Methods of Studying the Nervous SystemMethods of Studying the Nervous System

““when an axon of cell A is near enough to when an axon of cell A is near enough to excite a cell B and repeatedly or excite a cell B and repeatedly or persistently takes part in firing it, some persistently takes part in firing it, some growth process or metabolic change takes growth process or metabolic change takes place in one or both cells such that A’s place in one or both cells such that A’s efficiency, as one of the cells firing B, is efficiency, as one of the cells firing B, is increased.” increased.” (p. 62)(p. 62)

In other words:In other words:““cells that fire together, wire together.”cells that fire together, wire together.”

Hebb, D.O. (1949). The organization of Hebb, D.O. (1949). The organization of behavior: A neuropsychological theory. behavior: A neuropsychological theory. New York: John Wiley & Sons Inc.New York: John Wiley & Sons Inc.

If Wikipedia suggests caution, well…

Wikipedia states - …although this is an oversimplification of the nervous system not to be taken literally, as well as not accurately representing Hebb's original statement on cell connectivity strength changes. …simultaneous activation of cells leads to pronounced increases in synaptic strength. Such learning is known as Hebbian learning.

Hebbian Learning

“What has become known as ‘Hebb’s synapse’ or ‘learning postulate’ is one of the few aspects of the theory he did not consider completely original. Something like it had been proposed by many psychologists, including Freud in his early years as a neurobiologist.” (Milner, 1993)

Lack of novelty aside, the theory had an even bigger problems because Lack of novelty aside, the theory had an even bigger problems because current technology rendered it untestable. Then, in 1973…current technology rendered it untestable. Then, in 1973…

A hundred or so rapid high frequency stimulations of the PP resulted in A hundred or so rapid high frequency stimulations of the PP resulted in LTP at the recording site. LTP is the increased synaptic strength that LTP at the recording site. LTP is the increased synaptic strength that lasted for months or even longer, theoretically as long as a memory trace lasted for months or even longer, theoretically as long as a memory trace may exist.may exist.

Here is a modern electrophysiological Here is a modern electrophysiological recording apparatus that can both recording apparatus that can both stimulate and record electrical signals stimulate and record electrical signals from a 400 micron thick slice of the rat from a 400 micron thick slice of the rat hippocampus. hippocampus.

Just what you need to measure LTP.Just what you need to measure LTP.

Biopsychological research Biopsychological research often dependends on often dependends on advances in technologyadvances in technology• Brain imagingBrain imaging• recording neural activityrecording neural activity• lesion technologylesion technology

Standard X-ray techniques are good for visualizing bone in flesh (or metal in flesh given unfortunate circumstances)

Such techniques are not very useful for visualizing brain structures because X-rays primarily pass through soft tissue.

So this is a fake pic from someone trying to belittle Homer Simpson

Contrast X ray techniques

Use of X ray technology with other features that enhance contrast to visualize aspects of brain anatomy

Pneumoencephalography Angiography

Methods of visualizing the human brainComputerized Axial Tomography (CAT)

CAT is a 3-D X-ray constructed of a series of photographs representing horizontal sections through the brain.

Methods of visualizing the human brainComputerized Axial Tomography (CAT)

The X-ray tube and detector rotate in opposition around the brain at one level taking a series of measurements from which an image of one section is constructed.

Methods of visualizing the human brainMagnetic Resonance Imaging (MRI)

Provides high resolution 3-D images of the brain.

Methods of visualizing the human brainMagnetic Resonance Imaging (MRI)

Measures the waves emitted by hydrogen atoms when they are activated by radio-frequency waves in a magnetic field.

II. Methods of visualizing the human brainD. Positron Emission Tomography (PET)

Provides information about the metabolic activity of the brain.

Methods of visualizing the human brainPositron Emission Tomography (PET)

The patient is injected with radioactive 2-deoxyglucose (2-DG) which is taken up rapidly by active neurons.

Methods of visualizing the human brainPositron Emission Tomography (PET)

Because 2-DG cannot be metabolized, it temporarily accumulates in active (energy consuming) neurons and will indicate the brain regions that are active during performance of some test.

Methods of visualizing the human brainGiven the following images, what is your diagnosis of the patient?

CAT scan MRI scan PET scan

No metabolicactivity

Methods of visualizing the human brainFunctional MRI*

Provides information about increases in oxygen (blood) flow to brain regions that are active during performance of a task.

The BOLD signal - magnetic resonance of blood changes when oxygenated.

Methods of visualizing the human brainFunctional MRI*

Advantages over PET:1) Noninvasive2) Shows both structure and function3) Spatial resolution is better4) Can produce 3D images of activity

over the entire brain

magnetoencephalogram (MEG) - the magnetic fields produced by electrical brain activity. electroencephalogram (EEG) - the associated scalp potentials.

provide unique insights into the dynamic behavior of the human brain as they are able to follow changes in neural activity on a millisecond time-scale

Clusters of thousands of synchronously activated pyramidal cortical neurons are believed to be the main generators of MEG and EEG signals.

Transcranial Magnetic Stimulation

• Disrupts activity in an area of cortex by creating a magnetic field under a coil positioned next to the skull.

The God helmet

Parallel and Interactive MemorySystems in the Human Brain

and the limitations of fMRI studies

In this learning game you are the weather forecaster.You will learn how to predict rain or shine using a deck of four

cards:

Knowlton, B.J., Mangels, J.A., & Squire, L.R. (1996) Science, 273, 1399-1402.

Probabilistic Classification TaskProbabilistic Classification Task

(A) Performance on the probabilistic classification tasks by controls (CON, n = 15), amnesic patients (AMN, n = 12), patients with Parkinson’s disease (PD, n = 20), and a subgroup of PD patients with the most severe symptoms (PD*, n = 10). (B) Performance on the declarative memory task. Both PD and PD* groups exhibited entirely normal declarative memory for facts about the testing episode, despite their poor performance on the task itself. In contrast, amnesic patients exhibited a severe impairment in declarative memory for the testing episode but normal performance on the classification test.

Probabilistic Classification Tasks for fMRI StudiesProbabilistic Classification Tasks for fMRI Studies

Poldrack, R.A., Clark, J., Paré-Blagoev, E.J., Shohamy, D., Moyano, J.C., Myers, C., & Gluck, M.A. (2001). Nature, 414, 546-550.

a. Activation for FB compared to baseline (yellow = increase, blue = decrease); b. a. Activation for FB compared to baseline (yellow = increase, blue = decrease); b. Activation for PA compared to baseline; c. Regions exhibiting significant differences Activation for PA compared to baseline; c. Regions exhibiting significant differences between FB and PA tasks; d. Plot of task related signal change from the MTL region between FB and PA tasks; d. Plot of task related signal change from the MTL region exhibiting maximal task-dependent differences against a region in the right caudate that exhibiting maximal task-dependent differences against a region in the right caudate that exhibited significant negative correlation with the MTL in functional connectivity analysis. exhibited significant negative correlation with the MTL in functional connectivity analysis. Each data point represents a single subject.Each data point represents a single subject.

Results from event-related FMRI study of FB category learning (experiment 2). a, Regions exhibiting significant evoked activation (yellow) or deactivation (blue) for classification trials. Yellow arrow highlights region of caudate activation, white arrow highlights region of MTL deactivation. b, c, Depiction of parametric change in modelled evoked haemodynamic response across the initial 450-s scanning run (averaged across subjects) in b, left body of caudate nucleus (-12, 3, 21), and c, left MTL (-24, -3, -24). Red indicates positive, event-related response, blue indicates negative event-related response.

Poldrack, et al. (2001). Interactive memory systems in the human brain. Nature, 414, 546-550.

Left body of caudate nucleus

Left medial temporal lobe

What can/should we conclude from this study? The authors What can/should we conclude from this study? The authors state that the results:state that the results:

“…“…provide the first substantive evidence, provide the first substantive evidence, to our knowledge, for to our knowledge, for competition between memory systems in the human brain competition between memory systems in the human brain …the …the present study provides present study provides direct evidence direct evidence for competition at the neural for competition at the neural level by demonstrating three essential features of the MTL-striatum level by demonstrating three essential features of the MTL-striatum interaction. interaction. First, it shows that engagement of MTL and striatum is First, it shows that engagement of MTL and striatum is modulatedmodulated by whether the task encourages the use of declarative by whether the task encourages the use of declarative versus nondeclarative memory processes or strategiesversus nondeclarative memory processes or strategies. . Second, it Second, it demonstrates that engagement of these regions is demonstrates that engagement of these regions is negatively negatively correlatedcorrelated across subjects. Third, it demonstrates rapid across subjects. Third, it demonstrates rapid reciprocal reciprocal changes in the engagementchanges in the engagement of these regions of these regions. These data are . These data are concordant with animal lesion studies demonstrating that concordant with animal lesion studies demonstrating that the memory the memory systems based on the MTL and striatum can compete with one systems based on the MTL and striatum can compete with one another during learning.another during learning.””

Poldrack, R.A., Clark, J., Paré-Blagoev, E.J., Shohamy, D., Moyano, J.C., Myers, C., & Gluck, M.A. (2001). Nature, 414, 546-550.

Put on the critical thinking caps (save the God helmet for later)

However, the authors also However, the authors also state that their computational state that their computational theory:theory:

“…“…interprets both the earlier animal data and interprets both the earlier animal data and the present human imaging data as implying an the present human imaging data as implying an interaction between the hippocampus and other interaction between the hippocampus and other brain structures, in which the hippocampus has brain structures, in which the hippocampus has a modulatory role in learning by developing new a modulatory role in learning by developing new stimulus representations during early phases of stimulus representations during early phases of training training which are used by the striatum to which are used by the striatum to develop complex stimulus-response develop complex stimulus-response associations.associations.””

Poldrack, R.A., Clark, J., Paré-Blagoev, E.J., Shohamy, D., Moyano, J.C., Myers, C., & Gluck, M.A. (2001). Nature, 414, 546-550.