Revising Traumatic Memories in the Reconsolidation Window

October 6, 2017 · Posted in Potential Treatments · Comment 

elderly womanWe have previously described in the BNN how therapies can take advantage of the memory reconsolidation window to reduce the power of traumatic memories. Five minutes to one hour following active emotional recall of a traumatic event, a ‘window’ opens during which therapies can revise or extinguish the traumatic memory. A 2017 article by our Editor-in-Chief Robert M. Post and Robert Kegan in the journal Psychiatric Research describes how the reconsolidation window could theoretically be used to prevent recurring depressive episodes.

The theory is based on the idea that depressive episodes initially stem from stressors, but eventually become ingrained in the brain’s habit memory system. Cognitive behavioral therapy during the memory reconsolidation window might be a good way to disrupt these habit memories.

The memory reconsolidation window has already been used successfully to reduce traumatic memories and even to reduce heroin and cocaine cravings in addiction. The idea in changing traumatic memories, in the words of researcher Göran Högberg in a 2011 article in the journal Psychology Research in Behavior Management, is to “change a reliving intruding memory into a more distant episodic memory.” Post and Kegan suggest that work in depression would have a similar goal, to rework the triggering experience and render the depressive experience “less harsh, severe, [and] self-defeating (guilt-inducing).”
In exploring this new therapeutic approach, Post and Kegan suggest that it might be best to begin with patients whose depressive episodes are triggered by stressors.

The patient would be encouraged to recall the memory of the particular stressor and any emotions related to it. Then they would be prompted to reframe the memory, either by recognizing adaptive aspects of their response, focusing on their youth at the time of the stressor in the case of childhood memories, addressing any guilt the patient may feel, or other techniques used in trauma therapy. Evoking positive feelings during this period via relaxation exercises would be another useful practice.

In addition to targeting stressors that precede depression, the stress of the depressive experience itself could be a target of reframing during the reconsolidation window.
Questions remain, such as whether to target early or more recent memories, and whether this technique would be as useful in reducing manic episodes. Patient characteristics might also affect the success of this type of therapeutic intervention.

Post and Kegan also address how the therapy might be used in different stages of illness, and how it might be combined with other therapies, such as medications or procedures such as repeated transcranial magnetic stimulation (rTMS).

Breathing in Through the Nose Enhances Judgment and Memory

August 28, 2017 · Posted in Brain Imaging · Comment 

breathing through the nose

A 2016 study published in the Journal of Neuroscience reported that the rhythm of breathing changes electrical activity in the brain and can improve emotional judgments and recall. Breathing in through the nose seemed to produce benefits compared to breathing out or to breathing in through the mouth.

Participants more easily identified a fearful face if they viewed it while breathing in. They also had an easier time remembering objects they observed while breathing in. The effects were not seen if the participants breathed through their mouth.

The researchers, led by Christina Zelano, reported that there was a major difference in brain activity in the amygdala and hippocampus during inhalation versus exhalation. Breathing in, in addition to stimulating the olfactory cortex responsible for smell perception, seems to activate the entire limbic system, the emotional center of the brain.

High-Dose Vitamin D May Improve Cognition More Than Low-Dose Vitamin D

August 16, 2017 · Posted in Potential Treatments · Comment 

Woman taking vitaminVitamin D deficiency has been associated with dementia and cognitive decline, but supplements may help. In a study of 82 healthy individuals with low vitamin D levels, high-dose vitamin D supplements (4000 IU/day) improved visual/nonverbal memory more than did low-dose vitamin D supplements (400 IU/day) over 18 weeks.

The 2017 study took place in Canada, where short winter days can make it more difficult to get sufficient levels of vitamin D from sunlight. The higher-dose supplements raised blood levels of vitamin D compared with the lower-dose supplements.

Those who received the higher doses performed better at tests of visual memory such as the Pattern Recognition Memory Task and the Paired Associates Learning Task, but their performance on tests of verbal memory was not significantly different from those in the lower-dose group. This suggests that higher vitamin D levels are particularly important to visual/nonverbal memory.

The study by Jacqueline A. Pettersen was published in the journal Experimental Gerontology.

Single Dose of Modafinil Improved Memory in People in Remission from Depression

August 3, 2017 · Posted in Potential Treatments · Comment 

memory aidModafinil is a wake-promoting medication used to treat narcolepsy, but studies have also shown that it can improve cognition in people with schizophrenia or attention deficit hyperactivity disorder. It may also help people with lingering cognitive difficulties after recovering from a depression. A 2016 article in the journal Biological Psychiatry reported that a single 200mg dose of modafinil improved performance on tests of episodic memory and working memory (but not planning or attention).

The study by researcher Barbara Sahakian and colleagues included 60 patients who had recently recovered from a depression. They took some cognitive tests to establish a baseline of their performance. A week later, they were given either a placebo or a single dose of modafinil, and two hours later they completed the cognitive tests again. The modafinil group performed better on the memory-related tasks.

While side effects were limited, two participants who received modafinil had sleep disturbances that night.

Longer-term studies are needed to determine whether modafinil is safe and effective if taken over a longer period of time. Cognitive dysfunction can interfere with daily tasks such as work or school and put people at greater risk of relapse, so effective treatments have the potential to greatly improve quality of life for people in remission from depression.

Disrupting Memories of Cocaine Use Might Prevent Relapse

May 17, 2017 · Posted in Potential Treatments · Comment 

cocaine treatment

Cocaine users who want to abstain from the drug may find that encountering people or places who remind them of past cocaine use can increase their cravings for the drug and lead to relapse. Researchers are studying animals to see if disrupting the link between an environmental cue and the memory of cocaine’s effects could reduce cravings for the drug.

In a 2016 article in the journal Neuropsychopharmacology, researcher Melissa S. Monsey and colleagues reported that in rats, the amnesia-causing natural compound garcinol can weaken the cues that lead to a cocaine-seeking. Garcinol is derived from the rind of kokum (or Garcinia indica) fruit, which is native to the west coast of India.

Monsey and colleagues delivered the garcinol during a period when the rats’ brains were reconsolidating memories that linked an environmental cue with the pleasurable effects of cocaine.

For 12 days, the rats in the study could press a lever and receive an intravenous infusion of cocaine that was paired with a light and a sound. Then the lever stopped working for 8 days. Next, the researchers observed how the rats behaved when the light and sound returned.

The light and sound were meant to remind the rats of the previous times they received cocaine, prompting their brains to reconsolidate the memory linking the light/sound with the pleasurable effects of cocaine.

Half of the rats were given an injection of garcinol during this memory reconsolidation period. While all of the rats continued to seek out cocaine, in the garcinol-treated rats, the light/sound was no longer linked to cocaine. Their cocaine-seeking behavior from then on was unrelated to the light/sound, and the link between the light/sound and cocaine could not be reinstated in these rats.

This research on rats may help clarify how cravings are produced in the brain, and how they might be prevented or treated.

Editor’s Note: In 2012, Yan-Xue Xue and colleagues reported in the journal Science that in humans, psychological techniques can be used to help a patient unlearn the association between an environmental cue and the effects of a drug, using the same theory of the memory reconsolidation period. When patients in recovery from heroin addiction were prompted to revisit memories of heroin use 10 minutes before extinction training (in which they looked at heroin or heroin paraphernalia without receiving the drug), they ended up with fewer cravings for heroin 1, 30, and 180 days later compared to patients who did extinction training without revisiting memories of past heroin use (and thus without opening the memory reconsolidation window, which researchers believe opens 5 minutes to an hour after someone engages in active recall).

Early Marijuana Use Linked To Abnormal Brain Function, Low IQ

May 10, 2017 · Posted in Risk Factors · Comment 

young marijuana usersA study of depression and marijuana use found that using marijuana before the age of 17 was linked to abnormal brain function and lower IQ. In a 2016 article in the journal Acta Psychiatrica Scandinavica, researcher Elizabeth Osuch and colleagues described a study that compared four categories of youth: frequent pot users with depression, frequent pot users without depression, those with depression who did not use pot, and healthy individuals who did not use pot. The researchers also compared those who began using pot after the age of 17 to those who began earlier.

The main findings were that brain function in the areas of reward processing and motor control differed across the four groups. Depression was linked to deficits in brain function. Marijuana use did not correct these deficits, and in some parts of the brain, worsened them.

Those who had used marijuana before the age of 17 had abnormalities in memory, visuo-spatial processing, self-referential activity, and reward processing. Those who had started using marijuana at younger ages also had lower IQ scores.

Cinnamon Improves Memory in Mice

October 27, 2016 · Posted in Potential Treatments · Comment 

cinnamon improves learning in mice

A recent study found that mice that ate more cinnamon got better and faster at learning. In the study, published in the Journal of Neuroimmune Pharmacology in 2016, separated mice into good learners and poor learners based on how easily they navigated a maze to find food. After the poor learners were fed cinnamon for a month, they could find the food more than twice as quickly as before.

The benefits of cinnamon come from sodium benzoate, a chemical produced as the body breaks down the cinnamon. Sodium benzoate enters the brain and allows the hippocampus to create new neurons.

Feeding cinnamon to the poor learning mice normalized their levels of receptors for the neurotransmitter GABA, closing the gap with good learners. Sodium benzoate also improved the structural integrity of some brain cells. Cinnamon also can help sensitize insulin receptors.

Doctors hope these findings may eventually contribute to treatment research on Alzheimer’s and Parkinson’s diseases.

Cinnamon should be consumed in moderate quantities because the Chinese variety most commonly found in North American supermarkets has high levels of coumarin, a compound that can be toxic to the liver when consumed in large quantities. Ceylon (Sri Lankan) cinnamon has lower levels of coumarin.

Inflammation Plays a Role in Fear Memories

June 24, 2016 · Posted in Neurobiology · Comment 

inflammation in fear memories

People with post-traumatic stress disorder (PTSD) often experience fearful memories of the trauma they witnessed. Researchers are working to determine the neurobiological basis for these persistent fear memories in order to better treat PTSD. Current treatments mainly target the central nervous system. Because many people with PTSD have elevated levels of pro-inflammatory immune molecules in their blood, there has been a recent push to determine whether targeting that inflammation may be another way of treating PTSD.

A recent study by researchers Matthew Young and Leonard Howell used an animal model to learn more about the link between trauma, inflammation, and fear memories. The researchers exposed mice to a trauma that produced both a persistent fear response and an increase in inflammatory molecules in the blood. Some of the mice were also given antibodies to neutralize the inflammatory immune response. When the mice were exposed to a cue meant to remind them of the trauma, levels of the inflammatory molecule IL-6 spiked again. When the mice were given antibodies to neutralize IL-6 just before being exposed to the cue, they produced less of a fear reaction.

The researchers, who presented their work at a scientific meeting in December, concluded that traumatic experiences produce not only persistent fearful memories, but also an immune reaction. They believe that the spike in IL-6 following trauma plays a role in the persistence of those memories, and that elevated IL-6 in the blood may explain symptoms of PTSD and other disorders that involve fear learning (such as phobias).

Alzheimer’s Treatments May Work for Memory Dysfunction in Depression

April 11, 2016 · Posted in Potential Treatments · Comment 

memory problems in depression

In a recent BNN article on potential drugs for memory loss, we omitted two conventional classes of drugs used to treat Alzheimer’s Disease—acetylcholine esterase inhibitors (AChE-Is) and the blocker of glutamate NMDA receptors memantine (Namenda). This was intentional, as we hoped to suggest possible approaches prior to the use of these drugs for full-blown dementia. However, we neglected to cite a 1999 study by Fred Jacobsen in the Journal of Clinical Psychiatry that indicated that the AChE-I drug donepezil (Aricept) was effective in improving drug-induced memory dysfunction in patients without dementia. Side effects included insomnia, nausea, vomiting, and diarrhea.

Jacobsen has used AChE-Is to improve memory in over 80 patients with unipolar or bipolar depression, aged 19-85. In a 2016 personal communication to the BNN, he indicated that doses of 5mg/day are typically enough to improve memory. Higher doses of 10mg/day may be more effective, but increase the risk of switching into mania for patients with bipolar depression. Some of Jacobsen’s patients have used AChE-I drugs for 10–15 years without the drugs losing effectiveness. For some patients, Jacobsen has switched from prescribing donezepil to prescribing rivastigmine (Exelon or Exelon patch), which he finds they can more easily tolerate.

We should also remind readers of the BNN of our previous report on memantine (Namenda) for bipolar depressed patients with cognitive impairment. We wrote, “In an abstract presented at the 67th Annual Meeting of the Society of Biological Psychiatry in 2012, Dan V. Iosifescu reported that in a randomized 12-week study in which the anti-Alzheimer’s drug memantine was given to 72 euthymic bipolar subjects experiencing cognitive deficits, the drug was associated with improvement in spatial and working memory, verbal and episodic memory, and other indices that included measurements of attention and language skills. In conjunction with this treatment, a subgroup of subjects had increases in left hippocampal NAA (a measure of neuronal viability) and increases in choline in the right hippocampus. The initial improvements in these neuropsychological test results remained over 12 weeks of open follow-up.”

In an earlier proof-of-concept study published in the journal CNS Neuroscience and Therapeutics in 2009, Iosifescu had also reported that among nineteen subjects with bipolar disorder that was in remission, but who had residual cognitive deficits, open-label treatment with the AChE-I galantamine (extended release) at doses of 8–24 mg/day led to improvement in those cognitive symptoms after 4 months.

Memory Activates Epigenetic Changes in Mice Brain Cells

April 4, 2016 · Posted in Genetics, Neurobiology · Comment 

epigenetic changes to mouse brain cells

In a 2015 article in Nature Neuroscience, Stefan Bonn and André Fischer reported that when mice were prompted to use their long-term memory to recognize a specific environment, epigenetic changes occurred in their neurons and glia. Epigenetic changes refer to chemical alterations in DNA or histones (which give DNA structure) that increase or decrease the expression of certain genes. Sometimes environmental factors lead to a methyl or acetyl group joining a strand of DNA or histones, changing how easily the genes are turned on or off.

When the mice used their long-term memory, the main change that occurred was DNA methylation in their neurons. There were also changes to histones that were linked to memory acquisition but resulted in few changes in gene expression. The DNA methylation changes, on the other hand, changed neural pathways, leading to “rewiring” of the brain.

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