What's New in Neurofeedback

• Learning languages 'boosts brain'
• Scanners 'improve brain surgery'
• Walking a Good Workout for Your Brain
• Stroke victim robbed of her dreams
• Brain scans show hypnosis at work
• New theory on cause of dyslexia
• Single gene removes sex differences in mice brains
• Brain may produce its own antipsychotic drug

  All links at: http://news.yahoo.com/fc?tmpl=fc&cid=34&in=science&cat=brain_research

When Freud gave a name to our darkness, the unconscious, he set loose a process of distrust in ourselves and our self-knowledge that may never end. From this infernal creation descends a minion known as the placebo effect, the idea that the mind can make itself better if only each of us allow it. Healing through distraction, or concentration, or surrender. It's a interesting idea, if it works.

But does it.

Henry K. Beecher's influential 1955 paper "The Powerful Placebo," published in the Journal of the American Medical Association, was the first study to quantify the magnitude of the placebo effect and it is this paper which is the source of our layperson knowledge. Beecher claimed that about a third (35%) of 1082 patients were "satisfactorily relieved" by a placebo alone. This value was not carved in stone but merely a mathematical average of 15 clinical trials for a variety of diseases. Improvements ranged from 21 to 58 percent, so the reliability of the one-third number (or 35%) should have been questioned from the very start.

Forty years later, it was questioned. In the Journal of Clinical Epidemiology, Kienle and Kiene (1997) examined all of Beecher's studies and determined that "no evidence was found of any placebo effect in any of the studies cited by (Beecher)." One hundred percent off the mark! Impressive. Instead of a placebo effect, Kienle and Kiene (1997) concluded that the improvements reported in these groups of studies could be accounted for by the following: spontaneous improvement also known as recovery, symptom fluctuation, regression to the mean, concomitant treatments, scaling bias, obliging reports by patients, irrelevant response variables, experimental subordination, conditioned answers, psychosomatic phenomena, and other factors including an "active placebo" also known as an (active) treatment. No room for anything to do with the spooky unconscious (that is, psychological anticipation).

In a related paper the same authors wonder whether the placebo effect was largely illusory and may not exist at all. It would be a vestige of Freudian thought clinging to our post-modern thought (my words, not theirs). Gotzsche (1995) argued that the concept of placebo should be discarded altogether, but most disagree and continue to argue that psychological mechanisms underlay nonspecific effects (e.g., Kirsch, 1997). Freud, once unloosed, can never die.

As any physicist can tell you, studying a phenomenon, even one that doesn't have in basis in reality, can be interesting and even fruitful. For a placebo effect to exist, what neurobiological mechanisms must control it, what neuroanatomical or functional systems must be involved? What are the duration and dosage curves like and why? Levine volunteered endorphins to answer some of these questions. Others have gone so far to say that the placebo effect may occasionally be toxic! (cf. Shapiro & Shapiro, 1997; Freud kills). While important questions have yet to be addressed, some researchers in mental health began to sling the term around like mud at anything they did not have patent rights to. Perhaps with hindsight, Kienle and Kiene (1997) warned that "the placebo topic seems to invite sloppy methodological thinking." And sloppy thinking is the hurdle facing any treatment modality which competes (effectively) against the current standard.

The Ethics of Placebo Controls

In 1992, Russell Barkley argued that neurofeedback must be compared to the placebo condition before he would take any claim seriously. He suggested using sham feedback in his report (CHADDer Box). Human protection committees and researchers recognize how the "option" of false feedback may be unethical, as well as impractical -- another example of sloppy thinking. False feedback often "breaks the blind" of the patient. Children are particularly quick to detect when information on the monitor is not associated with their EEG. (An interesting finding in and of itself.) This means that a double-blind is unlikely to hold, and remains a fiction as it also exists in much of clinical research. (e.g., if clinicians and researchers involved in a double-blind cannot recognize which patient received the active treatment and which the sugar pill after awhile, then the treatment isn't very effective, is it?)

The Nuremberg Code formulated shortly after World War II in response to Nazi atrocities limits the extent of future human experimentation and was the precursor to the Declaration of Helsinki accepted by the World Health Organization in 1964, a declaration to which our governmental and regulatory bodies prescribe. The Declaration of Helsinki elevates concern for the health and rights of individual subjects over concern for society, for future patients, or for science.. "In any medical study," it asserts "every patient -- including those of a control group, if any -- should be assured of the best proven diagnostic and therapeutic method." Re-read that statement. It ends the use of placebo controls when a proven therapeutic method exists. A study that violates this provision should not be accepted for publication and any application to a regulatory body for a treatment which unnecessarily involved placebo -controlled trials ought be rejected.

Ought to be.

The Code of Federal Regulations under which the FDA operates includes mention of the use of placebo controls, thus deeming them acceptable for US biomedical research. Some researchers complain (in letter to BMJ, etc.) that without a placebo control, their grant proposals will never be funded. Even when alternative treatments are available, a placebo control is an implicit requirement in competitive funding situations. This de facto requirement includes disorders of moderate severity and pain, clearly in violation of the Declaration of Helsinki. Recently, non-inferiority trials have arisen as an alternative to placebo controls; trials in which an experimental treatment may not be superior to an already known active agent but is also not clinically or statistically inferior to that agent in its effectiveness. In this way, a researcher can fulfill their ethical obligation to all patients in a trial. In a sense, both the experimental group and non-experimental group are being providing the best treatment available.

Why are placebos used at all ?

I can think of three reasons why placebo controls are desirable:
1. To evaluate absolute efficacy: Placebo controls supposedly determine whether a new treatment is better than nothing.
2. To avoid difficult decisions about treatment effectiveness: Differences in cost, unintended (side) effects, drug interactions, and other factors may make comparisons between treatments of similar efficacy inexact and subjective.
3. To bolster statistical significance: As any psych grad student knows, it is much easier to detect statistical significance between a placebo and an active treatment than between two active treatments. (And it is less expensive to use a placebo condition than to increase the n, the other method of bolstering one's stats.)

Ignoring the ethics of requiring placebo controls, or even the phenomenological argument of whether placebo effects exist at all, I think we can distinguish a placebo from an active treatment by the following criteria:

1. Specificity: A single symptomalogical or functional domain is impacted by a treatment compared to nonspecific or multiple domains (This one will be difficult with neurofeedback as the functional improvement is regulatory, not focal.)
2. Toxicity: Use of the treatment can cause worsening of symptoms in some individuals. (Good thoughts rarely kill, though nocebos do exist.)
3. Long Duration: Changes associated with the treatment endure for weeks, months, or years.
4. Dose-dependence: Extent of changes reflect an accumulation of doses (cumulation and carry-over effects)
5. Time-dependence: Changes occur in response to a manipulated time-line. Symptom changes do not emerge before or long after treatment is complete, for instance. (time-effect curves)

Neurofeedback meets each of the above criteria for ADHD and epilepsy and other disorders, but most of this information -- such as long duration and dose dependence -- is in the clinical record only, unpublished, and therefore unavailable to our critics. I can see a research program, or a dozen, focused on these five criteria.

One day, I see myself sitting down for a neurofeedback training session, strapping on the electrodes, and saying, "I hope the placebo effect is strong today" -- and be mocking our rocky past.

-DK

News & Reviews NEW BOOKS

The Mind and the Brain : Neuroplasticity and the Power of Mental Force
by Jeffrey M. Schwartz, Sharon Begley;
Schwartz pioneered the use of PET in studying OCD. --www.amazon.com/exec/obidos/ASIN/0060393556/top100

Principles and Practice of Sleep Medicine
by Meir H. Kryger, et al
Encompasses pathophysiology, diagnosis, and treatment of disorders resulting from disruptions of sleep-wake cycles and circadian rhythm. --www.amazon.com/exec/obidos/ASIN/0721676707/top100

The Body Remembers: The Psychophysiology of Trauma and Trauma Treatment
by Babette Rothschild
Somatic memory of trauma experienced is discussed with case studies. --www.amazon.com/exec/obidos/ASIN/0393703274/top100

Wider than the Sky: The Phenomenal Gift of Consciousness
by Gerald M. Edelman
How do neurons give rise to subjectivity? From Nobel Laureate. Pertinent findings of modern neuroscience --www.amazon.com/exec/obidos/ASIN/0300102291/top100

Drugs, Behavior, and Modern Society
by Charles F. Levinthal
Controversies surrounding drug use and abuse with a focus on health and prevention. --www.amazon.com/exec/obidos/ASIN/0205323669/top100

The Epidemic: The Rot of American Culture, Absentee and Permissive Parenting...
by Robert Shaw
Definitely the author doesn't pull any punches: "(Spoiled) children are not an aberration. They are the natural outcome of the way we have been raising them," --www.amazon.com/exec/obidos/ASIN/0060011831/top100

Adult Children of Alcoholics: Expanded Edition
by Janet Woititz
Advice and information for adult children of dysfunctional families --www.amazon.com/exec/obidos/ASIN/1558741127/top100

Stimulant treatment over five years: adherence, effectiveness, and adverse effects. : Psychostimulants improve ADHD symptoms but adverse effects persist. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15100562

Use of the Calmset 3 biofeedback/relaxation system in nocturnal bruxism. : Single patient exhibited fewer bruxing episodes following treatment, which were sustained at 6 month followup. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15208977

The medial temporal lobe : Reviews function of MTL. No simple dichotomies for it versus hippocampus were found (e.g., and associative versus nonassociative memory, episodic versus semantic memory) www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15217334

Low emotional intelligence as a predictor of substance-use problems. : Poorer coping predicted drug-related problems, but not alcohol-related problems. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15237864

Neuropsychology of adults with ADHD: a meta-analytic review. : ADHD adults exhibit europsychological deficits in attention, behavioral inhibition, and memory www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15291727

Efficacy of treatment for child and adolescent traumatic stress. : Meta-analysis of 8 studies found treatment for traumatic stress led to greater improvement than either no treatment or routine community care. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15289252

128-Channel EEG Source Imaging in Epilepsy: Clinical Yield and Localization Precision. : Evaluated feasibility, clinical yield, and localization precision of high-resolution EEG source imaging of interictal epileptic activity. Foci was localized in 93% of patients, 79% exactly. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15284597

Abnormal EEG synchronisation in heavily drinking students. : Heavily drinking students had more synchronisation in theta and gamma bands during eyes closed, both with and without a task, interpreted as changes in hippocampal-neocortical connectivity. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15294207

Concept of psychical trauma: A bridge in interdisciplinary space. : Recent neuroscience findings in emotion and memory are integrated with psychoanalysis and the concept of trauma. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15310427

Perspectives on the estimation of effective connectivity from neuroimaging data. : Discusses model in use with event-related fMRI to estimate connectivity across the brain. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15319514

Does sleep or sleep deprivation increase epileptiform discharges? : Sleep deprivation does not increase the yield of epileptic discharge in pediatric EEGs. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15342836

Neuroscience research on the addictions : Advances in neuroimaging will eventually allow pre-onset addiction and other frightening invasions of privacy. www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15345277

Ironically, those well-situated in scientific or cultural fields are often the last to recognize change. Ripples must become swells before makers and shakers of the previous paradigm take notice, and by then, it is usually too late to respond or assist.

Here are a number of erroneous predictions, preceded by a few comments about prognostication itself:

• "There are two kinds of forecasters: those who don't know, and those who don't know they don't know." - J K Galbraith, economist.
• "The future is already here - it's just unevenly distributed." - William Gibson.
• Life can only be understood backwards, but it must be lived forwards. - Soren Kierkegaard, philosopher.
• "The past resembles the future more than one drop of water resembles another." - Ibn Khaldun.
• "I think there is a world market for maybe five computers." - Thomas Watson, chairman of IBM, 1943.
• "There is no reason anyone would want a computer in their home." - Ken Olson, founder of Digital Equipment Corp., 1977.
• "This 'telephone' has too many shortcomings to be seriously considered as a means of communication. The device is inherently of no value to us." - Western Union internal memo, 1876.
• "The telephone may be appropriate for our American cousins, but not here, because we have an adequate supply of messenger boys." - group of British experts, c.1900.
• "One day there will be a telephone in every major city in America" - Alexander Graham Bell, c.1880.
• "Good enough for our transatlantic friends... but (Edison's incandescent lamp is) unworthy of the attention of practical or scientific men" - British Parliament
• "When the Paris Exhibition closes, electric light will close with it and no more be heard of." -- Erasmus Wilson, Oxford professor, 1878.
• "Everything that can be invented has been invented." - Commissioner US Office of Patents, 1899.
• "I will ignore all ideas for new works on engines of war, the invention of which has reached its limits" - Sextus Julius Frontinus, 1st century A.D.
• "The bomb will never go off. I speak as an expert in explosives." - Admiral William Leahy, US Atomic Bomb Project.
• "As far as sinking a ship with a bomb is concerned, you just can't do it." - Rear-Admiral Clark Woodward, 1939
• "Stocks have reached what looks like a permanently high plateau." - Irving Fisher, Yale Professor of Economics, 1929.
• "1930 will be a splendid employment year." -U.S. Department of Labor, 1929.
• "A physicist who professed such heresies is unworthy to teach science." - German Minister of Education in response to Ohm publishing his ideas on electricity, now know as Ohm's law
• "The horse is here to stay, but the automobile is only a novelty." - Bank president, 1903, advising Henry Ford's lawyer not to invest in the Ford Motor Company.
• By the turn of this century, we will live in a paperless society. 'Roger Smith, chairman of General Motors, 1986
• "The abdomen, the chest, and the brain will forever be shut from the intrusion of the wise and humane surgeon." - JE Ericksen, Surgeon Extraordinary to Queen Victoria, 1873.
• "Law will be simplified [over the next 100 years]. Lawyers will have diminished, and their fees will have been vastly curtailed." -Junius Henri Browne, Journalist, 1893.
• "It would appear we have reached the limits of what it is possible to achieve with computer technology, although one should be careful with such statements; they tend to sound pretty silly in five years." -John von Neumann, computer scientist, 1949.
• "Jupiter's moons are invisible to the naked eye, and therefore can have no influence on the earth, and therefore would be useless, and therefore do not exist." - contemporary professor on Galileo's pronouncement concerning his discovery.
• Well-informed people know it is impossible to transmit the voice over wires and that were it possible to do so, the thing would be of no practical value. Editorial in Boston Post, 1865.
• "Before the twentieth century closes, the earth will be purged of its foulest shame, the killing of men in battle under the name of war." - Andrew Carnegie.

Recently, an adolescent with uncontrolled seizures had his corpus callosum partially severed to stop the seizures. Unfortunately, the procedure did not have the intended result. A vagal stimulator was then implanted. Again, the seizures continued. Since the neurologists and surgeons had no other remedy in mind, the mother asked whether neurofeedback might be tried. The neurologist was not caught at a loss for words: "Too experimental," he said.

Not exactly a prediction, but short-sighted nonetheless.