This document summarizes disorders of the sensory systems. It discusses reduced and increased sensitivity disorders as well as normal responses that are redirected. It describes the organization and processing of sensory information from the sensory organs through the central nervous system. Specific examples of disorders are given, such as hearing loss, tinnitus, and neuropathic pain. The involvement of non-classical ascending pathways and structures like the amygdala in generating symptoms is discussed. Potential treatments aimed at reversing neural plasticity, like TENS and sound stimulation, are also mentioned.

1. SENSORY SYSTEMS

2. Disorders of sensory systems
• Deficits
–Sensory organ
–Sensory nerves
–Central nervous system
• Hyperactivity
–Central neuropathic pain
–Tinnitus
–Tingling
• Normal response that is redirected
–Pain from touch
–Dizziness and vertigo from head
movements

3. Disorders of sensory systems
• Reduced sensitivity
–Hearing loss
–Visual impairment
• Incorrect response
–Hyperacusis
–Distorted sounds
–Allodynia
–Hyperpathia

4. Disorders of sensory systems
• Impaired conduction of the physical
stimulus to the receptors
• Impaired function of receptors
• Impaired function of sensory nerves
• Impaired or changed function of the
central nervous system

5. Reduced sensitivity
• Often caused by disorders of the sense
organs
• Injury to afferent nerves

6. Hyperactive sensory disorders
• Increased sensation of physical stimuli
• Altered sensation of physical stimuli
• Sensation without any physical stimulation

7. General organization of
sensory systems
• Conduction of the physical
stimulus to the receptors
• Sensory receptors
• Sensory nerves
• Central nervous system

8. Sensory transduction
• A physical stimulus generates a receptor
potential
• The receptor potential is a graded
potential
• The receptor potential is conducted
electrotonically to the spike generation site

9. Bipolar receptor cells (taste)

10. Initiation of nerve impulses
• Occurs at the first node of Ranvier

11. Two different types of receptors, with bipolar nerve fibers

12. Sensory transduction (mechanoreceptor in a muscle)

13. Central nervous system

14. HUMAN
Mouse
Chick

15. Cochlea
Reticular
formation
Cochlear
nucleus
MGB
Primary
auditory cortex
Midline
Inferior
colliculus
Ventral
thalamus
AN LL
Auditory nervous system
Ascending auditory pathways
From: Møller, 2005

16. Two different ascending sensory
pathways have been identified:
• The classical systems
• The non-classical systems

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

18. Non-classical auditory
pathways
Receive input from the
somatosensory system
Use the dorsal part of the
MGB
From: Møller, 2005

19. The classical ascending pathways
• The number of nuclei is different in
different sensory systems
• Use ventral thalamic nuclei that project to
primary sensory cortices
• Neurons processes only input from of one
sensory modality

20. Midline
LGN
Primary
visual cortex
LGN
Primary
visual cortex
Thalamus
Retinal
ganglion cells
Retinal
ganglion cells
SCN and
hypothalamus
Pretectal
nucleus
Superior
colliculus
External
eye muscles
Thalamus
Thalamus
Pulvinar
Light
reflexes
Other regions
of the CNS
Extrastriate
cortex
A B
From: Møller, 2005
Visual system
Classical ascending pathways Non-classical ascending pathways

21. The nonclassical pathways
• Use dorsal and medial thalamic nuclei that
project to secondary cortices and to other
parts of the CNS
• Receive input from more than one sense

22. Fig 3.3
Reticular formation
Thalamus
ventral
Limbic system Association cortex
Anterior
lateral tract
Medial
lemniscus
Thalamus
dorsal
SII
AROUSAL
"WHERE""WHAT"
Pain pathways
cortexSI
Somatosensory pathways
Classical pathways Non-classical pathways
From: Møller, 2005

23. Trigeminal
ganglion
Thalamus
Cerebral
cortex
Motor
nuclei
RF
Brainstem
Midbrain
Spinalcord

24. Processing after primary sensory
cortices
• Integration of input from different sensory
systems occurs in association cortices
• Parallel processing
• Stream segregation

25. The
neocortex
has six
layers

26. Simplified
diagram of the
connections to
and from the
different layers
of the cerebral
cortex
From: Møller: Sensory Systems, 2002

27. Maps
Tonotopic
Somatotopic

28. SURFACE VIEW

29. LOWER
BODY IS
REPRE-
SENTED
NEAR THE
MIDLINE

30. Tonotopic organization in the CN of a cat, as an
example of tonotopic organization in the auditory
system

32. Tonotopic organization in
the CN of a cat, as an
example of tonotopic
organization in the auditory
system

33. Parallel processing
Stream segregation

34. Parallel processing:
Cochlear nucleus

35. Function of sensory nervous
systems
• Processing of sensory input at the
peripheral level
– Convergence (spatial integration)
– Interplay between inhibition and excitation

36. Spatial integration:
Receptive field of a
dorsal column nucleus cell

37. Convergence of input to a secondary neuron

38. Lateral inhibition

39. Central processing of sensory
information
• Each stage enhances or suppress specific
Information

40. Parallel processing:
The same information is
processed in different structures
Stream segregation:
Different kinds of information is
processed in different structures
(“What” and “Where”)

41. Processing after primary sensory
cortices
• Integration of input from different sensory
systems occurs in association cortices

42. From: Møller: Sensory Systems, 2003
Stream segregation Cortical circuitry
Dorsal stream
“where”
Ventral stream
“what”

43. Sensory information can reach
other regions than sensory
regions
Motor systems
Memory
Emotional brain (limbic system)

44. Dorsal
medial
MGB
AII
Ventral
MGB
Thalamus
AAF
Endocrine
Behavioral
Autonomic
AI
ICX
DC
ICC
Amygdala
Association
cortices
AL ABL ACE
Nucleus
basalis
Arousal
and
plasticity
Cortex
"High Route"
"Low Route"
Polymodal
association
cortex
Other cortical
areas
From: Møller, 2005
Two different
routes to the
Amygdala from a
sensory system

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

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

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

48. Hypoactive sensory disorders
• Loss of sensitivity
– Hearing loss
– Poor vision
– Numbness
– Loss of vestibular (balance) function

49. Frequency in kHz
0
0.250.125 0.5 0.75 1 1.5 3 4 6 82
10
-10
20
30
40
50
60
70
80
90
100
110

50. HEARINGLEV
NOISE IMMISSION LEVEL

51. Courtesy of M. Charles Liberman
Genetic, epigenetic and environmental
Causes (and a stochastic component ?)

52. Age-related
hearing loss

53. 0
10
Left Ear
4000 Hz. Women
Right Ear
20
30
40
50
60
70
80
90
100
0-9 20-29 40-49 60-69 80-89
10-19 30-39 50-59 70-79 90-99 dB
Number
0
10
Left Ear
4000 Hz. Men
Right Ear
20
30
40
50
60
70
80
90
100
0-9 20-29 40-49 60-69 80-89
10-19 30-39 50-59 70-79 90-99 dB
Number
Normal variations in hearing loss of
70 year old individuals

54. 0
N=179
Men 70 years old
25
50
75
100
 92% 76-88% <76% <48% deaf
%
0
N=197
Women 70 years old
25
50
75
100
 92% 76-88% <76% <48% deaf
%
Left Ear
Right Ear
Left Ear
Right Ear
Variations in speech discrimination in
70 year old individuals

55. 0
10
-10
20
30
40
50
60
70
80
90
100
110
Frequency in kHz
0.250.125 0.5 0.75 1 1.5 3 4 6 82
Hearing loss in Ménière's disease

56. I: Pre-op Discr.=96% AS
II: 5 days post-op Discr.=0% AS
II
I
Frequency in kHz
0
0.250.125 0.5 0.75 1 1.5 3 4 6 82
10
-10
20
30
40
50
60
70
80
90
100
110
I: Pre-op Discr.=80% AS
II: 7 days post-op Discr.=30% AS
II
I
B
A
Frequency in kHz
0
0.250.125 0.5 0.75 1 1.5 3 4 6 82
10
-10
20
30
40
50
60
70
80
90
100
110
Effect of surgical injuries
to the auditory nerve:
Large decrease in speech
discrimination

57. Hyperactive sensory disorders
• Tinnitus
• Paresthesia
• Phosphenes
• Phantom sensations
• Central neuropathic pain

58. Subjective and objective tinnitus
• Different forms of tinnitus have very
different effects on an individual’s life

59. Similarities between chronic
pain and severe tinnitus

60. There are many forms of tinnitus
• Mild tinnitus:
Does not interfere noticeably with everyday life
• Moderate tinnitus:
May cause some annoyance and may be
perceived as unpleasant
• Severe tinnitus:
Affects a person’s entire life in major ways
Patients’ own perception varies between mild,
moderate and severe (disabling)

61. Important to have words for
disorders
• We cannot think about matters that do not
have names
• The same words is used to describe very
different forms of tinnitus and pain
• Using the same names for fundamentally
different disorders is a disadvantage in
treating these disorders

62. How prevalent is severe
tinnitus?
Some statistics show 50 million people
have tinnitus in the USA
The prevalence of severe (bothersome)
tinnitus is infrequent at young age; it
reaches 12-14% for people at age 65
according to one study

63. How prevalent is severe
pain?
Some pain was reported by 86% of
individuals above the age of 65
(Iowa study, 1994)
The prevalence of severe pain was 33%
for people at age 77 and above (Swedish
study, 1996)

64. Severe tinnitus affects a
person’s entire life in major
ways
• Prevents or disturbs sleep
• Interferes with or prevents
Intellectual work
• Often accompanied by altered
perception of sound

65. Severe pain affects a person’s
entire life in major ways
• Prevent or disturb sleep
• Interfere with or prevents intellectual work
• May cause suicide
May involve limbic structures causing
affective reactions
Often accompanied by abnormal sensations
from touch

66. Severe tinnitus is often
accompanied by altered
perception of sound
• Sounds are distorted
• Sounds have exaggerated loudness
(hyperacusis)
• Sounds are unpleasant
• Sounds are painful and arouse fear
(phonophobia)

67. Little is known about the cause
of subjective tinnitus
• Noise exposure
• Ototoxic antibiotic
• Acoustic tumors

68. The sympathetic nervous
system is involved in some
forms of severe tinnitus
Some forms of tinnitus
can be cured by sympathectomy

69. Deprivation of sound can cause
changes in neural processing such
as change in temporal integration
• Expression of neural plasticity

70. The anatomical location of the
abnormality that cause chronic pain
and tinnitus may be different from
that to which the pain or the tinnitus
is referred

71. The abnormal neural activity that
causes symptoms are not
generated at the location where
the symptoms are felt
Examples:
• Phantom pain
• Tinnitus with severed auditory nerve

72. The tinnitus in some patients can
be modulated by stimulation of
the somatosensory systems
(such as by electrical stimulation
of the median nerve)
“cross-modal” interaction

73. Non-classical auditory
pathways
Receive input from the
somatosensory system
Use the dorsal part of the
MGB
From: Møller, 2005

74. Other signs of involvement of the
somatosensory system
•Gaze related tinnitus
•Neck muscles and tinnitus
•TMJ and tinnitus
•Sensation of sound from touching the skin

75. Connections between spinal
C2 segment and the dorsal
cochlear nucleus
Can explain why electrical
stimulation of the skin behind the
ears can modulate tinnitus

76. Symptoms and signs of
neuropathic pain
and severe tinnitus
• Strong emotional components
• Depression
• High risk of suicide

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

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

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

80. Fig 3.7
Dorsal
medial
MGB
AII
Ventral
MGB
Thalamus
AAF
Endocrine
Behavioral
Autonomic
AI
ICX
DC
ICC
Amygdala
Association
cortices
AL ABL ACE
Nucleus
basalis
Arousal
and
plasticity
Cortex
"High Route"
"Low Route"
Polymodal
association
cortex
Other cortical
areas
From: Møller, 2005

81. CONCLUSION
ACTIVATION OF NON-CLASSICAL
ASCENDING SENSORY PATHWAYS
CAN CAUSE SYMPTOMS AND SIGNS
OF SEVERAL DISEASES

82. 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

83. Therapy
There is no treatment for tinnitus that is
comparative to common pharmacological
treatment of pain. Treatment of tinnitus has
been mainly benzodiazepines (GABAA agonists)

84. Reversal of neural plasticity
• “TENS” (transderm electric nerve
stimulation) has been used for many years
in treatment of chronic pain
• Recently sound stimulation in various
forms have been introduced in treatment
of severe tinnitus

85. Stimulation of somatosensory
system can relieve tinnitus
• Electrical stimulation
– of the ear and
– of the skin behind the ears have been used
to treat tinnitus
• Electrical stimulation of the auditory
cortex is in a stage of development
• Few systematic studies of efficacy have
been published