Posts tagged memory

Congenital amusia is a disorder characterized by impaired musical skills, which can extend to an inability to recognize very familiar tunes. The neural bases of this deficit are now being deciphered. According to a study conducted by researchers from CNRS and Inserm at the Centre de Recherche en Neurosciences de Lyon (CNRS / Inserm / Université Claude Bernard Lyon 1), amusics exhibit altered processing of musical information in two regions of the brain: the auditory cortex and the frontal cortex, particularly in the right cerebral hemisphere. These alterations seem to be linked to anatomical anomalies in these same cortices. This work, published in May in the journal Brain, adds invaluable information to our understanding of amusia and, more generally, of the “musical brain”, in other words the cerebral networks involved in the processing of music.

Congenital amusia, which affects between 2 and 4% of the population, can manifest itself in various ways: by difficulty in hearing a “wrong note”, by singing “out of tune” and sometimes by an aversion to music. For some of these individuals, music is like a foreign language or a simple noise. Amusia is not due to any auditory or psychological problem  and does not seem to be linked to other neurological disorders. Research on the neural bases of this impairment only began a decade ago with the work of the Canadian neuropsychologist Isabelle Peretz.

Two teams from the Centre de Recherche en Neurosciences de Lyon (CNRS / Inserm / Université Claude Bernard Lyon 1) have studied the encoding of musical information and the short-term memorization of notes. According to previous work, amusical individuals experience particular difficulty in hearing the pitch of notes (low or high) and, although they remember sequences of words normally, they have difficulty in memorizing sequences of notes.

In a bid to determine the regions of the brain concerned with these memorization difficulties, the researchers conducted magneto-encephalographs (a technique that allows very weak magnetic fields produced by neural activity to be measured at the surface of the head) on a group of amusics while they were performing a musical task. The task consisted in listening to two tunes separated by a two-second gap. The volunteers were asked to determine whether the tunes were identical or different.

The scientists observed that, when hearing and memorizing notes, amusics exhibited altered sound processing in two regions of the brain: the auditory cortex and the frontal cortex, essentially in the right hemisphere. Compared to non-amusics, their neural activity was delayed and impaired in these specific areas when encoding musical notes. These anomalies occurred 100 milliseconds after the start of a note.

These results agree with an anatomical observation that the researchers have confirmed using MRI: amusical individuals have an excess of grey matter in the inferior frontal cortex, accompanied by a deficit in white matter, one of whose essential constituents is myelin. This surrounds and protects the axons of the neurons, helping nerve signals to propagate rapidly. The researchers also observed anatomical anomalies  in the auditory cortex. This data lends weight to the hypothesis according to which amusia could be due to insufficient communication between the auditory cortex and the frontal cortex.

Amusia thus stems from impaired neural processing from the very first steps of sound processing in the auditory nervous system. This work makes it possible to envisage a program to remedy these musical difficulties, by targeting the early steps of the processing of sounds and their memorization.

(Source: www2.cnrs.fr)

Distortions and illusions within human memory are well documented in scientific and forensic work and appear to be a basic feature of memory functioning.

Yet several studies suggest that blind individuals, especially those without any visual experience, possess superior verbal and memory skills.

The researchers from the Department of Psychology ran memory tests on groups of congenitally blind people, those with late onset blindness and sighted people, in collaboration with a research assistant at Queen Mary, University of London.

Each participant was asked to listen to a series of word lists and then recall the words they heard. Past research has found that such words lists normally cause people to falsely “remember” words that are related to those heard, but that were never actually experienced. For example hearing ‘chimney’, ‘cigar’, and ‘fire’ can prompt some to produce a false memory of the word ‘smoke’ when asked to remember the list of words.

The researchers found that not only did the congenitally blind participants remember more words but were also less likely to create false memories of the related words. In contrast, the sighted and late blind participants remembered fewer words and were much more likely to falsely remember the related words that were not read to the participants.

Dr Achille Pasqualotto, postdoctoral researcher and first author of the study, said: “We found that congenitally blind participants reported significantly more correct words than both late onset blind and sighted people. Most of the congenitally blind participants avoided unrelated words, therefore congenitally blind participants can store more items and with a higher fidelity.”

Dr Michael Proulx who led the study added: “Our results show that visual experience has a significant negative impact on both the number of items remembered and the accuracy of semantic memory and also demonstrate the importance of adaptive neural plasticity in the congenitally blind brain for enhanced memory retrieval mechanisms.

“There is an old Hebrew proverb that believes the blind were the most trustworthy sources for quotations and that certainly seems true in this case. It will be interesting to see whether congenitally blind individuals would also be better witnesses in forensic studies.”

The researched is from the paper Congenital blindness improves semantic and episodic memory, published in the journal Behavioural Brain Research.

(Source: bath.ac.uk)

Despite decades of research, relatively little is known about the identity of RNA molecules that are transported as part of the molecular process underpinning learning and memory.

Now, working together, scientists from the Florida campus of The Scripps Research Institute (TSRI), Columbia University and the University of Florida, Gainesville, have developed a novel strategy for isolating and characterizing a substantial number of RNAs transported from the cell-body of neuron (nerve cell) to the synapse, the small gap separating neurons that enables cell to cell communication.

Using this new method, the scientists were able to identify nearly 6,000 transcripts (RNA sequences) from the genome of Aplysia, a sea slug widely used in scientific investigation.

The scientists’ target is known as the synaptic transcriptome—roughly the complete set of RNA molecules transported from the neuronal cell body to the synapse.

In the study, published recently in the journal Proceedings of the National Academy of Sciences, the scientists focused on the RNA transport complexes that interact with the molecular motor kinesin; kinesin proteins move along filaments known as microtubules in the cell and carry various gene products during the early stage of memory storage.

While neurons use active transport mechanisms such as kinesin to deliver RNA cargos to synapses, once they arrive at their synaptic destination that service stops and is taken over by other, more localized mechanisms—in much the same way that a traveler’s bags gets handed off to the hotel doorman once the taxi has dropped them at the entrance.

The scientists identified thousands of these unique sequences of both coding and noncoding RNAs. As it turned out, several of these RNAs play key roles in the maintenance of synaptic function and growth.

The scientists also uncovered several antisense RNAs (paired duplicates that can inhibit gene expression), although what their function at the synapse might be remains unknown.

“Our analyses suggest that the transported RNAs are surprisingly diverse,” said Sathya Puthanveettil, a TSRI assistant professor who designed the study. “It also brings up an important question of why so many different RNAs are transported to synapses. One reason may be that they are stored there to be used later to help maintain long-term memories.”

The team’s new approach offers the advantage of avoiding the dissection of neuronal processes to identify synaptically localized RNAs by focusing on transport complexes instead, Puthanveettil said. This new approach should help in better understanding changes in localized RNAs and their role in local translation as molecular substrates, not only in memory storage, but also in a variety of other physiological conditions, including development.

“New protein synthesis is a prerequisite for maintaining long term memory,” he said, “but you don’t need this kind of transport forever, so it raises many questions that we want to answer. What molecules need to be synthesized to maintain memory? How long is this collection of RNAs stored? What localized mechanisms come into play for memory maintenance? ”

(Source: scripps.edu)

Close family members of people with Alzheimer’s disease are more than twice as likely as those without a family history to develop silent buildup of brain plaques associated with Alzheimer’s disease, according to researchers at Duke Medicine.

The study, published online in the journal PLOS ONE on April 17, 2013, confirms earlier findings on a known genetic variation that increases one’s risk for Alzheimer’s, and raises new questions about other genetic factors involved in the disease that have yet to be identified.

An estimated 25 million people worldwide have Alzheimer’s disease, and the number is expected to triple by 2050. More than 95 percent of these individuals have late-onset Alzheimer’s, which usually occurs after the age of 65. Research has shown that Alzheimer’s begins years to decades before it is diagnosed, with changes to the brain measurable through a variety of tests.

Family history is a known risk factor and predictor of late-onset Alzheimer’s disease, and studies suggest a two- to four-fold greater risk for Alzheimer’s in individuals with a mother, father, brother or sister who develop the disease. These first-degree relatives share roughly 50 percent of their genes with another member of their family. Common genetic variations, including changes to the APOE gene, account for around 50 percent of the heritability of Alzheimer’s, but the disease’s other genetic roots are still unexplained.

“In this study, we sought to understand whether simply having a positive family history, in otherwise normal or mildly forgetful people, was enough to trigger silent buildup of Alzheimer’s plaques and shrinkage of memory centers,” said senior author P. Murali Doraiswamy, professor of psychiatry and medicine at Duke.

Duke neuroscience research trainee Erika J. Lampert, Doraiswamy and colleagues analyzed data from 257 adults, ages 55 to 89, both cognitively healthy and with varying levels of impairment. The participants were part of the Alzheimer’s Disease Neuroimaging Initiative, a national study working to define the progression of Alzheimer’s through biomarkers.

The researchers looked at participants’ age, gender and family history of the disease, with a positive family history defined as having a parent or sibling with Alzheimer’s. This information was compared with cognitive assessments and other biological tests, including APOE genotyping, MRI scans measuring hippocampal volume, and studies of three different pathologic markers (Aβ42, t-tau, and t-tau/Aβ42 ratio) found in cerebrospinal fluid.

As expected, the researchers found that a variation in the APOE gene associated with a greater risk and earlier onset of Alzheimer’s was overrepresented in participants with a family history of the disease. However, other biological differences were also seen in those with a family history, suggesting that unidentified genetic factors may influence the disease’s development before the onset of dementia.

Nearly half of all healthy people with a positive family history would have met the criteria for preclinical Alzheimer’s disease based on measurements of their cerebrospinal fluid, but only about 20 percent of those without a family history would have met such criteria.

“We already knew that family history increases one’s risk for developing Alzheimer’s, but we now are showing that people with a positive family history may also have higher levels of Alzheimer’s pathology earlier, which could be a reason why they experience a faster cognitive decline than those without a family history,” Lampert said.

The findings may influence the design of future studies developing new diagnostic tests for Alzheimer’s, as researchers may choose to exclude those with a positive family history – a group that has historically volunteered to participate in studies to better understand the disease – as healthy controls, given that they are more likely to develop Alzheimer’s pathology.

“Our study shows the power of a simple one-minute questionnaire about family history to predict silent brain changes,” Doraiswamy said. “In the absence of full understanding of all genetic risks for late-onset Alzheimer’s, family history information can serve as a risk stratification tool for prevention research and personalizing care.” He encouraged those with a known positive family history to seek out clinical trials specific to preventing the disease.

(Source: dukehealth.org)

Brain scans are increasingly able to reveal whether or not you believe you remember some person or event in your life. In a new study presented at a cognitive neuroscience meeting today, researchers used fMRI brain scans to detect whether a person recognized scenes from their own lives, as captured in some 45,000 images by digital cameras. The study is seeking to test the capabilities and limits of brain-based technology for detecting memories, a technique being considered for use in legal settings.

“The advancement and falling costs of fMRI, EEG, and other techniques will one day make it more practical for this type of evidence to show up in court,” says Francis Shen of the University of Minnesota Law School, who is chairing a session on neuroscience and the law at a meeting of the Cognitive Neuroscience Society (CNS) in San Francisco this week. “But technological advancement on its own doesn’t necessarily lead to use in the law.” But as the technology has advanced and as the legal system desires to use more empirical evidence, neuroscience and the law are intersecting more often than in previous decades.

In U.S. courts, neuroscientific evidence has been used largely in cases involving brain injury litigation or questions of impaired ability. In some cases outside the United States, however, courts have used brain-based evidence to check whether a person has memories of legally relevant events, such as a crime. New companies also are claiming to use brain scans to detect lies – although judges have not yet admitted this evidence in U.S. courts. These developments have rallied some in the neuroscience community to take a critical look at the promise and perils of such technology in addressing legal questions – working in partnership with legal scholars through efforts such as the MacArthur Foundation Research Network on Law and Neuroscience.

Recognizing your own memories

What inspired Anthony Wagner, a cognitive neuroscientist at Stanford University, to test fMRI uses for memory detection was a case in June 2008 in Mumbai, India, in which a judge cited EEG evidence as indicating that a murder suspect held knowledge about the crime that only the killer could possess. “It appeared that the brain data held considerable sway,” says Wagner, who points out that the methods used in that case have not been subject to extensive peer review.

Since then, Wagner and colleagues have conducted a number of experiments to test whether brain scans can be used to discriminate between stimuli that people perceive as old or new, as well as more objectively, whether or not they have previously encountered a particular person, place, or thing. To date, Wagner and colleagues have had success in the lab using fMRI-based analyses to determine whether someone recognizes a person or perceives them as unfamiliar, but not in determining whether in fact they have actually seen them before.

In a new study presented today, his team sought to take the experiments out of the lab and into the real world by outfitting participants with digital cameras around their necks that automatically took photos of the participants’ everyday experiences. Over a multi-week period, the cameras yielded 45,000 photos per participant.

Wagner’s team then took brief photo sequences of individual events from the participants’ lives and showed them to the participants in the fMRI scanner, along with photo sequences from other subjects as the control stimuli. The researchers analyzed their brain patterns to determine whether or not the participants were recognizing the sequences as their own. “We did quite well with most subjects, with a mean accuracy of 91% in discriminating between event sequences that the participant recognized as old and those that the participant perceived as unfamiliar, ” Wagner says. “These findings indicate that distributed patterns of brain activity, as measured with fMRI, carry considerable information about an individual’s subjective memory experience – that is, whether or not they are remembering the event.”

In another new study, Wagner and colleagues tested whether people can “beat the technology” by using countermeasures to alter their brain patterns. Back in the lab, the researchers showed participants individual faces and later asked them whether the faces were old or new. “Halfway through the memory test, we stopped and told them ‘What we are actually trying to do is read out from your brain patterns whether or not you are recognizing the face or perceiving it as novel, and we’ve been successful with other subjects in doing this in the past. Now we want you to try to beat the system by altering your neural responses.’” The researchers instructed the participants to think about a familiar person or experience when presented with a new face, and to focus on a novel feature of the face when presented a previously encountered face.

“In the first half of the test, during which participants were just making memory decisions, we were well above chance in decoding from brain patterns whether they recognized face or perceived it as novel. However, in the second half of the test, we were unable to classify whether or not they recognized the face nor whether the face was objectively old or new,” Wagner says. Within a forensic setting, Wagner says, it is conceivable that a suspect could use such measures to try to mask the brain patterns associated with memory.

Wagner says that his work to date suggests that the technology may have some utility in reading out brain patterns in cooperative individuals but that the uses are much more uncertain with uncooperative individuals. However, Wagner stresses that the method currently does not distinguish well between whether a person’s memory reflects true or false recognition. He says that it is premature to consider such evidence in the courts because many additional factors await future testing, including the effects of stress, practice, and time between the experience and the memory test.

Overgeneralizing the adolescent brain

A general challenge to the use of neuroscientific evidence in legal settings, Wagner says, is that most studies are at the group rather than the individual level. “The law cares about a particular individual in a particular situation right in front of them,” he says, and the science often cannot speak to that specificity.

Shen cites the challenge of making individualized inference from group-based data as one of the major ones facing use of neuroscience evidence in the court. “This issue has come up in the context of juvenile justice, where the adolescent brain development data confirms behavioral data that on average 17-year-olds are more impulsive than adults, but does not tell us whether a particular 17-year-old, namely the one on trial, was less able to control his/her actions on the day and in the manner in question,” he says.

Indeed, B.J. Casey of the Weill Medical College of Cornell University says that too often we overgeneralize the lack of self control among adolescents. Although adolescents do show poor self control as a group, some situations and individuals are more prone to this breakdown than others.

“It is not that teens can’t make decisions, they can and they can do so efficiently,” Casey says. “It is when they must make decisions in the heat of the moment – in presence of potential or perceived threats, among peers – that the court should consider diminished responsibility of teens while still holding them accountable for their behavior.” Research suggests that this diminished ability is due to the immature development of circuitry involved in processing of negative or positive cues in the environment in the subcortical limbic regions and then in regulating responses to those cues in the prefrontal cortex.

The body of research to date is at the group-level, however, and is not yet able to comment on the neurobiological maturity of an individual adolescent. To help provide more guidance on this issue in legal settings, Casey and colleagues are working alongside legal scholars on a developmental imaging study, funded by the MacArthur Foundation, that is examining behaviors relevant to juvenile criminal behavior, including impulsivity and peer influence.

Making real-world connections

The same type of work – to connect brain imaging to particular behaviors in the real-world – is ongoing in a number of other areas, including fMRI-based lie detection and linking negligence to specific mental states. “It’s a big leap to go from a laboratory setting, in which impulse control may be measured by one’s ability to not press a button in response to a stimulus, to the real-world, where the question is whether someone had requisite self-control not to tie up an innocent person and throw them off a bridge.” Shen says. “I don’t see neuroscience solving these big problems anytime soon, and so the question for law becomes: What do we do with this uncertainty? I think this is where we’re at right now, and where we’ll be for some time.”

“With a few notable exceptions such as death penalty cases, cases where a juvenile is facing a very stiff sentence, and litigating brain injury claims, ‘law and neuroscience’ is not familiar to most lawyers,” Shen says. “But this might change – and soon.” The ongoing work is vital, he says, for laying a foundation for a future that’s yet to come, and he hopes that more neuroscientists will increasingly collaborate with legal scholars.