Brain Development, Plasticity and Relationships to Developmental Disorders

1. Brain Development, Plasticity and Relationships to Developmental Disorders

2. Why Brain Plasticity is Important * Developmental Disabilities (Autism, Learning Disorders, Epilepsy, Mental Retardation): Diagnosis, understanding, prognosis, treatment * Normal Development: “Doctor, they say children need special attention for the first 3 years. Why? What should I do?” (Who else are they going to ask?) * Recovery from brain damage: Fetal Alcohol Syndrome; Alcohol-related neurodevelopmental disorder; Cerebral palsy; Perinatal hypoxia, Closed head injury; Stroke * Typical and atypical aging (“What about exercise and the brain?”)

3. I am Your Child “From birth, the brain is rapidly creating connections. By the time she is three, your baby’s brain has formed about 1000 trillion connections--about twice as many as adults have. A baby’s brain is super-dense, and will stay that way throughout the first decade of life. Beginning at about age eleven, a child’s brain gets rid of extra connections, gradually making order out of a thick tangle of "wires." The circuitry it ends up with is more powerful and efficient.”

4. I am Your ChildQ: How does the brain "know" which connections to keep?A: This is where early experience comes into play. When a connection is used repeatedly in the early years, it becomes permanent. In contrast, a connection that is not used at all, or often enough, is unlikely to survive. For example, a child who is rarely spoken to or read to in the early years may have difficulty mastering language skills later on. By the same token, a child who is rarely played with may have difficulty with social adjustment as she grows.

5. Origins of the Critical or Sensitive Period ConceptCharles R. StockardHans SpemannKonrad LorenzGilbert GottliebDavid Hubel & Torsten Wiesel

6. …it becomes evident that the course of embryonic development need not progress in a continuous manner, but may be stopped entirely for a considerable length of time or may be decidedly reduced in rate without necessarily injuring the end result. On the other hand, it is equally well known in a general way, and even more widely believed, that when a developing egg is injured in such a manner as to cause its development to stop, it is usually incapable of resuming development at all…. -Charles R. Stockard, Am. J. Anat., 1921

7. The Critical Period concept arose from embryology:As is well-known, a certain organ arises much earlier or later in the embryo than certain others. When these primary developmental changes are on the verge of taking place or when an important organ is entering its initial stage of rapid proliferation or budding, a serious interruption of the developmental progress often causes decided injuries to this particular organ, while only slight or no ill effects may be suffered by the embryo in general. Such particularly sensitive periods during development I have termed the ‘critical moments.’ -Charles R. Stockard, Am. J. Anat., 1921

8. Spemann & Mangold, 1924

9. Konrad Lorenz (O. Heinroth): Imprinting

10. Critical/Sensitive Periods and the BrainThe Developing Brain Overproduces Synapses

14. How do we resolve synapse loss with brain functional “improvement?”A Framework for Understanding Critical Periods and Lifelong Plasticity: Experience-Expectant and Experience-Dependent Development

15. Experience - Expectant Synapse Addition <- Experience -> High # of Synapses/Neuron Blooming Pruining Blooming Pruning Low Young Old Relative Age

16. Blakemore, Hubel & Wiesel

21. Experienced Eye Columns Deprived Eye Columns

22. Visual Cortex “Simple” Cell

24. “Vertical” “Horizontal”

25. Visual Development Process • What drives early synapse stabilization and loss is neural activity in optic nerve, driving lateral geniculate nucleus and cerebral cortex development. • Early in development, this activity is generated by the retina, even in the absence of visual experience, beginning the process. Vision takes over later. • Other features such as myelin (enhances axonal conduction) are also activity dependent (e.g., eye closure reduces myelination of axons in optic nerve).

26. Critical or Sensitive Periods • Generally Involve Specific Experiences that Occur Very Reliably in Development • “Visual Imprinting” on Mother Bird • Early Sensory System Development (e.g., Vision) • Some Early Aspects of Language Sound Recognition • Apparently some aspects of early social development • NOT, in General, Major Aspects of the Cognitive Development Process

27. Normal Social Development Requires Social Experience • Isolation of macaque monkeys during development impaired later social interactions, mating, and parenting (Harlow) • Rehabilitation (social exposure to young monkeys) is possible; earlier is better (Suomi) • Maternal deprivation early (removal of mother from the troop) affects social development even though infant “adopted” by adolescent or adult females in group (Cameron)

28. These effects of experience upon behavioral development appear to involve changes in the brain--as with sensory system development

29. Two Separate Processes Guide Synapse Formation • During early development, synapses are overproduced and experience selects which survive • During later development and adulthood, experience drives the formation of synapses

31. COMPLEX ENVIRONMENT PARADIGM

34. Rats Reared in Complex Environments Have More Synapses Per Nerve Cell EC=Environmental Complexity; SC=Social Condition; IC=Individual Condition

35. Synaptic Plasticity in the Brains of Rats in Complex Environments • Occurs at any age, at least until very old • There is no critical period for these effects, although they are larger in younger animals: Delaying experience can be detrimental • Other brain tissues also change--not just synapses

36. These Are Probably Not Studies of “Enrichment” • The rats in these studies are deprived of stimulation, relative to their natural environment • No one has studied the brain of an animal given enrichment above the natural level • We know little about enrichment and the brain • NORMAL DEVELOPMENT is important

37. Blood Vessels

39. Astrocytes and Oligodendrocytes also hypertrophy in Complex Environments

40. Conclusions • Critical or sensitive periods characterize relatively basic aspects of sensory and motor development • There are sensitive periods in development of some aspects of language perception • The first 3 years of life are important but not a single critical period after which intervention is ineffective • Development is a lifelong process, but the most important things are most sensitive to input early

41. Fetal Alcohol Syndrome Example of Prenatal Sensitive Period and of Physician’s Behavioral Intervention Applying knowledge of development

42. Characteristic Facial Features of Child with FAS Short Eyelid Opening, Flat Midface, Short Nose, Indistinct Philtrum (depression beneath the nose), Thin Upper Lip, Epicanthal Folds, Low Nasal Bridge, Minor Ear Abnormalities, Short Chin

43. Corpus callosum agenesis in FAS patients Control Thin c.callosum Absent c.callosum (From Mattson et al., 1994)

44. Loss of Purkinje cells in PML of rat exposed to alcohol postnatally

45. IQ distribution for FAS and FAE compared with the normal curve (From Streissguth et al., 1996)

46. Prevalence of Secondary Disabilities across the Life Span

47. History of Mental Health Problems (MHP) by sex, diagnosis and age at interview (n=415)

48. How Much is Too Much? • Outcome of maternal drinking during pregnancy depends on: • stage(s) of fetus development when drinking occurred • peak BAC reached during drinking episode(s) • mother’s individual situation (health and build, nutritional • status, level of alcohol dehydrogenase)

49. Change in Drinking by pregnant women after contact with Seattle Pregnancy and Health Program (From Little et al., 1984)

50. By asking if 1) the individual ever consumes five or more drinks on any occasion, and 2) if she ever feels that she should cut down on drinking, clinicians could detect 92% of the women identified as being at genuine risk by the intervention interview. --Streissguth, 1997