Neuroplasticity: A Paradigm Sea Change Latest Updated File

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Neuroplasticity-A Paradigm Sea Change

Dominick M. Maino, OD, MEd, FAAO, FCOVD-A

Disclosure Statement: Nothing to disclose

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Sea Change Origin
From Shakespeare's The Tempest, 1610:

ARIEL [sings]:

Full fathom five thy father lies;
Of his bones are coral made;
Those are pearls that were his eyes:
Nothing of him that doth fade
But doth suffer a sea-change
Into something rich and strange.

Presenter,
Title,
Contact info

Neuroplasticity-
A Paradigm Sea Change
Professor, Pediatrics/Binocular Vision
Illinois Eye Institute/Illinois College of Optometry

dmaino@ico.edu
http://www.MainosMemos.blogspot.com

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Sea Change Origin
From Shakespeare's The Tempest, 1610:

ARIEL [sings]:

Full fathom five thy father lies;
Of his bones are coral made;
Those are pearls that were his eyes:
Nothing of him that doth fade
But doth suffer a sea-change
Into something rich and strange.

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I. Sea Change
(Meaning)
A radical, and apparently
mystical, change.
It is change of such magnitude that it
alters the way we think and what we do
in a sweeping, far ranging, mind
expanding, mega-behavior
transformative fashion.

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Neuroplasticity
Up until recently….apparently unknown to many within the
professions of optometry and ophthalmology…..

The Brain
A. … is not just a static, soft, round mass, bathed in a fluid and surrounded by a hard case 8
B. … can change its form and resultant function through neuroplasticity

II. The Brain

… is not just a static, soft, round
mass, bathed in a fluid and
surrounded by a hard case

… can change its form and resultant
function through neuroplasticity

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III. Critical/Sensitive Periods

A. A critical period occurs when the individual is
sensitive to environmental influences and stimulation

1. The Precritical period: The initial formation of
neuronal circuits that is not dependent on visual
experience.

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Critical/Sensitive Periods

2. The Critical period: A distinct onset of robust
plasticity in response to the visual experience when
the initially formed circuit can be modified by
experience

3. Closure of the critical period: After the end of
the critical period, the same visual experience no
longer elicits the same degree of plasticity.

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Critical/Sensitive Periods

B. The concept of a critical period does not
imply that neuroplasticity ends after a certain
age.

C. Sensitive period begins and ends
gradually (not abruptly like the critical period)
and provides for maximum sensitivity
to stimuli.

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VI. Neuroplasticity and the Brain
A. Can adult brain neurons actually exhibit
neuroplasticity? The short answer is yes.
B. Resultant changes are noted in not
only functional outcomes but also in brain
anatomy and structure.

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IV. Neuroplasticity and Rehabilitation
Kleim & Jones note that:

A. The Key Principles of Experience-
Dependent Neural Plasticity

1. Use it or lose it

2. Use it and improve it

3. Specificity

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4. Repetition matters

5. Intensity matters

6. Time matters

7. Salience matters

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8. Age matters
9. Transference
10. Interference

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Use it or lose it. If you do not drive specific brain functions,
functional loss will occur.

Use it and improve it. Therapy that drives cortical function
enhances that particular function.

Specificity. The therapy you choose determines the resultant
plasticity and function.

Repetition matters. Plasticity that results in functional change
requires repetition.

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Intensity matters. Induction of plasticity requires the appropriate
amount of intensity.

Time matters. Different forms of plasticity take place at different
times during therapy.

Salience matters. It has to be important to the individual.

Age matters. Plasticity is easier in a younger brain, but is also
possible in an adult brain.

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Transference. Neuroplasticity, and the change in function that
results from one therapy, can augment the attainment of similar
behaviors.

Interference. Plasticity in response to one experience can interfere
with the acquisition of other behaviors.

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B: Examples of Changes in
Function and Structure
1.) Jugglers
2.) Typists

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B: Examples of Changes in Function and
Structure
1.) Jugglers

One study suggested that adults taught how to juggle demonstrated a
significant transient bilateral expansion of gray matter in the mid-
temporal area and the left posterior intraparietal sulcus between baseline brain scan and
follow-up. The findings were specific to training stimulus; individuals
who were
not instructed how to juggle demonstrated no change in gray
matter over the same period. These findings oppose the conventional
understanding that the anatomical structure of the adult brain does not change
over time

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B: Examples of Changes in Function and
Structure

2.) Typists

…long-term bimanual training also increases
gray matter volume in experienced adult typists.
These results suggest that learning not
only affects function, but also structure in
adult brains.

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V. Neuroplasticity and Optometry

A. Evolutionary neuroplasticity

B. Reactive plasticity

C. Adaptational plasticity

D. Reparation plasticity

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A. Evolutionary neuroplasticity

…. is ideally suited for the developmental O.D. who
specializes in vision function as it changes over time,
either with or without intervention.

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B. Reactive plasticity

….. can be thought of as the immediate effect that
initial optometric treatment may have on a system. This can
be reflected in an immediate, but often transient, change in
the individual‘s accommodative system—i.e., when an
uncorrected myope initially puts on his or her new
spectacles.

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V. Neuroplasticity and
Optometry

C. Adaptational plasticity

…. could describe the long-term effects of in-office optometric
vision therapy on disorders of the binocular vision system.

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V. Neuroplasticity and
Optometry

D. Reparation plasticity

…in contrast to adaptational
plasticity, reparation plasticity may
occur during treatment by a low
Vision specialist or an O.D.
Working with those who have
Experienced a traumatic brain
injury (TBI).

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The effects of plasticity can lead to either
positive or negative changes during
development (evolutionary plasticity), after
short-term exposure (reactive plasticity),
after long-term or continuous stimuli
(adaptational plasticity), and during
functional or structural recovery of damaged
neuronal circuits (reparation plasticity).
http://www.citeulike.org/user/jasoneprior/article/2856526

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VI. Management and Treatment of
Disorders of the Visual System and
Neuroplasticity

A. Refractive error development

B. Amblyopia

C. Strabismus

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D. Non-strabismus, non-amblyopic
binocular vision disorders

E. Learning related vision anomalies

F. Vision development/perception disorders

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VI. Management and Treatment of Disorders
of the Visual System and Neuroplasticity

A. Refractive error development
Several recent studies have noted that neuroplasticity may play a
role in refractive error development.

retinal defocus, use of progressive addition lenses,
drug studies (M1-antagonist/2% pirenzepine ) slow myopia
progression demonstrated nearly a 50% reduction in myopia
progression over a two-year period

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VI. Management and Treatment of Disorders of
the Visual System and Neuroplasticity

B. Amblyopia
Scheiman MM, Hertle RW, Beck RW, et al. Randomized trial of treatment of amblyopia in children aged
7 to 17 years. Arch Ophthalmol 2005 Apr;123(4):437-47.
Wallace DK, Chandler DL, Beck RW, et al. Treatment of bilateral refractive amblyopia in children three
to less than 10 years of age. Am J Ophthalmol 2007 Oct;144(4):487-96.
Cotter SA, Edwards AR, Arnold RW, et al. Treatment of strabismic amblyopia with refractive correction.
Am J Ophthalmol 2007 Jun;143(6):1060-3.
Repka MX, Wallace DK, Beck RW, et al. Two-year follow-up of a 6-month randomized trial of atropine
vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2005 Feb;123 (2):149-
57.
Wallace DK, Edwards AR, Cotter SA, et al. A randomized trial to evaluate 2 hours of daily patching for
strabismic and anisometropic amblyopia in children. Ophthalmology 2006 Jun;113(6):904-12.

Treatment of severe amblyopia with weekend atropine: results from 2 randomized clinical trials.
Levodopa/carbidopa in the treatment of amblyopia.

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B. Amblyopia
J Pediatr Ophthalmol Strabismus. 2009 Mar-Apr;46(2):87-90; quiz 91-2. Levodopa/carbidopa in the
treatment of amblyopia. Dadeya S, Vats P, Malik KP.

PURPOSE: To evaluate the role of levodopa/carbidopa in the treatment of amblyopia. METHODS:
Thirty patients with strabismic amblyopia between the ages of 3 and 12 years were part of this double-
blind, randomized study. Patients were divided into two groups. Group A received 0.50 mg + 1.25 mg of
levodopa/carbidopa per kilogram body weight three times daily after meals, with a protein rich drink,
whereas Group B received placebo. Both groups received full-time conventional occlusion until a visual
acuity of 6/6 was achieved or for a maximum of 3 months. RESULTS: The authors observed more than
two lines improvement in visual acuity that was greater in the levodopa group (15 of 15) than in the
placebo group (9 of 15) (P < .005). Furthermore, improvement in visual acuity of more than two lines
was greater in patients younger than 8 years (100%) than in patients older than 8 years of age (60%) (P =
.0026). There was also no significant reversal of the improved visual acuity in up to 6 months of follow-
up. CONCLUSION: Levodopa/carbidopa improves visual acuity in patients with
amblyopia and maintains improved visual acuity, especially in patients
younger than 8 years.

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B. Amblyopia
J Pediatr Ophthalmol Strabismus. 2008 May-Jun;45(3):174-6. The use of levodopa in the treatment of
bilateral amblyopia secondary to uncorrected high hypermetropia. Abrams MS.

The standard treatment of bilateral amblyopia secondary to uncorrected high bilateral hypermetropia has
been spectacles and time. The patient described here failed to show adequate improvement in visual
acuity after 18 months of standard treatment. Visual acuity improved dramatically when the
patient began taking levodopa, dropped precipitously when the medication was
discontinued, and returned quickly to post-treatment levels when levodopa was
restarted. Visual acuity remained stable when the medication was slowly tapered
and discontinued. This report suggests that dopamine may play a role in the pathophysiology of
bilateral amblyopia secondary to uncorrected high bilateral hypermetropia.

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B. Amblyopia

Bottom Line
Amblyopia can be treated at any age
May be able to use neuro-enhancing drugs
as a part of basic amblyopia therapy

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C. Strabismus and non-strabismic, non-amblyopic binocular
vision disorders
Clinical Trial of Treatments for Symptomatic Convergence Insufficiency in Children has
clearly demonstrated the superiority of in-office optometric vision therapy (in conjunction
with home therapy) vs. out-of-office therapy alone. The study concluded that optometric
vision therapy/orthoptics was more effective than pencil push-ups or placebo vision
therapy/orthoptics in reducing symptoms and improving clinical signs of convergence
insufficiency

Long-term effectiveness of treatments for symptomatic convergence insufficiency
in children (Optom Vis Sci. 2009 Sep;86(9):1096-103)
CITT patients improvements lasted a year

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Strabismus. 1999 Sep;7(3):169-74. Convergence insufficiency in
idiopathic Parkinson's disease responsive to levodopa. Racette BA,
Gokden MS, Tychsen LS, Perlmutter JS.

We report a patient with pathologically proven idiopathic Parkinson's
disease (IPD) who developed diplopia secondary to convergence
insufficiency during his motor "off" periods. Diplopia resolved with
onset of motor benefit from levodopa. Neuro-ophthalmologic
examination demonstrated convergence insufficiency during motor
"off" periods that was alleviated after onset of motor benefit from
levodopa. This is the first reported case of convergence insufficiency
in IPD responsive to levodopa.

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Bottom Line

Optometric Vision Therapy is the
most efficacious treatment available
for binocular vision disorders and the
treatment effects are long lasting.
Neuro-enhancing drugs
may assist us as well.

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E/F. Learning related vision
anomalies/ Vision
development/perception disorders

…..research includes an examination of the role vision plays in
reading, the effect of oculomotor, vergence and
accommodative/coherent motion therapy on reading eye movements
and reading speed, the diagnosis and treatment of perceptual
disorders, and the effect of therapy on various learning anomalies.

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E/F. Learning related vision anomalies/
Vision development/perception disorders

magnocellular (MC) deficit in dyslexia
L/M speed-matching ratio predicts reading in children.Chase C, Dougherty RF, Ray N,
Fowler S, Stein J.Optom Vis Sci. 2007 Mar;84(3):229-36.
Effect of attention therapy on reading comprehension. Solan HA, Shelley-Tremblay J,
Ficarra A, Silverman M, Larson S. J Learn Disabil. 2003 Nov-Dec;36(6):556-63.
Is there a common linkage among reading comprehension, visual attention, and
magnocellular processing? Solan HA, Shelley-Tremblay JF, Hansen PC, Larson S.
J Learn Disabil. 2007 May-Jun;40(3):270-8.
Lawton, T. Filtered Text and Direction Discrimination Training Improved Reading
Fluency for Both Dyslexic and Normal Readers. Optom Vis Dev 2008;39 (3):114.
Fischer B, Hartnegg K. Saccade control in dyslexia: Development, deficits, training
and transfer to reading. Optom Vis Dev 2008:39(4):181-190.

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E/F. Learning related vision anomalies/
Vision development/perception disorders

J Learn Disabil. 2003 Nov-Dec;36(6):556-63. Effect of attention therapy on reading
comprehension. Solan HA, Shelley-Tremblay J, Ficarra A, Silverman M, Larson S.

…. At the completion of attention therapy, the mean
standard attention and reading comprehension scores of
the experimental group had improved significantly. The
control group, however, showed no significant
improvement in reading comprehension scores after 12
weeks. Although uncertainties still exist, this investigation
supports the notion that visual attention is malleable and
that attention therapy has a significant effect on reading
comprehension in this often neglected population.

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VII. Vision dysfunction association
with acquired brain injury

A. Exotropia (or high exophoria/CI)

B. Accommodative dysfunction

C. Convergence insufficiency

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D. Decreased blink rate

E. Spatial disorientation

F. Pursuit/saccade dysfunction

G. Unstable ambient vision
(Magnocellular pathway).

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VII. Vision dysfunction association with
acquired brain injury
Current Research/Literature Reviews/Internet Resources

Stelmack JA, Frith T, Van Koevering D, Rinne S, Stelmack TR. Visual function in patients
followed at a Veterans Affairs polytrauma network site: an electronic medical record review.
Optometry. 2009 Aug;80(8):419-24.

RESULTS: Visual symptoms were self-reported by 76% of patients
with polytrauma and 75% of the patients with TBI. Problems with reading
(polytrauma 60% and TBI 50%) and accommodation (polytrauma 30% and
TBI 47%) were frequently found on eye examinations. Spectacles were the
treatment most frequently prescribed (polytrauma 62% and TBI 78%).
CONCLUSIONS: It is important for optometrists to be aware of the high
rates of self-reported symptoms and visual problems in military personnel
returning from deployment to the wars in Iraq and Afghanistan. Post-
traumatic stress disorder and depression may complicate optometric
evaluation and management.

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Avoidance of near tasks
Oculomotor-based reading difficulties
Eye tracking problems
Eye focusing problems
Eyestrain, Diplopia
Dizziness, Vertigo
Vision-derived nausea

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Increased sensitivity to visual motion
Visual inattention and distractibility
Short-term visual memory loss
Difficulty judging distances (relative and absolute
Difficulty with global scanning
Difficulty with personal grooming, especially involving the face
Inability to interact/cope visually in a complex social situation
(e.g., minimal eye contact)
Inability to tolerate complex visual environments (e.g., grocery store
aisles and highly-patterned floors)

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Ciuffreda KJ, Ludlam DP, Kapoor N. Clinical oculomotor training in traumatic brain injury. Optom Vis
Dev 2009;40(1):16-23.

Individuals with traumatic brain injury present with a constellation of
oculomotor dysfunctions and correlated symptoms. Simple and
effective clinical oculomotor-based training procedures will be
presented with respect to the versional, vergence, and
accommodative systems, and their interactions. These therapeutic
procedures can also be applied as needed to individuals with either
low vision, neurological dysfunctions, or general visual skills cases
manifesting similar oculomotor deficits.

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Leslie S. Myopia and accommodative insufficiency associated with
moderate head trauma. Opt Vis Dev 2009;40(1):25-31.

The majority of subjects reviewed had developed a stable degree of
myopia between 1.00 and 2.00 diopters, as well as an abnormally
high lag of accommodation. When their distance and near spatial area
of focus was compared, the majority were focused at an intermediate
area in space, suggesting a loss of control of accommodation in
space.

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VIII. Improving Brain Function and
Neuroplasticity

A. Brain Foods

B. Drugs

C. Exercise

D. Learning new and challenging things

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Neuroplasticity

A. Brain Foods
Jia X, McNeill G, Avenell A. Does taking vitamin, mineral and fatty acid supplements
prevent cognitive decline? A systematic review of randomized controlled trials. J Hum
Nutr Diet 2008 Aug;21(4):317-36.

Henriksen C, Haugholt K, Lindgren M. Improved cognitive development among
preterm infants attributable to early supplementation of human milk with
docosahexaenoic acid and arachidonic acid. Pediatrics 2008 Jun;121(6):1137-45.

Kidd PM. Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings
and structural-functional synergies with cell membrane phospholipids. Altern Med Rev
2007 Sep;12(3):207-27.

Gomez-Pinilla F. Brain foods: the effect of nutrients on brain function.
Neuroscience 2008;9(7)568-78.

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Neuroplasticity

B. Drugs
Maya Vetencourt JF, Sale A, Viegi A, et al. The antidepressant
fluoxetine (PROZAC) restores plasticity in the adult visual cortex.
Science 2008 Apr 18;320 (5874):385-8.
Kasper S, McEwen BS. Neurobiological and clinical effects of the
antidepressant tianeptine. CNS Drugs 2008;22(1):15-26.
Adamcio B, Sargin D, Stradomska A, et al. Erythropoietin enhances
hippocampal long-term potentiation and memory. BMC Biol 2008 Sep
9;6:37.
Chilosi A, Leuzzi V, Battini R, et al. Treatment with L-arginine
improves neuropsychological disorders in a child with creatine
transporter defect. Neurocase 2008;14(2): 151-61.

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Neuroplasticity

C. Exercise

Hunsberger JG et al. Antidepressant actions of the exercise-
regulated gene VGF. Nat Med 2007 Dec 2; 13:1476.

VGF may be a common pathway by which exercise induces
neuroplasticity and growth-factor genes; at least one of these might act
similarly to antidepressants in promoting an adaptive response to stress.
However, the tests used here may be modeling stress-induced
helplessness, not depression. ….exercise seems to induce multiple
interacting genes that enhance neuronal resilience

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Neuroplasticity
D. Learning new and challenging things

What have we (optometry & ophthalmology)
been thinking all these years?

Where did we miss the news
about neuroplasticity?

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IX. Improving Brain Function and Neuroplasticity

Optometric Clinical Applications
Huang JC. Neuroplasticity as a proposed mechanism
for the efficacy of optometric vision therapy and
rehabilitation. J Bev Optom 2009;20(4):96-100

Homologous area adaptation
Compensatory masquerade
Cross-modal reassignment
Map expansion

Equipotentiality
Vicariation

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Homologous area adaptation: a transfer of function
from a damaged brain area to a non-damaged brain area.
May be limited to early stages of human development and
may crowd a new brain area resulting in reduced
functionality of that brain area. (Competition between
spatial & verbal functioning)

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Compensatory masquerade: reorganizing of existing
neuro-pathways to us alternative cognitive strategies to
perform a task.

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Cross-modal reassignment: using new sensory input in
a brain structure deprived of its main input source
(changing processing from visual to tactile stimuli in the
blind)

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Map expansion: increase in brain mass due to
repeated behavior or exposure to stimuli

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Equipotentiality: anatomical areas of the brain can
perform disparate functions

Vicariation: redundant neural systems can operate
under abnormal conditions

This may explain why recovery is noted for many
neurological conditions (degenerative, psychiatric,
developmental, vascular, traumatic)

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Constraint therapy: Use it and improve it

Patching, penalization, “near activities” during
amblyopia therapy

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Optometric Clinical Applications/Optometric Vision Therapy

Kleim & Jones:

Use it or lose it. If you do not drive specific brain functions,
functional loss will occur.
If you want to improve oculomotor brain neuroplastic function &
structure, therapy should be specific for that brain function.
Use it and improve it. Therapy that drives cortical function enhances
that particular function.
If you use therapy to improve oculomotor dysfunction, it should
improve.
Specificity. The therapy you choose determines the resultant
plasticity and function.
You must choose therapy that is appropriate.

61


Kleim & Jones:

Repetition matters. Plasticity that results in functional change
requires repetition.
Do the therapy. Do it again. Do it yet again. No quick fix.
Intensity matters. Induction of plasticity requires the appropriate
amount of intensity.
Intensity means strength, force, concentration, power and passion.
Without these plasticity may not occur. Function may not improve,
Time matters. Different forms of plasticity take place at different
times during therapy.
Do the basics, than the more advanced therapeutic procedures.

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Kleim & Jones:

Salience matters. It has to be important to the individual.
Make the therapy matter to the patient.

Age matters. Plasticity is easier in a younger brain, but is also
possible in an adult brain.
Do not let age determine what therapy options you offer your
patients. Think of Susan Barry, PhD (StereoSue) and her success.
Offer your patients options. Let them choose. Be realistic about
outcomes….have outcome measures built into therapy program

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Kleim & Jones:

Transference. Neuroplasticity, and the change in function
that results from one therapy, can augment the attainment
of similar behaviors.
What you do during oculomotor therapy may affected
vergence therapy outcomes
Interference. Plasticity in response to one experience can
interfere with the acquisition of other behaviors.
Monitor. Evaluate progress. Discuss function in other areas
of your patients‘ life.

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Why pay attention to binocular vision dysfunctions
and neuroplasticity?
December 2009 issue of the Review of Optometry
The Binocular Vision Dysfunction Pandemic
In 2010, almost 170 million individuals will be wearing glasses. In
2010 there will also be up to 93 million amblyopes and 12 and a half
million strabismics. For children under 18 years of age that means
there will be more than 22 and a half million amblyopes and millions
of children with strabismus. A clinical trial to determine the
prevalence of binocular vision dysfunction within the general
population suggested the possibility of up to 56% or 173 million men,
women and children with symptoms associated with a binocular
vision dysfunction, 189 million (61%) with accommodative problems
and 118 million (38%) demonstrating various vergence
anomalies.

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Monroe J Hirsch Research Symposium
Teaching the Brain New Tricks

Petito: Insights into Darkness
Brain plasticity life long changes in the structure of the brain
Sensory substitution replacement of one sensory input by another
Measurement techniques
Voxel based morphometry…measures difference in brain volume
Fluorodeoxyglucose glucose analog. PET scan tells you
distribution and metabolism of brain
Cortical thickness measures
Visual cortex of the blind turns somatic: ―The eye of the tongue‖
Transcranial magnetic stmiulation non-invasive technique to
stimulate cortex

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Petito: Insights into Darkness
Blind Braille readers report tingling in fingers when pressure
phosphenes are applied. Blind feel tingling in tongue
Bind use tongue to perform orientation task, motion perception,
sensory perception. Visual cortex recruited in a variety of sensory
and cognitive tasks. (DM Can we use tongue as a VT tool?)

Dilks: Reorganizations of human adult visual system
When a region of sensory cortex is deprived of its bottom up
input, the deprived region begins to respond to stimuli that
normally activate adjacent cortex.

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Retinotopic map changes for stroke pts. Cortical reorganization in
adults occurs. Perceived objects….elongation in stroke & AMD
What happens to deprived cortex in AMD?
fMRI shows cortical reorganization in adults
Proposed mechanisms..
…Growth of new connections
…Unmasking of pre-existing connections *** this is true
happens within seconds

Bavelier
Action video games

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Bavelier
Action video games. Looked at attention. Gamers can track more
activities
Attention over space (me: peripheral awarenress?): Useful field
of view shrinks with age
Performance not VA related…is related to attention
Action game playing changes spatial resolution…overcoming
crowding in VA assessment (me: amblyopia therapy?)
Temporal resolution of vision Backward masking
change….brain changes
Visual sensitivity (contrast sensitivity) Post action game training
improves CSF

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Action video games correcting optics of the cortex (me this is
actualy OVT)
Games factor
Variable entry leanring….adapt task to skill level
Incremental learning tune task to subject‘s leanring steps
Motivation/arousal
Rewards
Self master/self confidence
Action games factors
Pacing..rate of exposure to info…increasing processing speed
Dynamic display
Rich environment
Rich motor involvement

70


Surgeons may be made to play action games
Pilot training
Amblyopia tx Dennis Levi research

Presenter,
Title,
Contact info

Neuroplasticity-A Paradigm Sea Change
This presentation is available at:
http://www.slideshare.net/DMAINO/neuropla
sticity-a-paradigm-sea-change-2459693
http://www.mainosmemos.blogspot.com/
My FaceBook Page
and
Twitter

Presenter,
Title,
Contact info

Questions About:
Neuroplasticity-
A Paradigm Sea Change?
Professor, Pediatrics/Binocular Vision
Illinois Eye Institute/Illinois College of Optometry

dmaino@ico.edu
http://www.MainosMemos.blogspot.com

73

Thanks to

http://www.covd.org/Home/OVDJournal/OVD401/tabid/263/D
efault.aspx
http://bipolarblast.files.wordpress.com/2009/08/neuro.jpg
http://www.specialcheers.com/images/animated_brain.gif
http://blog.marsdencartoons.com/wp-
content/uploads/2008/10/frankenstein-myspace-lightbeer.gif
http://www.shangralafamilyfun.com/gala-e/calvindream.gif
http://psychiatry.jwatch.org/cgi/content/full/2008/225/1

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