1. Electrophysiology

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

3. 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?

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

5. 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

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

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

8. 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

9. 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

10. 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?

11. 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

12. 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

13. 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

14. Subdural Grid
Intracranial electrodes cannot be used in human studies

15. 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

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

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

18. 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

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

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

21. Electroencephalography
EEG changes with various states and in response to stimuli

22. 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.

23. 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

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

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

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

27. 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

28. 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

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

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

31. 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

32. Brain Electrical Source Analysis
Initiate the model

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

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

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

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

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

38. 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

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

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

41. 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

42. 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