Transcript The visual system

Brain Transplant:
1992 NOVA Documentary
Follow up
List of Methods
Behavioral
Various tests of motor function - pupillary reflex, walking, sitting, standing,
talking, finger touching, balance (from a push), blinking (tap of forehead),
rigidity (movement of wrist or limb)
Nervous system
L-DOPA and other drug treatments (e.g., neuroprotection)
Chemical identification of MPTP
Adrenal tissue to brain transplant
Animal model of PD using MPTP
Nerve graft tissue transplant in monkeys and humans
Dissecting fresh fetal nerve cells from substantia nigra
Stereotaxic surgery –
intracerebral injection of fresh tissue suspension
into caudate and putamen (striatum)
postoperative care (baseball game)
immunosuppression therapy
PET scan of flora-dopa uptake in striatum and
Estimation of percentage of graft secreting dopamine
Follow-up questions
Given that it took George and Juanita two
years to show miraculous recovery, what
was the status of Connie at this time point
following surgery?
Are there any more recent reports of her
progress, or lack thereof?
What is her present condition?
Why didn’t NOVA report on her progress as
promised in the documentary?
JOURNEY OUT OF HOPELESSNESS GREENFIELD
WOMAN THANKS READERS WHOSE DONATIONS
RESTORED HER HUMANITY
from PARKINSN Archives: Sun, 28 May 1995
Langston, the renowned Parkinson's disease
scientist, described the essence of Connie's
improvement this way:
''What makes you human is the ability to interact
with other humans. If you lose that, and Connie
had, you lose the essence of life. It takes away
what makes you a person. Connie is still very
disabled, but she has regained her humanity.
She is no longer a statue in the corner.''
Local news report from 1995, a year after
Connie’s transplant
Writer Jim Trotter at the Mercury News
Two years ago, when I drove down with Langston from the Parkinson's
Institute to visit Connie in Greenfield, the scene was far different.
Sophisticated computer testing indicated that she was still cognitive,
that her brain comprehended, beyond the frozen mask. But even
with the aid of elaborate computer switches, she couldn't
communicate.
Now she is a smiling human being who can walk a bit and respond to
questions. Surgery to reattach her ankle ligaments will greatly
enhance her mobility. But Langston said overcoming language
''ignition failure'' -- the inability to talk spontaneously in expressing
one's thoughts -- will take more time. ''But when that happens, she
will really be back,'' he said.
I could not resist sitting down next to Connie and telling her how much I
admired her courage. She turned her eyes and said, ''Thank
you.'' Don't give up, I said. Painstakingly, but clearly, she
responded. ''I won't.''
Symptoms of PD
1) resting tremor (rhythmic shaking of an extremity),
2) slowness of movement (hypokinesia or
bradykinesia) - movements take much longer to execute
and there is also a general lack of movement (akinesia),
3) cogwheel rigidity (arms and legs become stiff with a
ratchet or jerky quality of movement - almost no other
disease produces this symptom),
4) slow shuffling gait, short steps with the patient bent
or flexed over (very characteristic of PD) and
5) loss of facial expression and lack of spontaneous
blinking which gives the appearance staring.
L-DOPA treatment
Reversed symptoms but the therapeutic window closed as
severe side effects set in – hallucinations, dyskinesia, and
uncontrollable movement
“Parkinson’s disease is not caused by transient
exposure to MPTP”
That is, only f you use
a strict neurobiological
marker as the
criterion.
The similarities in
behavioral changes
suggests strongly that
MPTP exposure
replicates virtually all
the behavioral
symptoms of PD.
Radiolabeled FD uptake in the striatum
Normal
PD
PD – reduced uptake in the
putamen
MPTP – uniform reductions
in both the caudate nucleus
and putamen
Moderate
MPTP
Severe
MPTP
NIH-sponsored placebo controlled trials
Winkler et al, 2005
Figure 1. Functional recovery after neural transplantation in Parkinson’s
disease (PD). Recovery is suggested to occur in two phases: phase one is
characterized by functional changes limited to the striatum, whereas in
phase two changes of cortical activation can also be detected.
Winkler et al, 2005
Figure 2. Allografts of
fetal dopaminergic
neurons are
accompanied by a
delayed immune/
inflammatory
response, which
could affect longterm survival and
functional efficacy
of the transplanted
dopaminergic
neurons.
variability in individual outcomes in the open label
studies suggest that other factors might contribute
to the success of the treatment.
1) preparation and composition of the graft tissue - prolonged
cold storage and use of solid grafts are not as good
2) selection of patients - older patients do not tend to benefit as
much as young patients due to less confined damage and
reduced ability to accept to graft
3) pre-graft medication – low-dose patients tend to benefit more
from graft. In fact, one of the controlled studies with older
patients with no significant group improvement there was a
correlation between the magnitude of the response to dose of Ldopa and the magnitude of the postsurgical improvement.
4) graft placement – grafts only innervate tissue 2-3 mm from the
graft site so benefits will depend on the location of the
placement and whether there is limited damage outside of the
striatum.
The authors conclude that standardized procedures for
selection of patients, graft preparation and
immunosuppresion, combined with tailoring the placement
of grafts may improve the outcome of this promising
therapy for PD.
MPTP exposure initiates long-term neurodegeneration
Practice questions
Where was the fetal tissue taken from and
where was it transplanted to?
Immunosuppresion is important for postsurgical improvement to occur in the first 6
months or after that time.
What was shown to be a misconception
regarding MPTP exposure and why?
What data suggests that MPTP does not
induce PD?
Hubel and Wiesel
Receptive fields of visual neurons
Neurons from all levels of the retinageniculate-striate pathway:
– Receptive fields of foveal area were smaller
than those from the periphery (high-acuity)
– Receptive fields were circular
– Receptive fields were monocular
– Receptive fields had excitatory and inhibitory
areas separated by a circular boundary
“on” firing when light was turned on
“off” firing inhibition when light was on followed by
a burst of activity when it was turned off
Receptive
fields
On-center cell
Off-center cell
Both respond
best to contrast
Lower Layer IV neurons
‘on’ or ‘off’ center-surround receptive
fields.
M-layer projections terminate just above
P-layer projections
Monocular
Simple cortical cells
Neurons from lower layer IV of striate
cortex are exceptions compared to all
other striate neurons, which are
categorized as simple or complex:
Simple cells
– Have “on” and “off” regions
– Are monocular
– Borders of “on” and “off” regions are straight
lines rather than circles (rectangular receptive
fields)
– Respond best when it’s preferred straight
edge is in a particular orientation and position
Complex cortical cells
Are more numerous
Have rectangular receptive fields
Respond best to straight line stimuli in a
specific orientation
Unresponsive to diffuse light
Differ from simple cells in 3 important ways:
1. Larger receptive fields
2. No “on-off” regions – responds best to a straight
edge stimulus of a particular orientation swept
across the receptive field (fires continuously)
3. Many complex cells are binocular (respond to
stimulation of either eye and will respond more
robustly to stimulation of both eyes simultaneously).
Receptive Fields in Striate
Cortex
SIMPLE
Rectangular
“on” and “off” regions,
like cells in layer IV
Orientation and
location sensitive
All are monocular
COMPLEX
Rectangular
Larger receptive fields
Do not have static
“on” and “off” regions
Not location sensitive
Motion sensitive
Many are binocular
Characteristics of complex cells
Respond best to straight-line stimuli
Of a particular orientation
swept across the receptive field
in a particular direction
Receptive fields of binocular complex cells
Occupy corresponding positions within the
visual fields of both eyes
Have the same straight-line orientation
preference
Binocular complex cells
fire more robustly when both eyes are stimulated
simultaneously
respond best when the preferred straight-line
stimulus falls on slightly different positions of the
two retinas – Retinal disparity
respond more robustly to stimulation of one eye
than to the same stimulation of the other eye Ocular dominance
Binocular cell
http://www.physiology.wisc.edu/yin/public/hubel_wiesel_binocular_cell.asf
Mapping the receptive field of a complex
binocular cell in primary visual (striate)
cortex.
Columnar organization of V1
1 right eye
2 right eye
Vertical
electrode
tract
3 right eye
4 right eye
1 right eye
Horizontal
electrode
tract
2 right eye
3 left eye
4 left eye
Hubel & Wiesel’s
model of the columnar
organization of the
primary visual cortex
 Big block of tissue
analyzes signals from one
area of the visual field
 Sub-blocks analyze
signals from the left and
right eyes
 Slices of block prefer
lines in a particular
orientation
Component theory of color vision
 Three kinds of color
receptors (cones)
each with a different
spectral sensitivity
 Color of a particular
stimulus is
determined by the
ratio of activity in the
three kinds of
receptors
Component theory of color vision
The evidence:
 Any color in the visible spectrum can
be matched by mixing together 3
different wavelengths of light in
different proportions.
 3 types of receptors must exist to
match all the colors in the visible
spectrum
Opponent-process theory of color vision
 Two different classes of cells in the visual
system for encoding color
 One class of cells signaled red by
changing its activity in one direction and
green by changing its activity in the
opposite direction
 Another class signaled blue and its
complement, yellow.
Opponent-process theory of color vision
The evidence:
 Complementary colors cannot exist
together (no reddish green or bluish
yellow)
 afterimage of red is green and the
afterimage of blue is yellow
Afterimage demo
Stare at fixation point for
1 minute
X
quickly shift gaze to the
point below
X
Which theory is correct?
The Answer: both (and a third one)
 Cones code color on a purely
component basis (different
photopigments maximally sensitive to
low, medium and high wavelengths of
light)
 Opponent processing of color occurs
at all other levels of the retinageniculate-striate system
Component theory of color vision
Microspectrophotometry - a technique for measuring the
absorption spectrum of the photopigments contained in
a single cone
Confirmed the
existence of 3
different kinds of
cones, each
containing a different
photo-pigment with
different characteristic
absorption spectrums
Retinex theory of color vision
Color is determined by reflectance – the
proportion of light of different wavelengths
a surface reflects
– Reflected light changes based on different
illumination
– The efficiency of light absorbed and reflected
by a surface is constant.
– The visual system compares the light
reflected by adjacent surfaces in at least 3
different wavelength bands.
Reflectance and Color Constancy
Incandescent
Light
A
C
D B F
E
Fluorescent
Light
A
C
G B I
H
A
C B
A
C B
Wavelengths absorbed: A, B & C
Wavelengths reflected: D, E & F
Wavelengths absorbed: A, B & C
Wavelengths reflected: G, H & I
Land (1977) experiment
Subjects adjusted the
intensity of each projector to
produce a pure white light in
a dark room
2. Subjects were then shown
Mondrians (Blue was adjusted to
1.
reflect the same combinations of
wavelengths just judged to be white)
Despite the adjustment, blue
still appeared as blue in the
Mondrian
4. However, when viewed in
isolation in a dark field it
appeared as white
3.
Principles of sensory
system organization
Three different types of sensory cortex:
1. Primary sensory cortex – receives most
of its input from thalamic relays
2. Secondary sensory cortex – receives
most of its input from the primary
sensory cortex of a system
3. Association cortex – receives input from
more than one sensory system
Visual areas of the cortex
Scotoma
Perimetry test
determines the area
of blindness in the
visual field of each
eye. Hemianopsia –
scotoma covering half
the visual field of both
eyes
Karl Lashley’s
scotoma experienced
during a migraine
Two Visual Streams
Two Visual streams: Two theories
‘What’ versus ‘Where’ (Ungerleider &
Mishkin, 1982) – kinds of information
processed
Ventral pathway – perception of what an
object is
Dorsal pathway – perception of where the
object is located
Two Visual streams: Two theories
‘What’ versus ‘How’ (Milner & Goodale,
1993) – the use to which information is
put.
Ventral pathway – conscious perception of
objects
Dorsal pathway – direct behavioral
interactions with objects
Visual agnosia
Gnosis means “to know”
Visual agnosics can see stimuli but do not
know what they are
– Movement agnosia
– Object agnosia
– Color agnosia
– Prosopagnosia (faces)
Prosopagnosia
Can recognize faces as faces but cannot
idenify particular faces, including their own
The farmer and bird watcher
General problem recognizing specific
objects that belong to complex classes of
objects
Due to damage to the fusiform face area
(border between visual occipital and
temporal areas)
FFA