Prepared by Jeffrey W. Grimm Western Washington University PowerPoint Presentation for Biopsychology, 8th Edition by John P.J. Pinel Prepared by Jeffrey W. Grimm Western Washington University 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. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Can the Brain Recover from Damage? Chapter 10 Brain Damage and Neuroplasticity Can the Brain Recover from Damage? Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Causes of Brain Damage Brain tumors Cerebrovascular disorders Closed-head injuries Infections of the brain Neurotoxins Genetic factors Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Brain Tumors A tumor (neoplasm) is a mass of cells that grows independently of the rest of the body – a cancer 20% of brain tumors are meningiomas – encased in meninges Encapsulated, growing within their own membranes Usually benign, surgically removable Copyright © 2011 Pearson Education, Inc. All rights reserved.

Brain Tumors Continued Most brain tumors are infiltrating Grow diffusely through surrounding tissue Malignant, difficult to remove or destroy About 10% of brain tumors are metastatic – they originate elsewhere, usually the lungs Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.3 An MRI of Professor P.’s acoustic neuroma. The arrow indicates the tumor. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Cerebrovascular Disorders Stroke – a sudden-onset cerebrovascular event that causes brain damage Cerebral hemorrhage – bleeding in the brain Cerebral ischemia – disruption of blood supply Third leading cause of death in the U.S. and most common cause of adult disability Copyright © 2011 Pearson Education, Inc. All rights reserved.

Cerebrovascular Disorders Continued 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 © 2011 Pearson Education, Inc. All rights reserved.

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 Ca2+ Copyright © 2011 Pearson Education, Inc. All rights reserved.

Damage Due to Cerebral Ischemia lnflux of Na+ and Ca2+ 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 mechanisms of damage vary with the brain structure affected Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.5 The cascade of events by which the stroke-induced release of glutamate kills neurons. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. 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 – when there is disturbance of consciousness following a blow to the head and no evidence of structural damage Copyright © 2011 Pearson Education, Inc. All rights reserved.

Closed-Head Injuries Continued While there is no apparent brain damage with a single concussion, multiple concussions may result in a dementia referred to as “punch-drunk syndrome” Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.6 A CT scan of a subdural hematoma. Notice that the subdural hematoma has displaced the left lateral ventricle. Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. 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 often had toxic psychosis due to mercury exposure Copyright © 2011 Pearson Education, Inc. All rights reserved.

Neurotoxins Continued Some antipsychotic drugs produce a motor disorder called tardive dyskinesia Some neurotoxins are endogenous (produced by the body) e.g. Auto-immune disorders Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Genetic Factors Most neuropsychological diseases of genetic origin are associated with recessive genes--why? Down syndrome 0.15% of births, probability increases with advancing maternal age Extra chromosome 21 created during ovulation Characteristic disfigurement, mental retardation, other health problems Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Programmed Cell Death All six causes of brain damage produce damage, in part, by activating apoptosis Copyright © 2011 Pearson Education, Inc. All rights reserved.

Neuropsychological Diseases Epilepsy Parkinson’s disease Huntington’s disease Multiple sclerosis Alzheimer’s disease Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Epilepsy Primary symptom is seizures, but not all who have seizures have epilepsy Epileptics have seizures generated by their own brain dysfunction Affects about 1% of the population Difficult to diagnose due to the diversity and complexity of epileptic seizures Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Epilepsy Continued 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 associated with high amplitude spikes ` Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Epilepsy Continued Seizures often preceded by an aura, such as a smell, hallucination, or feeling Aura’s nature suggests the epileptic focus Warns epileptic of an impending seizure Partial epilepsy – does not involve the whole brain Generalized epilepsy – involves the entire brain Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. 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 © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.8 Cortical electroencephalogram (EEG) record from various locations on the scalp during the beginning of a complex partial seizure. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Generalized Seizures Grand mal Loss of consciousness and equilibrium Tonic-clonic convulsions Rigidity (tonus) Tremors (clonus) Resulting hypoxia may cause brain damage Petit mal Not associated with convulsions A disruption of consciousness associated with a cessation of ongoing behavior Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Parkinson’s Disease A movement disorder of middle and old age affecting about .5% of the population Tremor at rest is the most common symptom of the full-blown disorder Dementia is not typically seen No single cause Associated with degeneration of the substantia nigra; these neurons release dopamine to the striatum of the basal ganglia Copyright © 2011 Pearson Education, Inc. All rights reserved.

Parkinson’s Disease Continued Almost no dopamine in the substantia nigra of Parkinson’s patients Autopsies often reveal Lewy bodies (protein clumps) in the substantia nigra Treated temporarily with L-dopa Copyright © 2011 Pearson Education, Inc. All rights reserved.

Parkinson’s Disease Continued Linked to about ten different gene mutations Deep brain stimulation of subthalamic nucleus reduces symptoms, but effectiveness slowly declines over months or years Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Huntington’s Disease A rare, progressive motor disorder of middle and old age with a strong genetic basis Huntingtin gene single, dominant gene Begins with fidgetiness and progresses to jerky movements of entire limbs and severe dementia Death usually occurs within 15 years Caused by a single dominant gene First symptoms usually not seen until age 40 Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Multiple Sclerosis A progressive disease that attacks CNS myelin, leaving areas of hard scar tissue (sclerosis) 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 © 2011 Pearson Education, Inc. All rights reserved.

Multiple Sclerosis Continued 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 linked to MS with any certainty Copyright © 2011 Pearson Education, Inc. All rights reserved.

Multiple Sclerosis Continued Recent focus on epigenetic mechanisms Gene/environment interactions An autoimmune disorder – immune system attacks myelin Drugs may retard progression or block some symptoms Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.11 Areas of sclerosis (see arrows) in the white matter of a patient with MS. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Alzheimer’s Disease Most common cause of dementia – likelihood of developing it increases with age Progressive, with early stages character-ized by confusion and a selective decline in memory Definitive diagnosis only at autopsy – must observe neurofibrillary tangles and amyloid plaques Copyright © 2011 Pearson Education, Inc. All rights reserved.

Alzheimer’s Disease Continued Several genes associated with early-onset AD synthesize amyloid or tau, a protein found in the tangles Which comes first, amyloid plaques or neuro-fibrillary tangles? Genetic research on early-onset AD supports amyloid hypothesis (amyloid first) Decline in acetylcholine levels is one of the earliest signs of AD Effective treatments not yet available Immunotherapy is promising in animal models Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.13 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 © 2011 Pearson Education, Inc. All rights reserved.

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 © 2011 Pearson Education, Inc. All rights reserved.

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 © 2011 Pearson Education, Inc. All rights reserved.

Kindling Model of Epilepsy Continued 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 © 2011 Pearson Education, Inc. All rights reserved.

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 introduced into mice Plaque distribution comparable to that in AD Unlike humans, no neurofibrillary tangles Copyright © 2011 Pearson Education, Inc. All rights reserved.

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 led to the finding that deprenyl can retard the progression of PD Copyright © 2011 Pearson Education, Inc. All rights reserved.

Neuroplastic Responses to Nervous System Damage Degeneration – deterioration Regeneration – regrowth of damaged neurons Reorganization Recovery Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. 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 regenerating axon makes a new synaptic contact, the neuron may survive Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.15 Neuronal and transneuronal degeneration following axotomy. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Neural Regeneration Does not proceed successfully in mammals and other higher vertebrates – 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 © 2011 Pearson Education, Inc. All rights reserved.

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 © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.16 Three patterns of axonal regeneration in mammalian peripheral nerves. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Mammal PNS Neurons Regenerate, CNS Don’t CNS neurons can regenerate if transplanted into the PNS, while 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 © 2011 Pearson Education, Inc. All rights reserved.

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 lesioned area now responded to an adjacent area – remapping occurred within minutes Studies show large scale of reorganization possible Copyright © 2011 Pearson Education, Inc. All rights reserved.

Cortical Reorganization Following Damage in Humans Brain-imaging studies indicate there is continuous competition for cortical space by functional circuits e.g. Auditory and somatosensory input may be processed in formerly visual areas in blinded individuals Copyright © 2011 Pearson Education, Inc. All rights reserved.

Mechanisms of Neural Reorganization Strengthened existing connections due to a release from inhibition? Consistent with speed and localized nature of reorganization Establishment of new connections? Magnitude can be too great to be explained by changes in existing connections Copyright © 2011 Pearson Education, Inc. All rights reserved.

Recovery of Function after Brain Damage Difficult to conduct controlled experiments on populations of brain-damaged patients Can’t distinguish between true recovery and compensatory changes Cognitive reserve – education and intelligence – thought to play an important role in recovery of function – may permit cognitive tasks to be accomplished in new ways Adult neurogenesis may play a role in recovery Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.21 Increased neurogenesis in the dentate gyrus following damage (These images are courtesy of Carl Ernst and Brian Christie, Department of Psychology, University of British Columbia.) Copyright © 2011 Pearson Education, Inc. All rights reserved.

Neuroplasticity and the Treatment of Nervous System Damage Reducing brain damage by blocking neurodegeneration Promoting recovery by promoting regeneration Promoting recovery by transplantation Promoting recovery by rehabilitative training Copyright © 2011 Pearson Education, Inc. All rights reserved.

Reducing Brain Damage by Blocking Neurodegeneration Various neurochemicals can block or limit neurodegeneration Apoptosis inhibitor protein – introduced in rats via a virus Nerve growth factor – blocks degeneration of damaged neurons Estrogens – limit or delay neuron death Neuroprotective molecules tend to also promote regeneration Copyright © 2011 Pearson Education, Inc. All rights reserved.

Promoting CNS Recovery by Promoting Regeneration While regeneration does not normally occur in the CNS, experimentally it can be induced directing growth of axons by Schwann cells Olfactory ensheathing cells Copyright © 2011 Pearson Education, Inc. All rights reserved.

Promoting Recovery by Neurotransplantation Transplanting fetal tissue Fetal substantia nigra cells 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 with improved mobility Copyright © 2011 Pearson Education, Inc. All rights reserved.

Promoting Recovery by Rehabilitative Training Monkeys recovered hand function from induced strokes following rehab training Constraint-induced therapy in stroke patients – tie down functioning limb while training the impaired one – creates a competitive situation to foster recovery Facilitated walking as an approach to treating spinal injury Copyright © 2011 Pearson Education, Inc. All rights reserved.

Promoting Recovery by Rehabilitative Training Continued 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 rodent hippocampus Copyright © 2011 Pearson Education, Inc. All rights reserved.

Phantom Limbs: Neuroplastic Phenomena Ramachandran’s hypothesis: phantom limb caused by reorganization of the somato-sensory cortex following amputation Amputee feels a touch on his face and also on his phantom limb (due to their proximity on somatosensory cortex) Amputee with chronic phantom limb pain gets relief through visual feedback: view in mirror of his intact hand unclenching as seen in mirror box Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 10.23 The places on Tom’s body where touches elicited sensations in his phantom hand. (Based on Ramachandran & Blakeslee, 1998.) Copyright © 2011 Pearson Education, Inc. All rights reserved.