The Limbic System: Components, Location, and Pathways

1. Lab 12 Emotion & Memory Components of the Limbic System

2. 4 ** 1 ** ** 5 Basal Forebrain 6 ** 2 area of hypothalamus 3

3. Ventromedial Prefrontal Cortex Orbitofrontal Cortex Basal Forebrain What is the ~location of the: Orbitofrontal Cortex? Ventromedial Prefrontal Cortex? Basal Forebrain?

4. 2 Olfactory Stria 3 Basal Forebrain 1 4

5. 4 anterior cingulate cortex septum pellucidum 5 Anterior Cerebral Arteries 3 anterior horn of lateral ventricle Orbitofrontal cortex Ventromedial prefrontal cortex 1 2 EMOTION CORTEX VENTRAL STRIATUM: nucleus accumbens + septal nuclei

6. Anterior cingulate cortex (ACC) 15 anterior cingulum 14 Anterior commissure 16 4 Basal forebrain 1 Basal forebrain 3 amygdala 13 Hypothalamus amygdala 17 anterior cingulum 2 5 6 7 VAP 8 10 12 9 11 (basal nucleus of Meynert)

7. Ventral Amygdalofugal Path (VAFP) What is the ~location of the: Lateral Hypothalmic Area? Lateral Hypothalamic Area With medial forebrain bundle Amygdala Amydala? Ventral Amygdalofugal Path?

8. Cingulate Gyrus 2 1 DM Nucleus of Thalamus 3 Cingulum

9. 4 1 amygdala Anterior commissure LGN 5 3 Visual radiations LGN 2 What is the ~location of the fast path from LGN to amygdala?

10. Location of ventral tegmental area (VTA) 3 MFB fibers en route to lateral reticular formation in rest of brainstem 1 (fibers) Location of ventral tegmental area (VTA) 2

11. Parabrachial nucleus Reticular formation with laterally descending fibers from MFB Locus Ceruleus PAG Rostral Raphe Nuclei What is the ~location of the: PAG? Parabrachial Nucleus? Locus Ceruleus? MFB? Rostral Raphe Nuclei? Rostral Pons Level

12. Facial motor nucleus What is the ~location of the: Facial Motor Nucleus? Rostral Pons Level

13. Hippocampal formation amygdala LGN IT Optic Radiations primary visual cortex Visual association ctx. Trace the path for cognitive recognition of a fearful visual stimulus from LGN to amygdala.

14. Anterior Cingulate Cortex Medial Prefrontal Cortex Orbitofrontal Gyri What is the ~location of the: Anterior Cingulate Cortex? Medial Prefrontal Cortex? Orbitofrontal Gyri?

15. 1 Fibers from Hippocampal Formation 2

16. 1 2 3

17. 1 fornix Internal Medullary lamina 4 anterior nucleus 2 5 LGN mammillo- thalamic tr. 3 12 Anterior nucleus Temporal horn of lateral ventricle 11 parahippo- campal gyrus Hippocampal formation 8 Entorhinal cortex Of parahippocampal gyrus 13 14 alveus 6 more parahippo- campal gyrus 9 fornix 7 10 Hippocampal formation

18. 1 Body of lateral ventricle 2 fornix anterior nucleus 3 mammillo- thalamic tr. 4 Mammillary nuclei 7 III ventricle 6 Temporal horn of lateral ventricle amygdala 5 8

19. Fornix (below septum pellucidum + medial to alveus) 2 1 alveus Anterior commissure 6 3 fornix Interventricular foramen Fornix (post-commissural part, en route to mammillary nuclei) 4 5 Fornix (splitting at anterior commissure) 7

20. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. What area of the brain is affected by the pathology? Left frontal lobe. Because of the midline shift, right frontal lobe might be affected

21. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. What is the pale circle at the tips of the arrows? It represents the territory of breakdown of the blood-brain barrier. In the brief period between IV injection of the tracer and the actual scan, the high signal tracer accumulates in the extracellular space in the area of breakdown of the blood brain barrier

22. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. What is the darker area surrounding the pale circle? It represents the territory of vasogenic brain edema – VBE – preferentially in the extracellular spaces of the white matter. There is less resistance to extracellular transport in the white matter than in gray matter. The area of VBE contains, water, salts, proteins that traveled through the extracellular spaces of the white matter before the injection of the tracer. Thus it does not have a high signal NOTE: Why would there be a halo of breakdown of the BBB around the mass? Most often, this happens because the mass is growing rapidly, so that vessels peripheral to the mass get compressed (tissue compression or increased tissue pressure), resulting in a compression ischemia of the area, which results in inadequate energy to maintain the barrier functions of endothelial cells of transport vessels. When the barrier functions fail, there is an exit of fluid (mostly water + solutes + protein) into the extracellular space. This fluid then pours into the extracellular space of the white matter to form vasogenic brain edema (VBE).

23. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. What are 3 (very general) possible causes for this lesion? • Rapidly growing tumor (which it is – a Glioblastoma multiformi or GM) • Intracerebral hemorrhage or ICH (based on the shape of the lesion and its surrounding BBB breakdown & VBE . However, time history is not great for an ICH, because an ICH would usually cause an acute episode that would be remembered. • 3) Abscess because the shape of the mass (contents of the abscess) is often similar to what is seen

24. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. Based on what is visible in the image, what structures are most likely affected by this lesion? Left side: prefrontal cortex including anterior cingulate, medial prefrontal and orbitofrontal cortex, lateral prefrontal cortex, olfactory structures, frontal eye field, Broca’s area, possibly precentral gyrus Right side: There may be compression of tissue due to the midline shift – similar structures as for the left

25. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. For each of the following structures, what symptoms would be possible for the difficulty this man had in his work: Anterior Cingulate & Other Emotion Cortex Lessened awareness of emotional cues in other people (so one can miss interpretation of what is said, etc); lessened awareness of “social rules” (so one can act in a way that is offensive (urinate on floor). Possible difficulty in behaving in a way that is considered appropriate socially

26. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. For each of the following structures, what symptoms would be possible for the difficulty this man had in his work: Lateral Prefronal Cortex Difficulty in thinking (analysis, etc.) and making decisions about future activities

27. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. For each of the following structures, what symptoms would be possible for the difficulty this man had in his work: Olfactory Structures Smell deficits

28. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. For each of the following structures, what symptoms would be possible for the difficulty this man had in his work: Frontal Eye Field (FEF) ONLY IF IT WAS AFFECTED A DAY OR LESS THAN THE EXAMINATION: eyes may be pointing toward one side (left side if affect on left FEF is more severe than any compression of right FEF). Otherwise, no findings.

29. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. For each of the following structures, what symptoms would be possible for the difficulty this man had in his work: Broca’s Area Difficulty in coming up with words – expressive aphasia

30. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. For each of the following structures, what symptoms would be possible for the difficulty this man had in his work: Precentral Gyrus (& anterior paracentral lobule) Cortical upper motor neurons. Deficits: contralateral weakness, hyperreflexia & hypertonia of muscles supplied by cortical fibers that were injured > 4 or 5 days before the examination; difficulty with complex hand movements, etc…

31. A 27-year-old male visited his family physician complaining of severe headaches that have bothered him for the past couple of weeks. In addition, he had other difficulties that interfered with his work. His boss asked him to see a doctor. He was sent for MRIs (with and without intravenous injection of a gadolinium tracer). A slice taken from the series with dye injection is shown below. For each of the following structures, what symptoms would be possible for the difficulty this man had in his work: Supplementary Motor & Premotor Areas Difficulty in complex movements, especially of the hands e.g. movements that require the two hands to work independently like putting pegs into a base held in one hand, rapidly alternating movements of both hands in opposite directions

32. Emotion Related Areas Lateral Prefrontal Cortex Broca’s Area FEF Motor Cortex Observe patient’s affect, emotional expressions and ask if there have been changes in “feelings” Ask questions about date, time, location, past history etc Any difficulty with language If this is acute, test for lateral gaze. Patient would have paralysis of lateral gaze to the side opposite the side of the lesion NOTE: Gaze paralysis due to cortical lesions are transient – one to two weeks. Alternate more primitive paths will take over with time. Test for muscle strength, tone and reflexes. Perform complex hand movements What clinical tests would you use to evaluate clinical signs?