Nature Reviews Neuroscience, Volume 2, November 2001 Learning by the rules The long accepted Rescoral-Wagner learning rule says that the likelihood of learning depends on an error signal, arising from the difference between what is expected to happen and what actually happens. Before any association is learned, any outcome is unexpected and thus learning occurs quickly. After many training experiences the association is learned so well that the outcome is predictable and thus, no further learning occurs. There is no error signal.

Neuroscience now bears out the reality of this process in humans. The responses of the midbrain dopamine neurons (essential in reward circuits) precisely predict formal learning theories. Now fMRI observations of the human response in the dorsolateral prefrontal cortex bears out the exact same result. Activity in the latter portion of the brain is high in the first few training trails, but decreased as subjects were able to successfully predict the outcome of a trial. But after learning, when an unexpected outcome occurred, activity increased again in the dorsolateral prefrontal cortex indicating new learning. The study provides evidence that neural activity across neurons and whole brain regions alike, reflect the predictions that come from formal learning.

Nature Reviews Neuroscience, Volume 2, November 2001 Mapping grey matter New evidence points to abnormalities in neurodevelopment in schizophrenic patients. In a study following adolescents with early onset schizophrenia over a period of five years, comparisons were made to normal subjects (control) and mediated-matched teens with other psychiatric disorders than schizophrenia.

It was found that all three groups lost grey matter as time progressed, but the amount of loss in schizophrenic patients was far more than normal adolescents, and also more than those with other disorders. The Loss, however, in the last two groups was fairly consistent across the brain. The schizophrenic patients, on the other hand, experiences loss in a wave-like pattern that began in the parietal cortices and progressed over the years to affect the temporal and frontal regions. Although the medication matched non-schizophrenic patients also showed a greater than normal loss of grey matter than the control subjects, the loss was less than that of schizophrenics and did not include loss in the temporal cortex.

Previous research has shown loss of grey matter in adult schizophrenic patients and their families which is attributed to genetic factors. Other areas of loss appears related to environmental factors, and of great interest is the current study is that the dynamic loss in teen schizophrenics is in the parietal cortices, related to environment. It may support the idea that an environmental trigger brings about the onset of schizophrenia

The diseases’ progression also may indicate that the faster loss in temporal cortices predicts more severe positive symptoms such as hallucinations and delusions. Loss in the frontal cortices may correlate with increased negative symptoms, such as the lack of emotional responses and poverty of speech. Stopping the progressive loss of grey matter will be key in halting the advance of schizophrenia.

Florida Times-Union, Jacksonville, FL November 14, 2001 Study Hints at female stress shield In a study conducted by German researchers, differences were found in the way men and women performed on memory tests given to college students following periods of stress. Men with high levels of cortisol, present during times of stress, were able to recall fewer words than males with low cortisol levels. There was no correlation in women. In earlier experiments, it was found that the reverse is true in older people – that men handle stress better than postmenopausal women.

The results of these two research projects may point to the importance of estradiol, the main estrogen produced by a woman’s ovaries. The production of that stops during menopause, and with it possibly the positive results resulting from the hormone. The estrogen replacement therapy many postmenopausal women take may safeguard the women from stress.

Discover, November 2001 The Unsatisfied Mind: Are reward centers in your brain wired for substance abuse? By Eric Haxeltine More and more evidence points to abnormalities in brain regions devoted to pleasure and motivation as being responsible for addictions such as those of nicotine use, alcohol, sex and gambling. Low sensitivity of neurons in the nucleus accumbens to dopamine (a neurotransmitter involved in the human reward system) is a common feature in most substance abuse.

Addicts are more prone to possess a variant of the DRD2 gene that leads to production of an abnormally low number of dopamine receptors. Chemicals of abuse increase the amount of dopamine in the brain, thus helping the “addicts” achieve the dopamine mediated pleasure that normal people naturally achieve. Chronic substance abuse produces long lasting changes in the brain that lead to increasing dependency, as the use of some substances (like cocaine) decrease the number of receptors in the brain and thus require users to increase dosages to get the same high. Severe withdrawal symptoms make “kicking” the habit extremely difficult. About a quarter of Americans suffer from some form of substance dependency.

This article includes two “Experiments” for readers to peruse to determine their own susceptibility to addiction.

Patients with Parkinson’s also have difficulties in performing this Wisconsin card task, indicating that the basal ganglia is implicated in the card sorting activity.

In research done by O. Monchi and others, it is apparent through use of fMRIs that parts of the prefrontal cortex are specifically active during such brain testing. There is also activity in parts of the basal ganglia, most notably the caudate nucleus and putamen. The pattern of activity changes during different stages of the test, as the portion of the prefrontal cortex important for monitoring information in working memory was activated when subjects were notified as to the correctness of their decision. Other regions of the cortex, as well as the caudate nucleus and medio-dorsal thalamus, activated only when negative feedback was given. This signaled the need for the respondent to alter or change his strategy, with all involved structures creating a physical neural loop crucial for the overall cognitive function. That allows for altering one’s strategy from an existing one to a new one.

More active during response was the putamen, integral for motor function, which allows subjects to carry out an action. However, the putamen activated only when negative feedback had been given by the tester, and connects through a second anatomical loop. These second loop may be more instrumental in performance of a novel action, such as performing in response to a new behavioral rule (the tester indicates error, requiring a change in strategy).

Nature Reviews Neuroscience, Volume 2, November 2001 Senses working overtime Hearing involves identification of the nature of sound as well as the source location. To accomplish these two tasks, the brain compares sounds as they are received by the two ears: thus developing and using specific processing circuits is essential. In the past, belief was that hthe activity and circuitiry involved in these two functions occurred only in neurons responsible to actively respond to incoming sound.

In the JOURNAL OF NEUROSCIENCE it has been reported that cohchlear neurons can exhibit spontaneous activity in the absence of external sensory input.”

Florida Times-Union, Jacksonville, FL November 12, 2001 Study: Lying causes changes in the brain Research results from The University of Pennsylvania were announced in San Diego. Neuropsychologist Ruben Gur reports that brain scans can quite accurately detect human lying, or suppression of the truth. Such findings may lead to a new method of lie-detecting in the future.

Whereas old-fashioned lie detector tests, or polygraphs, measure changes in blood and pressure and the skin, the new method detects differences in mental processes. It is known that anxiety and ability to self-control can affect the accuracy of a polygraph, but the brain activation measured in the new process is believed to be beyond self-control and emotions of the subject. Its results, therefore, will be accurate.

Florida Times-Union, Jacksonville, FL November 8, 2001 Common pain relievers may reduce Alzheimer’s In research in Florida and California non-steroidal anti-inflammatory drugs such as Motrin and Advil (ibuprofen) were found to reduce the harmful beta amyloid protein believed to be involved in Alzheimer’s Disease.

People taking such over-the-counter drugs have long shown a reduced risk of the disease. But, as reported in journal of NATURE, the verification of the drugs effects may lead to a new and effective drug to protect against the disease in the future. It may be therapeutic as well as preventative. One concern that holds back a whole-sale promotion of the use of these drugs is that quantities found effective would require 16 tablets per day. Such a large ingestion of ibuprofen can cause kidney and gastrointestinal difficulties.

There are months of tests ahead before a new drug would be proven and then approved for production. The hope, however, is that those in the earliest stages of Alzheimers would benefit greatly. Another common anti-inflammatory drug, aspirin, was not found to be effective in stemming or preventing the disease.

Discover, November 2001 Brain Rx: Magnets An alternative to shock therapy in the treatment of severe depression has recently come to the fore. It, however, has side affects that include confusion and loss of memory, plus it is likely to cause intense headaches. A new method, trans-cranial magnetic stimulation (TMS) is gentler and yet seemingly quite effective, delivering the current indirectly and thus avoiding major negative side effects.

A paddle containing coiled wire is held next to the head, producing an electrical current that passes through the wire generated magnetic field, Where this field meets brain tissue, it creates an electrical pulse that scrambles nere signals, causing a blackout in the region of the brain beneath the paddle.

Results of the use of this gentler procedure are quite encouraging. More than half of depressed patients who had failed to respond to medication, showed improvement after five days of TMS treatment. The results for obsessive-compulsive and schizophrenic patients was even more positive.

Because there is some inconsistency in research results that may be due to the variation in patient circuitry, TMS is not ready for clinics. More work needs to be done.

In this lengthy article, author Josie Glausiusz reveals work done by Dolores Malaspina from Columbia University and New York State Psychiatric Institute. In it, a surprising conclusion was reached: offspring of men post age 50 have more than a double chance for developing schizophrenia. It appears that in this malady, which counts one victim per one hundred people, a dormant retrovirus in the human genome is the prime candidate for the environmental trigger. Although the mutant genes that enable a brain to develop the abnormality may exist, there has to be a "trip" to turn it on. Maternal malnutrition, injuries to the head and rubella during gestation all may play a role.