1. Biomed 370 The Human Brain and Behavior

2. Course Objectives n Better understand the brain systems involved in regulating behavior n Learn about the diagnosis and treatment of major syndromes in psychiatry n Appreciate the importance of anatomy, neurochemistry and brain imaging for understanding the brain and behavior

3. Format n Lectures with patient demonstrations n One Midterm (40%) and a Final (60%) n Review sessions before each exam n Contact the TA’s for help n Top 15% receive honors n Exams will be multiple choice, often built around clinical cases.

4. Nancy Brim Stan Pelosi Marisa Kastoff

5. Key Points the Brain and Behavior n Brain dysfunction affects all aspects of medicine n Progress in the neurobiology of neurological and psychiatric disorders is advancing at a rapid rate n 370 will provide an overview of current knowledge to be modified as new information becomes available n Life-long learning is essential for understanding brain-behavior relationships n Clinical neuroscience is one field supported by advances in basic neuroscience n Brown has many excellent faculty on the cutting edge of clinical neuroscience research.

7. n Case reports have been pivotal in providing information about localization of function and pathogenesis of disease, and have greatly advanced the field of Behavioral Neurology and Neuropsychiatry.

9. n The MRI of my first patient with CADASIL that got me involved in studying the role of genetics in small artery disease of the brain Notch3 mutations chromosome 19

10. Key Points About Neural Systems and Behavior n Clusters of neurons are connected to other neuronal clusters in defined circuits. These circuits are organized into networks to perform specific functions. n Neurotransmitters within the neuronal assemblies are the chemical means of carrying out neuronal activity. n There is hemispheric asymmetry for many functions. n Injury circuits or degeneration of neurotransmitter systems can cause a disturbance in cognition, behavior, or sensorimotor function. n There is plasticity, redundancy and reserve following injury, but these all decline with age.

14. 4/2/1999 3/7/2002 3/15/2004

17. The Limbic System

18. Lecture Objectives n Become familiar with the anatomy and function of the limbic system n Understand how dysfunction in limbic structures can lead to neuropsychiatric symptoms

21. Limbic Divisions n Archicortical (blue) n Paleocortical (red)

22. Archicortical Division n Hippocampus, cingulate gyrus and Papez circuit n Modulates sensory processing, encoding of information and attentional control

24. Hippocampus

25. Entorhinal Cortex Entorhinal Cortex

27. Projected Prevalence of AD 16 14 12 0 2 4 6 8 10 2000 20102020203020402050 4 5.8 6.8 8.7 11.3 14.3 Millions 4 Million AD Cases Today— Over 14 Million Projected Within a Generation Year Evans DA et al. Milbank Quarterly. 1990;68:267-289.

28. Mesial Temporal Sclerosis 31 year old woman from Africa with frequent complex partial seizures and mild developmental delay. Can you find the hippocampi? What is wrong with her scan?

29. 39-year-old man with no past history of neurological or psychiatric illness brought to the hospital after a generalized seizure. In the ER he was confused and had a low-grade fever. Over the next 7 days he had short-term memory impairment and erratic behavior, sometimes wandering around the ward without clothes. He had trouble paying attention and could recall only one of three words at five minutes. Insight and judgment were impaired. Naming, repetition, calculations, writing and figure copying were intact.

34. A 30 year old man with schizophrenia was admitted to the hospital with florid psychosis after stopping his neuroleptics 3 months earlier. He had stopped eating regular meals and lost 45 pounds. He was hydrated with D5 NS in the ER and admitted to the Psychiatry Unit. 6 days after admission he developed ataxia and delirium. What does this FLAIR, non-contrast MRI show? Where is the abnormality and what caused it?

36. Cingulate Gyrus

38. H.M.

41. Paleocortical Division n Amygdala and orbitofrontal cortex, basal forebrain, hypothalamus and autonomic nervous system n Modulates fear responses and emotional memories n Integrates affect, drives, and object associations

42. Amygdala n Anterior and medial to the hippocampus n Clusters of nuclei, basolateral, centro- median n Connected to basal forebrain by stria terminalis n Connected to hypothalamus by ventral amygdalofugal pathway

46. Hypothalamus n Stimulation of the lateral hypothalamic area-aggressive, voracious, hypersexual n Stimulation of the ventromedial nucleus-placid and early satiety

48. Practice Questions n Key structure involved in episodic memory n Involved in processing emotional memories n The fornix connects the hippocampus to which structure?

49. n The ____ connects the amygdala to the septal nuclei in the base of the frontal lobe n The ventral amygdalofugal pathway connects to the amygdala to the _______ n The only primary sensory input to the amygdala is from the ______________