Cavanagh et al show that characterizing the temporal receptive field of integration of individual PFC neurons from their resting activity (via autocorrelation) helps predict their coding for value.  In short, taking into account the temporal dynamics of neuron spiking yields more information about their role in representing value than spike rates alone.

Cavanagh, Sean E., et al. “Autocorrelation structure at rest predicts value correlates of single neurons during reward-guided choice.” eLife 5 (2016): e18937.

As we learn about items in our environment, their neural representations become increasingly enriched with our acquired knowledge. But there is little understanding of how network dynamics and neural processing related to external information changes as it becomes laden with “internal” memories. We sampled spiking and local field potential activity simultaneously from multiple sites in the lateral prefrontal cortex (PFC) and the hippocampus (HPC)—regions critical for sensory associations—of monkeys performing an object paired-associate learning task. We found that in the PFC, evoked potentials to, and neural information about, external sensory stimulation decreased while induced beta-band (∼11–27 Hz) oscillatory power and synchrony associated with “top-down” or internal processing increased. By contrast, the HPC showed little evidence of learning-related changes in either spiking activity or network dynamics. The results suggest that during associative learning, PFC networks shift their resources from external to internal processing.

Brincat, S.L. and Miller, E.K (2016) Prefrontal networks shift from external to internal modes during learning  Journal of Neuroscience. 36(37): 9739-9754, 2016 doi: 10.1523/JNEUROSCI.0274-16.2016. View PDF

Mixed selectivity in dopamine neurons:
Tian, Ju, et al. “Distributed and Mixed Information in Monosynaptic Inputs to Dopamine Neurons.” Neuron (2016).

For more on the importance of mixed selectivity see:
Fusi, S., Miller, E.K., and Rigotti, M. (2016) Why neurons mix: High dimensionality for higher cognition.  Current Opinion in Neurobiology. 37:66-74  doi:10.1016/j.conb.2016.01.010. View PDF »

Rigotti, M., Barak, O., Warden, M.R., Wang, X., Daw, N.D., Miller, E.K., & Fusi, S. (2013) The importance of mixed selectivity in complex cognitive tasks. Nature, 497, 585-590, doi:10.1038/nature12160. View PDF »

Earl Miller is quoted in the New York Times:
What Could I Possibly Learn From a Mentor Half My Age? Plenty (New York Times, Sept 11, 2016)

“But part of the problem was me — a person in her mid-50s trying to learn something new. Earl Miller, a neuroscience professor at the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, explained why progress might be slow.

As you age, your dendrites — the antennas by which neurons receive information from other neurons — begin to shrink, he said. This is especially noticeable in the prefrontal cortex, which handles higher-order brain functions like focusing, staying on task and forming long-term memories.

The decline in these areas begins in your 40s and 50s and worsens from there, he said. This can make it tougher to focus. There’s also more of a limit to how many thoughts people can carry in their heads simultaneously.

“Your mind’s bandwidth is smaller,” he said. “You learn at a slower rate because less information is getting in.”

<But it’s not all bad news>

That sounds depressing. Isn’t there any mental upside to getting older?

Yes, there is, Professor Miller said. Older people tend to be more disciplined and diligent, he said, which can compensate for learning deficits. Based on their greater experience in the world, they are also very good at putting ideas and thoughts into categories — the very basis of knowledge and wisdom.

It’s true: “The older brain is a wiser brain,” he said. But it can also get into a rut because of its lack of plasticity.

The brain is like a muscle that benefits from mental exercises such as learning new things. The more you put your brain through its paces, the easier it will be to learn the next thing. “It’s always important to keep yourself cognitively engaged,” Professor Miller said.

Ott and Nieder show that stimulating dopamine D2 receptors enhancing working memory related activity in the prefrontal cortex.

Ott, Torben, and Andreas Nieder. “Dopamine D2 Receptors Enhance Population Dynamics in Primate Prefrontal Working Memory Circuits.”Cerebral Cortex (2016).

Read a profile of Earl Miller in Discover Magazine (October 2016) here:
Attention, Please: MIT neuroscientist Earl Miller has changed the way we think about working memory — the brain’s scratchpad.

Earl Miller Discover brain

A very nice experiment from Matt Chafee et al (as usual).  They show that neurons in the prefrontal cortex don’t have fixed properties.  Instead, they show “mixed selectivity” that changes with behavioral context and is biased toward stimuli that inhibit prepotent responses.  Sounds like cognitive control to me.

Blackman, Rachael K., et al. “Monkey prefrontal neurons reflect logical operations for cognitive control in a variant of the AX continuous performance task (AX-CPT).” The Journal of Neuroscience 36.14 (2016): 4067-4079.

The multidemand network is a set of frontoparietal areas in humans that are recruited for a wide range of cognitive-demanding tasks.  Mitchell et al use FMRI connectivity analysis to identify a putative homolog in monkeys.

Mitchell, Daniel J., et al. “A Putative Multiple-Demand System in the Macaque Brain.” The Journal of Neuroscience 36.33 (2016): 8574-8585.

From James J. DiCarlo MD, PhD
Peter de Florez Professor of Neuroscience
Head, Department of Brain and Cognitive Sciences
Investigator, McGovern Institute for Brain Research
Massachusetts Institute of Technology

On August 9, 2016, I released a public statement rebutting three allegations made about Professor Suzanne Corkin in the New York Times Magazine article, “The Brain that Couldn’t Remember,” by Mr. Luke Dittrich and that are reiterated in the book “Patient H.M.”   I fully stand by that earlier statement and it remains on our public web site.  However, I here share additional information that further rebuts the allegations against Professor Corkin.

1. Allegation that research records were or would be destroyed or shredded.  The evidence argues that this allegation is false.
Mr. Dittrich recorded an interview with Professor Corkin in which she says that she shredded H.M.-related material. But at the end of the interview, Professor Corkin says, “We kept the H.M. stuff” (this statement was in the recording posted by Mr. Dittrich but not in the transcript he included in the article). Her last statement is consistent with the voluminous research records that have actually been maintained. A former member of Professor Corkin’s laboratory, highly familiar with the H.M. documents, has reviewed photographs of the many file drawer contents and reported that all the files appear to still be there.  Professor Corkin’s assistant throughout this period (before and during her illness) reports that she was instructed to carefully maintain all records.  All the evidence we were able to find, from those who worked with Professor Corkin and from reviewing the actual filing cabinets filled with data from research with Henry Molaison, indicates that these records were maintained and not destroyed.

Given Professor Corkin’s conflicting statements in the recorded interview, it is regrettable that no one at the New York Times ever asked anyone at MIT about the supposed shredding.  The writer did contact MIT’s news office—but with an unreasonable two-hour deadline, and long after his book had already gone to press.

2. Allegation that Professor Corkin attempted to suppress the finding of an additional injury in left orbitofrontal cortex.  The evidence argues that this allegation is false.
The apparent source of the data suppression allegation was the one collaborator whose relationship to Professor Corkin was marred by conflict.  Professor Corkin’s other collaborators on this work have stated unequivocally that she made no attempt to suppress data during the process of writing up the papers or afterward.  We have interviewed many other scientists involved in the project, and all confirm that the allegations about attempted suppression of a finding are incorrect.  To the contrary, Professor Corkin took a highly professional and timely approach to interpreting the finding and reporting it prominently in scientific and public communications.

It is unfortunate that neither Mr. Dittrich nor the New York Times Magazine reported interviewing the many other, objective sources involved in this research and relied, apparently, on a single source of information from a conflicted collaborator.

Mr. Dittrich’s article implies that the presence of the frontal-lobe injury would fundamentally alter the interpretation of prior findings with Henry Molaison, and that it is for this reason that its presence was supposedly suppressed.  This is incorrect given the widely known and widely accepted science of the field.  The initial, seminal publications indicated, for the first time, that bilateral resection of the medial temporal lobes causes an inability to form memories for new events or facts, without affecting short-term memory on the order of seconds, general intelligence, or the ability to learn certain skills.  These core findings no longer depend on the particularities of Henry Molaison’s brain, because this role of the medial temporal lobe in memory has been validated and extended in hundreds of publications of research with other patients, with more precisely controlled animal studies, and with noninvasive neuroimaging.  Although questions and debates continue about more detailed characterizations of medial temporal lobe functions, the core findings are settled science.  Indeed, since the two publications reporting the additional small, unilateral frontal-lobe injury (Nature Communications, 2014 and Hippocampus 2014), it is noteworthy that neuroscientists have not called for any revision of the interpretation of the core findings with Henry Molaison because those findings are so widely replicated.  When Henry Molaison participated in many experiments with a genial enthusiasm, he often said, “What is learned from me will help others.”   Thanks to his gracious participation in research, and the work of many scientists, including Professor Corkin, what has been learned still stands.

It is regrettable that neither Mr. Dittrich nor the New York Times Magazine reported interviewing leading neuroscientists in the field to ask whether the report of a frontal-lobe injury altered interpretation of the prior publications involving Henry Molaison.

3.  Allegation that Professor Corkin no longer wanted the brain stored at UCSD was because she was unhappy about discovery of a second lesion.  The evidence argues that this allegation is false.
The transfer of H.M.’s brain to UC Davis had nothing to do with efforts to suppress findings, but was instead done in the sprit of open science — to facilitate research by any interested neuroscientists.

H.M. donated his brain to MIT and Massachusetts General Hospital (MGH) for the purpose of scientific research. MIT and MGH transferred custody to UCSD so that sectioning could be performed and the tissue could be shared with the scientific community for research purposes. The dispute that arose was about the sharing of the tissue and images of the sectioned brain with the scientific community.

MIT, MGH, and UCSD finally resolved the issue amicably by agreeing that the brain be transferred to the custody of a leading brain science researcher at UC Davis.

The three institutions further agreed that a peer committee of scientists from five different institutions would be in charge of distribution of the brain tissue for research. The goal was to facilitate scientific research and public access. Under the terms of this agreement, MIT and MGH have no greater rights to access the brain than any other institution, and the peer committee facilitates and ensures access to the brain tissues and images by the wider research community.

4. Allegation that there was something inappropriate in the selection of Henry Molaison’s guardian.  We know of no evidence to support this allegation.
In her book “Permanent Present Tense” (2013), Professor Corkin describes precisely the provenance of Mr. Molaison’s guardianship (page 201).

Briefly, in 1974 Mr. Molaison and his mother (who was in failing health; his father was deceased) moved in with Lillian Herrick, whose first husband was related to Mr. Molaison’s mother. Mrs. Herrick is described as caring for Mr. Molaison until 1980, when she was diagnosed with advanced cancer, and Mr. Molaison was admitted to a nursing home founded by her brother.

In 1991, the Probate Court in Windsor Locks, Connecticut, appointed Mrs. Herrick’s son, Tom Mooney, as Mr. Molaison’s conservator. (Mr. Mooney is referred to as “Mr. M” in the book because of his desire for privacy.) This family took an active interest in helping Mr. Molaison and his mother, and was able to help place him in the nursing home that took care of him.

Mr. Dittrich provides no evidence that anything untoward occurred, and we are not aware of anything untoward in this process. Mr. Dittrich identifies some individuals who were genetically closer to Mr. Molaison than Mrs. Herrick or her son, but it is our understanding that it was Mrs. Herrick and her son Tom Mooney who took in Mr. Molaison and his mother, and took care of Mr. Molaison for many years. Mr. Mooney was appointed conservator by the local court after a valid legal process, which included providing notice of a hearing and appointment of counsel to Mr. Molaison.

Over the last week, we have examined all the evidence we could find about these proceedings, and found nothing inappropriate or contrary to the best interests of Henry Molaison.

Read it on the MIT website

Read the review here

Then, pick up a copy of Suzanne Corkin’s excellent book, Permanent Present Tense