SYMPTOMS AND SIGNS CAUSED BY NEURAL PLASTICITY

1. SYMPTOMS AND SIGNS CAUSED BY NEURAL PLASTICITY

2. Signs and symptoms of disorders • Not everything can be seen on MRI or other imaging techniques • Not everything has positive laboratory tests

3. Neural plasticity play greater role in generating symptoms and signs than previously assumed • Plastic changes are reversible • Treatments without medicine and surgery may alleviate pain and tinnitus

4. Neural plasticity • The brain is far from being a fixed system but it is continuously shaped and re-shaped by what it receives from the outside world. • Sensory systems provide the input that shapes the brain.

5. NEURAL PLASTICITY • Adjust the nervous system to changing demands (based on sensory input) • Compensate for deficits through injury or diseases • Cause symptoms and signs of diseases

6. PROMOTERS OF NEURAL PLASTICITY • Deprivation of sensory input • Overstimulation

7. DEPRIVATION • “Use it or loose it”

8. NEURAL PLASTICITY • NEURAL PLASTICITY IS AN ABILITY OF THE NERVE CELLS TO CHANGE THEIR FUNCTION OR STRUCTURE • THE CHANGES OCCUR WITHOUT DETECTABLE MORPHOLOGIC CHANGES (USING STANDARD CLINICAL METHODS)

9. FUNCTIONAL CHANGES ARE CAUSED BY: • CHANGE IN SYNAPTIC EFFICACY • CHANGE IN NEURAL EXCITABILITY • ELIMINATION OF NERVE CELLS (APOPTOSIS) • CREATION OR ELIMINATION OF CONNECTIONS (AXONS AND DENDRITES)

10. SYMPTOMS AND SIGNS • HYPERACTIVITY • HYPERSENSITIVITY • CHANGE IN NEURAL PROCESSING • CHANGE IN PERCEPTION OF SENSORY INPUT • CHANGE IN MOTOR FUNCTION

11. HYPERACTIVITY • MUSCLE SPASM • TINNITUS • PARESTHESIA (TINGLING) • PAIN

12. Success of treatment supports hypotheses of neural plasticity • Pain can be alleviated by electrical stimulation • Tinnitus can be alleviated by sound stimulation

13. Hyperactivity of the vestibular system • Ménière's disease • Air puffs applied to the inner ear can reverse symptoms

14. HYPERSENSITIVITY • LOWERED THRESHOLD FOR SENSORY STIMULATION • EXAGGERATED REACTION ON SENSORY STIMULI

15. CHANGE IN NEURAL PROCESSING • ALLODYNIA (PAIN FROM INNOCUOUS STIMULATION) • HYPERPATHIA (LOWERED TOLERANCE TO MODERATE PAIN AND PROLONGED PAIN SENSATION) CROSS MODAL INTERACTION

16. MECHANISMS OF NEURAL PLASTICITY • CHANGE IN SYNAPTIC EFFICACY • NEW CONNECTIONS (SPROUTING)

17. UNMASKING OF DORMANT SYNAPSES MAY CAUSE: • INCREASE OF SENSORY RESPONSE AREAS • SPREAD OF MOTOR ACTIVATION (SYNKINESIS) • ACTIVATION OF NEW BRAIN REGIONS MAY (“RE-WIRING”)

18. EXTENSION OF ACTIVATION OF MOTOR AREAS MAY CAUSE SYNKINESIS • FACIAL SYNKINESIS AFTER INJURY TO THE FACIAL NERVE • LATERAL SPREAD OF BLINK REFLEX IN HEMIFACIAL SPASM

19. ACTIVITY DEPENDENT SYNAPTIC PLASTICITY • LONG TERM POTENTIATION (LTP) • LONG TERM DEPRESSION (LTD) • HIGH-FREQUENCY TRAINS ARE EFFECTIVE IN INDUCING LTP (IS THE “NOVEL STIMULATION” OFTEN REFEREED TO IN NEURAL PLASTICITY A HIGH FREQUENCY TRAIN?)

21. ACTIVITY DEPENDENT SYNAPTIC PLASTICITY • ACETYLCHOLINE IS IMPORTANT IN DEVELOPMENT • NICOTINIC ACETYLCHOLINE RECEPTORS MAY MODULATE GLUTAMATE RECEPTORS • MEDIATE LONG TERM CHANGES IN SYNAPTIC EFFICACY • AFFECT MATURATION OF THE NERVOUS SYSTEM

22. ACTIVITY DEPENDENT SYNAPTIC PLASTICITY • SYNCHRONOUS PRE AND POST-SYNAPTIC ACTIVATION PROMOTE NEURAL PLASTICITY • HEBB’S PRINCIPLE: “NEURONS THAT FIRE TOGETHER WIRE TOGETHER”

23. ACTIVITY DEPENDENT SYNAPTIC PLASTICITY • THE TEMPORAL PATTERN OF NEURAL ACTIVITY IS IMPORTANT

24. NEW BRAIN REGIONS MAY BECOME ACTIVATED • DISORDERS OF THE VESTIBULAR SYSTEM • AWARENESS OF HEAD MOVEMENTS • DIZZINESS • NAUSEA AND VOMITING

25. NEW BRAIN REGIONS MAY BECOME ACTIVATED • CHRONIC PAIN • ALLODYNIA • INVOLVEMENT OF THE SYMPATHETIC NERVOUS SYSTEM; RSD*) *) REFLEX SYMPATHETIC DYSTROPHY

26. NEW BRAIN REGIONS MAY BECOME ACTIVATED • ACTIVATION OF NON-SPECIFIC PATHWAYS THROUGH SUBCORTICAL ROUTES • INVOLVEMENT OF THE LIMBIC SYSTEM

27. Severe tinnitus is often associated with affective (mood) disorders • Depression • Phonophobia

28. The amygdala is involved in fear and other mood disorders

29. Symptoms and signs of neuropathic pain • Strong emotional components • Depression • High risk of suicide

30. The amygdala is involved in fear and other mood disorders • Subcortical connections to the amygdala may induce emotional response unconsiously • uncontrollable fear and rage

31. INVOLVEMENT OF LIMBIC SYSTEM STRUCTURES • AFFECTIVE DISORDERS • DEPRESSION IN PAIN AND TINNITUS

32. INVOLVEMENT OF LIMBIC SYSTEM STRUCTURES • EMOTIONAL REACTIONS TO STIMULI THAT NORMALLY DO NOT CAUSE SUCH REACTIONS • EXAMPLES: • CHRONIC PAIN (HYPERPATHIA) • SEVERE TINNITUS (PHONOPHOBIA)

33. Connections from the auditory system to the amygdala • Cortical-cortical connections (the “high route”) • Subcortical connections (the “low route”)

34. How can pain information reach the amygdala? • Through the thalamus • Through routes that are enhanced by expression of neural plasticity (re-routing of information)

35. MAIN CONNECTIONS TO THE AMYGDALA: • THALAMUS (MEDIODORSAL) • PREFRONTAL CORTEX • (VIA MEDIODORSAL THALAMUS) • SEPTAL NUCLEI • PERIAQUEDUCTAL GRAY (PAG) • TEMPORAL ASSOCIATION CORTEX • MOST CONNECTIONS ARE RECIPROCAL

36. The “high route” and the “low route” to the amygdala Auditory cortex Thalamus Connections from the amygdala From: Møller: Sensory Systems, 2002

37. Connections from a sensory system to the amygdala “the high route” From: Møller: Sensory Systems, 2003

38. SLOW CARRIES HIGHLY PROCESSED INFORMATION “SLOW AND ACCURATE” HIGH ROUTE

39. Connections from a sensory system to the amygdala “the low route” From: Møller: Sensory Systems, 2003

40. LOW ROUTE • IS FAST • CARRIES UNPROCESSED INFORMATION • “FAST AND AND DIRTY”

41. Connections from the amygdala From: Møller: Sensory Systems, 2003

42. CONCLUSION • ACTIVATION OF NON-CLASSICAL ASCENDING SENSORY PATHWAYS CAN CAUSE SYMPTOMS AND SIGN OF SEVERAL DISEASES

43. MANY REGIONS OF THE BRAIN ARE CONNECTED Which routes are active? Depends on synaptic efficacy

44. SENSORY INPUT CAUSES ABNORMAL EMOTIONAL REACTIONS • TINNITUS • PHONOPHOBIA AND HYPERACUSIS • DIZZINESS • ALLODYNIA • CHRONIC PAIN • AUTISM

45. INVOLVEMENT OF THE LIMBIC SYSTEM IN HEARING: • UNMASKING OF CONNECTIONS FROM THE CLASSICAL AUDITORY SYSTEM TO COMPONENTS OF THE LIMBIC SYSTEM INVOLVING: • MEDIO-DORSAL MEDIAL GENICULATE BODY • ASSOCIATION CORTICES • AMYGDALOID NUCLEI

46. Classical auditory pathways Non-classical auditory pathways From: Møller: Sensory Systems, 2003

47. ESCAPABLE AND INESCAPABLE FEAR

48. AUTISM • ABNORMAL PERCEPTION OF SENSORY INPUT • MAY BE CAUSED BY ABNORMAL INVOLVEMENT OF THE AMYGDALA

49. AUTISM • Kluver-Bucy wrote in 1939 regarding the effect of bilateral amygdalectomy in monkeys: • “Monkeys are no longer capable of functioning as members of social groups. They cannot recognize the social significance of the exteriorceptive (especially visual, auditory and olfactory) signals that regulate social behavior, or relate then to their own affective states (moods), which regulate approach to or avoidance of other members of the group and are thus the building blocks of social interactions. They avoid other members of the group and seem anxious and insecure”.

50. AUTISM • Similarities with the Klüver-Bucy syndrome