1. JHU BME 580.422 Biological Systems II Brain and Behavior Reza Shadmehr

2. In 1870, it was discovered that when one electrically stimulates the cortex of a dog, movements occur with the contralateral limb. Hints of localization of function: stimulation in the frontal lobe most easily and repeatedly produced limb movements. Wada test: When a patient is about to undergo neurosurgery, in some cases a procedure is performed to better understand the function of each hemisphere. A drug is injected into the carotid artery that supplies blood to one hemisphere. This effectively shuts down that hemisphere, paralyzing the opposite side of the body. If the language centers are on the right side, the patient will be unable to speak if that side is affected. The procedure lasts for a couple of minutes and then is washed out. Regions of the cortex specialize in aspects of control of perception and action 1.Principle of contralateral control of action 2.Language centers 3.Centers for perception of visual information

3. Before injection After injection in the right carotid artery Principle of contralateral control: each cerebral hemisphere controls movements of the opposite side of the body The “Wada” test Injection of anesthetic (sodium amobarbital) in the right internal carotid artery. When the right carotid artery is injected, the right cerebral hemisphere is inactivated, paralyzing the left side of the body. Note that the examiner is holding an object in hand. He is asking the patient to name the object.

4. Study of language as a window to localization of function in the brain Broca’s area: A place in the brain that is critical for producing language. The brain of patient Leborgne, known as “Tan”. Paul Broca (1824-1880)

5. Karl Wernicke (1848-1904) found patients that could speak, but failed to comprehend language. Study of language as a window to localization of function in the brain Wernicke’s area: A place in the brain that understands spoken or written language. Kandel et al. (2000) Principles of Neural Science

6. Study of vision as a window to localization of function in the brain Area V4: perception of color Area MT: perception of motion Area TEO: perception of faces

7. Memory and the human brain: stimulation experiments Neurosurgeon Wilder Penfield in 1950s applied electrical currents to different areas of the brain during surgery in epileptic patients. He found that stimulation of points in the temporal lobe produced vivid childhood memories, or pieces of old musical tunes. A 21 year old man reported: “It was like standing in the doorway at [my] high school. I heard my mother talking on the phone, telling my aunt to come over that night.” Another patient: “My nephew and niece were visiting at my home … they were getting ready to go home, putting on their coats and hats … in the dining room … my mother was talking to them.” (Penfield and Perot, Brain 86:595, 1963) R. Carter (1998) Mapping the Mind Places where stimulation evoked memories

8. 27 year old assembly line worker who had suffered from untreatable and debilitating temporal lobe seizures for many years. Surgeon removed medial portion of the temporal lobes bilaterally. H.M.’s seizures were improved, but there was a devastating side effect: he could no longer form long-term memories. After recovery from surgery, he maintained his vocabulary and language skills, maintained his high IQ, and ability to recall facts about his life that preceded the surgery: could remember job that he held, where he had lived, and events of childhood. normal immediate memory: he could retain a number for a short period of time. He could carry on a conversation. could not recognize people that he had talked to just the day before at the hospital. He did not what he ate at his last meal. R. Carter (1998) Mapping the Mind Corkin, Seminars in Neurology 4:249-259 1984. Memory and the human brain: patient HM

9. Immediate memory is intact in amnesia. However, what is lost is the ability to translate immediate memory into long-term memory. Delayed paired-comparison task in HM Clicks, flashes, tones, or hues were presented to HM and then some seconds later, the same or another cue was presented and he was asked to determine whether the two stimuli were the same or different.

10. Recall performance on a test of news events that occurred from 1951 to 2005. The scores for six patients with damage limited primarily to the hippocampal region and 13 controls have been aligned relative to the onset of amnesia. The data point at –5 represents 1–5 years before amnesia, the point at –10 represents 6–10 years before amnesia, and so on. Error bars indicate SEM. Bayley, Hopkins, Squire (2006) J Neurosci 26:13311. Healthy controls Hippocampal damage When the hippocampus is damaged, the patient does not lose the very old memories that were acquired long ago (more than 6-10 years before the damage). Rather, the damage reduces the ability of the brain to maintain memories from the near the time of the damage, and since the damage. Amnesia spares old memories

11. Amnesic patients show near normal ability to learn and store a motor skill. While viewing hand in mirror, H.M. tries to trace between the two lines. Number of errors refers to times that the border was crossed. Kandel et al. Principles of Neural Science 2000 (62-2) Could learn to do mirror writing: performance would improve with practice and remain good on next day, despite no conscious recall of prior practice. Lesions of the temporal lobe appear to affect forms of learning and memory that require a conscious record, and are called declarative memories.

12. What we learn from patient H.M. The ability to acquire new memories about facts, episodes of our lives, places that we have been, people that we know, etc. (declarative memories) is a function of the medial temporal lobe. The medial temporal lobe is not required for immediate memory. The medial temporal lobe is not the ultimate location where declarative memories are stored because H.M. can remember his childhood. Certain other memories (e.g., motor skills) can be learned normally without the medial temporal lobe. In that case, the amnesic patient knows how to do a task at an expert level but will claim that they have never done the task before.

13. Memories slowly become resistant to disruption: consolidation Deeply depressed patients were admitted to the hospital for electroconvulsive therapy. Before and after treatment, they were tested for their memory of TV programs that had been broadcast for a single season during one of the preceding 16 years. Experiment was performed in 1974. (chance is 25%) Before treatment, depressed patients remembered programs that had been broadcast recently better than older programs. After treatment, patients remembered the remote past normally, but their memory was poor for recent 1-3 years. Squire and Kandel, Memory: from mind to molecules, 1999, p. 102

15. Jerry Levy (1986) Brain asymmetry: facts and fallacies in statistical inference. Brain Cognition. 5(1):115-25.

16. Summary The CNS is anatomically divided into seven regions: spinal cord, medulla, pons, cerebellum, midbrain, diencephalon, and cerebral cortex The cortex has distinct functional regions: occipital lobe is for vision, temporal lobe houses audition and vision for perception (what is it?), parietal lobe houses vision for action (where is it?), frontal lobe houses the motor cortex. Movements are controlled by the hemisphere contralateral to the limb. Language functions are usually in the left hemisphere, whereas face recognition usually depends on the right hemisphere. There are distinct memory systems in the brain. Damage to the medial aspect of the temporal lobe causes amnesia, where immediate memory is intact, but the person cannot remember events of more than a few minutes ago. Medial temporal lobe is a sort of “gateway” to memory of facts and events. Motor memory does not depend on the medial temporal lobe.