Neuroscientists find the molecular 'when' and 'where' of memory formation

Neuroscientists have isolated the “when” and “where” of molecular activity that occurs in the formation of short-, intermediate-, and long-term memories. (Credit: iStockphoto/Guido Vrola)

— Neuroscientists from New York University and the University of California, Irvine have isolated the "when" and "where" of molecular activity that occurs in the formation of short-, intermediate-, and long-term memories. Their findings, which appear in the journal the Proceedings of the National Academy of Sciences, offer new insights into the molecular architecture of memory formation and, with it, a better roadmap for developing therapeutic interventions for related afflictions.

"Our findings provide a deeper understanding of how memories are created," explained the research team leader Thomas Carew, a professor in NYU's Center for Neural Science and dean of NYU's Faculty of Arts and Science. "Memory formation is not simply a matter of turning molecules on and off; rather, it results from a complex temporal and spatial relationship of molecular interaction and movement."

Neuroscientists have previously uncovered different aspects of molecular signaling relevant to the formation of memories. But less understood is the spatial relationship between molecules and when they are active during this process.

To address this question, the researchers studied the neurons in Aplysia californica, the California sea slug. Aplysia is a model organism that is quite powerful for this type of research because its neurons are 10 to 50 times larger than those of higher organisms, such as vertebrates, and it possesses a relatively small network of neurons — characteristics that readily allow for the examination of molecular signaling during memory formation. Moreover, its coding mechanism for memories is highly conserved in evolution, and thus is similar to that of mammals, making it an appropriate model for understanding how this process works in humans.

The scientists focused their study on two molecules, MAPK and PKA, which earlier research has shown to be involved in many forms of memory and synaptic plasticity — that is, changes in the brain that occur after neuronal interaction. But less understood was how and where these molecules interacted.

To explore this, the researchers subjected the sea slugs to sensitization training, which induces increased behavioral reflex responsiveness following mild tail shock, or in this study, mild activation of the nerve form the tail. They then examined the subsequent molecular activity of both MAPK and PKA. Both molecules have been shown to be involved in the formation of memory for sensitization, but the nature of their interaction is less clear.

What they found was MAPK and PKA coordinate their activity both spatially and temporally in the formation of memories. Specifically, in the formation of intermediate-term (i.e., hours) and long-term (i.e., days) memories, both MAPK and PKA activity occur, with MAPK spurring PKA action. By contrast, for short-term memories (i.e., less than 30 minutes), only PKA is active, with no involvement of MAPK.

The study's other co-authors were Xiaojing Ye, a postdoctoral fellow in NYU's Center for Neural Science, Andreea Marina, an undergraduate at UC Irvine at the time of the study. The research was conducted at NYU's Center for Neural Science and UC Irvine's Center for Neurobiology of Learning and Memory.

This work was supported by grants RO1 MH 041083 and RO1 MH 081151 from the National Institute of Mental Health, part of the National Institutes of Health, and a grant IOB-0444762 from the National Science Foundation.

 

Journal Reference:

  1. Xiaojing Ye, Andreea Marina, and Thomas J. Carew. Local synaptic integration of mitogen-activated protein kinase and protein kinase A signaling mediates intermediate-term synaptic facilitation in Aplysia. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1209956109

Intermittent binge drinking could cause significant brain impairment within months, study suggests

— A study of binge-drinking rodents suggests that knocking back a few drinks every few days may swiftly reduce one's capacity to control alcohol intake. Scientists at The Scripps Research Institute (TSRI) found signs of cognitive impairment in rats similar to that seen in established alcoholism after the animals had only a few months of intermittent access to alcohol.

The researchers linked the rats' impairment to a small group of neurons that inhibit "executive control" functions in the prefrontal cortex of the brain. These neurons were unusually active in the periods between drinking binges — and the more active they were, the more the rats drank when they next had access to alcohol. The finding, if confirmed in studies of humans, could lead to better treatments, preventive approaches and diagnostic tests for problem drinking and possibly other addiction-like behaviors.

"We suspect that this very early adaptation of the brain to intermittent alcohol use helps drive the transition from ordinary social drinking to binge drinking and dependence," said Olivier George, PhD, senior staff scientist at TSRI and lead author of the study.

"This research is giving us a window into the early development of the addiction process," said the study's senior author, George F. Koob, PhD, chairman of the Committee on the Neurobiology of Addictive Disorders and co-director of the Pearson Center for Alcoholism and Addiction Research at TSRI.

The new study appears online ahead of print in the Early Edition of the Proceedings of the National Academy of Sciences the week of October 15, 2012.

Binge Drinking Versus Consuming a Little Every Day

Scientists have long known that alcohol dependence and other addictions feature striking changes in the brain. These include an overactivity of stress-related circuits and a weakening of the prefrontal executive control circuits that normally act as a brake on emotional reactions and impulsive behaviors. What hasn't been understood is the sequence of neural events by which these changes come about.

To find out more about these early events, Dr. George set up a study of rats that had access to alcohol only three days per week (Tuesday, Thursday and Saturday). Previous research had shown that rats in this intermittent-access situation start out as modest drinkers, but eventually turn into binge drinkers, consuming even more than rats that have 24/7 access to alcohol. "It's like a lot of things in life that the brain perceives as good — if it loses access to it, you feel bad, you get into a negative emotional state, say a little bit frustrated, and so you take more the next time you have access," said Dr. George.

The team confirmed that the group of rats with intermittent access drank markedly more alcohol, on average, than those with continuous access after only six weeks. In tests conducted a few weeks later, during "dry" intervals between drinking bouts, the binge drinking rats scored poorly on measures of working memory, an essential element of executive control. Tests of their brain tissue also revealed that during these withdrawal periods — when the animals would have been expected to be craving alcohol — the prefrontal cortex seemed relatively disconnected from the structures it is meant to regulate, such as the emotion-related amygdala.

"We normally see such changes in the brains of humans or other animals that are highly dependent on alcohol, but here we found these changes in the rats after only a few months of intermittent alcohol use," said Dr. George.

Remarkably, these impairments did not appear at all in the drink-every-day rats, whose alcohol intake remained stable. "They just drink a bit like the French way, the equivalent of a couple of glasses of wine every day, and they're fine," said Dr. George. "They don't escalate."

As for the binge-drinking rats, their cognitive impairment went away if they were kept off alcohol for about two weeks — but the impairment would return if they simply drank again. "One can see the vicious cycle here," said Dr. George. "They drink to restore normal prefrontal function, but ultimately that leads to even greater impairment."

"This process would be of particular concern in adolescents and young adults, in whom the prefrontal cortex isn't even fully developed," Dr. Koob said.

Changes in the Brain

Further tests suggested that the immediate cause of the impairment in the binge-drinking rats was a small population of medial prefrontal cortex neurons known as GABA interneurons. These neurons are known to serve as "dimmer switches" for nearby excitatory neurons within the medial prefrontal cortex. In the binge-drinking rats, the GABA neurons were unusually active during periods of impairment. In general, the more active these GABA neurons are, the less the prefrontal cortex is able to do its primary job of exerting executive control over other, relatively impulse-driven brain regions.

The team also found hints that the GABA interneurons in the binge-drinking rats may be activated by adjacent prefrontal neurons that secrete the stress neurotransmitter CRF. This molecule is already closely associated with alcoholism. In alcohol-dependent rats, and likely in human alcoholics too, abstinence triggers a flood of CRF in the central nucleus of the amygdala — creating a feeling of anxiety that typically can only be alleviated by drinking again. "Now we see that that this early dysregulation of the prefrontal cortex by binge drinking may also be driven by CRF," Dr. Koob said.

The Koob lab and other teams of addiction researchers have begun to investigate CRF-blocking drugs as potential treatments for established alcohol dependence. The new results, Dr. Koob said, raise the possibility that such drugs might also work to prevent alcohol dependence. CRF may turn out to be a good target for diagnostic tests, too. "When someone develops a molecule that binds to CRF with high enough specificity, so that we can measure CRF activity in the living human brain with a PET scan, we might then have a good way to detect if someone is alcohol-dependent or on the path to dependency," he said.

In addition to Drs. Koob and George, the other contributors to the study, "Alcohol withdrawal activates GABA and corticotropin releasing factor (CRF) neurons in the medial prefrontal cortex (mPFC) that predict cognitive impairment and escalation of alcohol intake," are Chelsea Sanders, John Freiling, Edward Grigoryan, Shayla Vu, Camryn D. Allen, Elena Crawford, and Chitra D. Mandyam, all from TSRI.

The research was supported by grants from the National Institutes of Health (AA006420, AA008459, AA020608) and the Pearson Center for Alcoholism and Addiction Research at TSRI.


Journal Reference:

  1. Olivier George, Chelsea Sanders, John Freiling, Edward Grigoryan, Shayla Vu, Camryn D. Allen, Elena Crawford, Chitra D. Mandyam, and George F. Koob. Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1116523109

Men diagnosed with ADHD as children had worse outcomes as adults, study suggests

— Men who were diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) appeared to have significantly worse educational, occupational, economic and social outcomes in a 33-year, follow-up study that compared them with men without childhood ADHD, according to a report published Online First by Archives of General Psychiatry, a JAMA Network publication.

ADHD has an estimated worldwide prevalence of 5 percent, so the long-term outcome of children with ADHD is a major concern, according to the study background.

Rachel G. Klein, Ph.D., of the Child Study Center at NYU Langone Medical Center in New York, and colleagues report the adult outcome (follow-up at average age of 41 years) of boys who were diagnosed as having ADHD at an average age of 8 years. The study included 135 white men with ADHD in childhood, free of conduct disorder (probands), and a comparison group of 136 men without childhood ADHD.

"On average, probands had 2½ fewer years of schooling than comparison participants … 31.1 percent did not complete high school (vs. 4.4 percent of comparison participants) and hardly any (3.7 percent) had higher degrees (whereas 29.4 percent of comparison participants did). Similarly, probands had significantly lower occupational attainment levels," the authors note. "Given the probands' worse educational and occupational attainment, their relatively poorer socioeconomic status at [follow-up at average age of 41 years] is to be expected. Although significantly fewer probands than comparison participants were employed, most were holding jobs (83.7 percent). However, the disparity of $40,000 between the median annual salary of employed probands and comparisons is striking."

In further comparisons of the two groups, the men who were diagnosed with ADHD in childhood also had more divorces (currently divorced, 9.6 percent vs. 2.9 percent, and ever been divorced 31.1 percent vs. 11.8 percent); and higher rates of ongoing ADHD (22.2 percent vs. 5.1 percent, the authors suspect the comparison participants' ADHD symptoms might have emerged during adulthood), antisocial personality disorder (ASPD, 16.3 percent vs. 0 percent) and substance use disorders (SUDs, 14.1 percent vs. 5.1 percent), according to the results.

During their lifetime, the men who were diagnosed with ADHD in childhood (the so-called probands) also had significantly more ASPD and SUDs but not mood or anxiety disorders and more psychiatric hospitalizations and incarcerations than comparison participants. And relative to the comparison group, psychiatric disorders with onsets at 21 years of age or older were not significantly elevated in the probands, the study results indicate.

The authors note the design of their study precludes generalizing the results to women and all ethnic and social groups because the probands were white men of average intelligence who were referred to a clinic because of combined-type ADHD.

"The multiple disadvantages predicted by childhood ADHD well into adulthood began in adolescence, without increased onsets of new disorders after 20 years of age. Findings highlight the importance of extended monitoring and treatment of children with ADHD," the study concludes.


Journal Reference:

  1. Klein RG, Mannuzza S, Olazagasti M, et al. Clinical and Functional Outcome of Childhood Attention-Deficit/Hyperactivity Disorder 33 Years Later. Archives of General Psychiatry, 2012; DOI: 10.1001/archgenpsychiatry.2012.271

Does motherhood dampen cocaine’s effects?

Mother rats respond much differently to cocaine than female rats that have never given birth, according to new University of Michigan research that looks at both behavior and brain chemistry.

The findings may help lay the groundwork for more tailored human addiction treatment, based on scientific understanding of how gender, hormones and life experience impact drug use.

In an oral presentation at the Society for Neuroscience meeting, U-M researcher Jennifer Cummings, Ph.D., summarized findings from experiments with rats at the Molecular and Behavioral Neuroscience Institute, part of the U-M Medical School. She worked with Jill Becker, Ph.D., of the U-M Department of Psychology.

They identified clear differences in how intensely the "pleasure centers" in the mother rats' brains reacted to the drug, compared with non-mothers. Mother rats' brains released less of a chemical called dopamine, which helps cause the "high" from cocaine.

They also found an interaction with stress: mother rats that were exposed to periods of increased stress weren't willing to work as hard to get a dose of cocaine, compared with rats that had never given birth or mother rats that weren't exposed to the stress — even though the stressed mother rats showed an increased tendency to use cocaine when it was easy to get.

Taken together, the findings suggest that the experience of becoming a mother alters a female's overall response to cocaine — adding complexity to the issue of how best to treat addiction.

"While we have not yet identified a mechanism to explain these differences, they do suggest that the reward system and brain circuitry affected by cocaine is changed with maternal experience," says Cummings, a research investigator at MBNI and former postdoctoral fellow in Becker's laboratory. "The next step is to determine how factors such as hormone changes in pregnancy and early motherhood, and the experience of caring for offspring, might be differentially contributing to this response."

While rats and people are admittedly very different, research on rodents allows scientists like Cummings and Becker to study brain chemistry and drug-related behavior in detail, and pave the way for translating those findings to human drug treatment. With drug use and abuse among women on the rise, gender-specific understanding and treatment is becoming more important than ever, Cummings says.

In general, researchers already know that motherhood can give animals a better memory and ability to navigate compared with non-mothers — and that these effects last beyond the time that the mother is caring for her offspring.

The new research used a system that gave rats access to cocaine if they poked a dispenser with their noses a minimum number of times.

At first, when the number of pokes needed to get a dose was low, the mother rats took more drug than the non-mothers after exposure to a brief, stressful situation. But as the researchers ramped up the number of pokes needed to as high as 70, the stressed mothers became more likely to stop seeking doses.

The researchers also used a technique called microdialysis to measure the level of dopamine in the rats' brains, especially in an area called the nucleus accumbens which is considered the brain's "pleasure center."

In this measurement of neurological response, the mother rats' dopamine levels after receiving cocaine were much lower than those of non-mothers.

"Even though there was reduced dopamine release in the nucleus accumbens of rats that had been mothers, many of their behavioral responses to cocaine were the same or greater than non-mothers, indicating that there are downstream long term changes to the brains of the rats that had been mothers," says Becker.

The research focused on female rats that had given birth to and reared one litter of pups, compared with those that were virgins. Future experiments, Cummings says, might look at the impact of those that gave birth but didn't rear their pups, and those that reared pups born to other rats but never gave birth themselves.

Only through this careful research can the impact of hormones be teased apart from the impact of the actual motherhood experience.

The research was funded by two grants from the National Institute on Drug Abuse, part of the National Institutes of Health (NIH 5R21-DA27924-2 and NIH R01-DA012677).

In addition to her main appointment as a professor in the U-M Department of Psychology in the College of Literature, Science & the Arts, Becker also holds an appointment in the U-M Medical School's Department of Psychiatry and is a member of the U-M Neuroscience Program.

Do re mi fa … How do you know what comes next?

How do you remember a song — and why is it that a beginning pianist who forgets the middle of a melody needs to start over again to recall the tune?

Brain scientists at Georgetown University Medical Center now have a response to these questions. At Neuroscience 2012, the annual meeting of the Society for Neuroscience, the researchers reveal their solution to what has long been a fundamental puzzle in neuroscience: What does the brain have to do to process a new musical sequence, and what must it do to recall a song, once learned?

The answer, says Brannon Green, a graduate student who works in the laboratory of senior author, neuroscientist Josef Rauschecker, Ph.D., is that two different areas of the brain are used — one to learn a sequence and another to recall it — and that higher motor areas participate in both.

Green, Rauschecker, and three colleagues at Aalto University in Helsinki/Finland used functional magnetic resonance imaging (fMRI) with volunteers who listened to musical sequences while in the scanner. The participants heard early parts of a 30-second musical sequence 20 to 30 times, making that part of the melody familiar to them, while they heard the rest of the music only one to 10 times.

The researchers found that learning a novel sequence required use of the brain's motor areas, such as the basal ganglia and cerebellum, which would seem more likely to be used to move muscles to sing. In this study, these areas were active in learning the sequence of the parts of the tune — that one sound fired one neuron, and the next sound fired a second neuron, and so on.

"The motor system contains brain structures that nature invented to decode sequences, so to learn a melody, the auditory system hijacks the motor system," says Rauschecker.

"This is also the part of the brain you use to learn how to ski or dance," says Green. "This study shows that motor sequencing areas in the brain are really generalized sequencing areas that process both motor and auditory sequences."

Once the study participants learned the tune, the fMRI showed that brain activity switched from the motor regions to areas in auditory and prefrontal cortex, which are associated with long term memory of sounds. And it also showed that it didn't take as many neurons to remember the sequence as to initially learn it.

Rauschecker likens storage of a tune to dominoes stacked next to each other. "The tones are chunked together, chained to one another in a sequence. It's like pushing the first domino, and then they all fall, one after the other. The memory trace is tight; fewer neurons are needed for recall."

"That can explain why if you get stuck in the middle of a melody you are playing on a piano, it is easier to recall it if you start from the beginning of the tune," Green says.

Tipping the dominos at will also illustrates "how a symphony conductor is always ahead of the orchestra," Rauschecker says. "One cue triggers the next and then the next."

The research was funded by the National Science Foundation (PIRE-OISE-0730255) and the Academy of Finland's FiDiPro program. Rauschecker and his co-authors report having no personal financial interests related to the study.

Patients tell how magnetic therapy lifted their depression

Three patients who have suffered periodic major depression throughout their adult lives told an audience attending a Loyola Grand Rounds presentation how their lives have been transformed by a new magnetic therapy.

The treatment, called transcranial magnetic stimulation (TMS), sends short pulses of magnetic fields to the brain.

"I feel better now than I have in a very long time," said patient Jannel Jump. "I'm living a life now, rather than hiding from it."

Another patient said TMS brought him out of a depression so severe he couldn't get out of bed.

And a third patient said TMS "has helped me to have a glass-is-half-full outlook. I'm in a much better spot today."

The Food and Drug Administration approved TMS in 2009 for patients who have major depression and have tried and failed at least one antidepressant. The FDA has approved one TMS system, NeuroStar®, made by Neuronetics, said Dr. Murali Rao, MD, DFAPA, FAPM, Chairman of the Department of Psychiatry and Behavioral Neurosciences at Loyola University Chicago Stritch School of Medicine.

The patient reclines in a comfortable padded chair. A magnetic coil, placed next to the left side of the head, sends short pulses of magnetic fields to the surface of the brain. This produces currents that stimulate brain cells. The currents, in turn, affect mood-regulatory circuits deeper in the brain. The resulting changes in the brain appear to be beneficial to patients who suffer depression.

Each treatment lasts 35 to 40 minutes. Patients typically undergo three to five treatments per week for four to six weeks.

The treatments do not require anesthesia or sedation. Afterward, a patient can immediately resume normal activities, including driving. Studies have found that patients do not experience memory loss or seizures. Side effects may include mild headache or tingling in the scalp, mostly during stimulation.

Together, psychotherapy and antidepressants result in complete remission in about one-third of patients who suffer major depression. TMS is a noninvasive treatment option for the other two-thirds of patients, who experience only partial relief from depression or no relief at all, Rao said. He noted that TMS is recommended by the American Psychiatric Association's 2010 Treatment Guidelines.

Rao said treatment reports from 41 TMS treatment centers show that about 33 percent of TMS patients who previously had been treatment-resistant reported their depression had significantly lessened or gone away completely. This success rate is about twice as high as the success rate of patients who have tried three or more antidepressants. Loyola recently began recruiting for a study on whether TMS can benefit patients who suffer from both depression and debilitating tinnitus (ringing in the ears).

Calling Miss Congeniality: Do attractive people have attractive traits and values?

Research shows that people tend to perceive attractive adults as more social, successful, and well-adjusted than less attractive adults, a phenomenon that's been termed the "what is beautiful is good" stereotype. But is this really true? (Credit: iStockphoto)

— We've all been warned not to "judge a book by its cover," but inevitably we do it anyway. It's difficult to resist the temptation of assuming that a person's outward appearance reflects something meaningful about his or her inner personality.

Indeed, research shows that people tend to perceive attractive adults as more social, successful, and well-adjusted than less attractive adults, a phenomenon that's been termed the "what is beautiful is good" stereotype.

But could that really be true? Are physically attractive people really just as attractive on the inside as they are on the outside?

In a new article published in Psychological Science, a journal of the Association for Psychological Science, Lihi Segal-Caspi and Sonia Roccas of the Open University and Lilach Sagiv of The Hebrew University of Jerusalem investigated whether the "what is beautiful is good" stereotype holds up in the real world.

The researchers examined how traits, which describe what people are like, and values, which describe what people consider important, might be related to physical attractiveness.

Segal-Caspi and colleagues hypothesized that outside observers would perceive attractive women as more likely to have socially desirable personality traits than less attractive women. Specifically, they hypothesized that observers would judge attractive women to be more agreeable, extraverted, conscientious, open to experiences, and emotionally stable than less attractive women. They hypothesized that no such correlation would be found between women's attractiveness and their perceived values, since judgments about what constitutes a "good" value are likely to vary from observer to observer.

The researchers recruited 118 university students to serve as "targets" or "judges." The targets completed surveys about their values and their traits. They were then videotaped entering a room, walking around a table looking at the camera, reading a weather forecast, and leaving the room. Each judge saw a videotape of a different target, chosen at random, and evaluated the target's values and traits and then her attractiveness, along with other physical attributes.

Women who were rated as attractive were perceived as having more socially desirable personality traits, such as extraversion, openness to experience, and conscientiousness, just as the researchers hypothesized. Out of the ten types of values, however, only one was thought to be associated with attractiveness: Attractive women were perceived as more likely to value achievement than less attractive women.

But when the researchers looked at the targets' actual self-reported traits and values, they found the opposite relationships. Targets' attractiveness, as rated by the judges, was associated with with their self-reported values and not with their personality traits. Women who were rated as attractive were more likely to endorse values focused on conformity and submission to social expectations and self-promotion.

Segal-Caspi and colleagues conclude that although some people may think beauty and goodness go together, the results from this study indicate that beautiful people may tend to focus more on conformity and self-promotion than independence and tolerance.

This research was supported by a grant from the Israel Science Foundation (No. 774/06) to Sonia Roccas and Lilach Sagiv and by a grant from the Recanati Fund of the Business School at the Hebrew University to Lilach Sagiv.

 

Journal Reference:

  1. L. Segal-Caspi, S. Roccas, L. Sagiv. Don't Judge a Book by Its Cover, Revisited: Perceived and Reported Traits and Values of Attractive Women. Psychological Science, 2012; DOI: 10.1177/0956797612446349

Recovery of brain volumes with abstinence may vary for different brain regions

Chronic alcohol abuse can severely damage the nervous system, particularly cognitive functions, cerebral metabolism, and brain morphology. Building upon previous findings that alcoholics can experience brain volume recovery with abstinence, this study found that recovery of cerebral gray matter (GM) can take place within the first two weeks of abstinence, but may vary between brain regions.

Results will be published in the January 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Shrinkage of brain matter, and an accompanying increase of cerebrospinal fluid, which acts as a cushion or buffer for the brain, are well-known degradations caused by alcohol abuse," explained Gabriele Ende, professor of medical physics in the Department of Neuroimaging at the Central Institute of Mental Health. "This volume loss has previously been associated with neuropsychological deficits such as memory loss, concentration deficits, and increased impulsivity."

"Several processes likely account for changes in brain tissue volume observed through bouts of drinking and abstinence over the course of alcoholism," added Natalie May Zahr, a research scientist in the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine. "One process likely reflects true, irreversible neuronal cell death, while another process likely reflects shrinkage, a mechanism that would allow for volume changes in both negative and positive directions, and could account for brain volume recovery with abstinence."

"Gray matter (GM) and white matter (WM) are the main components of the brain that can be distinguished with magnetic resonance imaging (MRI)," explained Ende. "GM consists of neuronal cell bodies, neuropil, glial cells, and capillaries. WM mostly contains myelinated axon tracts."

"Myelin forms an insulating sheath around axons that increases the speed at which they are able to conduct electrical activity," added Zahr. "Because myelin is composed primarily of fat, it gives white matter its color. Cerebrospinal fluid (CSF) is a clear fluid that surrounds and thereby cushions the brain in the skull. Conventional brain structural MRI produces images of protons, with contributions primarily from water and some from fat. Tissue contrast is possible because of the fundamental differences in water content in the primary tissues of the brain: WM consists of about 70 percent water, GM 80 percent, and CSF 99 percent."

Ende and her colleagues examined 49 alcohol dependent (AD) patients (40 males, 9 females) from an inpatient alcohol-withdrawal treatment program as well as 55 non-AD but age- and gender-matched individuals or controls (42 males, 13 females) recruited from the community. The AD group was scanned within the first 24 hours of detoxification, and again after two weeks of supervised abstinence. Their scans were compared with those of the controls.

"We found evidence for a rather rapid recovery of the brain from alcohol induced volume loss within the initial 14 days of abstinence," said Ende. "Although brain shrinkage as well as a partial recovery with continued abstinence have been elaborately described in previous studies, no previous study has looked at the brain immediately at the onset of alcohol withdrawal and short term recovery. Our study corroborates previous findings of brain volume reduction for certain brain regions."

The findings also showed a volume reduction of the cerebellum at the time of detoxification. "This has rarely been observed in other studies at later time points after alcohol withdrawal," said Ende. "Two weeks after detoxification, this cerebellum reduction was nearly completely ameliorated. This was unknown previously, the amount of initial reduction in the cerebellum and its relatively fast recovery."

Ende added that an individual's ability to recover from AD appears to vary for different brain regions. "The function of the cerebellum is motor coordination and fine tuning of motor skills," she explained. "Even though we did not access the amelioration of motor deficits in our patients quantitatively, it is striking that there is an obvious improvement of motor skills soon after cessation of drinking, which is paralleled by our observation of a rapid volume recovery of the cerebellum. Higher cognitive functions like divided attention, which are processed in specific cortical areas, take a longer time to recover and this seems to be mirrored in the observed slower recovery of brain volumes of these areas."

"Many alcohol treatment programs only deal with the withdrawal stage of abstinence from alcohol, that is, the first three days," noted Zahr. "Based on the current study and others, suggesting that a minimum set of cognitive abilities is necessary to conquer alcohol addiction, clinicians should consider recovery programs that provide support for the recovering addict for a minimum of two weeks."

Ende agreed. "The ultimate goal of alcoholism treatment is the maintenance of abstinence," she said. "To achieve this, the affected person needs to suppress their drinking urges and relearn to value other pleasures. Brain volume loss hinders this difficult process, so a rapid volume gain is advantageous for the establishment of sober relearning."

"This study offers recovering alcoholics a sense of hope," said Zahr. "Hope that even within two weeks of abstinence, the recovering individual should be able to observe improvements in brain functioning that may allow for better insight and thus ability to remain sober. Indeed, a minimal of brain healing may be necessary before the addict is able to achieve the control necessary to maintain continued abstinence."


Journal Reference:

  1. Julia van Eijk, Traute Demirakca, Ulrich Frischknecht, Derik Hermann, Karl Mann, Gabriele Ende. Rapid Partial Regeneration of Brain Volume During the First 14 Days of Abstinence from Alcohol. Alcoholism: Clinical and Experimental Research, 2012; DOI: 10.1111/j.1530-0277.2012.01853.x

Studies report early childhood trauma takes visible toll on brain

 Trauma in infancy and childhood shapes the brain, learning, and behavior, and fuels changes that can last a lifetime, according to new human and animal research released today. The studies delve into the effects of early physical abuse, socioeconomic status (SES), and maternal treatment. Documenting the impact of early trauma on brain circuitry and volume, the activation of genes, and working memory, researchers suggest it increases the risk of mental disorders, as well as heart disease and stress-related conditions in adulthood.

The findings were presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news about brain science and health.

Today's findings show:

  • Physical abuse in early childhood may realign communication between key "body-control" brain areas, possibly predisposing adults to cardiovascular disease and mental health problems (Layla Banihashemi, PhD, abstract 691.12).
  • Rodent studies provide insight into brain changes that allow tolerance of pain within mother-pup attachment (Regina Sullivan, PhD, abstract 399.19).
  • Childhood poverty is associated with changes in working memory and attention years later in adults; yet training in childhood is associated with improved cognitive functions (Eric Pakulak, PhD, abstract 908.04).
  • Chronic stress experienced by infant primates leads to fearful and aggressive behaviors; these are associated with changes in stress hormone production and in the development of the amygdala (Mar Sanchez, PhD, abstract 691.10).

Another recent finding discussed shows that:

  • Parent education and income is associated with children's brain size, including structures important for memory and emotion (Suzanne Houston, MA).

"While we are becoming fully aware, in general, of the devastating impact that early life adversity has on the developing brain, today's findings reveal specific changes in targeted brain regions and the long-lasting nature of these alterations," said press conference moderator Bruce McEwen, PhD, from The Rockefeller University, an expert on stress and its effects on early brain development. "In doing so, this research points not only to new directions for the improved detection and treatment of resulting cognitive impairment, mental health disorders, and chronic diseases, but also emphasizes the importance of preventing early life abuse and neglect in the first place."

Family history of alcoholism may add to damaging effects of prenatal alcohol exposure

Prenatal exposure to alcohol (PAE) can lead to serious deficiencies associated with fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD), such as impairments in general intelligence, adaptive function, verbal learning and memory, attention, executive function, and visual-spatial functioning. The role of family history of alcoholism (FHP) in the neurocognitive effects of PAE has not yet been studied. This study used neuroimaging to examine spatial working memory (SWM) in children with histories of heavy PAE and children with confirmed FHP but not PAE, finding that FHP may in fact have an impact on neural functioning of children with PAE.

Results will be published in the January 2013 issue of Alcoholism: Clinical & Experimental Research.

"Children with histories of heavy PAE exhibit a broad range of neurocognitive deficits, including deficits in spatial working memory (SWM), which was the focus of this paper," explained Sarah N. Mattson, a professor of psychology at San Diego State University and corresponding author for the study. "Previous studies demonstrated that children with PAE may exhibit difficulties learning spatial locations and later recognizing if an object is in a previously learned location. This type of deficit could impact a variety of real-life behaviors and abilities like route finding, and remembering where personal items are located. This will be especially true when working memory is taxed, that is, when they have to hold one idea or object in memory while trying to do or remember something else."

Mattson explained that the main goal of this study was to tease apart what neurocognitive effects were due to PAE and what effects were due to having an FHP. "In order to address this question it was imperative to investigate a cognitive function that has been examined in both groups, children with PAE and children with an FHP," she said. "One such function is SWM. This is the first study to address the role of FHP in reported neurocognitive effects of PAE and to suggest there are multiple processes leading to differences in brain function in children with prenatal exposure."

"It is extremely important to examine the influence of FHP on the neurobehavioral effects of PAE," said Piyadasa W. Kodituwakku (Kodi), associate professor of pediatrics and neurosciences at the University of New Mexico School of Medicine. "Atypical brain development in children with FASD results from the interactive effects of PAE, genetic/epigenetic factors, and the quality of postnatal environment," he explained. "Investigators have hitherto been reluctant to include an FHP group in their research designs because of the difficulty of ruling out PAE in children from alcoholic families. Given that family members, particularly spouses, often drink together, one can always suspect that the child may have been exposed to some alcohol during pregnancy."

Mattson and her colleagues selected 53 right-handed children, aged 12 to 18 years, from two ongoing neuroimaging studies, one examining the teratogenic effects of alcohol, and one examining family history of alcohol use disorders (AUDs). The children were divided into three groups: 18 youth (14 males, 4 females) with histories of heavy PAE (ALC), 18 youth (12 males, 6 females) without PAE but with an AUD family history (FHP), and 17 youth (8 males, 9 females) with no PAE or AUD family history (CON). All participants underwent structural and functional imaging while engaging in a task designed to assess memory for spatial locations relative to a vigilance condition that assessed attention.

"This comparison of brain functioning during SWM, in children with PAE relative to children with an FHP and no exposure, suggests that some but not all aspects or regions of neural functioning within the alcohol-exposed population may in fact be associated with factors other than prenatal exposure, like an FHP," said Mattson. "Other aspects or regions were more specific to the effects of prenatal alcohol exposure and did not occur in the group of subjects without prenatal exposure."

Differences between the ALC group and the FHP and CON groups suggest that the left middle and superior frontal regions may be specifically affected among alcohol-exposed children. Conversely, differences among the ALC and FHP groups versus the CON group in the lentiform nucleus and insular region indicate these areas may be associated with FHP rather than PAE.

"The finding of increased BOLD response in the middle and superior frontal gyri in alcohol-exposed children during working memory task performance is interesting," said Kodituwakku. "Until this finding is replicated, it is hard to say what it signifies. The main contribution that this paper makes to the field of prenatal alcohol research is making an attempt to estimate the effects of FHP on neurocognitive functioning in children with FASD. However, this is a complex methodological issue because the effects of PAE, family history of alcoholism, and postnatal experiences are interactive, not just additive."

"The main idea is that there may be more than one brain functioning mechanism leading to SWM impairment in children prenatally exposed to alcohol," said Mattson. "Within the context of research on PAE, this paper suggests that differences in brain function in children with heavy PAE may stem from multiple developmental mechanisms, including the insult from PAE and functional differences based on family history. As the alcohol field moves towards intervention, these results suggest multiple approaches may be necessary to address difficulties in SWM or other neurocognitive impairments."


Journal Reference:

  1. Andria L. Norman, Jessica W. O'Brien, Andrea D. Spadoni, Susan F. Tapert, Kenneth Lyons Jones, Edward P. Riley, Sarah N. Mattson. A Functional Magnetic Resonance Imaging Study of Spatial Working Memory in Children with Prenatal Alcohol Exposure: Contribution of Familial History of Alcohol Use Disorders. Alcoholism: Clinical and Experimental Research, 2012; DOI: 10.1111/j.1530-0277.2012.01880.x