lecture 12 - MAP PLASTICITY AND PATHOLOGIES Flashcards
(32 cards)
fMRI – functional Magnetic Resonance
Imaging
Endogenous Contrast Mechanisms = BOLD CONTRAST
Brain: 2% body weight,
25% body glucose use
flow - arterioles |capillary bed | venues - ‘rest’
Increased flow –
arterioles| capillary bed | venules
‘active’
*Increased local flow
*Increase : ratio
*Increased MR signal
the reason we can use this to map the brain is the fact that the brain doesnt have a functional reserve - your muscles can go from aerobic to anaerobic metabolism and can rely upon stores and this doesnt happen in the brain which is why strokes are so devastating so you need a system that can get oxygenated blood exactly where it needs to go for normal function this is why we have a very sensitive spatial network where you only deliver oxygenated blood to areas that really need it. the major energy deficit within the brain is going to happen during info processing or action potentials being fired. we are always dealing with a relative change as the brains never really at rest as there will be a relative increase, a change in ratio between oxygenated and deoxygenated blood and that subtly changes our MR signal and allows to say that particular area is active when the person is doing X.
its a topographical imaging modality
MEG
diagram in notes
it directly records the neurones
only sensitive to cortex
used in a lot of investigations into how the maps might change
GOOD’ PLASTICITY: REPRESENTATION OF
FINGERS IN THE SOMATOSENSORY
CORTEX OF STRINGED INSTRUMENT
MUSICIANS
Thomas Elbert and colleague relied upon the fact that there are highly trained people in the population already and compare them to neurotypicals
they took stringed instrument players - when playing the violin there is a lot of co-activation Both temporally and spatially between certain fingers a lot more on average than someone thats not playing an instrument, a neurotypical within the population
elbert wanted to look at the representations of the fingers within the somatosensory cortex of humans using MEG - do this by putting someone in an MEG give them lots of taps to one finger, lots of taps to another one and you localise that in space. they were comparing the size of the responses from these fingers compared to the ptps other side which would not have been used in the same manner as your bowing if you not fretting a stringed instrument.
there is a great difference between their controls and their string players. there is also a weak linear correlation with the size of the response/ the mass of neurones responding picked up by MEG in the string players when they actually started musical practice. suggests adult plasticity and an evolving process of plasticity aswell. if you start early you have a massive finger within your somatosensory cortex because you have been using it a lot.
there is a group difference aswell
its a nice early study showing evidence for adult plasticity also showing you dont have to do extreme manipulates to get these effects
its changing the map - so what does that mean for using the map for things that dont involve playing a stringed instrument. is that problematic, is there ‘bad’ plasticity?
phantom limbs
first described by French surgeon Ambrose barre in the 16th century but most info in modern times is from American civil war surgeon Silas wier Mitchell in the 19th century - then if you have a leg taken off in the battlefield used to die of blood loss, shock or septicaemia etc a lot more people lived on after American civil war so there was a big population of amputees and a lot went to their doctors and saying they could feel it was still there - a Lot of people were dismissed and there was an idea it was a manifestion of grief as it was before psychoanalytical theory but Mitchell took it seriously enough but didn’t make a scientific paper on it he wrote a scientific monologue a fictionalised account called the case of George dedlow and popularised the idea of phantom limbs with the public and with the medical profession in the west aswell.
this is a phenomenon that persists into the 21st century - its not just a perceptual phenomena - 70-80% with a traumatic limb amputation have phantom limb and phantom limb pain
phantom limb pain is a problem as its not something that in a significant percentage of people that you can treat with using normal analgesics - so its seems to be essentially a central phenomena rather than a peripheral one or it may be driven by things centrally and might be modulated peripherally
people with phantom limb pain report very stereotypical pattens of pain. if have a upper limb amputation most patients commonly have feeling of pain in the elbow thats not there anymore. like the phantom hand is digging into the palm to the point almost of causing tissue damage. in the Lower limbs you may feel like its being squashed like a steamroller, feel as if you have red hot pokers going through it. basically something thats not there is essentially being damaged by something thats also not there. central representations are being activated
there is no map of pain in S1 we have a map of pain touching discrimination, we have a medial amniscal system that gives us a map of the skin surface. theres pain receptors in there aswelll but theres a lot of controversy about whether or not we have a somatic topical map of pain in the same way we have a somatic topical map of the body. but the idea you could feel something that was to there spurred on some neurologists to try and investigate this further using similar techniques that had been done in non-human primates
Representation of fingers on
cheek and stump of a right
limb amputee. (From Ramachandran, 2000)
image in notes
he investigated a population of patients were he was able to elicit sensations in the phantom, if he stroked on the side of the face, theres also one of the shoulder. the numbers in the diagram refer to the digits. this happens as the head and shoulder used to be innervated by the afferent fibres coming back from the hand. suggests there had been some kind of reorganisation within the map reflecting this peripheral pathology.
These points on the body
surface yield referred sensations
in the phantom hand.
“My phantom hand sometimes
itches like crazy… But now, I
know exactly where to scratch”
–”Tom”
does this mean if you take away the hand in humans you dont get a hand silent zone in S1 and what you get if you touch the areas next on the map is an activation.
so he used the MEG and mapped the patients reference points on the intact side ge the face and upper arm and hand and then you can map those areas on the side of the amputation so you look for a mirror image as you have 2 S1s
the green and red areas have moved in the image medially towards the middle and the blue has moved laterally. if you take away the middle digit the area that was responding to the middle digit is now equally activated by touching digit four and digit two so there is perceptual remapping but it doesnt tell us a lot about pain
iS PERCEPTUAL REMAPPING THE
WHOLE STORY?
Are the sensations stable?
In some cases, yes, others, change over time. Not certain if remapping follows fine-grained
perceptual change.
Are the sensations modality-specific?
Again – variable over time and between patients.
is there a relationship between PLP – phantom limb pain – and the
remapping in S1? dont know yet but if the remapping has anything to do with the pain maybe if we change the mapping, we can change the pain
PLP AND CORTICAL REMAPPING - Flor et al., 1995
she saw 100 ex German soldiers who had had upper limb amputations - a large and stable population
SIGNIFICANT correlation exists between the EXTENT of remapping and the
INTENSITY of phantom limb pain (PLP)
image of brain from top - flor stimulated digit 2, digit 5 and the mouth on the intact size and she would just look at the mouth on the lesion side - all of her Analysis was on what is the difference between the representation of the mouth and the face on the side thats had the amputation and on the side that hasn’t
found theres a medial shift of the mouth representation - its significantly different and has moved towards where we would expect the hand to be - and that correlates with the amount of subjective pain felt by people
within subject study = good
there is noise as the two S1s dont look exactly the same but this is all relative - about relative shifts in maps. how do we know how stable that is, so one of hertz colleagues Stefan Knecht investigated how those sensations changed over time
knect et al
in the graphs we have bizarrely bilateral points which elicit this sensation
our map within S1 only represents the skin surface on one side, so even though S1 may be our thermometer of what’s going on our insight will see other changes aswelll
the map doesn’t stay solid either and nor does the skin surface over which is felt
a lot of amputees undergo a process called telescoping so right after their amputation the phantom arm feels like its basically occupying the same space as where the arm was. over time this disappears and you end up with the sensation of a hand sitting on a stump and the size of that skin surface also changes overtime so the feeling of where they localise these points on the phantom arm itself is something that changes aswell but knect was still interested to what extent the amount of miss localisations in these areas correlated with the different sensations - by putting points on the skin and asking where they felt it was it on the hand or was it on the skin itself - sometimes would use light touch, a tuning fork for vibration, a light thermal painful stimulus . its only pain that appears to be correlated with those aspects. is it only in phantom limb pain that this happens
Remapping in Other Disorders?- DYSTONIA
Meunier et al., 2001
Dystonia is caused by the CO-CONTRACTION of agonist and antagonist muscles - spasms and can’t move
many different forms eg genetic
can have torsoninal dystonia where all of your core muscles contact at once so its very difficult to do anything
thought also to be driven by problems in the periphery not centrally
to study - task related or experience related dystonia is most useful - these are very subtle eg writers cramp , and to musicians where they can no longer play their instruments but its not a muscular issues as if you do normal EMGs and test all the muscles involved in the synergy the musicians would use they are fine but if you ask them to sit down and play the piano or get mouth ready to play the trumpet then you get dystonia so its a very specific synergy that perhaps overlearned
plasticity - you may get tipped over into a state where the normal state of things is the brain treats those areas as joined not just at a somatosensory level but a muscular level and there is no longer the ability to move one and not the other and maybe thats the case for the agonist and antagonist muscles aswell
dystonia - what do things look like centrally?
easier to study as all of the skin surfaces are still intact and you can compare the dystonic to the non-dystonic hand
meunier et al 2001
most people studied suffered from writers cramp - a lot of these people had been secretaries for a lot of their life and were very fast at typing so the amount of experience and synergies between certain muscles was pretty extreme and their ability to write and type after this was severely effected - for a lot of them it was only in one side and not the other
on the normal site - in the image in notes - the different colours are representations within the somatosensory cortex of just tapping on the normal side and localising to make a response so you get a nice map
going down you have
- red = D5
- Blue = D4
- green = D3
- yellow = D2
but on the dystonic side its all mixed up and they are sitting on top of each other - either they have been joined toegther or something completely different
good as within ptp study so have an idea of what map should look like so you can track novel rehabilitations to see if the map is getting back to what we’d expect then we hope function would follow as well - quite often the metrics change first before you see behavioural changes
map changes track rehabilitation
meunier et al
in healthy subject - normal somatotopic order of finger representation
untreated WC (writers cramp) - disorganised somatotopic order of finger representation
rehabilitated WC - ‘supernormal’ - somatotopic order of finger representation - map knows representations should not be joined together they all should be completely seperate
what we know about map and plasticity allows us to create new ways to sort it out especially in cases like PLP and dystonia which are difficult to treat with pharmacological means
‘Mirror Box’ Therapy for Phantom Limb Pain…
ramachandran
* Patient concentrates on
VISUAL IMAGE of ‘lost limb’
* In some patients this
MODULATES Phantom
Limb Pain (PLP)
it works on a small percentage of people with PLP not sure why but its very cheap
you have a box with a mirror on one side and there are holes for you to put your arms through. if your an amputee you put your intact arm in one side and look at the reflection of the arm and try to position your phantom in the same position in space where the reflection is. if you move the intact arm in a lot of people you get movement of the phantom and the more you do this overtime it can help with some aspects of phantom limb pain eg after a few sessions can relieve the pain of sensation of those fingers digging in
this is another level of plasticity - spatial configuration of the body
proprioception
just as we have maps for extero receptors that are receiving info from the outside world we also have intero receptor Maps as well giving you back info from the relative size of stretch on your muscles, the angles of your joints, the stretch on your tendons as well and all of these things can be put together to give you a sense of where you are in space - its adjusts your position eg making sure you dont fall over
even though the system is implicit it is devastating to lose it
Ian Waterman – Patient
‘IW’
- Lost FINE TOUCH and
PROPRIOCEPTION due to
autoimmune response at age 19 - Has NO ‘body sense’ or
‘position sense’ when eyes are
closed - Yet somehow managed to regain
the ability to walk and use limbs
again. - using visual feedback - PLASTICITY? Is the ‘body image’
plastic…? - he can still control his muscles but he doesn’t get feedback from it unless he’s looking at them
- normally in these cases of neuropathy can’t move and just are a bowl of jelly in a wheelchair
THE ‘BODY SCHEMA
Concept introduced into clinical neurology at the beginning of last
century (e.g. Wernicke, 1900). Heavily dependent on Helmholtz’s
ideas of ‘unconscious inference’.
- Subsequently developed by Head and Holmes (1911). They
postulated that the spatial perception of one’s body is updated
‘on-line’ by successive changes in position.
‘By means of perpetual alterations in position we are
always building up a postural model of ourselves
which constantly changes. Every new posture
or
movement is recorded on this plastic schema, and
the activity of the cortex brings every fresh group of
sensations evoked by altered posture into relation
with it..[…]anything which participates in the
conscious movement of our bodies is added to the
model of ourselves and becomes part of those
schemata:
Head and Holmes, 1911
it talks about every movement changing the position of the body in space and also this idea of a body schema the idea of where the body is in space can be influenced by vision, by feedback from the muscles, from the skin but also from the Brain deciding where it wants to go -very important
NEUROBIOLOGICAL INFLUENCES
What are the neurobiological mechanisms underlying the
conscious perception of the body?
i. bottom-up, stimulus-driven influences and
ii. top-down, modulatory influences originating within the nervous system
- ‘Top-down’ influences need not solely originate from areas traditionally
viewed as ‘sensory‘ or ‘cognitive’ areas i.e. ‘efference copy’ (von
Helmholtz,1886). Thus
both afferent sensory information and influences
from the motor system can influence the sensory experience of one’s
body. influence by both knowing where the head is in space and the relative positions of visual space with respect to the rest of the body and influenced by almost where the body has been, where it is now and where it wants to go - the ideas of afference and efference copy (the predicted sensory info of the movement) are important for that - This information can take a number of different forms (Jeannerod, 1990):
for example, the initial spatial configuration of the body before
movement, the predicted goal of the movement, the sensory information
generated by the movement (
reafference), or the
predicted sensory
information (efference copy) of the movement.
early neurology of afference and efference copy - neurobiological substrates
.
Wolpert and Kuwato, 2000
Different ‘states’ of the motor system
Graziano and
Gross, 1998
An example of the
convergence of sensory
information in
‘multimodal’ cortical areas
did a lot of micro electrode mapping in the areas of the brain that are kind of inbetwen the parietal and visual cortex - so they get influences from position son the body, vision etc lots and lots of things coming together - trying to see if theres a master map - one ultimate place where everything would come together (does not seem to be case) SO should think about different states of a system which the brain being able to weigh influence more in some cases rather than others as the brain is a generative system, a bayesian system so thinks about not only what’s happening but evidence before aswell
can uncover this by doing a simple perceptual illusion
images in notes
WHAT HAPPENS WHEN
INFORMATION FROM
DIFFERENT MODALITIES
CONFLICTS?
The rubber hand illusion (Botvinick & Cohen, 1998)
need a willing ptp, an arm like object, a couple of paintbrushes and you set it up so the person can’t see their real arm anymore and put fake arm in position close to it and stroke fake and real arm at same time
* Visual information comes from the rubber hand –
Proprioception comes from the real hand.
* Visual and tactile input is synchronized
after 10 mins of exposure - more detail in notes
people feel as if the fake arm is there or feel as if the touch is coming from that location or feel as if the feeling on their hand they can’t see if cause by the paintbrush stroking the fake arm - happens in 20 to 30s of stroking
it uncovers the changing synchronous input to S1 and some of the computational principles of the tactile map. it uncovers some of the computations of the how the brain weighs relative evidence from different sense to work out where we are in space - works out how likely it is that I would see that thing being touched and it feels like my arm - theres a mismatch between what proprioception and vision and touch is telling the brain and its in perfect synchrony and it wins the race of where your arm is in space
CONSTRAINT SATISFACTION
Tactile input from
this location
Visual input from
this location
Localization discrepancy is mediated by position sense. To
resolve the discrepancy, is position sense distorted?
RUBBER HAND EXPERIMENT 2:
30 MINUTE EXPOSURE.
INDICATE THE LOCATION OF THE LEFT
HAND WITH THE RIGHT (BELOW THE
TABLE)
For those who
experienced the illusion
more consistently, there
was a localization bias
towards the rubber hand.
TO WHAT DEGREE IS THE RUBBER HAND
INCORPORATED INTO THE BODY SCHEMA?
Ehrsson et al., 2007 induced the
rubber hand illusion while in an
MRI scanner
* “Occasionally made brisk
stabbing movements with a
sharp needle toward the rubber
hand”
* Subjects reported feelings of
both ownership of the rubber
hand, and anxiety when it was
threatened
found - Pre-supplementary motor area (area that is preparing plans to move your Hand if it feels its threatened) was activated
when the real hand was threatened, and when
the rubber hand was threatened in the
synchronous brushing condition. it was not active at all if it was just a stabbing motion towards the rubber hand if they had not gone through the ownership illusion.
Threats to a rubber hand you feel is your own
elicits a response in preSMA similar to if it
were your own hand.
During asynchronous brushing, threatening the
rubber hand did not activate pre-SMA.
Activity in the insula and anterior
cingulate cortex (ACC, associated with
anxiety) and was correlated with the
degree to which individuals
experienced the illusion of ownership
…BUT HOW DO MAPS KNOW TO STAY
IN EITHER THEIR ’GOOD’ OR ‘BAD’
CONFIGURATIONS? TUNE IN
NEXT…TIME.
anatomy of the skin and its receptive organs
skin - complex and vital organ
can’t survive without it
Our cells, which must be bathed by a warm fluid, are protected from the hostile environment by the skin’s outer layers. Theskin participates in thermoregulation by producing sweat to cool the body, or by restricting its circulation of blood to conserve heat. Its appearance varies widely across the body, from mucous membrane to hairy skin to the smooth, hairless skin of the palms and the soles of the feet, which is known as glabrous skin. Skin consists of subcutaneous tissue, dermis, and epidermis and contains various receptors scattered throughout these layers. Glabrous skin contains a dense, complex mixture of receptors, which reflects the fact that we use the palms of our hands and the inside surfaces of our fingers to actively explore the environment. In contrast, the rest of our body most often contacts the environment passively when other things come into contact with it.
Figure 7.16 shows the appearance of free nerve endings and the four types of encapsulated somatosensory receptors, also known as mechanoreceptors: Merkel’s disks, Ruffini corpuscles, Meissner’s corpuscles, and Pacinian corpuscles.
perception of cutaneous stimulation
The three most important qualities of cutaneous stimulation are touch, temperature, and pain. These qualities, along with itch, are described in the sections that follow.
TOUCH Stimuli that cause vibration in the skin or changes in pressure against it (tactile stimuli) are detected by mechanoreceptors-the encapsulated receptors shown in Figure 7.16 and some types of free nerve endings. Movement of the dendrites located in the mechanore-ceptors cause ion channels to open, and the flow of ions into or out of the dendrite causes a change in the membrane potential.
Most information about tactile stimulation is precisely localized —that is, we can perceive the location on our skin where we are being touched. However, a case study by Olausson et al. (2002) discovered a new category of tactile sensation. Read the case study below to learn
more about a unique examole of cutaneous stimulation. Our cutaneous senses are often used to analyze shapes and textures of stimulus objects that are moving with respect to the surface of the skin. Sometimes, the object itself moves, but more often, we do the moving ourselves. If an object is placed in your palm and you are asked to keep your hand still, you will have a great deal of difficulty recognizing the object by touch alone. If you are then allowed to move your hand, you will manipulate the object, letting its surface slide across your palm and the pads of your fingers. You will be able to describe the object’s three-dimensional shape, hardness, texture, slipperiness, and so on. In order to describe it, your motor system must cooperate, and you need kinesthetic sensation from your muscles and joints, in addition to the cutaneous information. Our somatosenses work dynamically with the motor system to provide useful information about the nature of objects that come into contact with our skin.
temperature
TEMPERATURE There are two categories of free nerve-ending thermal receptors: those that respond to warmth and those that respond to coolness. Cold sensors in the skin are located just beneath the epidermis, and warmth sensors are located more deeply in the skin. We can detect thermal stimuli over a very wide range of temperatures, from less than 8° C (noxious cold) to over 52° C (noxious heat). At present we know of six mammalian thermoreceptors that help us detect this wide range of temperatures (Bandell et al., 2007;
Romanovsky, 2007).
Some of the thermal receptors respond to particular chemicals as well as to changes in temperature. For example, one receptor helps detect coolness, such as peppermint or menthol. These chemicals provide a cooling sensation because they bind with and stimulate
the receptor and produce neural activity that the brain interprets as coolness. Chemicals can also bind with receptors to produce the sensation of heat.
pain
Pain perception, like thermoreception, is accomplished by the networks of free nerve endings in the skin. There appear to be at least three types of pain receptors (usually referred to as nociceptors, or “detectors of noxious stimuli”). High-threshold mechanorecep-tors are free nerve endings that respond to intense pressure, which might be caused by something striking, stretching, or pinching the skin. A second type of free nerve ending appears to respond to extremes of heat, to acids, and to the presence of capsaicin, the active ingredient in chile peppers that make them feel “hot” (Kress and Zeilhofer, 1999) (Figure 7.17). Mice lacking the pain receptor sensitive to capsaicin showed less sensitivity to painful high-temperature stimuli and would drink water to which capsaicin had been added (Caterina et al., 2000). The mice responded normally to other noxious mechanical stimuli. Presumably, these receptors are responsible for pain produced by burning of the skin and to changes in the acid /base balance within the skin. These receptors are responsible for the irritating effect of chemicals such as ammonia on the mucous membranes of the nose (Dhaka et al., 2009). These receptors also appear to play a role in regulation of body temperature. In addition, Ghilardi et al. (2005) found that a drug that blocks TRPV1 receptors reduced pain in patients with bone cancer, which is apparently caused by the production of acid by the tumors.
Another type of pain receptor is found in the cilia of auditory and vestibular hair cells.
This type of receptor is sensitive to pungent irritants found in mustard oil, wintergreen oil, horseradish, and garlic and to a variety of environmental irritants, including those found in vehicle exhaust and tear gas (Bautista et al., 2006; Nilius et al., 2007). The primary function of this receptor appears to provide information about the presence of chemicals that produce inflammation.
Another noxious sensation, itch (or, more formally, pruritus) is caused by skin irritation and has an interesting relationship with pain. Scratching reduces itching because pain suppresses itching (and, ironically, itching reduces pain). Histamine and other chemicals released by skin irritation and allergic reactions are important sources of itching. Experiments have shown that painful stimuli such as heat and electrical shock can reduce sensations of itch produced by an injection of histamine into the skin, even when the painful stimuli are applied up to 10 cm from the site of irritation (Nilsson et al., 1997; Ward et al., 1996). Little is known about the receptors that are responsible for the sensation of itch, but at least two different types of neurons transmit itch-related information to the CNS (Johanek et al., 2007).
