1. CHAPTER 11 The Body Senses and Movement The Body Senses Movement disorders Learning disorders

2. Parkinson’s disease Parkinson’s disease: characterized by –Motor tremors –Rigidity –Loss of balance and coordination, –Difficulty in moving, especially in initiating movements The symptoms are caused by deterioration of the substantia nigra. –neurons of the substatia nigra send dopamine-releasing axons to the striatum. –The striatum: composed of the basal ganglia ’ s caudate nucleus and putamen nucleus accumbens. –Upsets balance between direct and indirect pathways

3. Some forms likely genetic: –Recent whole-genome study of Parkinson’s patients identified 12 genes that likely contribute to the disease. –Two of the implicated genes may play role in the development and programmed death of dopamine-producing neurons. –Two others result in deviant proteins that are components of Lewy bodies Lewy bodies: abnormal clumps of protein that form within neurons. –Lewy bodies found in several brain locations in some Parkinson’s patients –Also found in people with form of dementia, dementia with Lewy bodies. –Lewy bodies likely contribute to cognitive deficits and depression that also often accompany Parkinson’s disease. etiology

4. Typically treated by administering levodopa (L-dopa), –precursor for dopamine. Why use precursor? –Dopamine not cross the blood-brain barrier –L-dopa will –in the brain is converted to dopamine. Problem: –Treatments increase dopamine throughout brain –Causes significant side effects including Restlessness involuntary movements hallucinations. –As more neurons die, more drug is required, increasing the side effects. –Eventually, no neurons left to treat! treatment

5. Huntington’s chorea Huntington’s disease –Degenerative disorder of the motor system –Cell loss in the striatum and cortex. –Is genetic: dominant gene trait Progressive disorder –Onset typically in late 20’s, early 30’s –Years before a diagnosis, begins with jerky movements that result from impaired error correction. –At mid stage: involuntary movements appear first as fidgeting then as movements of the limbs –Late stage: writhing of the body facial grimacing Loss of motor control and death

6. Huntington’s Much more severe symptoms than Parkinson’s disease: – Cognitive and emotional deficits are a universal characteristic of Huntington’s disease –In contrast to other movement disorders such as Parkinson’s. –https://www.youtube.com/watch?v=JzAPh2v-SCQhttps://www.youtube.com/watch?v=JzAPh2v-SCQ –https://www.youtube.com/watch?v=rplp3rGzn5Yhttps://www.youtube.com/watch?v=rplp3rGzn5Y Deficits include –Impaired judgment –Difficulty with a variety of cognitive tasks –Depression, often with bipolar tendencies –Personality changes Motor symptoms are due to the degeneration of neurons in the striatum Defective or degenerated neurons in the cortex probably account for the psychological symptoms.

8. Huntington’s disease results for a mutated form of the Huntingtin gene. –Is dominant trait gene –If you have the gene, you will get the disease –50/50 chance of passing it on –Ethical dilemma created with identification of gene: Should you be tested? The loss of neurons is probably due to the accumulation of this gene’s protein excess –Protein called huntingtin –Function is unknown other than role in Huntington’s. etiology

9. Myasthenia gravis –Disorder or muscular weakness –Caused by reduced numbers of sensitivity of acetylcholine receptors. Drugs that inhibit the action of AChe give temporary relief from the symptoms of myasthenia gravis. –Remember: AChe breaks down Ach in synapse. –Inhibitors increase amount of neurotransmitter available at the neuromuscular junction. Myasthenia gravis

10. Multiple sclerosis Motor disorder with many varied symptoms –Caused by deterioration of myelin (demyelination) and neuron loss in the central nervous system. –Demyelination causes slowing or elimination of neural impulses –This reduces the speed and strength of movements. As the disease progresses, unmyelinated neurons die, leaving areas of sclerosis, or hardened scar tissue. –Result: person experiences muscular weakness, tremor, impaired coordination, urinary incontinence, and visual problems. –Symptoms may wax and wane autoimmune reactions Several drugs are available: modify immune activity in multiple sclerosis patients –Slow the progress of the disease –Do not repair the harm already done. –Early detection and treatment is critical

11. Figure 11.23 The brain of a deceased MS patient The arrows indicate areas of sclerosis, or hardened scar tissue.

12. Learning and motor disruptions Strong link between descending motor pathway abnormalities and a variety of genetic, behavioral, learning and psychological disorders. Learning and psychological disorders linked to descending motor pathway disturbances include –Dyslexia, –Tourette ’ s syndrome, –Several genetic forms of mental retardation –Autism –ADHD. The common link between all of these disorders: Inability to appropriately inhibit some behavioral patterns while disinhibiting others.

13. distonia Primary dystonia: –Movement disorder resulting from basal ganglia dysfunction –Some cognitive dysfunction, as well –May be related to the ability to detect different emotional facial expressions. –https://www.youtube.com/watch?v=mJIBBGZfk44https://www.youtube.com/watch?v=mJIBBGZfk44 Patients with primary dystonia show isolated deficits in –Recognition of disgust –but NOT ability to detect happiness, surprise, sadness or anger Dystonia resulting from basal ganglia dysfunction demonstrates the role of the basal ganglia in cognitive behavior such as emotion recognition.

14. 22q11.2 deletion syndrome 22q11.2 deletion syndrome (22qDS): –Genetic “error” – caused by the deletion of a small piece of chromosome 22. Children with 22qDS show a wide spectrum of disabilities –cognitive and motor deficits –physical anomalies –ADHD, –poor executive visual attention, –poor sensorimotor processing, –learning disabilities with primary impairment in working memory. –https://www.youtube.com/watch?v=mrk_LUQXLOkhttps://www.youtube.com/watch?v=mrk_LUQXLOk –up to 25 times more likely to develop autism, pervasive developmental disorders, and schizophrenia. may have early functional abnormalities in corticostriatal pathways linking the prefrontal cortex and basal ganglia structures.

15. Lesch-nyan syndrome Rare genetic disorder caused by a mutation in the gene coding for the enzyme hypoxanthine-quanin phosphoribosyltransferase Characterized by –hyperuricemia, –motor disorders – severe and compulsive self mutilation. –https://www.youtube.com/watch?v=1U6LDpF_LFEhttps://www.youtube.com/watch?v=1U6LDpF_LFE linked to descending motor pathway dysfunction Why? Disconnect between the prefrontal cortex and the basal ganglia –caused by DA dysfunction –Result: dysfunctional DA signal which accidentally reinforces early injurious behavior –Initial injurious behavior occurs because of motor dysfunction resulting in clumsiness and awkward movements that incidentally produce self injury. –Behavior becomes well learned and automated behavior –Result: Pattern of severe self mutilation.

16. Tourette’s syndrome Tourette syndrome (TS) characterized by –Stereotyped involuntary movements, or tics. –Result of structural and functional abnormalities of the basal ganglia –Link between motor system and limbic system is disturbed –Result is spontaneous disinhibiton of competing motor and limbic system Treatment: –Typically: antipsychotic medication (Dopamine D2 antagonists) because reduce available DA in system –Unfortunately, compound learning deficits –Alternative: biofeedback and learned control of tics

17. Language disorders Language disorders may be due to poor regulation by the basal ganglia and related structures. Procedural deficit hypothesis (PDH) may explain specific language impairments –Disorder due to abnormal development of the basal ganglia –Basal ganglia modulates the procedural memory system. Because of procedural memory functions, Basal Ganglia also modulate: –Learning and execution of specific motor and cognitive skills –Especially skills critical for understanding and using aspects of grammar. –Grammar involves word order, structure, rules for language Lexical (word) and declarative memory (memory for facts/basic knowledge) not affected because these behaviors depend on other brain structures

18. Speech apraxia –Difficulty with pronunciation, production of speech –Particular phonemic characteristics of speech apraxia may be due to subcortical dysfunction. Observations of those with speech apraxia show: –Greater phoneme substitution errors than any other type of error –Errors occur significantly more often in the initial rather than the medial or final word position. –These errors likely due to disinhibition of competing phonemes during speech –Suggests speech motor planning occurs at subcortical and cortical brain levels.

19. stuttering Strong link between stuttering and basal ganglia dysfunction. –Stuttering similar to other basal ganglia disorders such as Parkinson ’ s disease and dystonia. –Stuttering is alleviated with interventions such as rhythm effects, chorus speech, and singing: retraining brain Basal ganglia-thalamocortical motor circuits through the putamen play a key role in stuttering. –Stuttering due to impaired ability of the basal ganglia to produce timing cues for the initiation of the next motor segment in speech. –Dysfunction due to abnormalities in the dopamine error-detection feedback system, –Pharmacologic interventions such as DA antagonists thus effective in alleviating stuttering Also behavioral training programs: Singing –Why? Singing involves rhythm, rate control, changes in intonation –May allow alternative control of speech

20. adhd Descending motor system plays strong role in ADHD. Pattern of cognitive deficits consistent with prefrontal executive problems: Individuals with ADHD may exhibit –inattention, –difficulty with self regulation –response inhibition deficits (impulsivity) –restlessness or hyperactivity, and even apathy Exist at least two subtypes, according to the DSM-IV – Inattention dimension : associated with significant neuropsychologic impairment – Hyperactive or impulsive dimension: no neuropsychologic impairments. Symptoms appear to be related to too much “ disinhibition ”,

21. ADHD and Brain changes Studies have shown: Children with ADHD have smaller –Total cerebral volume. –Frontal lobe volume –Regions of the basal ganglia, particularly caudate nucleus Studies with typical children show that caudate size decreases as child matures- result of normal “ pruning ” of neurons. In contrast, children with ADHD: –Appear to start out with smaller caudate nuclei, –With maturation the decline is significantly greater than typicals –The size differential of caudate nuclei between ADHD and typical children increases with age. Right hemisphere structures more affected than left hemisphere structures for children with ADHD

22. ADHD Several other related structures appear to be abnormal in children with ADHD. Relative decrease in size of cerebellum Reduction in area of anterior or posterior corpus callosum ADHD may be due to a dysfunction of the prefrontal-subcortical system: –Children with ADHD may have delayed development in their frontostriatal circuits. –These circuits are understimulated, or under utilized –Why do DA agonists (ritalin, adderall) work? Speed up system!