Neural Prosthetic Improved Short Term Memory Coding and Recall

MedicalResearch.com Interview with:

Robert E. Hampson, PhD Professor, Physiology & Pharmacology School of Medicine Wake Forest

Dr. Hampson

Robert E. Hampson, PhD
Professor, Physiology & Pharmacology
School of Medicine
Wake Forest

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are many diseases and injuries that affect human memory, and many types of memory deficits, from inability to recall stored memories to the inability to make new memories.  We focused on problems with making new memories, and identifying the brain activity associated with those memories.  We found that we could identify when the brain formed “codes” for new memory, and when those codes were incorrect or faulty.  By identifying what both “strong” and “weak” naturally occurring codes should be, we influence the process to strengthen the weak codes, resulting in better memory.

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Virtual Reality Study Helps Identify How Memories Are Stored and Retrieved

MedicalResearch.com Interview with:

Halle Dimsdale-Zucker University of California, Davis Center for Neuroscience | Ph.D. Candidate

Halle Dimsdale-Zucker

Halle Dimsdale-Zucker
University of California, Davis
Center for Neuroscience | Ph.D. Candidate

Dynamic Memory Lab

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study sought to test competing models for how different types of retrieved contextual information (spatial, episodic – which is spatial AND temporal information) are supported by the hippocampus and its subfields. We only found differences between the subfields when people were spontaneously reactivating episodic, but not spatial information. This is surprising because a dominant view of the hippocampus is that it is specialized to represent spatial information.

What this suggests is that when there is more than just spatial information that can be remembered that the hippocampus is able to flexibly represent whatever information is most task-relevant for remembering and distinguishing items from one another.

Intriguingly, we found that different subfields represented shared episodic contextual information and item-unique contextual information. This highlights that our memories need to both link together common features of related events while retaining the event-specific details.

UC Davis neuroscientists are using virtual reality to investigate how memories are organized. Graduate student Halle Dimsdale-Zucker showed subjects movies created with virtual sketching software and asked them questions about objects inside the houses. She was able to show that different regions of a brain structure called the hippocampus play different roles in remembering items in context. Credit: Halle Dimsdale-Zucker, UC Davis

UC Davis neuroscientists are using virtual reality to investigate how memories are organized. Graduate student Halle Dimsdale-Zucker showed subjects movies created with virtual sketching software and asked them questions about objects inside the houses. She was able to show that different regions of a brain structure called the hippocampus play different roles in remembering items in context.
Credit: Halle Dimsdale-Zucker, UC Davis

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Our Memory System Is Adapted To Helping Us Raise Children

MedicalResearch.com Interview with:
“Cute babies” by daily sunny is licensed under CC BY 2.0Benjamin M. Seitz
Doctoral Student
Department of Psychology, Learning & Behavior
University of California, Los Angeles

MedicalResearch.com: What is the background for this study? What are the main findings?

 

Response: The adaptive memory literature is based on two crucial theories.

The first is that we process information on different ‘levels’ and these different levels of processing information strongly influence our ability to later remember that information.

The second is that our evolutionary history has shaped our cognitive abilities and that these abilities therefore perform optimally when performing tasks related to evolutionary fitness. It has been established that processing words based on their relevancy to an imagined ancestral survival scenario yields incredible memory performance far superior than processing those same words based on their relevancy to similar imagined scenarios that do not involve the survival element or ancestral environment.

Our study demonstrates that thinking about raising offspring in an ancestral environment while processing words leads to a similar benefit to recall of those words as when thinking about survival, suggesting the human memory system while also useful in helping our species survive may have also been particularly useful in helping us raise our offspring.

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No Convincing Evidence of Memory Dysfunction Due To Statins

MedicalResearch.com Interview with:

Dr-Beth-Taylor

Dr. Taylor

Beth A. Taylor, PhD
Director of Exercise Physiology Research, Hartford Hospital Associate Professor, Kinesiology
University of Connecticut

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hydroxy-methyl-glutaryl (HMG) CoA reductase inhibitors (statins) are the most effective medications for managing elevated concentrations of low-density lipoprotein cholesterol (LDL-C).  Although statins are generally well-tolerated, they are not without side effects, and mild central nervous system (CNS) complaints such as memory loss and attention decrements are the second most commonly reported adverse effect of these drugs.

Studies assessing cognitive effects of statins vary widely and have produced inconclusive findings. Despite the equivocal data on adverse cognitive side effects with statin therapy, in 2012 the FDA announced a safety label change for statins, based on published case reports of memory loss and confusion and data from the Adverse Events Reporting System. One possibility for these equivocal findings is that studies involving the effects of statins on cognition typically have assessed cognitive function using traditional cognitive tests, which may yield small effect sizes and demonstrate high intra-participant variability. This may explain the discrepancy between clinical trials and patient self-reports, and could be addressed by utilizing CNS tests that directly assess brain parameters.

To the best of our knowledge and literature review, this study is the first to investigate the effects of statins on the central nervous system by utilizing fMRI to assess brain neural activation in healthy adults treated with 80 mg atorvastatin or placebo.

We detected few changes attributable to statin therapy with standardized neuropsychological tests, a finding similar to that from previous clinical trials. However, participants on atorvastatin demonstrated altered patterns of neural activation on vs. off statin compared to participants treated with placebo. Unexpectedly, the treatment groups differed at both timepoints. The clinical implications of these findings are unclear and warrant additional clinical trials.

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Chronic Inflammation in Midlife May Predispose To Smaller Brain Volumes and Memory Ability In Seniors

MedicalResearch.com Interview with:
Keenan A. Walker, PhD
Johns Hopkins University School of Medicine
Baltimore, MD

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is quite a bit of evidence linking immune function with dementia. For example, several of the risk genes for Alzheimer’s disease are known to play a key role in immune functioning and the regulation of inflammation. We conducted the current study to determine whether systemic inflammation earlier in life might be a risk factor for neurodegeneration decades later. This long temporal window allows us to get closer to understanding causality. That is, which comes first – systemic inflammation or brain volume loss.

Using a large community sample, we found that individuals with higher levels of blood inflammatory markers during midlife tended to have smaller brain volumes in select regions and reduced memory ability as older adults. We found the strongest associations between systemic inflammation and brain volume loss in brain regions most vulnerable Alzheimer’s disease.

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Long Term Memories Can Be Selectively Erased

MedicalResearch.com Interview with:
Samuel Schacher, PhD and
Jiangyuan Hu, PhD,
Department of Neuroscience
Columbia University Medical Cente
New York State Psychiatric Institute
New York, NY 10032, USA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is well established that learning and memory requires changes in the properties of specific neural circuits in the brain activated by the experience. The long-term storage of the memory is encoded through changes in the function of the synapses within the circuit. Synapses are sites of communication between neurons, and the changes in their function come in two varieties: increases in strength and decreases in strength. The encoding of memories typically requires some combination of these synaptic changes, synaptic plasticity, which can last a long time to contribute to long-term memory. Thus the maintenance of a memory will require the persistent change (long-term synaptic memory) in the function of specific synapses.

But memories come in different flavors. In the original experiment by Pavlov, a neutral tone, which dogs ignore, came to predict the immediate appearance of a meal. After several of these pairings, the dogs would become happily excited just with the tone. The same type of conditioning could have a negative valence – the tone could proceed a shock to one of the dog’s paw. Now the neutral tone would predict a negative stimulus and the dog would express fearful behavior just with the tone (associative learning). A non-associative form of memory would be the same types of stimuli but without the preceding neutral stimulus. At random times the animal will be given a meal or a shock. The behavior of the animal for some time will take on the positive or negative features of its environment – a contented versus depressed condition.

Each of these forms of long-term memory would be maintained by increases in the strength of specific synapses.

The questions addressed in our study published in Current Biology, based on previous work in my lab and the lab of my colleague Wayne Sossin at McGill, were:

1) Do the same molecules maintain increases in synaptic strength in the neurons of the circuit after stimuli that produce long-term classical conditioning (associative learning) and long-term sensitization (non-associative learning)?
2) If different molecules maintain the different synaptic memories, is it possible to reverse or erase the different synaptic memories by interfering with the function of the different molecules?
3) If true, can we reverse the different synaptic memories expressed in the same neuron by interfering with the function of the different molecules.

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Transcranial Brain Stimulation May Improve Cognition and Memory

MedicalResearch.com Interview with:
Michael CTrumbo
Sandia National Laboratories
Department of Psychology
Psychology Clinical Neuroscience Center
The University of New Mexico
Albuquerque, NM 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The impetus for this study can be found in claims made by several commercial enterprises that you can get cognitive benefits from brain training games intended to enhance working memory (the amount of information you can hold and manipulate in your mind at one time). However, a burgeoning body of research shows working memory training games often do not provide the benefits claimed. Research led by my colleague Laura Matzen shows evidence that working memory training may actually impair other kinds of memory.

A key concept in demonstrating improvement of the working memory system is task transfer – if working memory has been improved, then that improvement should be evident when attempting tasks aside from the trained task, to the extent that these new tasks utilize working memory. Brain stimulation combined with working memory training might work when training by itself falls short because stimulation allows for manipulation of brain plasticity in brain regions that are relevant to working memory task performance. If you’re improving connectivity in a brain region involved in working memory, then you should get transfer to other tasks to the extent that they rely on that same brain region. When you’re having people do tasks in the absence of brain stimulation, it’s not clear if you’re getting this general improvement in working memory brain areas. You might be getting very selective, task kind of improvements due to use of task-specific strategy development.

Therefore, the current study was designed to see if noninvasive brain stimulation paired with different types of working memory training might result in improvement not only in the trained task, but in related tasks. The findings suggest that particular parings of stimulation parameters and training programs result in working memory improvement. This is important because working memory is a critical component of many everyday tasks, such as reading and language comprehension, and working memory deficits are common in a number of disease states, such as depression. Working memory decline is also evident as part of the healthy aging process, beginning as early as your mid-20s. Therefore, a safe, reliable way to improve working memory stands to benefit both healthy and clinical populations in a variety of task domains which are critical to achieving a high quality of life.

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Doxycycline May Mute Painful Memories Associated With PTSD

MedicalResearch.com Interview with:
Dominik R Bach, PhD, MD

University of Zurich

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Posttraumatic stress disorder (PTSD) can occur after a psychological trauma such as physical violence, abuse, or natural disaster. It is characterised by increased arousal, flashbacks, and nightmares that reflect memories of the trauma. Current therapies include talking therapy, but it is costly and does not work in everybody. This is why we were looking for ways of reducing aversive memories with a drug. In the current study, we found that the antibiotic doxycycline impairs the formation of negative memories in healthy volunteers.

To form memories, the brain needs to strengthen connections between neurons. It has recently emerged that for strengthening such connections particular proteins are required that sit between nerve cells, so-called MMPs. They are involved in many disorders outside the brain, such as certain cancers and heart disease. This is how we already know that doxycycline suppresses the activity of MMPs. Since doxycycline is relatively safe and readily accessible, our research was relatively straightforward.

76 healthy volunteers – half women, half men – came to the laboratory and received either placebo (a sugar pill) or 200 mg doxycycline. They then took part in a computer test in which one screen color was often followed by a mildly painful electric shock and another color was not.

A week later, volunteers came back to the lab. They were shown the colors again , this time followed by a loud sound but never by shocks. The loud sounds made people blink their eyes – a reflexive response to sudden threat. This eye blink response was measured. Volunteers who had initially been under placebo had stronger eye blink after the color that predicted electric shock than after the other color. This “fear response” is a sensitive measure for memory of negative associations. Strikingly, the fear response was 60% lower in participants who had initially taken doxycycline.

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More than a Feeling: Emotions Determine What You Remember

MedicalResearch.com Interview with:

Signy Sheldon, PhD Assistant Professor Department of Psychology McGill University Montreal, QC, CAN

Dr. Signy Sheldon

Signy Sheldon, PhD
Assistant Professor
Department of Psychology
McGill University
Montreal, QC, CAN

MedicalResearch.com: What is the background for this study?

Response: It is clear to most people that emotion and memory are strongly linked – thinking about our past experiences is often accompanied with a strong feelings, sometimes good and sometimes bad.

In psychological research, many investigations have looked at how emotional memories are remembered differently than non-emotional memories. A lot of this research has found that the valence of a memory, whether it is positive or negative, will impact how detailed a past event can be recalled. Much less research as looked at how the emotions we feel at the time of remembering can also influence the way that memory is recalled. This is a very important area of research. If emotions during remembering can influence what memories are accessed and how we experience these memories, this would suggest that our memories are tagged and organized according to emotions.

In this study, we looked at how different aspects of emotion can affect the types of past experiences we bring to mind to further investigate how emotions direct memory retrieval.

To do this, we had participants listen to unfamiliar excerpts of music that ranged in both memory valence (positive and negative) and arousal (high or low levels). To each piece of music, participants were asked to think of a past memory and then describe their experience of that event they were remembering.

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Optical Manipulation May Be Able To Erase Fearful Memories

MedicalResearch.com Interview with:
Takuya Takahashi M.D. Ph.D.

Professor, Department of Physiology
Yokohama City University
Graduate School of Medicine
Yokohama Japan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A number of patients suffer from traumatic fear memories (eg. PTSD). At this point, there exists no treatment to control aversive fear memories.

People can form aversive fear memory from traumatic events such as disasters and accidents. These fear memories can induce depression and anxiety disorders (eg. panic disorders). Therefore, it is crucial to understand the molecular mechanism underlying fear memory formation and this could lead to the invention of novel technology to control fear memories.

We have previously reported that the formation of fear memory modifies synapses by the incorporation of AMPA receptors at hippocampus. Further, this molecular events are required for the fear memory formation (Mitsushima et al. PNAS 2011, Mitsushima et al. Nature Communications 2013).

Here, we invented the novel technology to erase fear memory by the optical manipulation of AMPA receptor, an important molecule at glutamatergic synapses.

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