1. POWERPOINT PRESENTATION FOR BIOPSYCHOLOGY, 9TH EDITION BY JOHN P.J. PINEL PREPARED BY JEFFREY W. GRIMM WESTERN WASHINGTON UNIVERSITY COPYRIGHT © 2014 PEARSON EDUCATION, INC. ALL RIGHTS RESERVED. This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network; preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease, or lending of the program.

2. Can the Brain Recover from Damage? Chapter 10 Brain Damage and Neuroplasticity Copyright © 2014 Pearson Education, Inc. All rights reserved.

3. Learning Objectives LO1: Discuss 6 causes of brain damage. LO2: Discuss 5 major neurological diseases. LO3: Describe 3 animal models of human neurological disease. LO4: Compare anterograde and retrograde degeneration. LO5: Discuss neural reorganization and recovery of function after brain damage. LO6: Summarize the history of treatment of Parkinson’s disease with neurotransplantation. LO7: Describe research on the use of rehabilitative training to treat the effects of brain damage. Copyright © 2014 Pearson Education, Inc. All rights reserved.

4. Causes of Brain Damage Brain Tumors Cerebrovascular Disorders Closed-Head Injuries Infections of the Brain Neurotoxins Genetic Factors Copyright © 2014 Pearson Education, Inc. All rights reserved.

5. Brain Tumors A tumor (neoplasm) is a mass of cells that grows independently of the rest of the body: a cancer. 20 percent of brain tumors are meningiomas—that is, encased in meninges. Encapsulated; growing within their own membranes Usually benign; surgically removable Copyright © 2014 Pearson Education, Inc. All rights reserved.

6. Brain Tumors (Con’t) Most brain tumors are infiltrating. Grow diffusely through surrounding tissue Malignant; difficult to remove or destroy About 10 percent of brain tumors are metastatic; they originate elsewhere, usually the lungs. Copyright © 2014 Pearson Education, Inc. All rights reserved.

7. FIGURE 10.1 A meningioma. Copyright © 2014 Pearson Education, Inc. All rights reserved.

8. FIGURE 10.3 An MRI of Professor P.’s acoustic neuroma. The arrow indicates the tumor. Copyright © 2014 Pearson Education, Inc. All rights reserved.

9. Cerebrovascular Disorders Stroke: a sudden-onset cerebrovascular event that causes brain damage Cerebral hemorrhage: bleeding in the brain Cerebral ischemia: disruption of blood supply Stroke is the third leading cause of death in the U.S. and the most common cause of adult disability. Copyright © 2014 Pearson Education, Inc. All rights reserved.

10. Cerebrovascular Disorders (Con’t) Cerebral hemorrhage: blood vessel ruptures Aneurysm: a weakened point in a blood vessel that makes a stroke more likely; may be congenital (present at birth) or due to poison or infection Cerebral ischemia: disruption of blood supply Thrombosis: a plug forms in the brain Embolism: a plug forms elsewhere and moves to the brain Arteriosclerosis: wall of blood vessels thicken, usually due to fat deposits Copyright © 2014 Pearson Education, Inc. All rights reserved.

11. FIGURE 10.4 An angiogram that illustrates narrowing of the carotid artery (see arrow), the main pathway of blood to the brain. Copyright © 2014 Pearson Education, Inc. All rights reserved.

12. Damage Due to Cerebral Ischemia Does Not Develop Immediately Most damage is a consequence of excess neurotransmitter release—especially glutamate. Blood-deprived neurons become overactive and release glutamate. Glutamate overactivates its receptors, especially NMDA receptors, leading to an influx of Na + and Ca 2+. Copyright © 2014 Pearson Education, Inc. All rights reserved.

13. lnflux of Na + and Ca 2+ triggers: The release of still more glutamate A sequence of internal reactions that ultimately kill the neuron Ischemia-Induced Brain Damage Takes time Does not occur equally in all parts of the brain The mechanisms of damage vary with the brain structure affected. Damage Due to Cerebral Ischemia (Con’t) Copyright © 2014 Pearson Education, Inc. All rights reserved.

14. FIGURE 10.5 The cascade of events by which the stroke- induced release of glutamate kills neurons. Copyright © 2014 Pearson Education, Inc. All rights reserved.

15. Closed-Head Injuries Brain injuries due to blows that do not penetrate the skull: the brain collides with the skull. Contrecoup injuries: contusions are often on the side of the brain opposite to the blow. Contusions: closed-head injuries that involve damage to the cerebral circulatory system; hematoma (bruise) forms Concussions: a disturbance of consciousness following a blow to the head and no evidence of structural damage Copyright © 2014 Pearson Education, Inc. All rights reserved.

16. While there is no apparent brain damage with a single concussion, multiple concussions may result in a dementia referred to as “punch-drunk syndrome.” Closed-Head Injuries (Con’t) Copyright © 2014 Pearson Education, Inc. All rights reserved.

17. FIGURE 10.6 A CT scan of a subdural hematoma. Notice that the subdural hematoma has displaced the left lateral ventricle. Copyright © 2014 Pearson Education, Inc. All rights reserved.

18. Infections of the Brain Encephalitis: the resulting inflammation of the brain by an invasion of microorganisms Bacterial infections Often lead to abscesses, pockets of pus May inflame meninges, creating meningitis Treat with penicillin and other antibiotics Viral infections Some preferentially attack neural tissues. Some can lie dormant for years. Copyright © 2014 Pearson Education, Inc. All rights reserved.

19. Neurotoxins Neurotoxins may enter general circulation from the GI tract or lungs, or through the skin. Toxic psychosis: chronic insanity produced by a neurotoxin The Mad Hatter: hat makers in 18th- and 19th-century England often had toxic psychosis due to mercury exposure. Copyright © 2014 Pearson Education, Inc. All rights reserved.

20. Neurotoxins (Con’t) Some antipsychotic drugs produce a motor disorder called tardive dyskinesia. Some neurotoxins are endogenous (produced by the body). E.g., auto-immune disorders Copyright © 2014 Pearson Education, Inc. All rights reserved.

21. Genetic Factors Most neuropsychological diseases of genetic origin are associated with recessive genes. Why? Down Syndrome Down syndrome occurs in 0.15 percent of births; probability increases with advancing maternal age. An extra chromosome 21 is created during ovulation. Characteristic disfigurement, mental retardation, other health problems Copyright © 2014 Pearson Education, Inc. All rights reserved.

22. Programmed Cell Death All six causes of brain damage produce damage, in part, by activating apoptosis. Copyright © 2014 Pearson Education, Inc. All rights reserved.

23. Neuropsychological Diseases Epilepsy Parkinson’s disease Huntington’s disease Multiple sclerosis Alzheimer’s disease Copyright © 2014 Pearson Education, Inc. All rights reserved.

24. Epilepsy The primary symptom is seizures, but not all who have seizures have epilepsy. Epileptics have seizures generated by their own brain dysfunction. Epilepsy affects about 1 percent of the population. It is difficult to diagnose due to the diversity and complexity of epileptic seizures. Copyright © 2014 Pearson Education, Inc. All rights reserved.

25. Epilepsy (Con’t) Types of Seizures Convulsions: motor seizures Some are merely subtle changes of thought, mood, or behavior. Causes Brain damage Genes: over 70 known so far Faults at inhibitory synapses Diagnosis EEG: electroencephalogram Seizures are associated with high amplitude spikes. ` Copyright © 2014 Pearson Education, Inc. All rights reserved.

26. Seizures are often preceded by an aura, such as a smell, hallucination, or feeling. The aura’s nature suggests the epileptic focus. The aura warns the epileptic of an impending seizure. Partial epilepsy: does not involve the whole brain Generalized epilepsy: involves the entire brain Epilepsy (Con’t) Copyright © 2014 Pearson Education, Inc. All rights reserved.

27. Partial Seizures Simple Symptoms are primarily sensory or motor or both (Jacksonian seizures). Symptoms spread as epileptic discharge spreads. Complex Often restricted to the temporal lobes (temporal lobe epilepsy) Patient engages in compulsive and repetitive simple behaviors (automatisms). More complex behaviors seem normal. Copyright © 2014 Pearson Education, Inc. All rights reserved.

28. Generalized Seizures Grand Mal Loss of consciousness and equilibrium Tonic-clonic convulsions Rigidity (tonus) Tremors (clonus) The resulting hypoxia may cause brain damage. Petit Mal Not associated with convulsions A disruption of consciousness associated with a cessation of ongoing behavior Copyright © 2014 Pearson Education, Inc. All rights reserved.

29. FIGURE 10.7 Cortical EEG recorded during epileptic attacks. Notice that each trace is characterized by epileptic spikes (sudden, high-amplitude EEG signals that accompany epileptic attacks). Copyright © 2014 Pearson Education, Inc. All rights reserved.

30. Parkinson’s Disease Parkinson’s is a movement disorder of middle and old age affecting about 0.5 percent of the population. Tremor at rest is the most common symptom of the full-blown disorder. Dementia is not typically seen. No Single Cause Parkinson’s is associated with degeneration of the substantia nigra; these neurons release dopamine to the striatum of the basal ganglia. Copyright © 2014 Pearson Education, Inc. All rights reserved.

31. Parkinson’s Disease (Con’t) There is almost no dopamine in the substantia nigra of Parkinson’s patients. Autopsies often reveal Lewy bodies (protein clumps) in the substantia nigra. Parkinson’s disease can be treated temporarily with L-dopa. Copyright © 2014 Pearson Education, Inc. All rights reserved.

32. Parkinson’s Disease (Con’t) Parkinson’s is linked to about ten different gene mutations. Deep brain stimulation of subthalamic nucleus reduces symptoms, but its effectiveness slowly declines over months or years. Copyright © 2014 Pearson Education, Inc. All rights reserved.

33. Huntington’s Disease Huntington’s disease is a rare, progressive motor disorder of middle and old age with a strong genetic basis. Huntingtin gene Single, dominant gene Huntington’s disease begins with fidgetiness and progresses to jerky movements of entire limbs and severe dementia. Death usually occurs within 15 years. It is caused by a single dominant gene. First symptoms are usually not seen until age 40. Copyright © 2014 Pearson Education, Inc. All rights reserved.

34. Multiple Sclerosis MS is a progressive disease that attacks CNS myelin, leaving areas of hard scar tissue (sclerosis). The nature and severity of deficits vary with the nature, size, and position of sclerotic lesions. Periods of remission are common. Symptoms include visual disturbances, muscle weakness, numbness, tremor, and loss of motor coordination (ataxia). Copyright © 2014 Pearson Education, Inc. All rights reserved.

35. Multiple Sclerosis (Con’t) Epidemiological studies find that incidence of MS is increased in those who spend childhood in a cool climate. MS is rare amongst Africans and Asians. Only some genetic predisposition and only one chromosomal locus have been linked to MS with any certainty. Copyright © 2014 Pearson Education, Inc. All rights reserved.

36. Multiple Sclerosis (Con’t) Recent Focus on Epigenetic Mechanisms Gene–environment interactions An autoimmune disorder: the immune system attacks myelin. Drugs may retard progression or block some symptoms. Copyright © 2014 Pearson Education, Inc. All rights reserved.

37. FIGURE 10.10 Areas of sclerosis (see arrows) in the white matter of a patient with MS. Copyright © 2014 Pearson Education, Inc. All rights reserved.

38. Alzheimer’s Disease Alzheimer’s is the most common cause of dementia; one’s likelihood of developing it increases with age. Alzheimer’s disease is progressive; early stages are characterized by confusion and a selective decline in memory. Definitive diagnosis is only possible at autopsy; one must observe neurofibrillary tangles and amyloid plaques. Copyright © 2014 Pearson Education, Inc. All rights reserved.

39. Alzheimer’s Disease (Con’t) Several genes associated with early-onset AD synthesize amyloid or tau, a protein found in the tangles. Which comes first, amyloid plaques or neurofibrillary tangles? Genetic research on early- onset AD supports the amyloid hypothesis (amyloid first). Decline in acetylcholine levels is one of the earliest signs of AD. Effective treatments are not yet available. Copyright © 2014 Pearson Education, Inc. All rights reserved.

40. FIGURE 10.11 Amyloid plaques (stained blue) in the brain of a deceased patient who had Alzheimer’s disease. Copyright © 2014 Pearson Education, Inc. All rights reserved.

41. FIGURE 10.12 The typical distribution of neurofibrillary tangles and amyloid plaques in the brains of patients with advanced Alzheimer’s disease. (Based on Goedert, 1993, and Selkoe, 1991.) Copyright © 2014 Pearson Education, Inc. All rights reserved.

42. Animal Models of Human Neuropsychological Diseases Experiments regarding neuropathology are not usually possible with human subjects. Animal models are often utilized. For example: Kindling Model of Epilepsy Experimentally induced seizure activity Transgenic Mouse Model of Alzheimer’s Mice producing human amyloid MPTP Model of Parkinson’s Drug-induced damage comparable to that seen in PD Copyright © 2014 Pearson Education, Inc. All rights reserved.

43. Kindling Model of Epilepsy A series of periodic brain stimulations eventually elicits convulsions: the kindling phenomenon. Neural changes are permanent. Produced by stimulation distributed over time Copyright © 2014 Pearson Education, Inc. All rights reserved.

44. Kindling Model of Epilepsy (Con’t) Convulsions are similar to those seen in some forms of human epilepsy—but they only occur spontaneously if kindled for a very long time. Kindling phenomenon is comparable to the development of epilepsy (epileptogenesis) seen following a head injury. Copyright © 2014 Pearson Education, Inc. All rights reserved.

45. Transgenic Mouse Model of Alzheimer’s Disease Only humans and a few related primates develop amyloid plaques. Transgenic: genes of another species have been introduced Genes accelerating human amyloid synthesis are introduced into mice. Plaque distribution comparable to that in AD Unlike humans, no neurofibrillary tangles Copyright © 2014 Pearson Education, Inc. All rights reserved.

46. MPTP Model of Parkinson’s Disease The Case of the Frozen Addicts Synthetic heroin produced the symptoms of Parkinson’s. Contained MPTP MPTP causes cell loss in the substantia nigra like that seen in PD. Animal studies provide the means to identify potentially useful treatments for PD. Copyright © 2014 Pearson Education, Inc. All rights reserved.

47. Neuroplastic Responses to Nervous System Damage Degeneration: deterioration Regeneration: regrowth of damaged neurons Reorganization Recovery Copyright © 2014 Pearson Education, Inc. All rights reserved.

48. Degeneration Cutting axons (axotomy) is a common way to study responses to neuronal damage. Anterograde: degeneration of the distal segment between the cut and synaptic terminals Cut off from cell’s metabolic center; swells and breaks off within a few days Retrograde: degeneration of the proximal segment between the cut and cell body Progresses slowly; if the regenerating axon makes a new synaptic contact, the neuron may survive. Copyright © 2014 Pearson Education, Inc. All rights reserved.

49. FIGURE 10.13 Neuronal and transneuronal degeneration following axotomy. Copyright © 2014 Pearson Education, Inc. All rights reserved.

50. Neural Regeneration Does not proceed successfully in mammals and other higher vertebrates: the capacity for accurate axonal growth is lost in maturity. Regeneration is virtually nonexistent in the CNS of adult mammals and unlikely, but possible, in the PNS. Copyright © 2014 Pearson Education, Inc. All rights reserved.

51. Neural Regeneration in the PNS If the original Schwann cell myelin sheath is intact, regenerating axons may grow through them to their original targets. If the nerve is severed and the ends are separated, they may grow into incorrect sheaths. If ends are widely separated, no meaningful regeneration will occur. Copyright © 2014 Pearson Education, Inc. All rights reserved.

52. FIGURE 10.14 Three patterns of axonal regeneration in mammalian peripheral nerves. Copyright © 2014 Pearson Education, Inc. All rights reserved.

53. Mammal PNS Neurons Regenerate; CNS Don’t CNS neurons can regenerate if transplanted into the PNS, whereas PNS neurons won’t regenerate in the CNS. Schwann cells promote regeneration. Neurotrophic factors stimulate growth. CAMs provide a pathway. Oligodendroglia actively inhibit regeneration. Copyright © 2014 Pearson Education, Inc. All rights reserved.

54. Neural Reorganization Reorganization of primary sensory and motor systems has been observed in laboratory animals following: Damage to peripheral nerves Damage to primary cortical areas Lesion one retina and remove the other; V1 neurons that originally responded to the lesioned area now respond to an adjacent area. Remapping occurs within minutes. Studies show that large-scale reorganization is possible. Copyright © 2014 Pearson Education, Inc. All rights reserved.

55. FIGURE 10.16 Reorganization of the rat motor cortex following transection of the motor neurons that control movements of the vibrissae. The motor cortex was mapped by brain stimulation before transection and then again a few weeks after. (Based on Sanes et al., 1990). Copyright © 2014 Pearson Education, Inc. All rights reserved.

56. Cortical Reorganization Following Damage in Humans Brain-imaging studies indicate that there is continuous competition for cortical space by functional circuits. E.g., auditory and somatosensory input may be processed in formerly visual areas of the brains of blinded individuals. Copyright © 2014 Pearson Education, Inc. All rights reserved.

57. Mechanisms of Neural Reorganization Are existing connections strengthened due to a release from inhibition? Consistent with speed and localized nature of reorganization Are new connections established? Magnitude can be too great to be explained by changes in existing connections. Copyright © 2014 Pearson Education, Inc. All rights reserved.

58. Recovery of Function after Brain Damage It is difficult to conduct controlled experiments on populations of brain-damaged patients. Researchers can’t distinguish between true recovery and compensatory changes. Cognitive reserve—education and intelligence—is thought to play an important role in recovery of function; this may permit cognitive tasks to be accomplished in new ways. Adult neurogenesis may play a role in recovery. Copyright © 2014 Pearson Education, Inc. All rights reserved.

59. FIGURE 10.18 Increased neurogenesis in the dentate gyrus following damage. The left panel shows (1) an electrolytic lesion in the dentate gyrus (damaged neurons are stained turquoise) and (2) the resulting increase in the formation of new cells (stained red), many of which develop into mature neurons (stained dark blue). The right panel displays the comparable control area in the unlesioned hemisphere, showing the normal number of new cells (stained red). (These images are courtesy of my friends Carl Ernst and Brian Christie, Department of Psychology, University of British Columbia.) Copyright © 2014 Pearson Education, Inc. All rights reserved.

60. Neuroplasticity and the Treatment of CNS Damage Reducing Brain Damage by Blocking Neurodegeneration Promoting Recovery by Promoting Regeneration Promoting Recovery by Transplantation Promoting Recovery by Rehabilitative Training Copyright © 2014 Pearson Education, Inc. All rights reserved.

61. Reducing Brain Damage by Blocking Neurodegeneration Various neurochemicals can block or limit neurodegeneration. Apoptosis inhibitor protein: introduced in rats via a virus Neurotrophic factors (BDNF, GDNF) block degeneration of damaged neurons. Neuroprotective molecules also tend to promote regeneration. Copyright © 2014 Pearson Education, Inc. All rights reserved.

62. Promoting CNS Recovery by Promoting Regeneration While regeneration does not normally occur in the CNS, it can be induced experimentally by directing the growth of axons by Schwann cells. Copyright © 2014 Pearson Education, Inc. All rights reserved.

63. Promoting Recovery by Neurotransplantation Transplanting Fetal Tissue Fetal substantia nigra cells were used to treat MPTP-treated monkeys (PD model). Treatment was successful. Limited success with humans Transplanting Stem Cells E.g., embryonic stems cells implanted into damaged rat spinal cord Rats with spinal damage showed improved mobility. Copyright © 2014 Pearson Education, Inc. All rights reserved.

64. Promoting Recovery by Rehabilitative Training Monkeys recovered hand function from induced strokes following rehab training. Constraint-induced therapy in stroke patients—tying down the functioning limb while training the impaired one—creates a competitive situation to foster recovery. Facilitated Walking as an Approach to Treating Spinal Injury Copyright © 2014 Pearson Education, Inc. All rights reserved.

65. Benefits of Cognitive and Physical Exercise Correlations in human studies between physical/cognitive activity and resistance or recovery from neurological injury and disease Rodents raised in enriched environments are resistant to induced neurological conditions (epilepsy, models of Alzheimer’s, Huntington’s, etc.). Physical activity promotes adult neurogenesis in the rodent hippocampus. Promoting Recovery by Rehabilitative Training (Con’t) Copyright © 2014 Pearson Education, Inc. All rights reserved.

66. Phantom Limbs: Neuroplastic Phenomena Ramachandran’s hypothesis: phantom limb is caused by reorganization of the somato-sensory cortex following amputation. The amputee feels a touch on his face and also on his phantom limb (due to their proximity on somatosensory cortex). An amputee with chronic phantom limb pain gets relief through visual feedback: view in mirror of her intact hand unclenching, as seen in mirror box. Copyright © 2014 Pearson Education, Inc. All rights reserved.

67. FIGURE 10.20 The places on Tom’s body where touches elicited sensations in his phantom hand. (Based on Ramachandran & Blakeslee, 1998.) Copyright © 2014 Pearson Education, Inc. All rights reserved.