The Mystery’s of the Brain

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Interview with Dr David Loewenstein is a Professor of Psychiatry and Behavioral Sciences at the Miller School of Medicine at the University of Miami. He obtained his Ph.D. in clinical psychology from Florida State University and did a psychology internship at the University of Washington School of Medicine in Seattle, Washington. He is board certified in clinical neuropsychology. Dr. Loewenstein joined the faculty of the University of Miami in 1986. He is Director of Psychological Services and Neuropsychology Laboratories for the University of Miami Department of Psychiatry and is Director of Research and Neuropsychology for the Wien Center for Alzheimer’s Disease and Memory Disorders at Mount Sinai Medical Center in Miami Beach, Florida.Dr. Loewenstein is the author of almost 90 scientific journal articles and book chapters on aging, Alzheimer’s Disease, neuroimaging and diagnostic as well as cross-cultural issues in neuropsychology.


Susie Hi David
David Hi Susie - Just got back from Washington DC from my grant reviews. Good to be home!
Susie Good to have you back!!!!!
David Thanks! How are you
Susie I am fanatic
David Great!
Susie I seem to have moved another big milestone which I am pleased about
David Tell me
Susie it seems I have hit some new neuro issues that I haven’t before and have lots of questions that I would love to get answers too but we don’t know who to ask, even my physio is struggling a little to be able to answer my questions and understand what and why things are happening because she is not a neuro therapist she is a musculoskeletal and we both would love some answers but we don’t know where to go because it seems they are profound issues that we would both like to know more about or it maybe what I am asking and wanting to know might not have answers. it is hard and bit profound to explain but when u have a period of time when not too busy maybe u might be interested and point me in directions from your own field or maybe ask someone in the brain field for me I suppose you could say I been bursting to tell you but knew you were away and very busy.

David If you can, send me the questions in an e-mail to dloewenstein@att.net and I can see if I can be helpful. If I don't know or can't research the answers perhaps I can ask others.
Susie that would be cool if u could help us as I think I’m giving my physio nightmares because I like to know what’s happening and understand what’s going on but with this we can’t. As a result she has gone off to do some reading. It might be a long email if that’s ok
David No problem. Give me a couple of days to think about the questions.
Susie Oh its ok take as long as you need it might take a while for me to get it out of head and down on paper
David No problem.
Susie But this link might give u a little insight if I can get it up as strong as my mind is if we could possibly get some answers then I believe I might be a step closer to understanding Cerebral Palsy
David That would be terrific.
Susie It’s just like watching your baby take first steps I believe I am that close to understanding it, I just can’t touch it yet
http://www.livingwithcerebralpalsy.com/blogger/2008/09/in-gym.html
Is the link
David Let me check it out for a minute....
Susie This is the follow on http://www.livingwithcerebralpalsy.com/blogger/2008/09/sunday-is-my-rest-day.html
David Looks great! Probably outside of my area of expertise...
Susie
The main question is what is connecting to allow me to be able to walk one handed that hasn’t connected before now, and what has made it possible for it to connect. This is just one area of many questions I have asked and my Physio has gone off to read up on it. I suppose to start with it’s a case of knowing the brain function of what parts of the brain what functions is what I need to look at first.

David
I think that the question is a) have existing connections been altered; b) have other pathways been activated; c) is there some compensatory mechanisms that work around direct pathways or d) is it something else that has not been considered? We often see behaviour and infer changes that may or not occur in the brain. That is why functional neuroimaging such as MRI or PET scans (Positron emmssion) tomography would be the best way to see if there are any changes in brain activation in response to treatment or different therapies.
Susie The only problem is I am not sure if I can still have MRI scans
David Is that because of the magnet?
Susie Yes and the metal in my spine
David
Well, PET does not require a magnet but it is investigational for the brain and you would have to find someone that does it. It measures changes in brain oxygen or cerebral metabolism (how the brain is using glucose).
Susie Right, it just intrigues me and as I say it might just unlock the reasons for cerebral palsy, well in my opinion anyway.


David
Without measuring the brain directly, since everyone’s' brains are wired somewhat differently and because CP has many manifestations in the brain, it would be difficult to isolate neural mechanisms. However, it something works for someone, which is very important! Just harder to understand why...
Susie yes I can understand that because the next question would be from that , would be if it works for one how easy would it be to manipulate it so that all types of CP gets results? And if it could be then we have unlocked it
David
I think one would first have to show that a treatment generalizes to several individuals with a specific type of CP, comparing it to an adequate control condition.
Susie
Yes you read my mind there because I was thinking of saying all forms - so all with Spastic Diplegia and so on
David
In a number of studies things work for a few people but do not generalize to the group as a whole. So even with one form, there may be high responders, medium responders and no responders. So the first step would be to see what the high responders have in common.
Susie because technically according to most of the books I have looked at most of them say in diplegia say only certain limbs effected now in reality it does differ
David
Yes and in ages
Susie
To see if say I had had this stimulation for want of a better word at the age of Rachel say, would the same things of happened or is it because I’m older it’s happened. Now my mind says would have been better at Rachel’s age because I would be more receptive at that age but I don’t know. As a result this leads to me asking or explaining that I felt as though my cp had gone and there is some evidence of this in me, in that I am moving better and I no loner have the spasticity etc


David
That is why it is so important to have a controlled study with pre and post measures with a control group and persons that are relatively homogeneous for a condition. Age has a tremendous effect because brain plasticity is much greater than when you are younger. When the radiologist sees the white-matter damage in Rachel, he is amazed that her cp is not worse... but she worked around the deficits by rewiring part of her brain
Susie But my Physio also say’s it is because I perceive it differently to how I did ten yrs ago when I first met her and I also agree.
David
Exactly. CP by definition is a poorly described term. It merely describes motor system impairments that result from central nervous system deficits at birth. EEG is another way I forgot to mention in looking at brain function. Structural MRI only looks at the structure of the brain... it does not measure functional connectivity.
Susie
I doubt I will never fully understand it but I would like to give it ago
David
It is a very complicated area indeed. As a scientist, I lead my whole life looking for break-troughs and if I am lucky. An experiment will yield some better understanding but never explain the whole complexity of memory disorders. However, I think that if you don't ask questions, you never get answers so I am pleased that you are investigating this! If it were memory disorders, I probably could be more helpful...
Susie
You see years ago this never crossed my mind but in last three years I have wanted to know
David
The brain is the great unsolved mystery of the universe! Keep searching... whatever you find, the journey itself is often worth it for a bright, curious mind so this then leads to the question as something connecting in the part of brain that’s responsible for learning
Susie Yes which then asks what’s made we curious all of a sudden

David
Of course motor and procedural memory is modulated by the basal ganglia system, episodic memory is mediated by the hippocampus and they all work together in complex feedback loops. It just blows my mind!
Susie
Yes so you see that cp is governed by memory isn’t it for example I am able to put one foot in front of other so to speak and somewhere my brain remembers this
David
That is procedural or motor memory. These are automatic programs modulated by the deep frontal lobe systems, most notably the basal ganglia and putamen.
Susie
But in some conditions they start off automatic and then switch off like patients with Alzheimer’s
David
But interestingly enough, Alzheimer's patients do not lose these abilities until very late in the disease. They lose short-term memory which is mediated by the hippocampus and related structures. So there are many different types of memory...
Susie
The reason is mention this is my uncle in Canada has just passed away from this
David
Very sorry to hear this...
Susie he was able to walk and then gradually because wheelchair dependant although this also interestingly wonders ok they might switch off so to speak gradually but then does this happen in older age anyway, but is maybe accelerated in people who have a underlying condition ? I suppose it works the other way?? In people who are always in a wheelchair.
David
What happens in Alzheimer's is that as the disease progresses it starts encroaching on these procedural memory structures and kills brain cells and their connections. However, the recent memory deficits precede this by as much as decades. A good model for older people in the basal ganglia system is Parkinson's Disease.
Susie
The procedural memory isn’t triggered so person isn’t able to walk because maybe the cell has already died from birth or maybe this is missing in some people in the genetic structure, like when people have a missing chromosome oh wow this is amazing stuff for me
David
In every disease, something attacks the neuron, the dendrite connections to other neurons and neurotransmitters. In some cases, the primary motor neurons are damaged and there is not motor function. In other cases, the modulating system like the basal ganglia does not properly use signals. In MS, it is actually demyelisation of the axons so the nerve impulses are not transmitted. Thus, brain dysfunction can occur because of cell damage, dedritic thinning or damage. Neurotransmitter difficulties etc. It is like a very complicated car engine. So many things can happen that will make the car fail to run 1) no gas; 2) damaged engine; 3) no starter; 4) loose wires etc.
The brain is simply the most complex and wondrous organ in the body. There is so much we have yet to understand. It is important to ask the right questions as you are...

Susie
So in CP the brain is full of loose wires and it hasn’t worked out where they are to go to
David
Could be... or damaged areas or areas that are damaged in their connectivity in some way...
Susie And it kind of wires them wrongly and sort of fuses them but in some areas they do wire properly and the motor fires up when the oxygen gets through.
David
Or the brain tries its best to rewire around the deficits to the best of its capability. The younger you are, the easier it is to rewire although plasticity can occur when one is older...
Susie So it’s a bit like a pinball machine
David
The question is that with billions of brain cells and over a trillion connections how can be best understand what happens...

Susie
In that you have the ball at the start and you pull the plunger and it fires it up and hits the sensors, So that it's like a message is getting sent and it hits the sensors the lights come on and connect And sometimes it fails and drops through the flippers

David That a good analogy. Now consider that every sensor is dependent on the integrity of every other sensor. You can have a malfunction at any point in the pathway.
Susie and sometimes if the timing is correct it flips it back and tries reconnecting the ball jams along the pathway and it needs a nudge to getting it going and that might be a hand or leg movement
David Exactly, and it can reset in some circumstances. It is like an intermittent problem. For some persons, if the primary sensors are deficient however, resetting is very difficult.
Susie Or your lungs inflating to force air back to nudge it and the harder u pull the plunger the further the ball/message goes.
David Thus, some persons may have more or less problems resetting or even setting at all relative to the extent of their problems. You can put all the gasoline that you want in a car, if it lacks certain mechanism it is not going to start no matter what you do. In certain cases you can help it to turn over.
Susie
Therefore stimulating the primary sensor
David
The messages that are sent by the brain are not only one way; they are always self-modulating and often reciprocal.

Susie
Yes and it’s the reciprocal nature that kind of stimulates the primary sensor? Because sometimes no matter how many times you use the flippers the ball still fails

David
Thus, I would expect the efficacy of any therapy to be dependent on a) the integrity structures that are involved; b) the communications between structures. You are right; there are feedback loops all along the way. Different therapies may target different structures or functional subsystems of the brain. We have long known that aspirin is effective only recently have we understood why. The only way to think about new things is to explore all the possibilities. You are very intelligent and I enjoy how you frame this.