Lecture 2
Methods in Neurophysiology
Or
How to measure the brain?
Magnetic resonance imaging (MRI): Produces 2-D
and 3-D images with high spatial resolution
D image-2 D image-3
Copyright © 2009 Allyn & Bacon
Neurophysiology
• Neurophysiology is a method of research used
to obtain information produced by the
electrical and magnetic signals in the active,
functioning brain
Neuronal electrical properties
V=I R
V – Difference in electrical potential between
two points (interior and exterior of a cell)
I – Electrical current – Ion movement
R- Resistance - membrane or ion channel
.different methods used in neuroscience
Resolution
:Temporal resolution
The accuracy with which one can measure
when an event (e.g. a physiological change)
.occurs
:Spatial resolution
The accuracy with which one can measure where
an event (e.g. a physiological change) is
.occurring
?What is patch-clamp
Patch-clamping is an electrophysiological technique
in which
we are able to CLAMP the VOLTAGE of an isolated
piece of
.cell membrane (or whole-cell)
By clamping the voltage we are able to observe
CURRENTS that flow through ION CHANNELS.
Patch-clamp recording allows us to measure very
.small currents - in the pA range (10-12 A)
Patch clamp
Study of single or multiple Ion channels
Glass micropipette that has an open tip
diameter of about one micrometer
It is sealed onto the surface of the cell
membrane , rather than inserted through it
If you keep the voltage constant you can
observe changes in current
The patch-clamp circuit
FBR
+
Amplifier
Technical
The high gain operational amplifier is
connected in the circuit so that the current
flowing through the ion channel is measured
as a voltage drop across the feedback resistor
The FBR has a resistance of 50 G .)FBR(
allowing very small currents (10-12 A)
.to be measured
Patch of cell membrane with ion channel
A patch-clamp rig
Cerebellar slice
In Vitro
In Vivo
Rokni 2009
Invasive Electrophysiological Recording
Methods
• Intracellular unit recording
– Membrane potential of a neuron
• Extracellular unit recording
– Firing of a neuron
• Multiple-unit recording
– Firing of many neurons
Invasive EEG recording •
Invasive Electrophysiological Recording Methods (continued)
Copyright © 2009 Allyn & Bacon
Extra cellular recording
Measuring electrical activity in a living animal
The electrode is a microelectrode, with a tip size of about 1 micrometer
The action potentials typically about 1 mV
,
?How is it sound
Study
Extra cellular recording in Epileptic patients
Responsive Neurostimulator
System (RNS)
DBS – Deep Brain Stimulation
EEG- Electroencephalography
recording of electrical activity
Clinical – epilepsy, coma, sleep
Experimental – mental, motor,
sensory (pain)
24 electrodes on the sculp
The scalp electrical potentials t
EEG are due to the extracellula
ionic currents caused by dendr
electrical activity
The signal pass many layers – that why
many neurons needed
Summation of the synchronous activity
of thousands or millions of neurons
Two parameters: Amplitude and rate
EEG rates – Alfa – 8-13Hz
Beta – above 14 Hz – low
amp
Teta – 4-7 Hz
Delta – below 4 Hz - high
amp
Some typical
-electro
encephalo-
grams and
their
psychological
correlates
Copyright © 2009 Allyn & Bacon
Methods of Visualizing the Living Human
Brain: Function
Positron emission tomography (PET)
Positron emission •
tomography (PET)
Magnetoencephalo- •
graphy (MEG)
Brain image archives •
Transcranial magnetic •
stimulation
Copyright © 2009 Allyn & Bacon
Lesion Methods
• Remove, damage, or destroy a part of the brain
to observe impact on behavior
– Aspiration lesions – suction cortical tissue
– Radio-frequency lesions – heat destroys tissue
– Knife cuts – may damage surrounding area
– Cryogenic blockade – “reversible lesion”
• Lesion studies must be interpreted carefully
because it is difficult to make small, precise
lesions in the brain
Lesion
Methods
)continued(
Two methods of
deactivating a brain
structure: a subcortical
knife cut lesion and a
“reversible lesion” by
cooling to just above
freezing using a
cryoprobe
TMS - Transcranial magnetic stimulation
weak currents are induced in the tissue by rapidly changing
magnetic field
Transcranial magnetic stimulation – TMS
Method: Single or paired pulse TMS
The pulse(s) causes a population of neurons
to depolarize and discharge an action potential
Repetitive transcranial magnetic stimulation – rTMS
rTMS can increase or decrease the excitability
depending on the intensity of stimulation
Psychophysics or Behavioral methods
The scientific study of the relation between stimulus
and sensation or action
Actually all the clinical studies
Non invasive
Cognitive or motor test
Input Output
Morris Water Maze
(Spatial learning and memory)
For rodents
Must use visual
Cues
Measures spatial
learning and
memory
Rotorod test
Rodent is placed on a
rotating rod
rodent’s ability to remain on
the rotating rod is recorded
Sensorimotor coordination
Behavioral test for human
Concentration in different hours computerized dynamic posturography
Motor performance
RT
Movement speed
What else..
Combination between two methods
To test:
The neural changes in the
primary motor cortex
During learning a new skil.
After effect
Washout trials
Examples of cell activity recorded in the
primary motor cortex
Tuning curve
A kinematic cell
A dynamic cell
?Where are we going
Brain Computer Interface
• A Brain-Computer Interface is a communication
system that do not depend on peripheral nerves
and muscles
• Applications:
– Patient with severe movement disorders: Control
external devices (neuroprosthesis, wheelchair) by
mental focus
– Entertainment (games)
– Military Use (fighter pilots)
BCI system
• BCI system based on classification of motor
imagery related brain activity changes in ongoing
EEG
– Electrodes placed on the scalp
– Movement imagination (left hand, right hand, foot or
tongue)
Primary Motor Cortex
Primary Somato Sensory Cortex
Motor execution vs. Movement imagination
Execution
Imagination
time 500ms ERD ERS
Simplified model of the BCI system
Experiments
• Rotate the cube by mental focus
•Feature extraction: adaptive
autoregressive parameter
•Feedback: rotation, size, color of
cube
Observation of Movement
Further work
• Virtual flat
• Navigastion: e.g
moving into bathroom
