Useful information: The readings are from 2 text books: 1) Carlson “Physiology of Behavior” latest (10th) edition (2009) and 2) Andreassi “Psychophysiology” 5th edition (2007). Other readings and most class notes are on my web site: To get to web site…. Google J Peter Rosenfeld On list that GOOGLE brings up , you’ll see Rosenfeld Lab Home Page Find out about current research in the Rosenfeld lab.Get information on groups.psych.northwestern.edu/rosenfeld/home.html *Click it. You’ll see: Note the buttons Clicking “publications” or “classes” gets you where you need to be for this course. If you took 312-1….. Then clicking “classes” then “312-2” and “Publications” gets you to all nontext assigned readings. That’s all you need to know. Otherwise, you may want to click”classes”, then “312-1” and go to bottom of page for powerpoint presentations, and review the one called, “2. EEG,ERPs, & relation to single neuronal activity.” and check out the first 29 slides. If, from “Classes,” you go to the 312-2 site… ….You’ll see the texts, the syllabus, lists of papers, chapters and powerpoint presentations (including this very presentation!) which go with this course. Let’s do for real… Topic 1: Continuation of Neural Coding from 312-1 You may recall that we previously subdivided this topic into 3 subtopics: 1) Sensory coding, 2) Motor coding, 3) Coding of Psychological Events. We saw that the brain represents sensory events in terms of neuronal firing patterns. Remember the following? Or what about this? These are neural representations of somatic sensory sensations… Of course you read in 312-1 about neuronal representation of visual and auditory events. These are sensory codes. There are also codes for motor events, that is, firing patterns in the motor cortex and elsewhere that correlate with muscle action leading to body movements. These are motor codes. Now for the almost unmanageably complex and largely unknown neural representations of “pure” psychological events…. ….such as cognitions associated with emotions(love, hate, sexual arousal, perceptions), memories (real and false), learning (classicalautomatic and instrumental), deceptions (altruistic and selfserving), and so on… This giant topic started out with the title, “Neural Coding of Behavior” in the 1950s. We now refer to this effort also as “Neural Correlates of Behavior.” Note that word, “Behavior…” (rather than “cognition” which is a much broader and more sensible term). That’s because the 1950s was the heyday at most universities of the Psychological Movement known as “Behaviorism” that dominated academic Psychology. In case you forgot, here is the Wikipedia definition: Behaviorism (or behaviourism), also called the learning perspective (where any physical action is a behavior), is a philosophy of psychology based on the proposition that all things that organisms do—including acting, thinking and feeling—can and should be regarded as behaviors. The behaviorist school of thought maintains that behaviors as such can be described scientifically without recourse either to internal physiological events or to hypothetical constructs such as the mind. Behaviorism comprises the position that all theories should have observational correlates but that there are no philosophical differences between publicly observable processes (such as actions) and privately observable processes (such as thinking and feeling). Now this was crazy, and has been largely replaced by Cognitive Psychology… But a convenient thing about behaviorism was its simplification of psychological things to observable behavior (omitting invisible thoughts and such). So if you wanted to study the neural substrates of learning, all you had to do was study the “neural correlates of observable behavior,” which is where that term came from. So the typical experiment in Neural Correlates of Behavior went like this: OK, you are interested in learning, so pick a standard learning protocol (paradigm): Training animals like cats to run down a maze to get food. 1. Get them hungry via food deprivation. 2. Put them at the ‘start’ end with the food many feet away at the ‘goal’. 3. Define ‘learning’ as the state obtained when they can run through the maze at top speed 5 times in a row with no wrong turns. How do you study the neural coding of this process? What neural events do you study? That was easy to answer: There was no method back in the 50s to record action potentials from single neurons in freely moving animals. (It is still not so easy to do.) So you have to study population neural activity such as EEG (spontaneous brain waves) recorded from “chronically implanted” animals. From Carlson From my chapter: OK, so back in 50’s we could record EEG from freely moving animals… But a bigger question is: “From where do you record the EEG?” Well this is a learning experiment so just put the electrodes in the learning center(s). Where’s that? There’s the problem: In the 50’s We didn’t know what or where the learning center(s) is (are) and how they connect or how they interact. If we knew that we wouldn't need to do these experiments. So how did the neural correlators in the 50s proceed? They used reason. They reasoned that learning must involve association (ala John Stuart Mill and the British Associationists).. So clearly, one needed record from places where associations are formed. Such as association cortices…2-3 in each side? The special thing about association areas are that in those places… Different sensory pathways come together and “talk to each other” (synapse on the same neurons), so that one can form an association between say the tone CS and the smell of food as in Pavlovian conditioning—or between bar press and food in Skinnerian conditioning. Any other such places? (Class?) Yes, reticular formation, so we should put a few electrodes up and down the r.f. too, maybe 4 or 6? (So far, 16 sites) But learning also involves motivation and reinforcement, so we probably need 2 more on each side of hypothalamus. (total now 20.) Animals have to see & hear stimuli and smell food, so in those sensory systems, figure to add 12 more to cover thalamus and cortex, bilaterally. We might be now up to 40! Why the exclamation point? Well 40 wires coming from the animal’s recording socket is a lot. Rats like this with just 6 wires are not big enough, one must use a cat or dog. In 50’s these head preamps were unavailable. One had to use wires embedded with mercury powder. Very Heavy. A cat with 40 of them would “run” down the maze with head tilted over. But that’s what they did! (Not terribly natural.) Besides the question of how many electrodes and where to put them.. ..was the question of what neural events to analyze from the ongoing EEG. What would a page of ongoing EEG look like, taken from a live subject like a cat? Here’s page of 14 site’s worth in about 30 sec… This actually is unusually pretty This is more realistic---but I digress In the old days, there were no FFTs etc.. Just amplitude and frequency. So the old neural correlators of the 1950s would plot amplitude and frequency for each of the 40 brain sites during, say, pre-learning, early learning, mid-learning, asymptote learning, and extinction. The results read like this: “In early learning, the visual cortex amplitude is high but the frequency is low, but the …..etc” It was like the stock market: “In January, Boeing was up but… Microsoft was low, but Apple was up, but GE was middling while Exxon and ATT were recovering…etc, etc…. In Spring, however, Boeing and Exxon crashed, while Microsoft and GE reached new historic highs….etc etc…” If every lab got the same results, no matter how complex, well OK. But in 1961, there were 2 well-known review papers that summarized the neural correlates literature: One: High nervous functions: brain functions and learning ER John - Annual Review of Physiology, The other: Electrophysiological contributions to the neural basis of learning F Morrell Physiological Reviews, 1961 These papers both summarized over a thousand studies…. They both should have ended the neural correlates literature, because both essentially noted the same thing, namely, that no labs replicated themselves, let alone others!!! The literature did taper off, producing 2 reactions, and 2 new literatures: The reactions: 1) The Operant Controlled Neural Event (“OCNE”) approach: Operant Conditioning of ERP components. 2) The Cognitive Psychophysiology literature: The less radical and longer lasting carefully controlled scientific study of ERP indicators of psychological events. (We’ll start with the first reaction now) The “OCNE” approach began with a paper* outlining this first reaction. The paper involved 3 things: 1. A systematic critique of the neural correlates literature. 2. The rather ambitious program outlined in reaction (Note title): 3. An empirical description and demonstration of the method. *The paper was by Fox & Rudell (1968) Science, and is on 312-2 web page, article 9 1. The critique: A) F&R cited the replicability issues as noted by John and Morrell in the ‘61 reviews. B) problem of choosing electrode sites and neural parameters for study. C) Correlation approach: let animals do their own thing and see what neural events from what sites correlate. That’s not controlled science. D) Time base issues: Learning takes days vs. EEG, ERPs, action potentials that are measured in milliseconds. One cannot make laws connecting things measured in such different units. (The “reduction problem”—see Bergmann, “The Philosophy of Science.” 1966 The OCNE approach was supposed to solve all these problems… We’ll see if it did (and how) later, after we consider OCNE’s empirical approach, which went something like this: “The old neural correlators wanted to see systematic & reliable brain wave changes by training behavior and looking for brain wave correlates. Why bother? If you want see a brain wave change, TRAIN IT DIRECTLY.” That is, specify a brain wave variable from some brain site, and operantly condition it like a bar press, by rewarding its occurence. The following figure, from the F&R ‘68 paper, shows 2 sets of superimposed photic erps (visual eps) elicited by a light flash, recorded from chronically installed electrodes in a freely moving Cat’s visual area 19 (tertiary visual cortex). (Why there? It’s convenient on top.) The cats had been operated on and electrodes as well as a milk tube …had been installed. They were recovered and each one was run in a chamber (former hollowed out ‘fridge) as the strobe lights flashed every 3 seconds, evoking the eps. The 2 sets of waves shown next are during baseline (A) and training (B) within one day: The area between the lines had been pre-selected as the critical area, i.e., F&R had decided that the cat was to lower the amplitude of the EP amplitude between the lines. (They saw that in the naïve cat, this was a variable amplitude.) Every time the cat did so, a computer (6’x3’x3’) detected this and caused a relay to close, delivering ~ 1cc milk through the tube implanted that ended in the roof of the hungry cat’s mouth. So F & R decided to treat a deviant ERP amplitude like a bar press and give the cat a reward for making them. These EP amplitudes varied within a bell curve, and F&R rewarded deviant samples in the blue tail at left. They chose rare but occasionally occurring samples with a finite probability (.16) of occurrence. Of course the cats were able to do it, increasing negativity: Of course the naysayers said, “well, it’s simply the effect of milk on the EP…” i.e., the non-contingent or non- associative or unconditional effect of reinforcement. It isn’t learning. There was evidence. Others had shown that food or shock affects ERPs. I did myself with Routtenberg. But then how do you explain the following? Now the cats are making the criterion segment go UP. they are increasing positivity The naysayers can’t have it both ways…. If the unconditional/non- associative effect of milk is making wave go up then the down effects are learning If the unconditional/nonassociative effect of milk is making wave go down then the up effects are learning So we do have the learning of something going on here… But what, exactly? In other words, the naysayers were not done complaining. Before we get there, however, what did Fox say was the importance of the demonstration? 1. OCNE solves problem of choosing electrode sites and neural parameters for study. Well that’s sort of true. You pre-specify what brain wave variable you train, and from where you record it. In this first demonstration, convenience and common sense guided the choice….(continued) In other words, As noted, site was chosen for surgical convenience and familiarity to Fox, who knew that at the segment chosen (170190 ms post stimulus), the EP amplitude was typically variable, high to low values. He intuited that the variability was tied to some behavioral state which he hoped could be operantly conditioned. (The tricky, slippery part is identifying that state. We never have. We still don’t know the significance of the effect.) Fox also concluded The neural correlate approach was not controlled science. The OCNE approach makes the neural event the independent variable, not the dependent variable. This was bogus. It is the reinforcement contingency which is directly manipulated as the independent variable. As just noted, we still don’t know its behavioral correlate. He also stated: OCNE solves the time base incompatibility problem that learning takes days, as opposed to EEG, ERPs, action potentials that are measured in milliseconds. Not exactly. The OCNE method simply treats an EP segment like a behavior but since it is already neural, it is forced onto a compatible time base. It’s not a behavior like a CR paw lift is. There are some incontrovertible benefits of OCNE that Fox didn’t mention (& maybe didn’t appreciate!): 1. Replication was not a problem: Hundreds of cats, rats, humans have been trained to self-control all sorts of ERPs as we’ll see. 2. Obvious clinical applications? (If you change a visual EP, do you change vision? We’ll come back to this. 3. OCNE uniquely can work out neural code/mechanisms of voluntary movement in an unrestrained animal (vs. Mountcastle’s curarized,sedated cats). This too is shown later…(continued)… A final, most important benefit: 4. Operant neural conditioning offers a method of testing the generality of putative laws of learning, (of which there are precious few known). This because it may be a new response system. (Laws Theories that account for phenomena like learning.) A fellow named John Garcia showed how critical novel response systems are in his now classical taste aversion conditioning studies in dogs. From the 40s to the 60s, the king of learning theory was not Skinner (who opposed theories), but Kenneth Spence …the head of Psychology at Iowa (one reason I went there). Spence had found what he regarded as a law of classical conditioning (a learning protocol), stating that the ideal CS-UCS interval was about ½ second. This was developed with human blink conditioning, rat eye-lid conditioning, and rabbit nictitating membrane conditioning in rabbits. Here was the typical supportive datum: Then Garcia showed that if you exposed a dog to a food…. …followed immediately by xirradiation, 3-5 hours later he got terribly sick and vomited the day away (radiation sickness). Thereafter, the dog would never touch that particular food again. Other dogs could be similarly trained to avoid different foods. Which are CS, UCS, UCR, CR ? Well here is a classically conditioned avoidance response… Involving a 3-5 hour CS-UCS interval. Not = .5 sec. Garcia showed that the response system determined the optimal CS-UCS interval, and that Spence’s putative learning law was not general. Physiological explanations based on .5sec would be wrong. OCNE could also be a novel response system … …with which to test putative operant conditioning laws (magnitude of reinforcement effect, acquisition/extinction law, etc.) BUT…first you have to show that operantly conditioned learning laws were not trivially mediated by known motor systems. Best example of Trivial Mediation… …is what the naysayers said: “All the cats are learning is to move their heads oriented towards the light flash to make big wave, and away to make small wave. That is, they are learning certain movements and resulting receptor orientations. Learning movements is not novel, not independent of skeletal motor systems involved in, say, bar pressing.” Another example, time-locked movements feedback into visual EP That is, a cat can flex his elbow joint at just the right time so that the somatic sensory feedback can get to cortex and influence the criterion segment (Rosenfeld & Fox, 1972). (Yes all sensory systems can get all over cortex, directly, and/or via reticular formation, strange as it seems…) Also, non-time-locked movements Which means running around a lot or holding still. Bures & Buresova had shown in Czechoslavia in early 70’s that such behavior in rats affected all components of flash-evoked potential. If that’s what F & R’s cats were doing, no big deal, not a novel learned behavior. There were attempts to partially control trivial mediation… …but less than satisfactory. F&R painted chambers white and regular ITI as well as latish component latency (170 ms) allowed for timelocked movements to occur. In 1969 (Science) I ran humans with earphones to control for receptor orientation (and also to ask how) but nothing else was controlled and the asking of how was not helpful. Until Hetzler’s PhD study, there was no simultaneous control of all possible trivial mediation. So let’s go there … ppt #4 on web site for 312-2. OK—we have inadvertently opened topic of Biofeedback… …in the process of concluding “Neural Coding.” So what is Biofeedback? It means feeding back to a biological organism (e.g., a patient) information about a sick system to which he ordinarily has no conscious access: high blood pressure, for example. How is this done? …Usually by recording the physiological activity with a transducer with an electrical output to a display. How did Biofeedback start? Was it originally a clinical development? No. It had a dual origin: First origin was… …the psychophysiologists who believed that mental problems had external physiological correlates, so that if one could control the ‘outside’—e.g., heart rate--- one could then control the inside mental problem—anxiety(!) This bass ackwards anti-Freudian approach had minimal influence. The much more important influence was that of Neal Miller.. … a major psychologist from the HullSpence learning theoretical background at Yale. Miller was wrestling with a question in learning theory: Is there more than one fundamental learning process? One for each form of learning: operant vs. Pavlovian conditioning? Or is there only one fundamental mechanism—association? At the time in 50s,60s, most people were 2 process theorists. Evidence? Operant conditioning seems to work best with voluntary responses mediated by skeletal muscles (bar presses, mazes, key pecks) whereas Autonomic (ANS) responses (salivation, heart rate changes) seem to work best with Pavlov’s CS-UCS pairing (classical, Pavlovian conditioning). Besides, they reasoned… It was obviously impossible to voluntarily control heart rate (for example): Try it. Lower it. See, you can’t do it. Miller didn’t buy this, reasoning that “absence of evidence is not evidence of absence.” Maybe you didn’t look hard enough in the haystack for the needle. The one common denominator in both forms of learning was association. CS-UCS association in Pavlovian Conditioning… Response-Reinforcer association in Operant (Skinnerian) conditioning. * Maybe, voluntary control of ANS responses (= Biofeedback) is harder and takes longer. There were good reasons to suspect so: voluntary muscle route is more direct: So Miller & DiCara proceeded to train Curarized rats to alter HR …for Lat. Hyoth. Stim reward. • Why curare? What to do with trivial mediation? Why not reward with rat chow? • Why bidirectional training? • What were results? First Results: Heart Rate Next: Operant control of Salivation, formerly Pavlov’s property (Note it takes time): Next: Intestinal motility: Rats not supposed to have much because they can’t vomit like dogs ca! Next: Urine formation rate! The Newsweek photo of one ear red, the other white: One more critical example: Blood Pressure control… All these Results… Made clear that Autonomic responses could be operantly conditioned = voluntarily controlled. So much for 2 process theories of learning. Miller made major evidence evaporate. Perhaps more important, incredible clinical potential. So much so that Miller’s new lab at Rockefeller U/Cornell Med became a Mecca And then, during the Vietnam war, other folks became interested. At a CIA (we think) sponsored meeting in DC, after Surwit described his method of training folks to control skin temperature, a shady character in dark glasses (in darkened room) and trench coat asked, “So with this method, a guy could stay in freezing water a bit longer if the pick-up submarine was late?” But then it came toppling down Actual graph from Miller-- Visceral learning: Recent difficulties with curarized rats and significant problems for human research. NE Miller… - 1974 – In Cardiovascular Psychophysiology, ed. By Obrist et al., Aldine Press Miller started bad-mouthing Leo Di Cara, who could get no grants, grads…. Neither could the rest of us doing research in biofeedback … Di Cara committed suicide. …and then Miller ran into a urologist named Lapides at a Rockefeller cocktail party, and told the story of failure to replicate. Lapides in turn told Miller of the 1957(!) demo in J. Urology … …in which a batch of med student “volunteers” offered to be curarized and were then asked to urinate, using only the visceral muscles of the bladder, as the skeletal abdominal muscles were blocked. They were easily able to do this, to turn both off and on a urine stream while curarized. In other words, Lapides et al. (1957) had shown that it was indeed possible to voluntarily command (operantly condition) autonomically controlled visceral muscle, thus having accomplished Miller’s main research goal before Miller ever got started with the first rat studies in the 1960s! This accomplishment had two effects: (1) It validated Miller’s one process learning theory (from left field). (2) It made Biofeedback an ok clinical and research endeavor again. Examples of Clinical success stories with “lower body” biofeedback(BF): 1. Fecal Incontinence: NIH issued a consensus opinion (1993) that BF is the treatment of choice. 2. Asthma and breathing disorders. 3. Headache: tension and migraine. 4. Reynaud’s Syndrome. More… (5) Stroke rehab with motor unit control. (6) As for cardiovascular BF, is it “a promise unfulfilled with only statistical not clinical effects”? BP was until Steptoe’s interbeat interval BF; and HR can only be clinically significantly speeded, but there is an application in PVC control. Clinical BF “above the neck” called Neurofeedback, or brainwave BF Most is bogus, but there are 3-4 promising applications: (1) Sterman and epilepsy with SMR EEG control. This started accidentally as he was a sleep researcher studying vets---ultimately cats, and training increased changes in SMR (1213Hz) EEG spindle bursts. Ultimately, to prove he wasn’t capitalizing on his charm.. He ran cats induced to have grand mal seizures with the toxic drug, monomethylhydrazine. After training, cats injected with a dose sufficient to cause instant grand mal seizures (sometimes, death) in most cats in control group, had no grand mal seizures and latencies were delayed by hours for petit mal effects. 3 had no symptoms at all! It was time to move to humans. A human patient after months of training: Changes in power spectra with SMR training also led to reduced seizure occurrence. (2) Lubar’s Theta Beta ratio for ADD. He trained AD(H)D boys to increase the Beta(10-30Hz)-to Theta (5-8Hz) ratio. This was based on the finding that ADD was associated with too much theta and not enough Beta— compared to age cohort normals. Lubar et al., 1995: By 2002, Monastra et al. showed neurofeedback to be better than Ritalin—and longer lasting. (3) (?) R-L alpha asymmetry training for depression Results (Rosenfeld 2000) (4.)A heroic application: Birbaumer: “Locked in” patients with high spinal cord lesions lack all ability to communicate. Birbaumer has trained them to generate DC potentials in patterns corresponding to letters so they can communicate. http://www.innovationmagazine.com/innov ation/volumes/v4n3/features2.shtml Brain-Computer Interface Wolpaw, Birbaumer et al. Clin.Neurophysiol.(2002) The patient shown…. …eventually wrote a thank-you note to Birbaumer with BCI device. Dear Mr Birbaumer, Hopefully you will come to visit me once you have received this letter. I cordially thank you and your team, particularly Ms Kuebler, for making me a good pupil who often knows the correct letters (meaning teaching me to write). Ms Kuebler has an artistic skill in motivating people. Without her this letter would never had been written. This has to be celebrated. I would therefore like to invite you and your team very cordially at the earliest opportunity. With best regards, Hans Peter Salzmann Biofeedback has one big pro and one big con: The pro is that it has no bad side effects ever reported. The con is that most of the studies have not been verified with large “double blind” placebo controls. OK, where are we? Remember the next slide? The reactions: 1) The Operant Controlled Neural Event (“OCNE”) approach: Operant Conditioning of ERP components. 2) The Cognitive Psychophysiology literature: The less radical and longer lasting carefully controlled scientific study of ERP indicators of psychological events. (We’ll start with the first reaction now) This last slide followed the lecture some weeks ago…. …in which we discussed that after the neural correlators failed, there were 2 reactions. One was OCNE which led to biofeedback, which we are now done with. The other reaction: The Cognitive Psychophysiology literature: The less radical and longer lasting carefully controlled scientific study of ERP indicators of psychological events. This involves some repetition from 312-1. So go to 312-1 web site The second powerpoint presentation, starting at slide 14….and finishing with slide 29. Then go to powerpoint presentation 2 # 1 on 312site for example of applied psychophysiology in Detection of Deception: the oldest and still very lively sub-field. BUT FIRST------ Based for openers on Polygraph. Polygraph: Does not mean “lie detector.” Means a machine with many (poly) channels of visually presented (graphical) information; in inked paper or laptop display format. A Polygraph machine can be and is used in many fields of Psychophysiology 2 Major Protocols currently used : Comparison (“Control”) Question Test (CQT)-- beloved by enforcers, ‘cuz it’s easy to use (“Didja do it?”) and tends to elicit confessions—but hated by academics who prefer the Guilty Knowledge Test (GKT better known as the Concealed Information Test (CIT), since knowledge can’t be guilty (just perps.) Both utilize autonomic arousal. Why do us professors frown on CQT? Pre-test interview cannot be standardized. It compares arousal responses to relevants. & “controls.”There can never be true comparison control questions in the scientific sense of control.(Yet there could be better versions.) High false positive rate (which CIA et al. don’t care about….) Why do we love CIT? It compares arousal (?) responses to critical (probe) and non-critical (irrelevant) stimuli. There are usually 6 or more multiple choice questions with 1 + 5 choices per question. (Throw away 1st.) Thus for each item, the P(chance hit) = 1/5=.2 For 6 INDEPENDENT items, probability of subject hitting on all 6 by chance =P = .2^6 = .2 x .2 x .2 x .2 x .2 x .2. Use Bernoulli for chance hits on < 6. Thus you can reduce the false positive P as low as you like by adding independent items (not always so easy). Problems with these tests: They are not very accurate: estimated hit rates vary from .5 to .85, CIT is better. CQT has very high false positive rate. CIT has high false negative rate. Both vulnerable to CMs. So we went to P300-based tests in late ‘80s. (Rosenfeld et al., 1987,1988.) OK, now: go to powerpoint presentation # 1 on 312- 2 site for example of applied psychophysiology in Detection of Deception: New Topic: The method of ablation or experimental lesions. One usually makes them with electrolysis (DC applied to brain). But residues are left at cathode. These can become stimulative or epileptogenic. So AC (RF) lesions also done. KCL can make a reversible lesion. Best lesions are cell or axon specific. (Kainic Acid for neurons.) The first topic to which lesions were applied was the most complex: Learning & Memory. This was a mistake. But for the first lesion maker, Lashley, the father of modern neuroscience, it was ok, because he was the first. He used all kinds of paradigms especially brightness discriminations and mazes to see how cortical (eventually, sub cortical) asperation lesions affected learning, memory, post-op retention, re-learning. He found 2 major principles-Mass Action: the more damage, the greater the deficit. Equipotentiality: One piece of cortex can replace the function of another. His major study used mazes at 3 difficulty levels: Mass action is shown in the following slides: The first shows difficulty effect: Here is pure mass action: Here is model integrating complexity and mass action interaction: ..and here is equipotentiality: That should have been the end of the lesion/stimulation method applied to higher cognitive phenomena.. It was not, and many years were spent repeating Lashley in other sensory cortices. So then people looked at emotion and more than 2000 papers on limbic system lesionstimulation effects were done up to the 1980s, and probably still going on at some places. Self stimulation story (rats press for brain stim) wasted a lot of time. Now, besides brain wave types, people are trying to localize higher cognitive function with fMRI, and are (some of them) making similar mistakes. (See the November 2010 issue of Psychological Science.) Lesions have been useful as long as one examines location for simple functions and necessity of those loci… An example is in the study of the recently discovered endogenous opiate system. Liebeskind & Mayer 1972-3 discovered that VCG stimulation inhibits pain. Then, following M&L’s work, I stumbled in.. Mayer’s thesis: 1) effects of applied opiates (stimulation) (2) cross tolerance(stim & opiates) studies and extensive study of sites in brain supporting self stimulation and/or analgesia… Go to powerpoint # 5 on 312-2 web page.