Recent replies to "The ethics of using brain-boosting drugs"

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Thu, 26 Jun 2008 13:47:55 -0000

News about Ritalin and Prefrontal Function.
From ScienceDaily
Thanks to Malcolm Dean for forwarding it to me.
Alfredo

University of Wisconsin-Madison (2008, June 25). How Ritalin Works In
Brain To Boost Cognition, Focus Attention.

ScienceDaily (June 25, 2008) — Stimulant medications such as Ritalin
have been prescribed for decades to treat attention deficit
hyperactivity disorder (ADHD), and their popularity as “cognition
enhancers” has recently surged among the healthy, as well. What’s now
starting to catch up is knowledge of what these drugs actually do in
the brain. In a paper publishing online this week in Biological
Psychiatry, University of Wisconsin-Madison psychology researchers
David Devilbiss and Craig Berridge report that Ritalin fine-tunes the
functioning of neurons in the prefrontal cortex (PFC) – a brain region
involved in attention, decision-making and impulse control – while
having few effects outside it.

Because of the potential for addiction and abuse, controversy has
swirled for years around the use of stimulants to treat ADHD,
especially in children. By helping pinpoint Ritalin’s action in the
brain, the study should give drug developers a better road map to
follow as they search for safer alternatives. At the same time, the
results support the idea that today’s ADHD drugs may be safer than
people think, says Berridge. Mounting behavioral and neurochemical
evidence suggests that clinically relevant doses of Ritalin primarily
target the PFC, without affecting brain centers linked to over-arousal
and addiction. In other words, Ritalin at low doses doesn’t appear to
act like a stimulant at all.

“It’s the higher doses of these drugs that are normally associated
with their effects as stimulants, those that increase locomotor
activity, impair cognition and target neurotransmitters all over the
brain,” says Berridge. “These lower doses are diametrically opposed to
that. Instead, they help the PFC better do what it’s supposed to do.”

A behavioral disorder marked by hyperactivity, impulsivity and the
inability to concentrate, ADHD has been treated for more than a
half-century with Ritalin, Adderall and other stimulant drugs. New
reports also indicate these meds have lately been embraced by healthy
Americans of all ages as a means to boost mental performance.

Yet, despite their prevalence, we know remarkably little about how
these drugs work, especially at lower doses that have been proven
clinically to calm behavior and focus attention in ADHD patients, says
Berridge. In 2006, his team reported that therapeutic doses of Ritalin
boosted neurotransmitter levels primarily in the PFC, suggesting a
selective targeting of this region of the brain. Since then, he and
Devilbiss have focused on how Ritalin acts on PFC neurons to enhance
cognition.

To answer this, the pair studied PFC neurons in rats under a variety
of Ritalin doses, including one that improved the animals’ performance
in a working memory task of the type that ADHD patients have trouble
completing. Using a sophisticated new system for monitoring many
neurons at once through a set of microelectrodes, the scientists
observed both the random, spontaneous firings of PFC neurons and their
response to stimulation of an important pathway into the PFC, the
hippocampus.

Much like tiny microphones, the electrodes record a pop every time a
neuron fires, Devilbiss explains. Analyzing the complex patterns of
“voices” that emerge is challenging but also powerful, because it
allows study of neurons on many levels.

“Similar to listening to a choir, you can understand the music by
listening to individual voices,” says Devilbiss, “or you can listen to
the interplay between the voices of the ensemble and how the different
voices combine.”

When they listened to individual PFC neurons, the scientists found
that while cognition-enhancing doses of Ritalin had little effect on
spontaneous activity, the neurons’ sensitivity to signals coming from
the hippocampus increased dramatically. Under higher, stimulatory
doses, on the other hand, PFC neurons stopped responding to incoming
information.

“This suggests that the therapeutic effects of Ritalin likely stem
from this fine-tuning of PFC sensitivity,” says Berridge. “You’re
improving the ability of these neurons to respond to behaviorally
relevant signals, and that translates into better cognition, attention
and working memory.” Higher doses associated with drug abuse and
cognitive impairment, in contrast, impair functioning of the PFC.

More intriguing still were the results that came from tuning into the
entire chorus of neurons at once. When groups of neurons were already
“singing” together strongly, Ritalin reinforced this coordinated
activity. At the same time, the drug weakened activity that wasn’t
well coordinated to begin with. All of this suggests that Ritalin
strengthens dominant and important signals within the PFC, while
lessening weaker signals that may act as distractors, says Berridge.

“These results show a new level of action for cognition-enhancing
doses of Ritalin that couldn’t have been predicted from single neuron
analyses,” he says. “So, if you’re searching for drugs that might
replace Ritalin, this is one effect you could potentially look for.”

He and Devilbiss also hope the research will help unravel an even
deeper mystery: exactly how neurons encode complex behavior and
cognition.

“Most studies look at how something that impairs cognition affects PFC
neurons. But to really understand how neurons encode cognitive
function, you want to see what neurons do when cognition is improved,”
says Berridge. “So this work sets the stage for examining the
interplay among PFC neurons, higher cognition, and the action of
therapeutic drugs.”

The work was funded by the National Institute on Drug Abuse, the
National Institute of Mental Health and the UW-Madison Discovery Seed
Grant Program.

Reply from Elisabeth Daegling

Elisabeth Daegling — Fri, 11 Jan 2008 13:58:38 -0000

Dear Alfredo,

Alfredo: However, for those (like me) who work in this context, “functional” students are often “disfunctional” in the sense that they do not play the game we would like them to play.

Elisabeth: This description will fit.:-)

For experimental data see:
Mölle,M., Schwank, I., Marshall, L., Klöhn, A.,& Born, J.(2000): Dimensional complexitiy and power spectral measures of the EEG during functional versus predicative problem solving. Brain & Cognition, Vol.22 No.3, 547-563

Schwank, I.: Analysis of Eye-Movement During Functional versus Predicative Problem Solving. 2nd Conference of the European Society for Research in Mathematics Education 24th – 27th Feb. 2001, Marinske Lazne
http://www.ikm.uni-osnabrueck.de/mitglieder/schwank/schwank_e/schwank_e.html

Best regards,
Elisabeth

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Fri, 11 Jan 2008 11:40:09 -0000

Dear Elisabeth:

As I understand your explanation, “functional” people are those who jump from the stimulus to a (subjectively defined) goal, without representing the means to achieve it. “Predicative” people are those who analyse the stimulus (e.g. Kanisza illusory triangle) and report their representation of it, only relating it to a goal if they are asked to make such a connection.
In the current paradigm of executive functions in cognitive neuroscience, “functional” people are at risk of being classified as having a prefrontal function disorder.
Maybe in a different context (e.g. in the future of our own society) the “functional” behavior turns out to be adaptive, but at this moment they constitute a problem for the educational system. Possibly the whole system is built on sand. However, for those (like me) who work in this context, “functional” students are often “disfunctional” in the sense that they do not play the game we would like them to play.
Possibly this kind of behavioral tendency is based on prefrontal neural network properties, as proposed by Avi. Experimental data on this regard would be helpful.

Best,

Alfredo

Reply from Elisabeth Daegling

Elisabeth Daegling — Thu, 10 Jan 2008 20:03:31 -0000

Sorry, I apologize for writing Ari instead of Avi.

I don´t know whether the following may be helpful: I´ve read your claim for a paradigm shift and for a new way to think about mental orders.
I do not believe that AD(H)D will be apparent at the neural network level but I hypothesize that this assumption applies to mental disorders like agnosia.

Reply from Elisabeth Daegling

Elisabeth Daegling — Thu, 10 Jan 2008 18:05:47 -0000

Dear Ari,

please let me first distinguish between predicative and functional thinking on the one hand (which I hypothesize to be caused upon a rule and its variances, and I hypothesize that this difference must be apparent at the neural network level) and functional persons without AD(H)D and functional AD(H)D people.
I´m sorry, but at present we do not have any explanations what may cause the difference between persons within and those without AD(H)D.
But it seems to me to be supposable that there will be pathological causes for AD(H)D, maybe the higher density of the dopamine transporter or a smaller volume of several structures in the right hemisphere (see f.e.: Semrud-Clikeman et al. 1994; Castellanos et al. 1996; Berquin et al. 1998).

Best regards,
Elisabeth

Reply from Avi Peled

Avi Peled — Thu, 10 Jan 2008 06:50:28 -0000

Elizabeth – do you have any idea for a plausible explanation? Do you believe the answer can be apparent at the (neural) network level even if underling multiple sub-threshold pathology exists at lower levels (genes molecules)?

Reply from Elisabeth Daegling

Elisabeth Daegling — Wed, 09 Jan 2008 20:52:39 -0000

Dear Alfredo,

Thank you for your reply and your questions.

Alfredo: I am unable to find a parallel for the distinction of predicative and functional kinds of thinking in the context of Epistemology.

Elisabeth: In fact there do not exist any parallels for this distinction.
It´s a very new idea.

Alfredo: Could you review this distinction with a bit more of detail?

Elisabeth:I´ll like to try and I apologize for the deficiency due to the lack of terms to describe an idea which has been never thought before.
If it is not clear-cut it will be harder to find different modes of brain activity underlying each kind of thinking.
The terms predicative and functional in this context stem from Mrs Schwank and she explained it in the following way: she was teaching a deaf boy but the action- orientated approach to logical concept formation which has been developped for these pupils was not successful. Schwank found out that this boy preferred a cognitive structure in which the relationsbetween different mathematical objects and their symbolic description form the basic of his thinking.Such a thinking in relations is normally by the use of predicates and this means by the use of language. Thus, she named it predicative kind of thinking. And by teaching another pupil, a very bright boy Schwank found out that this boy always tried to arrange certain relations between the start situation and the goal. This kind of thinking she named „functional kinnd of thinking.“ The preference for one of these modesmeans that a persons is translating an external given problem into his personal internal conceptual representation.
As mentioned above I achieved the same results with my test persons. I showed them a graphic of Kanizsa`s triangle and asked them to name what they spontaneously would see. The larger (normal) group of persons saw one or two triangle(s), a star, a mickymouse…; the smaller (ADHD) group either asked for the goal /function of this experiment (what´s the matter with it?) or described a process: balls which are impressed by the angles of a triangle; people who speak into emptiness.. I found out that the persons of the larger group concentrated their attention on single details of the graphic – lines, angles, circles – relating them to 3D-objects – triangle, star, etc. The persons of the ADHD group concentrate their attention on a process and its effects. These are two very different kinds of perception, because the people have answered immediately without reflecting their answers. Now I wanted to experience about the reason which constitutes two different kinds of perception:
I remembered that Mr. Dörner once made mention of two rules – and the correlation between the rules and the behavior of the test persons strikes to me imediately. The rules were the „Aktionsschema“, a condition-action-effect-rule – and a variance called „production-rule“ – the condition-effect-action-rule (If, then..). There is an evidence that the condition-action-effect rule applies to the behavior of the normal people and that the second variance applies to the behavoir of „ADHD“-people. Hence I hypothesize that information processing must run based upon either the first (predicative) or the second (functional)variance of the rule. Or in other words: the „behavior“ of the neurons must be „ rule-describing“.
I suppose that the difficulties of ADHD pupils result from teaching methods which do not match with the rule which their brain uses for concept learning and to construct the reality.

@ Ari: I agree to Dr. Szasz´s statement. But there exists a deviance in the behavior of ADHD people which we may not deny. And we need a plausible explanation why they behave in this way.

Best regards
Elisabeth

Reply from Avi Peled

Avi Peled — Wed, 09 Jan 2008 07:03:46 -0000

sorry forgot the quatations –
DSM

CBP

really sorry

Reply from Avi Peled

Avi Peled — Wed, 09 Jan 2008 07:00:39 -0000

sorry – the linkes again DSM:http://neuroanalysis.googlepages.com/Whydoweneedanewdiagnosticsystemforps.ppt
and CBP:http://neuroanalysis.googlepages.com/WhatisClinicalBrainProfilingCBPandho.pps

Reply from Avi Peled

Avi Peled — Wed, 09 Jan 2008 06:58:24 -0000

Thanks for your response, my interest in the problems of psychaitric diagnosis come from my personal attempt to contribute to a more brain-related diagnostic system please see my link about DSM:http://neuroanalysis.googlepages.com/Whydoweneedanewdiagnosticsystemforps.ppt see the proposed CBP:http://neuroanalysis.googlepages.com/WhatisClinicalBrainProfilingCBPandho.pps
Thanks for the interest
Avi

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Tue, 08 Jan 2008 11:47:34 -0000

Dear Avi:

Dr. Szasz’s rethoric is convincing, but possibly there are “objective” brain correlates for many cases of ADHD.
Calling it a disorder or a disease is an ethical issue, and I agree with him that “disease” is not good. The criticism that I make to his speech (partially reproduced in the YouTube address you indicated) is that in some cases there is effectively a disorder, the child is suffering from it, the proper use of drugs is beneficial to her, and she, parents and school teachers report that the use of the drug was beneficial. If the drug does not have bad collateral effects and is not additicve, who – and why – will tell that it is wrong?
My ethical concern about these drugs is that the scientific community still does not know deeply how they affect the complexity of brain functions. It is the same kind of criticism that can be made to broad commercialization and consumption of transgenic food.

Best Regards,

Alfredo

Reply from Avi Peled

Avi Peled — Mon, 07 Jan 2008 13:08:59 -0000

As for ADHD please see: http://www.youtube.com/watch?v=Qj7GmeSAxXo What do you say about that?

Reply from Alfredo Pereira Jr

Alfredo Pereira Jr — Mon, 07 Jan 2008 12:24:14 -0000

Dear Elisabeth:

Many thanks for your detailed message and new ideas on the subject. Please check the comments posted at the NN Forum, specially the contribution of Steven Rose.
I am unable to find a parallel for the distinction of predicative and functional kinds of thinking in the context of Epistemology. Formal Logics seems to be both predicative (when studying the structure of sentences) and functional (when studying argumentation). In Mathematics, a function is just a kind of univocal relation.
Could you review this distinction with a bit more of detail? If it is not clear-cut it will be harder to find different modes of brain activity underlying each kind of thinking.

Best Regards,

Alfredo

Reply from Elisabeth Daegling

Elisabeth Daegling — Mon, 24 Dec 2007 11:49:48 -0000

Thank you for the links.
I ´ve been particularly interested in the discussion about ADHD and its treatment. But I´m a little disappointed because essential factors were neglected and the following two points are not quite correct:
1.Quote: „Both methylphenidate and atomoxetine increase the levels of the neurotransmitter noradrenaline“
Atomoxetine regulates the availableness of noradrenaline; methylphenidate reduces the density of the dapomine transporter gene (see: Cook et al. 1995. „Association of attention-deficit disorder and the dopamine transporter gene“. In: American Journal of Human Genetics. /Krause et al. 2000. „Neurobiologie der Aufmerksamkeitsdefizit –Hyperaktivitätstörung“. In: Psycho)
2.Qote: „ADHD is (...) characterized by core cognitive and behavioral symptoms of impulsivity, hyperactivity and / or inattention“
The main kriterion is inattention! ADHD therefore is characterized by inattention, impulsivity and / or hyperactivity. A smaller group of persons labeled „ADHD“ suffer from ADD without hyperactivity .

The last twenty years I ´ve been working with families whose children suffer from ADHD. And children prescribed Ritalin (methylphenidate) wouldn´t survive the school without medication, because their main problem is the lack of understanding – but not due to inattention.
People with ADHD - children and adults – do not really suffer from a disorder but rather from the lacking acceptance and the sometimes humbling reactions of their social environment.

Moreover I cast into doubt, that ADHD is about a disease or even an illness. Another interpretation of this behavior seems to be more plausible:
The German psychologist Dietrich Dörner dietrich.doerner@ppp.uni-bamberg.de
had become well-known by his studies concerning complex problem solving. He found out that the decisions of the participiants led to devastating and disastrous long term consequences. He concluded that the cause of the unability of decision making in complex situations originates in the way in which the human brain works: present-orientated, reducing complex data to a central variable and its core traits, and unable to consider or rather foresee the long-term consequences arising from actions in a current situation. I pointed out to Mr. Dörner that this statement may not generally fit and that there exists a minority of people being predestined to solve complex problems – people supposed to „suffer“ from ADHD.
Mr. Dörner told me about the of the German math scientist Inge Schwank – the predicative vs. functional kind of thinking – because I had achieved the same result like Schwank – albeit by other means and however, thirteen years later. Schwank wrote: „There exist two cognitive structures in which the thinking processes are expressed. One structure is built up by predicates (relations) and the other one is built up by functions (operations)”. ( s. Schwank, I. 1986.Cognitive Structures of Algorithmic Thinking“. In: “Proceedings of the 10th Conference for Psychology of Mathematics Education, University of London, p.199) schwank@mathematik.uni-osnabrueck.de
In 2003 we started a little project to prove whether ADHD-people belong to the functional thinking group – and our last study corroborates our hypothesis.

Now the question is: How does the human brain work to create either predicative or functional structures (electrophysical patterns?), in which our thinking processes and (un-)conscious experiences are expressed (and probably stored)? I assume that the answer of this question contents the explanation, too, of the deviant behavior of ADHD labelled people.

many regards Elisabeth Daegling