Darryle Schoepp

Merck isnt letting its first big Phase III failure in Alzheimers get in the way of its ambitions in the field. The pharma giant just grabbed worldwide rights to a preclinical tau-targeted antibody, lining up a parallel shot at a prime suspect in the development of the memory-wasting ailment.

Merck $MRK struck its deal with Japans Teijin Pharma, including an upfront and milestones which it didnt disclose (and rarely does). Now its neuroscience R&D group will take over development, reserving a royalty split if this one ever makes it to the market.

Merck has the most advanced BACE drug verubecestat, which moves upstream to halt development of amyloid beta in development. Back in February Merck shuttered its EPOCH trial for verubecestat in mild-to-moderate Alzheimers after the external data monitoring committee concluded that the drug was a bust, with virtually no chance of success. But the pharma giant is continuing its work on the drug with a separate Phase III in very early stage prodromal patients.

While toxic clusters of amyloid beta in the brain have long been considered the most likely cause of the disease, there has been growing attention for tau as well. That in turn has helped generate a growing consensus that any company that wants to make an impact on the disease, after 15 long years of clinical failure, will need to come up with cocktail therapies that cover a variety of targets. The tau-abeta combo is the first step in that direction, though theres no real certainty yet on exactly which mechanisms should be targeted.

Teijin Pharma scientists have made important progress to advance this investigational anti-tau antibody to this stage of development, said Darryle Schoepp, vice president, neuroscience discovery, Merck Research Laboratories. Merck remains committed to developing meaningful therapeutic options for the treatment of Alzheimers and other neurological diseases.

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Right on the heels of a PhIII failure, Merck neuroscience doubles down with a new drug targeting tau - Endpoints News

Neuroscience and intelligence refers to the various neurological factors that are partly responsible for the variation of intelligence within a species or between different species. A large amount of research in this area has been focused on the neural basis of human intelligence. Historic approaches to study the neuroscience of intelligence consisted of correlating external head parameters, for example head circumference, to intelligence.[1] Post-mortem measures of brain weight and brain volume have also been used.[1] More recent methodologies focus on examining correlates of intelligence within the living brain using techniques such as magnetic resonance imaging (MRI), functional MRI (fMRI), electroencephalography (EEG), positron emission tomography and other non-invasive measures of brain structure and activity.[1]

Researchers have been able to identify correlates of intelligence within the brain and its functioning. These include overall brain volume,[2] grey matter volume,[3] white matter volume,[4] white matter integrity,[5] cortical thickness[3] and neural efficiency.[6] Although the evidence base for our understanding of the neural basis of human intelligence has increased greatly over the past 30 years, even more research is needed to fully understand it.[1]

The neural basis of intelligence has also been examined in animals such as primates, cetaceans and rodents.[7]

One of the main methods used to establish a relationship between intelligence and the brain is to use measures of Brain volume.[1] The earliest attempts at estimating brain volume were done using measures of external head parameters, such as head circumference,[1] however, such approximations proved to be inaccurate when estimating brain size.[1] More recent methodologies that were employed to study this relationship are post-mortem measures of brain weight and volume. However, such measures also proved to be somewhat inconclusive, yielding diverging results depending on sex, which hemisphere was examined and on the type of intelligence measured.[8]

The most widespread methodology in contemporary neuroscience to measure brain volume and size is MRI. MRI is a non-invasive technique used to study the brain structure and function (using fMRI) of living subjects.[1] Overall, larger brain size and volume is associated with better cognitive functioning and higher intelligence. The correlations range from 0.0 to as high as 0.6, and are predominantly positive.[1] The specific regions that show the most robust correlation between volume and intelligence are the frontal, temporal and parietal lobes of the brain.[9][10][11] Therefore, it can be safely concluded that larger brains predict greater intelligence.[12][13]

However, researchers have cautioned against oversimplifying this view. A meta-analytic review by McDaniel found that the correlation between Intelligence and in vivo brain size was larger for females (0.40) than for males (0.25).[14] The same study also found that the correlation between brain size and Intelligence differed for age within sex, with children showing smaller correlations.[14] Furthermore, the hypothesis has been put forward that the relationship between larger brain volumes and higher intelligence is facilitated not by the global increase of brain volume, but instead by the enlargement of selective parts of the brain associated with specific tasks.[9] For example, monolingual adolescents learning new words is displayed growth in gray matter density in bilateral posterior supramarginal gyri directly related to the number of words learned.[15] Similarly, learning to juggle increased grey matter volume in the occipito-temporal cortex for subjects who could not juggle previously,[16] indicating that brain volume is dependent on a large variety of things and not a perfect measure for intelligence.

Another point of caution is that while larger brain volume is associated with higher intelligence, this relationship only explains a modest amount of variance within the distribution of intelligence itself. The correlations reported between brain volume, brain size and intelligence only explain 12% to 36% of the variance in the distribution of intelligence.[8][9] The amount of variance explained by brain volume also depends on the type of intelligence measured.[8] Up to 36% of variance in verbal intelligence can be explained by brain volume, while only approximately 10% of variance in visuospatial intelligence can be explained by brain volume.[8] These caveats imply that there are other major factors influencing how intelligent an individual is apart from brain size.[1] In a large meta-analysis consisting of 88 studies Pietschnig et al. (2015) estimated the correlation between brain volume and intelligence to be about correlation coefficient of 0.24 which equates to 6% variance.[17] Researcher Jakob Pietschnig showed that this strength of the positive association of brain volume and IQ has been overestimated in the literature, but still remains robust. He has stated that "It is tempting to interpret this association in the context of human cognitive evolution and species differences in brain size and cognitive ability, we show that it is not warranted to interpret brain size as an isomorphic proxy of human intelligence differences".[17] Another 2015 study by researcher Stuart J Ritchie found that brain size explained 12% of the variance in intelligence among individuals.[18]

Grey matter has been examined as a potential biological foundation for differences in intelligence. Similarly to brain volume, global grey matter volume is positively associated with intelligence.[1] More specifically, higher intelligence has been associated with larger cortical grey matter in the prefrontal and posterior temporal cortex in adults.[3] Furthermore, both verbal and nonverbal intelligence have been shown to be positively correlated with grey matter volume across the parietal, temporal and occipital lobes in young healthy adults, implying that intelligence is associated with a wide variety of structures within the brain.[19]

There appear to be sex differences between the relationship of grey matter to intelligence between men and women.[20] Men appear to show more intelligence to grey matter correlations in the frontal and parietal lobes, while the strongest correlations between intelligence and grey matter in women can be found in the frontal lobes and Broca's area.[20] However, these differences do not seem to impact overall Intelligence, implying that the same cognitive ability levels can be attained in different ways.[20]

One specific methodology used to study grey matter correlates of intelligence in areas of the brain is known as voxel-based morphometry (VBM). VBM allows researchers to specify areas of interest with great spatial resolution, allowing the examination of grey matter areas correlated with intelligence with greater special resolution. VBM has been used to correlate grey matter positively with intelligence in the frontal, temporal, parietal, and occipital lobes in healthy adults.[21] VBM has also been used to show that grey matter volume in the medial region of the prefrontal cortex and the dorsomedial prefrontal cortex correlate positively with intelligence in a group of 55 healthy adults.[22] VBM has also been successfully used to establish a positive correlation between grey matter volumes in the anterior cingulate and intelligence in children aged 5 to 18 years old.[23]

Grey matter has also been shown to positively correlate with intelligence in children.[23][24][25] Reis and colleagues[25] have found that grey matter in the prefrontal cortex contributes most robustly to variance in Intelligence in children between 5 and 17, while subcortical grey matter is related to intelligence to a lesser extent. Frangou and colleagues[24] examined the relationship between grey matter and intelligence in children and young adults aged between 12 and 21, and found that grey matter in the orbitofrontal cortex, cingulate gyrus, cerebellum and thalamus was positively correlated to intelligence, while grey matter in the caudate nucleus is negatively correlated with intelligence. However, the relationship between grey matter volume and intelligence only develops over time, as no significant positive relationship can be found between grey matter volume and intelligence in children under 11.[23]

An underlying caveat to research into the relationship of grey matter volume and intelligence is demonstrated by the hypothesis of neural efficiency.[6][26] The findings that more intelligent individuals are more efficient at using their neurons might indicate that the correlation of grey matter to intelligence reflects selective elimination of unused synapses, and thus a better brain circuitry.[27]

Similar to grey matter, white matter has been shown to correlate positively with intelligence in humans.[1][4] White matter consists mainly of myelinated neuronal axons, responsible for delivering signals between neurons. The pinkish-white color of white matter is actually a result of these myelin sheaths that electrically insulate neurons that are transmitting signals to other neurons. White matter connects different regions of grey matter in the cerebrum together.These interconnections make transport more seamless and allow us to perform tasks easier. Significant correlations between intelligence and the corpus callosum have been found, as larger callosal areas have been positively correlated with cognitive performance.[1] However, there appear to be differences in importance for white matter between verbal and nonverbal intelligence, as although both verbal and nonverbal measures of intelligence correlate positively with the size of the corpus callosum, the correlation for intelligence and corpus callosum size was larger (.47) for nonverbal measures than that for verbal measures (.18).[28] Anatomical mesh-based geometrical modelling[29][30][31] has also shown positive correlations between the thickness of the corpus callosum and Intelligence in healthy adults.[32]

White matter integrity has also been found to be related to Intelligence.[5] White matter tract integrity is important for information processing speed, and therefore reduced white matter integrity is related to lower intelligence.[5] The effect of white matter integrity is mediate entirely through information processing speed.[5] These findings indicate that the brain is structurally interconnected and that axonal fibres are integrally important for fast information process, and thus general intelligence.[5]

Contradicting the findings described above, VBM failed to find a relationship between the corpus callosum and intelligence in healthy adults.[21] This contradiction can be viewed to signify that the relationship between white matter volume and intelligence is not as robust as that of grey matter and intelligence.[1]

Cortical thickness has also been found to correlate positively with intelligence in humans.[3] However, the rate of growth of cortical thickness is also related to intelligence.[27] In early childhood, cortical thickness displays a negative correlation with intelligence, while by late childhood this correlation has shifted to a positive one.[27] More intelligent children were found to develop cortical thickness more steadily and over longer periods of time than less bright children.[27] Studies have found cortical thickness to explain 5% in the variance of intelligence among individuals.[18] In a study conducted to find associations between cortical thickness and general intelligence between different groups of people, sex did not play a role in intelligence.[33] Although it is hard to pin intelligence on age based on cortical thickness due to different socioeconomic circumstances and education levels, older subjects (17 - 24) tended to have less variances in terms of intelligence than when compared to younger subjects (19 - 17).[33]

Cortical convolution has increased the folding of the brains surface over the course of human evolution. It has been hypothesized that the high degree of cortical convolution may be a neurological substrate that supports some of the human brain's most distinctive cognitive abilities. Consequently, individual intelligence within the human species might be modulated by the degree of cortical convolution.[34]

The neural efficiency hypothesis postulates that more intelligent individuals display less activation in the brain during cognitive tasks, as measured by Glucose metabolism.[6] A small sample of participants (N=8) displayed negative correlations between intelligence and absolute regional metabolic rates ranging from -0.48 to -0.84, as measured by PET scans, indicating that brighter individuals were more effective processors of information, as they use less energy.[6] According to an extensive review by Neubauer & Fink[35] a large number of studies (N=27) have confirmed this finding using methods such as PET scans,[36] EEG[37] and fMRI.[38] However, evidence contradicting the neural efficiency hypothesis also exists.[35]

fMRI and EEG studies have revealed that task difficulty is an important factor affecting neural efficiency.[35] More intelligent individuals display neural efficiency only when faced with tasks of subjectively easy to moderate difficulty, while no neural efficiency can be found during difficult tasks.[39] In fact, more able individuals appear to invest more cortical resources in tasks of high difficulty.[35] This appears to be especially true for the Prefrontal Cortex, as individuals with higher intelligence displayed increased activation of this area during difficult tasks compared to individuals with lower intelligence.[40][41] It has been proposed that the main reason for the neural efficiency phenomenon could be that individuals with high intelligence are better at blocking out interfering information than individuals with low intelligence.[42]

Some scientists prefer to look at more qualitative variables to relate to the size of measurable regions of known function, for example relating the size of the primary visual cortex to its corresponding functions, that of visual performance.[43][44]

In a study of the head growth of 633 term-born children from the Avon Longitudinal Study of Parents and Children cohort, it was shown that prenatal growth and growth during infancy were associated with subsequent IQ. The studys conclusion was that the brain volume a child achieves by the age of 1 year helps determine later intelligence. Growth in brain volume after infancy may not compensate for poorer earlier growth.[45]

There is an association between IQ and myopia. One suggested explanation is that one or several pleiotropic gene(s) affect the size of the neocortex part of the brain and eyes simultaneously.[46]

In 2007, Behavioral and Brain Sciences published a target article that put forth a biological model of intelligence based on 37 peer-reviewed neuroimaging studies (Jung & Haier, 2007). Their review of a wealth of data from functional imaging (functional magnetic resonance imaging and positron emission tomography) and structural imaging (diffusion MRI, voxel-based morphometry, in vivo magnetic resonance spectroscopy) argues that human intelligence arises from a distributed and integrated neural network comprising brain regions in the frontal and parietal lobes.[47]

A recent lesion mapping study conducted by Barbey and colleagues provides evidence to support the P-FIT theory of intelligence.[48][49][50]

Brain injuries at an early age isolated to one side of the brain typically results in relatively spared intellectual function and with IQ in the normal range.[51]

Another theory of brain size in vertebrates is that it may relate to social rather than mechanical skill. Cortical size relates directly to a pairbonding life style and among primates cerebral cortex size varies directly with the demands of living in a large complex social network. Compared to other mammals, primates have significantly larger brain size. Additionally, most primates are found to be polygynandrous, having many social relationships with others. Although inconclusive, some studies have shown that this polygnandrous statue correlates to brain size.[52]

Several environmental factors related to health can lead to significant cognitive impairment, particularly if they occur during pregnancy and childhood when the brain is growing and the bloodbrain barrier is less effective. Developed nations have implemented several health policies regarding nutrients and toxins known to influence cognitive function. These include laws requiring fortification of certain food products and laws establishing safe levels of pollutants (e.g. lead, mercury, and organochlorides). Comprehensive policy recommendations targeting reduction of cognitive impairment in children have been proposed.[53]

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Neuroscience and intelligence - Wikipedia

By Benedict CareyThe New York Times

MONTREAL At 98,Brenda Milner is not letting up in a nearly 70-year career to clarify the function of many brain regions frontal lobes, and temporal; vision centers and tactile; the left hemisphere and the right usually by painstakingly testing people with brain lesions, often from surgery.

Her prominence long ago transcended gender, and she is impatient with those who expect her to be a social activist. Its science first with Milner, say close colleagues,in her lab and her life.

Milner, a professor of psychology in the department of neurology and neurosurgery at McGill University in Montreal, is best known for discovering the seat of memory in the brain, the foundational finding of cognitive neuroscience. But she also has a knack for picking up on subtle quirks of human behavior and linking them to brain function.

Perched recently on a chair in her small office, resplendent in a black satin dress and gold floral pin and banked by moldering towers of old files, she volleyed questions rather than answering them.

People think because Im 98 years old I must be emerita, she said. Well, not at all. Im still nosy, you know, curious.

Milner continues working because she sees no reason not to. Neither McGill nor the affiliated Montreal Neurological Institute and Hospital has asked her to step aside.

She has funding: In 2014, she won three prominent achievement awards that came with money for research. She has a project: a continuing study to investigate how the healthy brains intellectual left hemisphere coordinates with its more aesthetic right one in thinking and memory.

And she has adapted to the life as an undeniably "senior" senior researcher. I come into the office about three days a week or so, that is plenty, Milner said.

And I have some rules, she added. I will take on postdoctoral students, but not graduate students. Graduate students need to know youll be around for five years or so, and well she chuckled, looking up at the ceiling well, its very difficult if they have to switch to someone else, you know.

Milners current project is, appropriately enough, an attempt to weave together two of brain sciences richest strands of research, both of which she helped originate a lifetime ago.

One is the biology of memory.

Milner changed the course of brain science for good as a newly minted Ph.D. in the 1950s by identifying the specific brain organ that is crucial to memory formation.

She did so by observing the behavior of a 29-year-old Connecticut man who had recently undergone an operation to relieve severe epileptic seizures. The operation was an experiment: On a hunch, the surgeon suctioned out two trenches of tissue from the mans brain, one from each of his medial temporal lobes, located deep below the skull about level with the ears. The seizures subsided.

But the patient, an assembly line worker named Henry Molaison, was forever altered. He could no longer form new memories.

Concerned and intrigued, the surgeon contacted researchers Wilder Penfield and Milner at the Montreal Neurological Institute, who had previously reported on two cases of amnesia in patients treated there. Thus began a now-famous collaboration.

She started taking the night train from Montreal to give a battery of tests to Molaison, who was known in research reports as H.M. to protect his privacy.

In a landmark 1957 paper, Milner wrote with Molaisons surgeon, she concluded that the medial temporal areas including, importantly, an organ called the hippocampus must be critical to memory formation. That finding, though slow to sink in, upended the accepted teaching at the time, which held that no single area was critical to supporting memory.

Milner continued to work with Molaison and later showed that his motor memory was intact: He remembered how to perform certain physical drawing tests even if he had no memory of having learned them.

The finding, reported in 1962, demonstrated that there are at least two systems in the brain for processing memory: one that is explicit and handles names, faces and experiences; and another that is implicit and incorporates skills, like riding a bike or playing a guitar.

I clearly remember to this day my excitement, sitting there with H.M. and watching this beautiful learning curve develop right there in front of me, Milner said. I knew very well I was witnessing something important.

The other strand her new research project incorporates is hemispheric specialization: how the brains two halves, the right and the left, divide its mental labor.

The new project is aimed at understanding how hemispheric coordination aids memory retrieval under normal circumstances, in people without brain injuries. Milner leads a research team that has been taking exhaustive MRI brain images from participants while they solve problems and take memory tests.

Does the artistic right hemisphere provide clues to help its more logic-oriented other half retrieve words? If so, which kinds of clues seem most powerful?

In one experiment, participants in the brain scanner tried to recall a list of words they had just studied. Some of those words were concrete, like dog or house, conjuring specific imagery; others, like concept or strategy, were not. The scans carefully track activation across hemispheres moment to moment, as retrieval happens. The findings hold tremendous potential to help people with early dementia, some brain injuries and even learning disabilities.

People with early signs of dementia can have trouble with imagery, and by the time the disease is advanced, theyve lost that ability, said Joelle Crane, a clinical psychologist at the Montreal Neurological Institute. One area this new work might help us with is in training people to learn in a more visual way.

For Milner, after a lifetime exploring the brain, the motive for the work is personal as well as professional. I live very close; its a 10-minute walk up the hill, she said. So it gives me a good reason to come in regularly.

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98-year-old neuroscience pioneer gives no thought to slowing down - The Columbus Dispatch

We caught up with Prof. Andrea Brand at the BNA Neuro Fest in Birmingham, UK, and asked her about her research investigating nutritional modulation of neural stem cells.

Andrea also explains how her lab employ their DamID technique to investigate protein-DNA interaction and chromatin changes in vivo.

To finish, Andrea highlights some of the reserach challenges her lab hope to overcome in the future.

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Lab Tube Meets Prof. Andrea Brand at the BNA Festival of Neuroscience 2017 - Technology Networks

Facebook is branching out into the field of neuroscience research with the creation of its own scientific lab dedicated to devising new marketing techniques for agencies, brands and media firms.

The Center for Marketing Science Innovation is still under construction in Manhattan but Facebooks director of advertising research gave Ad Week a sneak peak of the fledgling facility, which takes the underwhelming appearance of a GPs surgery.

This unassuming facade bellies a hi-tech operation behind the scenes however with neuroscience specialists to help guide marketers, publishers and brands toward impactful content.

To achieve this Facebook has built a variety of rooms designed to mimic common viewing environments such as a living area or conference suite with an array of monitors tracking every twitch and glance of strapped in guinea pigs.

By keeping tabs on heart rate, facial movements and eye movements of participants as they scroll through profiles or consume TV content it is hoped to gain a better understanding of how such imperceptible biological reactions correspond to real world behavior.

Speaking to Ad Week Daniel Slotwiner, Facebooks director of advertising research, explained: A lot of what we dont understand is where peoples eyes are going when theyre on the platform. We know how much time people are spending on the platform, so this is really about how that time is spent and what features on our product theyre looking at.

Facebook isnt the first organisation to take an interest in biological cues for reading engagement, with a landmark Imperial College London study enabling marketers to get to know us better than we know ourselves.

The new centre is expected to be finished within the next few weeks.

More here:
Facebook establishes neuroscience centre dedicated to marketing studies - The Drum