Recording
• Patch Clamp Recording
• ECG
• EEG- Brain activity Recording
• PET, MRI, fMRI ,CAT

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Single-unit recording

• It is the use of an electrode to record the
  electrophysiological activity (action potentials)
  from a single neuron.

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• An electrode introduced into the brain of a
  living animal will detect electrical activity
  that is generated by the neurons adjacent to the
  electrode tip. If the electrode is a
  microelectrode, with a tip size of 3 to 10
  micrometers, the electrode will often isolate the
  activity of a single neuron.

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• The activity consists of the voltages generated
  in the extra cellular matrix by the current
  fields outside the cell when it generates an
  action potential. Recording in this way is
  generally called "single-unit" recording.

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• The recorded action potentials look very much
  like the action potentials that are recorded
  intracellularly, but the signals are very much
  smaller (typically about 0.1 mV).

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• Recordings of single neurons in living animals
  have provided important insights into how the
  brain processes information, following the
  hypothesis put forth by Edgar Adrian that unitary
  action potential events are the fundamental means
  of communication in the brain.

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• Microelectrodes used for extra cellular
  single-unit recordings are usually very fine
  wires made from tungsten or platinum-iridium
  alloys that are insulated except at their extreme
  tip and are less often glass micropipettes filled
  with a weak electrolyte solution similar in
  composition to extra cellular fluid.

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• Hubel and Wiesel were awarded the Nobel Prize in
  Physiology or Medicine in 1981.

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The patch clamp technique

• It is a laboratory technique in electrophysiology
  that allows the study of single or multiple ion
  channels in cells.

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• The technique can be applied to a wide variety of
  cells, but is especially useful in the study of
  excitable cells such as neurons, cardiomyocytes,
  muscle fibers and pancreatic beta cells. It can
  also be applied to the study of bacterial ion
  channels in specially prepared giant
  spheroplasts.

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• It is a laboratory technique in electrophysiology
  that allows the study of single or multiple ion
  channels in cells

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• Erwin Neher and Bert Sakmann developed the patch
  clamp in the late 1970s and early 1980s.
• This discovery made it possible to record the
  currents of single ion channels for the first
  time, proving their involvement in fundamental
  cell processes such as action potential
  conduction.

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• Neher and Sakmann received the Nobel Prize in
  Physiology or Medicine in 1991 for this work.

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• Patch clamp recording uses, as an electrode, a
  glass micropipette that has an open tip diameter
  of about one micrometer, a size enclosing a
  membrane surface area or "patch" that often
  contains just one or a few ion channel molecules

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• In some experiments, the micropipette tip is
  heated in a microforge to produce a smooth
  surface that assists in forming a high resistance
  seal with the cell membrane.
• The interior of the pipette is filled with a
  solution matching the ionic composition of the
  bath solution, as in the case of cell-attached
  recording, or the cytoplasm for whole-cell
  recording

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• Unlike traditional two-electrode voltage clamp
  recordings, patch clamp recording uses a single
  electrode to record currents.

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• ELECTROCARDIOGRAPH

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• As cardiac impulses pass through the heart,
  electrical currents spread into the tissues
  surrounding the heart, and a small portion of
  these currents spread throughout the surface of
  the body.

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• If electrodes are placed on the skin on opposite
  sides of the heart, electrical potential
  generated by these currents can be recorded.

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• Electrocardiograph is an instrument which records
  the electrical activity of the heart during a
  cardiac cycle.

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• A record of the minute electrical pulses
  generated by the heart used to determine the
  condition of the patients heart is the
  ElectroCardioGram.

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• Electrodes are placed on the chest and limbs, and
  the impulses which they detect are amplified by
  the electrograph to which the electrodes are
  connected.

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• The ECG was developed by William Einthoven of
  Leiden University, England between 1903 and 1910

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• Electrical impulses in the heart originate in the
  sinoatrial node and travel through the heart
  muscle where they impart electrical initiation of
  systole or contraction of the heart.
• The electrical waves can be measured at
  selectively placed electrodes (electrical
  contacts) on the skin.

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• Electrodes on different sides of the heart
  measure the activity of different parts of the
  heart muscle.
• An ECG displays the voltage between pairs of
  these electrodes, and the muscle activity that
  they measure, from different directions, also
  understood as vectors.

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• This display indicates the overall rhythm of the
  heart and weaknesses in different parts of the
  heart muscle.
• It is the best way to measure and diagnose
  abnormal rhythms of the heart, particularly
  abnormal rhythms caused by damage to the
  conductive tissue that carries electrical
  signals, or abnormal rhythms caused by levels of
  dissolved salts (electrolytes), such as
  potassium, that are too high or low. In
  myocardial infarction (MI), the ECG can identify
  damaged heart muscle

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• The ECG cannot reliably measure the pumping
  ability of the heart for which ultrasound-based
  (echocardiography) or nuclear medicine tests are
  used.

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• A typical electrocardiograph runs at a paper
  speed of 25 mm/s, although faster paper speeds
  are occasionally used. Each small block of ECG
  paper is 1 mm².
• At a paper speed of 25 mm/s, one small block of
  ECG paper translates into 0.04 s (or 40 ms).
• Five small blocks make up 1 large block, which
  translates into 0.20 s (or 200 ms).
• Hence, there are 5 large blocks per second.

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• A standard signal of 1 mV must move the stylus
  vertically 1 cm, that is two large squares on ECG
  paper.

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Leads used in ECG

• Limb Leads
• Leads I, II and III are the so-called limb leads
• Lead I is a dipole with the negative (white)
  electrode on the right arm and the positive
  (black) electrode on the left arm.
• Lead II is a dipole with the negative (white)
  electrode on the right arm and the positive (red)
  electrode on the left leg.
• Lead III is a dipole with the negative (black)
  electrode on the left arm and the positive (red)
  electrode on the left leg.

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Augmented limb

• Leads aVR, aVL, and aVF are 'augmented limb
  leads'. They are derived from the same three
  electrodes as leads I, II, and III. However, they
  view the heart from different angles
• Lead aVR or "augmented vector right" has the
  positive electrode (white) on the right arm. The
  negative electrode is a combination of the left
  arm (black) electrode and the left leg (red)
  electrode, which "augments" the signal strength
  of the positive electrode on the right arm.

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• Lead aVL or "augmented vector left" has the
  positive (black) electrode on the left arm. The
  negative electrode is a combination of the right
  arm (white) electrode and the left leg (red)
  electrode, which "augments" the signal strength
  of the positive electrode on the left arm.
• Lead aVF or "augmented vector foot" has the
  positive (red) electrode on the left leg. The
  negative electrode is a combination of the right
  arm (white) electrode and the left arm (black)
  electrode, which "augments" the signal of the
  positive electrode on the left leg

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Precordial

• The precordial leads V1, V2, V3, V4, V5, and V6
  are placed directly on the chest. Because of
  their close proximity to the heart, they do not
  require augmentation

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Waves and intervals

• A typical ECG tracing of a normal heartbeat (or
  cardiac cycle) consists of a P wave, a QRS
  complex and a T wave.
• A small U wave is normally visible in 50 to 75
  of ECGs. The baseline voltage of the
  electrocardiogram is known as the isoelectric
  line.
• Typically the isoelectric line is measured as the
  portion of the tracing following the T wave and
  preceding the next P wave.

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Schematic representation of normal ECG
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P wave

• During normal atrial depolarization, the main
  electrical vector is directed from the SA node
  towards the AV node, and spreads from the right
  atrium to the left atrium.
• This turns into the P wave on the ECG, which is
  upright in II, III, and aVF and inverted in aVR
  . A P wave must be upright in leads II and aVF
  and inverted in lead aVR to designate a cardiac
  rhythm as Sinus Rhythm.

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• The relationship between P waves and QRS
  complexes helps distinguish various cardiac
  arrhythmias.
• The shape and duration of the P waves may
  indicate atrial enlargement

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QRS complex

• The QRS complex is a structure on the ECG that
  corresponds to the depolarization of the
  ventricles.
• Because the ventricles contain more muscle mass
  than the atria, the QRS complex is larger than
  the P wave.

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• In addition, because the His/Purkinje system
  coordinates the depolarization of the ventricles,
  the QRS complex tends to look "spiked" rather
  than rounded due to the increase in conduction
  velocity.
• A normal QRS complex is 0.08 to 0.12 sec (80 to
  120 ms) in duration represented by three small
  squares or less, but any abnormality of
  conduction takes longer, and causes widened QRS
  complexes

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PR/PQ interval

• The PR interval is measured from the beginning of
  the P wave to the beginning of the QRS complex.
• It is usually 120 to 200 ms long. On an ECG
  tracing, this corresponds to 3 to 5 small boxes.
  In case a Q wave was measured with a ECG the PR
  interval is also commonly named PQ interval
  instead.
• A PR interval of over 200 ms may indicate a first
  degree heart block.

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• A short PR interval may indicate a pre-excitation
  syndrome via an accessory pathway that leads to
  early activation of the ventricles, such as seen
  in Wolff-Parkinson-White syndrome.
• A variable PR interval may indicate other types
  of heart block.

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• The duration, amplitude, and morphology of the
  QRS complex is useful in diagnosing cardiac
  arrhythmias, conduction abnormalities,
  ventricular hypertrophy, myocardial infarction,
  electrolyte derangements, and other disease
  states.

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• "Buried" inside the QRS wave is the atrial
  repolarization wave, which resembles an inverse P
  wave.
• It is far smaller in magnitude than the QRS and
  is therefore obscured by it.

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ST segment

• The ST segment connects the QRS complex and the T
  wave and has a duration of 0.08 to 0.12 sec (80
  to 120 ms).
• It starts at the J point (junction between the
  QRS complex and ST segment) and ends at the
  beginning of the T wave.

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• The typical ST segment duration is usually around
  0.08 sec (80 ms).
• The normal ST segment has a slight upward
  concavity.

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T wave

• The T wave represents the repolarization (or
  recovery) of the ventricles.
• The interval from the beginning of the QRS
  complex to the apex of the T wave is referred to
  as the absolute refractory period.

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• The last half of the T wave is referred to as the
  relative refractory period (or vulnerable
  period). Tall or "tented" symmetrical T waves may
  indicate hyperkalemia.
• Flat T waves may indicate coronary ischemia or
  hypokalemia.

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QT interval

• The QT interval is measured from the beginning of
  the QRS complex to the end of the T wave.
• Normal values for the QT interval are between
  0.30 and 0.44 seconds.

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• The QT interval as well as the corrected QT
  interval are important in the diagnosis of long
  QT syndrome and short QT syndrome.
• The QT interval varies based on the heart rate,
  and various correction factors have been
  developed to correct the QT interval for the
  heart rate.

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• The QT interval represents on an ECG the total
  time needed for the ventricles to depolarize and
  repolarize

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U wave

• The U wave is not always seen. It is typically
  small, and, by definition, follows the T wave. U
  waves are thought to represent repolarization of
  the papillary muscles or Purkinje fibers.
  Prominent
• An inverted U wave may represent myocardial
  ischemia or left ventricular volume overload

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Computed Axial Tomography (CAT)

• Computed tomography (CT) is a medical imaging
  method employing tomography.
• Digital geometry processing is used to generate a
  three-dimensional image of the inside of an
  object from a large series of two-dimensional
  X-ray images taken around a single axis of
  rotation.

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• CT scan was invented by Sir Godfrey Hounsfield
• He got Nobel prize in 1979 for the discovery

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CT Scanner
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CT Image of Brain
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Brain Images
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• The word "tomography" is derived from the Greek
  tomos (slice) and graphein (to write).
• Computed tomography was originally known as the
  "EMI scan" as it was developed at a research
  branch of EMI, a company best known today for its
  music and recording business.
• It was later known as computed axial tomography
  (CAT or CT scan) and body section röntgenography.

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Positron emission tomography (PET)

• Positron emission tomography (PET) is a nuclear
  medicine imaging technique which produces a
  three-dimensional image or picture of functional
  processes in the body

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• The system detects pairs of gamma rays emitted
  indirectly by a positron-emitting radionuclide
  (tracer), which is introduced into the body on a
  biologically active molecule.

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• Images of tracer concentration in 3-dimensional
  space within the body are then reconstructed by
  computer analysis.
• In modern scanners, this reconstruction is often
  accomplished with the aid of a CT X-ray scan
  performed on the patient during the same session,
  in the same machine.

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• If the biologically active molecule chosen for
  PET is FDG, an analogue of glucose, the
  concentrations of tracer imaged then give tissue
  metabolic activity, in terms of regional glucose
  uptake.

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• To conduct the scan, a short-lived radioactive
  tracer isotope, is injected into the living
  subject (usually into blood circulation).
• The tracer is chemically incorporated into a
  biologically active molecule
• The molecule most commonly used for this purpose
  is fluorodeoxyglucose (FDG), a sugar, for which
  the waiting period is typically an hour.

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• As the radioisotope undergoes positron emission
  decay (also known as positive beta decay), it
  emits a positron, a particle with the opposite
  charge of an electron.
• After traveling up to a few millimeters the
  positron encounters and annihilates with an
  electron, producing a pair of annihilation
  (gamma) photons moving in opposite directions.

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• These are detected when they reach a scintillator
  in the scanning device, creating a burst of light
  which is detected by photomultiplier tubes or
  silicon avalanche photodiodes

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PET
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PET IMAGE
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PET Image of Brain
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PET Acquisition Process
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Radioisotopes

• Radionuclides used in PET scanning are typically
  isotopes with short half lives such as carbon-11
  (20 min), nitrogen-13 (10 min), oxygen-15 (2
  min), and fluorine-18 (110 min).

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• These radionuclides are incorporated either into
  compounds normally used by the body such as
  glucose (or glucose analogues), water or ammonia,
  or into molecules that bind to receptors or other
  sites of drug action. Such labelled compounds are
  known as radiotracers.

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Applications

• PET is both a medical and research tool
• It is used heavily in clinical oncology (medical
  imaging of tumors and the search for metastases),
  and for clinical diagnosis of certain diffuse
  brain diseases such as those causing various
  types of dementias
• PET is also an important research tool to map
  normal human brain and heart function.

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Magnetic resonance imaging (MRI)

• Magnetic resonance imaging (MRI), or nuclear
  magnetic resonance imaging (NMRI), is primarily a
  medical imaging technique most commonly used in
  radiology to visualize the structure and function
  of the body. It provides detailed images of the
  body in any plane.

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MRI
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• NMR was discovered by Bloch and Purcell in 1952

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MRI Image of Brain
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• MRI provides much greater contrast between the
  different soft tissues of the body than computed
  tomography (CT) does, making it especially useful
  in neurological (brain), musculoskeletal,
  cardiovascular, and oncological (cancer) imaging

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• Unlike CT, it uses no ionizing radiation, but
  uses a powerful magnetic field to align the
  nuclear magnetization of (usually) hydrogen atoms
  in water in the body.

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• Radiofrequency fields are used to systematically
  alter the alignment of this magnetization,
  causing the hydrogen nuclei to produce a rotating
  magnetic field detectable by the scanner.
• This signal can be manipulated by additional
  magnetic fields to build up enough information to
  construct an image of the body.

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• The body is mainly composed of water molecules
  which each contain two hydrogen nuclei or
  protons.
• When a person goes inside the powerful magnetic
  field of the scanner these protons align with the
  direction of the field.

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• A second radiofrequency electromagnetic field is
  then briefly turned on causing the protons to
  absorb some of its energy.
• When this field is turned off the protons release
  this energy at a radiofrequency which can be
  detected by the scanner.

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• The position of protons in the body can be
  determined by applying additional magnetic fields
  during the scan which allows an image of the body
  to be built up. These are created by turning
  gradients coils on and off which creates the
  knocking sounds heard during an MR scan.

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• Diseased tissue, such as tumors, can be detected
  because the protons in different tissues return
  to their equilibrium state at different rates.

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Applications

• In clinical practice, MRI is used to distinguish
  pathologic tissue (such as a brain tumor) from
  normal tissue.
• One advantage of an MRI scan is that it is
  harmless to the patient. It uses strong magnetic
  fields and non-ionizing radiation in the radio
  frequency range
• Compare this to CT scans and traditional X-rays
  which involve doses of ionizing radiation and may
  increase the risk of malignancy, especially in a
  fetus.

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MRI Signs

• Safe Conditional Unsafe

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Functional MRI (fMRI)

• It is a type of specialized MRI scan. It measures
  the haemodynamic response related to neural
  activity in the brain or spinal cord of humans or
  other animals

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• It is one of the most recently developed forms of
  neuroimaging.
• Since the early 1990s, fMRI has come to dominate
  the brain mapping field due to its low
  invasiveness, lack of radiation exposure, and
  relatively wide availability.

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f MRI Image
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Electroencephalography (EEG)

• EEG is the recording of electrical activity along
  the scalp produced by the firing of neurons
  within the brain.

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• In clinical contexts, EEG refers to the recording
  of the brain's spontaneous electrical activity
  over a short period of time, usually 20-40
  minutes, as recorded from multiple electrodes
  placed on the scalp

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• EEG used to be a first-line method for the
  diagnosis of tumors, stroke and other focal brain
  disorders, but this use has decreased with the
  advent of anatomical imaging techniques such as
  MRI and CT.

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• EEG was discovered in 1929 by a German
  psychiatrist Hans Berger
• In 1932 by a British electrophysiologist, Edgar
  Adrian won Nobel prize for the demonstration of
  electrical impulses from brain

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EEG
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1 Second EEG
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• It is generally accepted that the activity
  measured by EEG is electrical potentials created
  by the post-synaptic currents, rather than by
  action potentials.
• More specifically, the scalp electrical
  potentials that produce EEG are due to the
  extracellular ionic currents caused by dendritic
  electrical activity (whereas the fields producing
  magnetoencephalographic signals are associated
  with intracellular ionic currents).

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Wave patterns

• delta waves.
• Delta is the frequency range up to 3 Hz. It tends
  to be the highest in amplitude and the slowest
  waves. It is seen normally in adults in slow wave
  sleep. It is also seen normally in babies

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Delta Wave
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• Theta is the frequency range from 4 Hz to 7 Hz.
  Theta is seen normally in young children. It may
  be seen in drowsiness or arousal in older
  children and adults it can also be seen in
  meditation

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Theta Wave
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• Alpha is the frequency range from 8 Hz to 12 Hz.
  Hans Berger named the first rhythmic EEG activity
  he saw, the "alpha wave." This is activity in the
  8-12 Hz range seen in the posterior regions of
  the head on both sides, being higher in amplitude
  on the dominant side. It is brought out by
  closing the eyes and by relaxation.

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Alpha Wave
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• Beta is the frequency range from 12 Hz to about
  30 Hz.
• It is seen usually on both sides in symmetrical
  distribution and is most evident frontally.
• Low amplitude beta with multiple and varying
  frequencies is often associated with active, busy
  or anxious thinking and active concentration.
  Rhythmic beta with a dominant set of frequencies
  is associated with various pathologies and drug
  effects, especially benzodiazepines.

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Beta Wave
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• Gamma is the frequency range approximately 26100
  Hz.
• Gamma rhythms are thought to represent binding
  of different populations of neurons together into
  a network for the purpose of carrying out a
  certain cognitive or motor function.

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Gamma Wave
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Medical Imaging Instruments

• Barium X ray X ray
• CT Scan X ray
• Bronchography Optical
• Endoscopy Optical
• PET Nuclear
• MET Nuclear
• Echocardiograph Ultrasound

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• ECG Bioelectricity
• Electromyograph EMG Bioelectricity
• EEG Bioelectricity