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

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

etiology 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

etiology 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.

treatment 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!

Huntington’s chorea Huntington’s disease Progressive disorder 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

Huntington’s Much more severe symptoms than Parkinson’s disease: Cognitive and emotional deficits In contrast to other movement disorders such as Parkinson’s. 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.

Figure 11.21 Loss of brain tissue in Huntington’s disease Left, a section from a normal brain; right, a section from a person with Huntington’s disease. The enlarged lateral ventricle in the diseased brain is due to loss of neurons.

etiology 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.

Myasthenia gravis 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.

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. 11

Lesch-nyan syndrome Linked to descending motor pathway dysfunction Why? Disconnect between the prefrontal cortex and the basal ganglia 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. 12

https://www.youtube.com/watch?v=1U6LDpF_LFE

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. 14

Language disorders Language disorders may be due to poor regulation by the basal ganglia and related structures. 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 15

Language disorders 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. Lexical (word) and declarative memory (memory for facts/basic knowledge) not affected because these behaviors depend on other brain structures 16

Speech apraxia 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.

stuttering Strong link between stuttering and basal ganglia dysfunction. Due to impaired ability of the basal ganglia to produce timing cues for the initiation of the next motor segment in speech. Pharmacologic interventions such as DA antagonists are effective! Also behavioral training programs: Singing Why? Singing involves rhythm, rate control, changes in intonation May allow alternative control of speech

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 Inattention dimension Hyperactive or impulsive dimension Symptoms appear to be related to too much “disinhibition”,

distonia Movement disorder resulting from basal ganglia dysfunction 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. 20

distonia 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. 21

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. 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. 22

Tourette’s syndrome Tourette syndrome (TS) characterized by Treatment: 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 23

Bottom line: Motor system involves delicate balance of many parts of brain, from parietal lobe down through basal ganglia, cerebellum, and even frontal lobe When this delicate balance is upset, many different deficits and differences result Good news: We understand this system and have an arsenal of treatment available for most disorders