Electrophysiology

Neurons are Electrical Remember that Neurons have electrically charged membranes they also rapidly discharge and recharge those membranes (graded potentials and action potentials)

Neurons are Electrical Importantly, we think the electrical signals are fundamental to brain function, so it makes sense that we should try to directly measure these signals but how?

Intracranial and “single” Unit Single or multiple electrodes are inserted into the brain may be left in place for long periods

Intracranial and “single” Unit Single electrodes may pick up action potentials from a single cell An electrode may pick up the signals from several nearby cells spike-sorting attempts to isolate individual cells

Intracranial and “single” Unit Simultaneous recording from several electrodes allows recording of multiple cells

Intracranial and “single” Unit Output of unit recordings is often depicted as a “spike train” and measured in spikes/second Stimulus on Spikes

Intracranial and “single” Unit Output of unit recordings is often depicted as a “spike train” and measured in spikes/second Spike rate is almost never zero, even without sensory input in visual cortex this gives rise to “cortical grey” Stimulus on Spikes

Intracranial and “single” Unit By carefully associating changes in spike rate with sensory stimuli or cognitive task, one can map the functional circuitry of one or more brain regions

Intracranial and “single” Unit Some complications: Suppose we observe an increase in spike rate in two discrete regions of the brain in response to a sensory stimulus: What are the possible interpretations?

Intracranial and “single” Unit Some complications: Suppose we observe an increase in spike rate in two discrete regions of the brain in response to a sensory stimulus: What are the possible interpretations? Area A “drives” area B Area B “drives” area A Area A and B are controlled by a third area independently

Intracranial and “single” Unit Some complications: Suppose we observe an increase in spike rate in two discrete regions of the brain in response to a sensory stimulus: What are the possible interpretations? Area A “drives” area B Area B “drives” area A Area A and B are controlled by a third area independently and their activity is unrelated How might you differentiate these possibilities

Intracranial and “single” Unit How might you differentiate these possibilities Timing of spikes might help: if A and B are synchronized they are probably functionally related if A leads B then it is likely to be the first in the signal chain

Subdural Grid Intracranial electrodes cannot be used in human studies

Subdural Grid Intracranial electrodes cannot be used in human studies It is possible to record from the cortical surface Subdural grid on surface of Human cortex

Electroencephalography It is also possible to record from outside the skull altogether!

Electroencephalography pyramidal cells span layers of cortex and have parallel cell bodies their combined extracellular field is small but measurable at the scalp!

Electroencephalography The field generated by a patch of cortex can be modeled as a single equivalent dipolar current source with some orientation (assumed to be perpendicular to cortical surface) Duracell

Electroencephalography Electrical potential is usually measured at many sites on the head surface

Electroencephalography Electrical potential is usually measured at many sites on the head surface More is sometimes better

Electroencephalography EEG changes with various states and in response to stimuli

The Event-Related Potential (ERP) Embedded in the EEG signal is the small electrical response due to specific events such as stimulus or task onsets, motor actions, etc.

The Event-Related Potential (ERP) Embedded in the EEG signal is the small electrical response due to specific events such as stimulus or task onsets, motor actions, etc. Averaging all such events together isolates this event-related potential

The Event-Related Potential (ERP) We have an ERP waveform for every electrode

The Event-Related Potential (ERP) We have an ERP waveform for every electrode

The Event-Related Potential (ERP) We have an ERP waveform for every electrode Sometimes that isn’t very useful

The Event-Related Potential (ERP) We have an ERP waveform for every electrode Sometimes that isn’t very useful Sometimes we want to know the overall pattern of potentials across the head surface isopotential map

The Event-Related Potential (ERP) We have an ERP waveform for every electrode Sometimes that isn’t very useful Sometimes we want to know the overall pattern of potentials across the head surface isopotential map Sometimes that isn’t very useful - we want to know the generator source in 3D

Brain Electrical Source Analysis Given this pattern on the scalp, can you guess where the current generator was?

Brain Electrical Source Analysis Given this pattern on the scalp, can you guess where the current generator was? Duracell

Brain Electrical Source Analysis Source Analysis models neural activity as one or more equivalent current dipoles inside a head-shaped volume with some set of electrical characteristics

Brain Electrical Source Analysis Initiate the model

Brain Electrical Source Analysis Project “Forward Solution” Initiate the model

Brain Electrical Source Analysis Project “Forward Solution” Initiate the model Compare to actual data

Brain Electrical Source Analysis Project “Forward Solution” Adjust the model Compare to actual data

Brain Electrical Source Analysis Project “Forward Solution” This is most likely location of dipole Compare to actual data

Brain Electrical Source Analysis EEG data can now be coregistered with high-resolution MRI image Anatomical MRI

Brain Electrical Source Analysis EEG data can now be coregistered with high-resolution MRI image 3D volume is rendered and electrode locations are superimposed Anatomical MRI

Brain Electrical Source Analysis EEG data can now be coregistered with high-resolution MRI image

Magnetoencephalography For any electric current, there is an associated magnetic field Electric Current Magnetic Field

Magnetoencephalography For any electric current, there is an associated magnetic field magnetic sensors called “SQuID”s can measure very small fields associated with current flowing through extracellular space Electric Current Magnetic Field SquID Amplifier

Magnetoencephalography MEG systems use many sensors to accomplish source analysis MEG and EEG are complementary because they are sensitive to orthogonal current flows MEG is very expensive