Neuropsychological assessment more efficient than MRI for tracking disease progression in memory clinic patients

Progression of disease in memory clinic patients can be tracked efficiently with 45 minutes of neuropsychological testing, new research shows. MRI measures of brain atrophy were shown to be less reliable to pick up changes in the same patients. This finding has important implications for the design of clinical trials of new anti-Alzheimer drugs. If neuropsychological assessment is used as the outcome measure or “gold standard,” fewer patients would be needed to conduct such trials, or the trials may be of shorter duration. Investigators at the University of Amsterdam, The Netherlands, have shown that progression of disease in memory clinic patients can be tracked efficiently with 45 minutes of neuropsychological testing. MRI measures of brain atrophy were shown to be less reliable to pick up changes in the same patients. This finding has important implications for the design of clinical trials of new anti-Alzheimer drugs. If neuropsychological assessment is used as the outcome measure or “gold standard,” fewer patients would be needed to conduct such trials, or the trials may be of shorter duration. The US Food and Drug Administration and its counterparts in other countries, such as the European Medicines Agency, require that pharmaceutical companies test and prove the effectiveness of new drugs through experimental studies. In the case of Alzheimer’s disease, this means amelioration of cognitive and behavioral symptoms or at least slowing down the rate of cognitive and behavioral decline. Until now the outcome measures in this type of research have been cognitive and behavioral rating scales, such as the Alzheimer Disease Assessment Scale (ADAS). If the effect of a new drug cannot be demonstrated with such a scale, the drug will not be approved. The problem with scales like the ADAS is that they are quite crude and cannot pick up subtle changes, especially in early stages of the disease. As an alternative, MRI measures of brain atrophy have been proposed as outcome in clinical trials, because of allegedly better properties to detect subtle changes. This implies that fewer patients are needed in clinical trials of new drugs to show a treatment effect. The Dutch investigators tested this claim at the memory clinic of the Academic Medical Centre, University of Amsterdam, by comparing neuropsychological assessment and MRI measures of brain atrophy in 62 patients with no or early cognitive impairment, but no dementia. At baseline and after two years, neurologists examined the study participants and judged whether or not their cognition was normal. After two years of follow-up, twenty-eight patients were considered to be normal, and 34 had mild cognitive impairment or had progressed to dementia, mostly Alzheimer’s disease. At baseline and at follow-up all patients had a state-of-the-art MRI scan, and memory and other cognitive functions were tested with five standard neuropsychological tests. In the group that the neurologists considered normal at follow-up, cognitive performance was indeed normal at baseline, and it remained so after two years. In the group that was considered impaired, however, cognition was already abnormal at baseline and it declined considerably over the next two years. The MRI measures concerned volumes of the left and right hippocampus, which are extremely important for memory functioning, and are the first to degenerate during the Alzheimer disease process. The volume of the hippocampus decreased less than 1% in the normal group during the follow-up interval, and more than 3% in the impaired group. The pattern of findings was similar for both techniques, but MRI showed less pronounced differences between both groups at baseline than the cognitive tests, and more importantly, less pronounced differences in rate of change. Using figures on rates of change as collected in this study, one may calculate the numbers of patients that would be needed for a hypothetical clinical trial of a new drug. The investigators concluded that only half as many patients would be needed if neuropsychological assessment were used as the gold standard rather than MRI measures of brain atrophy. However, Dr, Edo Richard, one of the neurologists conducting the study, says, “Whichever outcome is selected, evaluation of functioning as it can be noticed by patients will always be needed to confirm the clinical relevance of any treatment effect.” Journal Reference: 1.Ben Schmand, Anne Rienstra, Hyke Tamminga, Edo Richard, Willem A. van Gool, Matthan W.A. Caan, Charles B. Majoie. Responsiveness of Magnetic Resonance Imaging and Neuropsychological Assessment in Memory Clinic Patients. Journal of Alzheimer’s Disease, January 2014 DOI: 10.3233/JAD-131484

Chronic pain research delves into brain: New insight into how brain responds to pain

Source:University of Adelaide Summary:New insights into how the human brain responds to chronic pain could eventually lead to improved treatments for patients, researchers say. Chronic pain is common throughout the world. More than 100 million Americans are believed to be affected by chronic pain. "People living with chronic headache and other forms of chronic pain may experience reduced quality of life, as the pain often prevents them from working, amongst other things. It is therefore imperative that we understand the causes of chronic pain, not just attempt to treat the symptoms with medication," the lead author said.Share This Neuroplasticity is the term used to describe the brain's ability to change structurally and functionally with experience and use. "Neuroplasticity underlies our learning and memory, making it vital during early childhood development and important for continuous learning throughout life," says Dr Ann-Maree Vallence, a Postdoctoral Fellow in the University of Adelaide's Robinson Institute. "The mechanisms responsible for the development of chronic pain are poorly understood. While most research focuses on changes in the spinal cord, this research investigates the role of brain plasticity in the development of chronic pain." Chronic pain is common throughout the world. In Australia, approximately 20% of adults suffer moderate to severe chronic pain. More than 100 million Americans are believed to be affected by chronic pain. Dr Vallence, who is based in the Robinson Institute's Neuromotor Plasticity and Development Group, has conducted a study on patients with chronic tension-type headache (CTTH), a common chronic pain disorder. CTTH is characterized by a dull, constant feeling of pressure or tightening that usually affects both sides of the head, occurring for 15 days or more per month. Other symptoms include poor sleep, irritability, disturbed memory and concentration, and depression and anxiety. "People living with chronic headache and other forms of chronic pain may experience reduced quality of life, as the pain often prevents them from working, amongst other things. It is therefore imperative that we understand the causes of chronic pain, not just attempt to treat the symptoms with medication," Dr Vallence says. In this study, participants undertook a motor training task consisting of moving their thumb as quickly as possible in a specific direction. The change in performance (or learning) on the task was tracked by recording how quickly subjects moved their thumb. A non-invasive brain stimulation technique was also used to obtain a measure of the participants' neuroplasticity. "Typically, when individuals undertake a motor training task such as this, their performance improves over time and this is linked with a neuroplastic change in the brain," Dr Vallence says. "The people with no history of chronic pain got better at the task with training, and we observed an associated neuroplastic change in their brains. However, our chronic headache patients did not get better at the task and there were no associated changes in the brain, suggesting impaired neuroplasticity. "These results provide a novel and important insight into the cause of chronic pain, and could eventually help in the development of a more targeted treatment for CTTH and other chronic pain conditions," she says

Play it again, Sam: How the brain recognizes familiar music

Source:McGill University Summary:Research reveals that the brain’s motor network helps people remember and recognize music that they have performed in the past better than music they have only heard. A recent study sheds new light on how humans perceive and produce sounds, and may pave the way for investigations into whether motor learning could improve or protect memory or cognitive impairment in aging populations.Share This For the study, researchers recruited twenty skilled pianists from Lyon, France. The group was asked to learn simple melodies by either hearing them several times or performing them several times on a piano. Pianists then heard all of the melodies they had learned, some of which contained wrong notes, while their brain electric signals were measured using electroencephalography (EEG). Credit: Palmer, Mathias McGill University[Click to enlarge image] For the study, researchers recruited twenty skilled pianists from Lyon, France. The group was asked to learn simple melodies by either hearing them several times or performing them several times on a piano. Pianists then heard all of the melodies they had learned, some of which contained wrong notes, while their brain electric signals were measured using electroencephalography (EEG).Credit: Palmer, Mathias McGill University Research from McGill University reveals that the brain's motor network helps people remember and recognize music that they have performed in the past better than music they have only heard. A recent study by Prof. Caroline Palmer of the Department of Psychology sheds new light on how humans perceive and produce sounds, and may pave the way for investigations into whether motor learning could improve or protect memory or cognitive impairment in aging populations. The research is published in the journal Cerebral Cortex. "The memory benefit that comes from performing a melody rather than just listening to it, or saying a word out loud rather than just hearing or reading it, is known as the 'production effect' on memory," says Prof. Palmer, a Canada Research Chair in Cognitive Neuroscience of Performance. "Scientists have debated whether the production effect is due to motor memories, such as knowing the feel of a particular sequence of finger movements on piano keys, or simply due to strengthened auditory memories, such as knowing how the melody tones should sound. Our paper provides new evidence that motor memories play a role in improving listeners' recognition of tones they have previously performed." For the study, researchers recruited twenty skilled pianists from Lyon, France. The group was asked to learn simple melodies by either hearing them several times or performing them several times on a piano. Pianists then heard all of the melodies they had learned, some of which contained wrong notes, while their brain electric signals were measured using electroencephalography (EEG). "We found that pianists were better at recognizing pitch changes in melodies they had performed earlier," said the study's first author, Brian Mathias, a McGill PhD student who conducted the work at the Lyon Neuroscience Research Centre in France with additional collaborators Drs. Barbara Tillmann and Fabien Perrin. The team found that EEG measurements revealed larger changes in brain waves and increased motor activity for previously performed melodies than for heard melodies about 200 milliseconds after the wrong notes. This reveals that the brain quickly compares incoming auditory information with motor information stored in memory, allowing us to recognize whether a sound is familiar. "This paper helps us understand 'experiential learning', or 'learning by doing', and offers pedagogical and clinical implications," said Mathias, "The role of the motor system in recognizing music, and perhaps also speech, could inform education theory by providing strategies for memory enhancement for students and teachers." This study was conducted within the framework of the European Erasmus Mundus Auditory Cognitive Neuroscience exchange program, in which North American researchers complete a research project in collaboration with a European laboratory for 6-12 months.

The Brain Processes Complex Stimuli More Cumulatively Than We Thought

The finding represents a new view of how the brain creates internal representations of the visual world. "We are excited to see if this novel view will dominate the wider consensus" said senior author Dr. Miyashita, who is also Professor of Physiology at the University of Tokyo's School of Medicine, "and also about the potential impact of our new computational principle on a wide range of views on human cognitive abilities." The brain recalls the patterns and objects we observe by developing distinct neuronal representations that go along with them (this is the same way it recalls memories). Scientists have long hypothesized that these neuronal representations emerge in a hierarchical process limited to the same cortical region in which the representations are first processed. Because the brain perceives and recognizes the external world through these internal images, any new information about the process by which this takes place has the power to inform our understanding of related functions, including knowledge acquisition and memory. However, studies attempting to uncover the functional hierarchy involved in the cortical process of visual stimuli have tried to characterize this hierarchy by analyzing the activity of single nerve cells, which are not necessarily correlated with neurons nearby, thus leaving these analyses lacking. In a new study appearing in the 12 July issue of the journal Science, lead author Toshiyuki Hirabayashi and colleagues focus not on single neurons but instead on the relationship between neuron pairs, testing the possibility that the representation of an object in a single brain region emerges in a hierarchically lower brain area. "I became interested in this work," said Dr. Hirabayashi, "because I was impressed by the elaborate neuronal circuitry in the early visual system, which is well-studied, and I wanted to explore the circuitry underlying higher-order visual processing, which is not yet fully understood." Hirabayashi and colleagues analyzed nerve cell pairs in cortical areas TE and 36, the latter of which is hierarchically higher, in two adult macaques. After these animals looked at six sets of paired stimuli for several months to learn to associate related objects (a process that can lead to pair-coding neurons in the brain), the researchers recorded neuron responses in areas TE and 36 of both animals as they again performed this task. The neurons exhibited pair association, but not where the researchers would have thought. "The most surprising result," said senior author Dr. Yasushi Miyashita "was that the neuronal circuit that generated pair-association was found only in area TE, not in area 36." Indeed, based on previous studies, which indicated that the number of pair-coding neurons in area TE is much smaller, the researchers would have expected the opposite. During their study, Miyashita and other team members observed that in region TE of the macaque cortex, unit 1 neurons (or source neurons) provided input to unit 2 neurons (or target neurons), which -- unlike unit 1 neurons -- responded to both members of a stimulus pair. "The representations generated in area TE did not reflect a mere random fluctuation of response patterns," explained Dr. Miyashita, "but rather, they emerged as a result of circuit processing inherent to that area of the brain." In area 36, meanwhile, members of neuron pairs behaved differently; on average, unit 1 as well as unit 2 neurons responded to both members of a stimulus pair. Neurons in area 36 received input from area TE, but only from its unit 2 neurons. Taken together, these findings lead the authors to hypothesize the existence of a hierarchical relationship between regions TE and 36, in which paired associations first established in the former region are propagated to the latter one. Here, area 36 represents the next level of a so-called feed forward hierarchy. The work by Hirabayashi and colleagues suggests that the detailed representations of objects commonly observed in the brain are attained not by buildup of representations in a single area, but by emergence of these representations in a hierarchically prior area and their subsequent transfer to the brain region that follows. There, they become sufficiently prevalent for the brain to register. The work also reveals that the brain activity involved in recreating visual stimuli emerges in a hierarchically lower brain area than previously thought. Moving forward, the Japanese research team has plans to expand upon this research, thus continuing to contribute to studies worldwide that aim to give scientists the best possible tools with which to obtain a dynamic picture of the brain. As a next step, the team hopes to further elucidate interactions between the various cortical microcircuits that operate in memory encoding. Dr. Miyashita has conjectured that these microcircuits are manipulated by a global brain network. Using the results of this latest study, he and colleagues are poised to further evaluate this assumption. "It will also be important to weave the neuronal circuit mechanisms into a unified framework," said Dr. Hirabayashi," and to examine the effects of learning on these circuit organizations." Equipped with their new view of cortical processing, the team also hopes to trace the causal chain of memory retrieval across different areas of the cortex. "I am excited by the recent development of genetic tools that will allow us to do this," said Dr. Miyashita. A better understanding of object representations from one area of the brain to the next will shed even greater light on elusive aspects of this hierarchical organ

Brain Frontal Lobes Not Sole Center of Human Intelligence, Comparative Research Suggests

May 13, 2013 — Human intelligence cannot be explained by the size of the brain's frontal lobes, say researchers.  Research into the comparative size of the frontal lobes in humans and other species has determined that they are not -- as previously thought -- disproportionately enlarged relative to other areas of the brain, according to the most accurate and conclusive study of this area of the brain.

It concludes that the size of our frontal lobes cannot solely account for humans' superior cognitive abilities.

The study by Durham and Reading universities suggests that supposedly more 'primitive' areas, such as the cerebellum, were equally important in the expansion of the human brain. These areas may therefore play unexpectedly important roles in human cognition and its disorders, such as autism and dyslexia, say the researchers.

The study is published in the Proceedings of the National Academy of Sciences (PNAS) today.

The frontal lobes are an area in the brain of mammals located at the front of each cerebral hemisphere, and are thought to be critical for advanced intelligence.

Lead author Professor Robert Barton from the Department of Anthropology at Durham University, said: "Probably the most widespread assumption about how the human brain evolved is that size increase was concentrated in the frontal lobes.
"It has been thought that frontal lobe expansion was particularly crucial to the development of modern human behaviour, thought and language, and that it is our bulging frontal lobes that truly make us human. We show that this is untrue: human frontal lobes are exactly the size expected for a non-human brain scaled up to human size.

"This means that areas traditionally considered to be more primitive were just as important during our evolution. These other areas should now get more attention. In fact there is already some evidence that damage to the cerebellum, for example, is a factor in disorders such as autism and dyslexia."

The scientists argue that many of our high-level abilities are carried out by more extensive brain networks linking many different areas of the brain. They suggest it may be the structure of these extended networks more than the size of any isolated brain region that is critical for cognitive functioning.

Previously, various studies have been conducted to try and establish whether humans' frontal lobes are disproportionately enlarged compared to their size in other primates such as apes and monkeys. They have resulted in a confused picture with use of different methods and measurements leading to inconsistent findings