by Athina Tzovara, Julia Kam, Valentina Borghesani, AmanPreet Badhwar
‘If you never did you should. These things are fun and fun is good’ - Dr. Seuss
Live Review for Kids
The OHBM Diversity and Inclusivity Committee is exploring an exciting and new direction this year: we will be engaging kids in the scientific review process! We asked five prominent scientists in the field of brain mapping and neuroscience to write a short article explaining their research to kids. The articles are written for the Frontiers for Young Minds (https://kids.frontiersin.org/, a journal dedicated to young readers of 8-15 years old. Once written, the articles are assigned to five young reviewers, who will work together with a neuroscientist mentor to critique the articles and prepare questions for the scientists.
During the virtual OHBM meeting, the five scientists will give a short presentation on their article. Following this, young reviewers will have 5-10 mins to grill the scientists with questions, based on the review they prepared with their mentors. Finally, the panel of young reviewers will decide whether to accept the paper or not. Thanks to the enthusiasm of our scientists, we have gathered five engaging topics: Caitlin Mills will talk about the neural correlates of boredom, Tonya White will explain why some kids are more easily frustrated than others, Fady Girgis will walk us through the use of brain surgery to treat epileptic seizures, AmanPreet Badhwar will present on biomarkers of Alzheimer’s disease, while Christoph Korn and Gabriela Rosenblau will talk about social learning in adolescence. After the virtual meeting, all accepted papers will be published online in a joined OHBM-themed release of Frontiers for Young Minds. All articles will then be combined in the form of an e-book, with the common theme of brain mapping.
Our goal with this activity is to communicate science to kids, develop their critical thinking ability, and nurture their inherent curiosity towards understanding the functions and anatomy of the human brain. Join the live review online and witness how Caitlin, Tonya, Fady, Aman, Gabriela and Christoph will handle the grilling by these critical kid reviewers!
Online family-friend brain-art activities - A collaboration with the OHBM Brain-Art SIG
At last year's meeting in Rome, a drawing corner was provided where children in attendance could freely craft. Their art pieces were progressively displayed on a panel within the BrainArt exhibit (see figures below). For this special virtual edition of OHBM, we will be providing links to online resources that kids can explore and enjoy at home such as printable activities (e.g., build your own brainhat) and coloring sheets (e.g., online coloring books).
Example of the kids drawing corner at OHBM 2019 in Rome
Kids and their caregivers can also dive into the exciting world of TEAM REMARKABLZ - an exciting world of diversity and inclusion aware science superheroes (https://www.theremarkablz.com/). Free Educational Resources include: printable colouring pages, science experiments, and topics that combine science and art (https://www.theremarkablz.com/freeresources).
Some examples of Science Superheroes waiting to welcome kids of all ages!
Images courtesy of www.theremarkablz.com
The Diversity and Inclusivity Committee is committed to supporting all families within the OHBM Community. We strive to offer activities and spaces (however virtual) where parents and kids can develop a shared passion for science: no matter their age, language, or educational system.
This year, we hope to engage them with our renewed collaboration with the Brain-Art SIG and adding the format of the live scientific review, but we wish for these initiatives to keep growing and diversifying as the Community they serve. To this end, we welcome comments and suggestions to ensure that any future OHBM annual meeting, whether online or in-person, will be a great experience for grown-ups as well as kids!
by Ekaterina Dobryakova
In preparation for this year’s Annual Meeting, we spoke to one of the keynote speakers, Dr. Claudia Buss. Claudia is an Associate Professor at the University of California, Irvine and a Professor of Medical Psychology at the Charité University Medicine in Berlin. In a virtual meeting, I sat down with Dr. Buss to discuss her captivating research in the field of developmental programming and newborn infant neuroimaging.
Ekatarina Dobryakova (ED): Dr. Buss, thank you for dedicating your time for this interview. Before we get into more specific questions, I was wondering whether you mind sharing a bit about how you came to do the work that you're doing, and what got you to follow this passion in research.
Claudia Buss (CB): Since I started studying psychology, I have always been very interested in the interface of the mind and the brain. Specifically, in how stress can affect the brain, and then, consequently, health and disease, specifically psychiatric disease. My mentor during my doctoral training was Dirk Hellhammer, who unfortunately recently passed away. He was really the one who stimulated my interest in stress biology and fetal programming of health and disease. He also taught me that if you want to understand the origins for disease susceptibility, you have to go back to the very early period of life, when an individual develops. The brain is highly plastic at that time and therefore can integrate information about the environment during development. Dirk introduced me to the concept of developmental programming.
The origins for basically all common complex disorders, including psychiatric disorders, can be traced back to very early life, when the susceptibility for these disorders is laid. I'm particularly very interested in the developing brain, because there is no other organ that develops over such a protracted period of time. More specifically, I am interested in how cues about maternal stress during and before pregnancy, and even during mothers’ own development, can affect the developing fetal brain. I investigate which biological signals provide information to the fetus about maternal stress.
ED: This is fascinating. What are the challenges of this research area given that you want to study individuals in their prenatal stage.
CB: Gaining information about the fetal origins of risk for psychiatric disorders in humans is best achieved by prospective longitudinal studies. These start during pregnancy and, ideally, follow up the offspring during critical developmental periods from fetal to infant to child to adolescence, with serial measures of brain, cognitive, and affective development. This ideally requires large study samples, which we usually don't have. However, our studies to date have provided a first proof of principle that there are associations between variation in the prenatal environment and alterations in the neonatal brain. At this point, postnatal events will have had minimal influence. Longer term changes and risks for psychiatric disorders have to be studied in large samples. Therefore, multicenter studies such as, the HEALthy Brain and Child Development Study and the Lifespan Baby Connectome Study are extremely valuable.
Further, to gain information about prenatal origins of susceptibility for psychiatric disorders, it is crucial to record many aspects of the prenatal environment and then serially assess the brain during the period of most rapid development. This is especially important during the first two years of life.
It is very important to have a neonatal baseline measure and then characterize the developmental trajectory from this point. Because we acquire MRI scans from neonates and young infants during natural sleep (so we never sedate the children), scan acquisition is extremely laborious and requires very, very committed and patient staff, as well as the cooperation of parents, because sometimes children take a long time to fall asleep and scans need to be repeated. We often discuss this amongst our collaborators, that study sites are only successful if there are people who are committed to this being done. It needs to be a priority because it's so laborious.
In terms of other challenges, the developing and immature brain is very different from an adult brain. Common data processing tools that have been developed and optimized for adult scans cannot be used. I'm very fortunate to collaborate with leading experts in the field, specifically Damien Fair from OHSU and Martin Styner from UNC, who have greatly contributed to developing methods that address these specific challenges.
Of course, another challenge common to all observational human studies is that inferences about causality cannot be drawn. This is why animal models that allow experimental manipulation is a very crucial complementation to the human observational studies on fetal programming.
ED: It’s obvious that there are a lot of layers to your research. Longitudinal studies by themselves present a lot of challenges, without adding a layer of scanning such a young pediatric population and having additional layers of technological challenges. So you already touched upon this before, but when you just started in this area of research, what was the most inspiring or motivating scientific work that sparked your interest even more aside from the inspiration you got from your mentors?
CB: The field received a lot of attention when the first papers on fetal programming of health and disease came out from David Barker’s lab. They showed that there were associations between lower birth weight and risk for cardiovascular disease in later life. Then, more and more epidemiological studies found associations between adverse birth outcomes, such as lower birth weight and shorter length of gestation, and basically all common complex disorders, including psychiatric disorders.
The idea was that it's not the low birth weight per se that's increasing the risk for later disease. Lower birth weight was found to be an indicator of an adverse prenatal environment which affects later disease susceptibility. So people started thinking: what kind of environmental conditions (i.e., nutrition, smoking, stress) during fetal life can program the organism in a way to predispose that individual for later disease? Through which pathways do these risk factors affect the developing fetus?
Another study that was really interesting to me was a study by Gilbertson et al. published in Nature Neuroscience in 2002. In a very elegant study design they found that a smaller hippocampal volume is a risk factor for developing Post Traumatic Stress Disorder (PTSD) after combat trauma exposure. Before that, it wasn't really clear whether the smaller hippocampal volume resulted from the trauma and due to the neurotoxicity of stress, or whether these patients had a smaller hippocampal volume to begin with, predisposing them to developing PTSD after trauma exposure. This study actually showed that it was smaller hippocampal volume predisposing them to PTSD. This made me want to find out what might be the origins of smaller hippocampal volumes.
I was pretty sure that genetics wouldn't explain hippocampal volumes, but that it rather would be an interaction with the environment and environmental factors, especially in early life and especially during critical periods of brain development. The Gilbertson paper made me want to study what might lead to these neuro-phenotypes that then increase vulnerability and susceptibility for psychiatric disorders.
ED: So are you seeing lower hippocampal volumes in pediatric populations, given the environmental factors during fetal development later in life.
CB: Yes, there are associations between adverse birth outcomes and smaller hippocampal volume, and lower birth weight and shorter length of gestation. Also, something we haven't published yet but we're just about to publish, is an association between maternal stress during pregnancy and smaller hippocampal volumes in newborns. Other groups have shown this as well. There's quite a bit of work now on alterations of the limbic system in association with prenatal stress.
ED: Stress is a hot topic now. When you're talking about stress, how do you define it in your research? Is it more chronic stress or a particular type of stress? One can say that even exercise is a stress to your body, for example.
CB: That's a very good question. I mainly define stress as an increase in stress-sensitive biological markers, specifically endocrine markers like cortisol or immune markers like proinflammatory cytokines, but also metabolic markers. What we know is that there are many different stressors, like stress at work, anxiety, depressive symptoms, death and sickness of someone close, lack of social support. All these factors have the potential to alter maternal biology. And the fetus needs to receive a biological cue to be able to adapt its development. The fetus doesn't care whether the mother is stressed because her boss is stressing her out, because she has conflicts with her partner, or because someone is sick. The fetus cannot interpret that; the fetus only gets biological cues through the placenta. Thus, stress of the mother has to translate into a biological signal, so that the fetus can respond to it.
Whether stress-associated biological changes occur depends on many things in the maternal constitution, such as maternal genetic makeup, social support, coping strategies, all these will determine whether the mothers’ stress that she experiences actually translates into a biological signal that the fetus can then receive. This is why I would refrain from calling certain stressors more harmful than others. There are some colleagues who think there's some evidence for that, but I don't think there is strong evidence. What is pretty clear is that acute stress and alterations in biological mediators of stress are very unlikely to alter fetal development. So it would have to be chronic stress exposure and chronic elevations of these stress mediators. I would even go as far as saying that maternal acute stress, from time to time, is good because the fetus gets exposed to certain variation in stress-sensitive biological mediators, which prepares him for extrauterine life.
Even when talking about the long-term neurodevelopmental consequences of chronic stress, you may view these as harmful because they increase risk for mental health disorders but you could also look at them from an evolutionary perspective and consider them adaptive because the changes may increase chances of survival in a more stressful environment (for example altered neural circuitry that supports high vigilance may on the one hand increase risk for anxiety disorders but may also serve an important purpose in a dangerous environment).
ED: Is there any research where you follow the kids who were exposed to chronic stress and how they fare later in life, even when they do develop psychiatric disorders?
CB: The studies that we have done mainly characterized newborn neuro-phenotypes based on MRI studies in association with different types of stressors. We have looked at elevated cortisol concentrations, and then also inflammation during pregnancy. There, we do see associations with newborn brain anatomy and also connectivity, and these neuro-phenotypes predict behavior at the age of two years. We have followed up these kids again at five years. But it's a rather small sample size; our sample size wasn't that big to begin with. We started out with about 120 mother-child pairs, where we had complete data during pregnancy of three time points during pregnancy and then the newborns. So by the age of five, the sample size was quite small: around 70. But in early childhood we also see associations between chronic systemic maternal inflammation during pregnancy and neuro-cognitive function, for example. We are now participating in the ECHO initiative, which may better allow answering questions about prenatal origins of psychiatric disorders because ECHO integrates many prospective longitudinal US studies into a common research protocol to answer questions related to developmental programming of health and disease.
ED: This is so interesting, and again, shows how multilayered your research is. What would you say are the most pressing methodological issues in your field of research?
CB: Improving processing pipelines for neonatal MRI data is a pressing issue. As I said, my collaborators are at the forefront of working on this and great advances have already been made in the context of the developing Human Connectome Project and the Baby Connectome Project. When I started this work 10 years ago there were very few groups who actually did newborn infant neuroimaging. Now, more and more people have become interested in this field and there are big consortia focusing on MRI-based characterization of early brain development. So a lot of progress has been made compared to 10 years ago. But I think there's still a lot of work ahead of us to be at a comparable state as we are for adult image processing.
Then, I think there is still room for optimizing acquisition protocols based on recent experiences. Weighing resolution and signal-to-noise ratio to scan time is important, as we always have to be very cognizant that, usually, newborns sleep pretty well for about 40 minutes and then after that, they start waking up. My experience, if you can keep the protocols below 40 or 45 minutes, you're good. Thus, my recommendation is to stay below 45 minutes and if you want to scan different modalities, you really have to weigh what is important to you.
I think what is also a pressing issue is to harmonize measures of the prenatal environment because, as you are pointing out, what people mean when they refer to stress and the way they define stress may differ a lot. Further, evaluating the quality of biological assays is very important. I'm not sure that this receives enough attention. I think there is this notion that biological measurements are more objective and valid than psychological self-report measures. However, there are problems and inaccuracies associated with biological assays as well, which deserve attention to obtain reliable and comparable study results. Right now, there is a lot of heterogeneity in the way prenatal stress is being defined in studies studying its neurodevelopmental consequences and it's therefore hard to say whether there is one study that specifically replicates what another study has found, as there are all these nuances between how the prenatal environment was characterized and then what aspects of the offspring brain was looked at. That really complicates the picture and I think there we can definitely improve.
ED: Absolutely. Hopefully such initiatives like OHBM’s Replication Award will start the wave of researchers trying to replicate previous findings and remove the barriers for replication studies. Another topic I would like to talk about is mentorship. What do you think are the most important things to do as a mentor?
CB: I feel that continuous communication and support for my students and regular meetings are crucial. Only if you're constantly communicating, you can monitor progress and detect barriers to progress. I also think it's crucial to foster intrinsic motivation for students’ work because I feel it is important to burn for what you are doing and what you're researching. Only then can you conduct these laborious studies and stay on top of things and stay motivated. I think one way of keeping students motivated is a very early introduction to international experts in the field, having research exchanges, visiting international laboratories and conferences, and being able to present one’s own work to peers.
What I also learned from my mentor, Pathik Wadhwa at UCI, is that having a well-grounded conceptual framework in the context of which research questions are being developed is very crucial. This is why I like to begin the training of my students by developing concept and perspectives papers in the respective fields that they are working on. I think that helps them get established in the field and provides a good basis and conceptual framework for doing their own empirical studies and developing their own research questions.
ED: Indeed, intrinsic motivation is very important. To round out our conversation, I was wondering whether you have thoughts about the OHBM conference going virtual in 2020. What are the silver linings given the current situation that hopefully will improve?
CB: Well, with the OHBM conference going virtual, potentially even more people can attend the conference because it will be more accessible, it doesn’t include traveling, which is good from an environmental perspective and also saves time. I think it could also be an advantage to take the time and listen in more detail to presentations that you're really interested in, and being able to go back and listen to them again. What we will be missing, of course, is the Q&A after the talks and interacting with peers during coffee breaks that's also really important at conferences. But I would assume that if there are specific questions, the speakers can be contacted, so I don't see too much of a downside. We just have to make the best of the situation that we're in. And I think having a virtual meeting is definitely better than not having a meeting and not hearing about the advancements in our field.
ED: Absolutely. The conference should still be very interesting and engaging. Thank you so much for your time.
Authors: Claude Bajada, Nils Muhlert, Ilona Lipp
Infographic: Roselyne Chauvin
Expert editors: Alfred Anwander, Jurgen Gatt
Newbie editor: Caroline Jantzen
Neuroanatomy is one of the most exciting topics in neuroscience! Some readers may disagree, but for now, humor us and read along. With the help of this On-Demand post, we will convince you not only that anatomy is a useful endeavour but that it is one where much beauty is found.
Our journey starts with the fundamental notion that the structure and the function of objects are tightly coupled; sometimes in ways that are not obvious. Understanding the complexity of the brain’s structure, hopefully, allows researchers to build more accurate models of brain function.
Neuroscience has however become such a transdisciplinary subject that it is not unexpected to meet a top scientist who has never seen a cadaveric brain. Indeed, while most neuroscientists have acquired a basic understanding of brain anatomy, learning about the main gyri, sulci and nuclei, few remember the function or location of the mysterious substantia innominata or of the periaqueductal grey.
If you are one of such scientists, fear not, you are not alone. Neuroanatomy is a vast and somewhat arcane subject, steeped in history. As such, for the sake of our sanity and yours, in this singular blogpost we decided to restrict our dealings to the topics that are most commonly tackled within the neuroimaging community. This is an overview of the major landmarks and structures that one can expect to see on an MRI scan and the ongoing conundrum of how to subdivide the brain into useful (sub)regions for further analysis - parcellation (See OHBM How-To Machine Learning on performing data-driven parcellation of MRI data).
Why is understanding anatomy important?
Getting from MRI DICOM files to a statistical map of significant clusters that shows differences between two experimental groups requires no anatomical knowledge whatsoever. But coming up with sensible brain based hypotheses, interpreting findings and communicating them to your fellow colleagues relies on a common language in the field: anatomy.
In his video, David Van Essen (from min. 0:50) details the basic features of human brains, such that we have two hemispheres of about 1000 cm2 volume and a 2-4mm thick cortex that is highly convoluted. While providing an overview of the developmental mechanisms leading to the adult brain as we know it, he points out the huge individual variability in brain anatomy that requires us to apply flexible approaches to neuroimaging studies. These approaches include advanced image registration and the use of atlases, but also functional localisers, individual tractography, individual parcellations and last, but not least, knowing our anatomy.
A knowledge of anatomy can make your life as a neuroscientist a lot easier. For example, it can aid placement of volumes of interest in MR spectroscopy, it can allow you to evaluate the output of automated segmentation pipelines, and, of course, help you quickly identify patterns of activity before receiving confirmation from atlases. Interested in doing some fancy high field, layer-specific, fMRI (see Noam Harel’s video)? Anatomical knowledge is vital! Also, recent evidence suggests that it can help increase the reproducibility of findings between labs, by improving accuracy and reducing noise when carrying out tractography in diffusion MRI. Understanding anatomy has clear implications for neuroimagers!
Nomenclature, Etymology and Orientation in the Brain
One of the first battlegrounds for the new student of anatomy is understanding the cryptic vocabulary of experts. Throughout the videos presented in the OHBM on-demand anatomy courses, various experts refer to different parts of the brain on the assumption that we all share a similar understanding of the language. To bring everyone to the same page, we will review the major terms that are crucial to understand before diving into any neuroimaging study.
Anatomy uses many words borrowed, butchered, and stolen from Latin and Greek. Cerebrum is Latin for “that which is carried toward the head.” Cephalon is ancient Greek for head. Encephalon is the substance that is found inside the head, the cauliflower-resembling organ we now know as the brain. Any word encountered that has elements of these words refers to the brain. For example, the word cerebellum is the diminutive of cerebrum. The diencephalon (across the brain) is made up of the thalami (chambers), hypothalamus (below the thalamus) and epithalamus (above the thalamus). Knowing the etymology of the words makes remembering these ludicrously named structures easier. Readers are referred to this amusing article for more.
Orientation is also often done in Latin. In their talks, Svenja and Julian Caspers regularly use two different ways of describing orientation in the brain. The terms superior, anterior, inferior and posterior (SAIP) versus the terms dorsal, ventral, rostral, and caudal (DVRC). While elite neuroanatomists would have no difficulty using these terms, for the neophyte they can be confusing. They actually refer to two completely independent coordinate systems. The SAIP approach is a real world orientation system. The terms themselves are intuitive and most people need little more explanation than the terms themselves. DVRC is another story! This is an orientation system that depends on the organism itself, the terms relate to parts of the body, once again, in Latin. Dorsal means towards the back, ventral is towards the belly, rostral is towards the beak (or nose), while caudal is toward the tail. Our bipedal nature makes this orientation system unintuitive - at the level of the spine, brainstem and cerebellum, rostral means towards the top of our body (upwards towards the nose), but in the cerebrum, rostral means towards the front of our body (forwards towards the nose). If it is still murky in your heads we would advise dipping into an introductory neuroanatomy textbook for some pretty pictures of the two orientation systems.
When you hear the term medial, this means “towards the middle of the brain”, whilst lateral indicates “towards the sides”.
The frames of reference in neuroanatomy change for the cerebrum compared to the cerebellum, brainstem and spinal cord. For quadrupeds, like sheep, no such change is seen. Walking on two feet is great for reaching things, but not so great for keeping neuroanatomy simple!
Another important set of terms relate to the way one can slice a brain. This is generally what we do when viewing MR images. Axial, or horizontal, slices allow you to scroll through the brain from top to bottom through the axis of the brain; sagittal slices from left to right derived from the latin word for arrow (think of the way an archer holds their bow and arrow). Finally, coronal sections provide a view of the brain as if it were cut through with a burning hairband shaped crown from ear to ear, slices moving anterior to posterior.
(Yawn) Thank you for that primer, but when I look at an MRI scan, I still feel completely lost!! How do I get my head around it?
MRI scans are tricky, they are often viewed as two dimensional slices and depending on the cut, and on the individual, it can still be very difficult to orient yourself, especially when the person was not lying straight in the scanner. As Svenja states in her video (min. 1:20), there are some general organising gross anatomical features that remain relatively consistent across individuals. These are called landmarks.
So, what are the major landmarks in the brain?
Some aspects of anatomy are pretty clear. Every healthy human brain has a cerebellum, brainstem and cerebrum... and a substantia innominata, of course. It has ventricles filled with corticospinal fluid, white matter that looks homogeneous on a conventional MRI scan, easily spottable subcortical gray matter nuclei, and cortical gray matter. Looking at a whole human brain from the outside shows a cortical folding pattern with specific sulcal and gyral structures, which have been labelled and can be used to orient yourself around the occipital, temporal, parietal and frontal lobes. In his video, Julian explains the main sulcal and gyral landmarks and how to find them in structural MR images. For example, if you spot an ‘M’ and ‘U’ in a lateral sagittal section, you have most likely found the central sulcus and precentral sulcus (from min. 11:36). An omega sign in a superior axial section indicates that you have found the motor cortex, while the cingulate sulcus appears as a bracket sign (from min. 14:40). The Figure below summarizes Julian’s guide to landmark spotting strategies.
How to find the major landmarks in the brain on MRI scans (compilation of Julian Casper’s slides)
These landmarks are definitely useful, but they seem quite vague for reporting the spatial locations of my findings!
A wise anatomy professor once complemented one of the authors of this piece (CJB) by stating that he was the owner of a “gelatinous mass of a brain.” Despite the gyral formations, the brain does indeed look like one amorphous clump of jelly.
Notwithstanding the repeated news headlines claiming that Neuroscientists have found the region of the brain responsible for X, it is notoriously difficult to consistently define brain regions across different individuals. While the macrostructure of the brain, such as the main sulcal and gyral pattern, is useful to orient yourself on a whole brain or MRI scan, its macrostructure does not necessarily relate very well to the underlying brain function, which might be more closely related to the neuronal microstructure of a cortical brain area. To decide how to define brain areas based on cell anatomy, we first need to think about what neural features to use in order to separate them (also see this paper for cortical parcellations).
Academic Journal Articles often refer to specific brain regions such as Brodmann area 17. Is this parcellation based on neural features?
Yes! During the late 19th and early 20th century, anatomists started discovering that, while the cortex looks fairly homogeneous to the naked eye, it consists of various layers that differ in their cell type, cell composition, and function. Anatomists such as Cecile and Oskar Vogt, Constantin von Economo, and Korbinian Brodmann spent their time observing microscopic features of the cerebral cortex and classifying it according to similarity. These areas have become known as parcels. Undoubtedly the most famous parcellation scheme is Korbinian Brodmann’s 1909 atlas.
In her video, Nicola Palomero-Gallagher shows some of the main historical cortical parcellations. She points out that the parcellation you get depends largely on how boundaries are defined. She then explains how more quantitative and objective approaches are used for not only finding parcellations in individual post-mortem brains, but also how this can be taken further into generating population maps that reflect individual variability in the boundaries of the areas. Cytoarchitecture is not the only feature that was used to parcellate the brain. At the same time that Brodmann was using cytoarchitecture, the Vogts tended to use myeloarchitecture to define regions. In his video, Matt Glasser explains how myelin-sensitive MRI contrasts can be used to study cortical myeloarchitecture and how that helps align cortical surfaces across individuals. But there is no reason to simply stop there, why not use the distribution of receptors for neurotransmitters to delineate brain areas?
Nicola explaining the cytoarchitectonic profiles of the primary and secondary visual cortices.
In fact, while the cyto- and myeloarchitecture of the cortex tells us something about the type of processing happening in a cortical region, neuroreceptor density can also tell us quite a bit about different neural functions and how they become impaired in disease states. However, as Karl Zilles explains in his video, while cortical regions differ in their receptor fingerprints, there does not seem to be a clear relationship between the parcellations based on cyto- and myeloarchitectonics and those based on neurotransmitter receptor maps.
Karl showing neurotransmitter receptor profiles of different cortical regions
How can I link my imaging research to the histological parcellation of the brain?
Functionally, the cortex is often divided based on the order of information processing: primary sensory areas are the first ones to receive sensory information, secondary areas do further processing, and association areas integrate information from different sensory modalities. Some functional units clearly match the microstructural organisation of the brain. For this reason, Brodmann’s atlas is often used to report the location of activation in functional imaging studies.
Particularly high correspondence between function and microstructure has been reported for primary areas. In her video, Katrin Amunts explains how to identify the primary areas cytoarchitectonically, including the primary motor cortex (from min. 3:00), the primary auditory cortex (from min. 8:20), the primary visual cortex (from min. 9:20), and Broca’s area (from min. 12:37). However, how well can these cytoarchitectonically distinct areas be localised based on the anatomical landmarks visible on conventional MRI scans differs. In her video, Nicola Palomero-Gallagher provides examples for brain regions where the gyrification patterns nicely coincide with the microstructure and where it does not. Practical examples of how to make use of the correspondence in the visual system are given by Kalanit Grill-Spector in her video. She explains the anatomical localisation and microstructural features of place-selective regions within the so-called collateral sulcus (from min. 5:30) and face-selective regions in the so-called mid-fusiform sulcus (from min. 09:53). (For a good overview of the visual system also see Rainer Goebel’s video (from min. 3:12)). Primary areas are also characterized by specific mesoscopic organisation called topography (explained in Daniel Margulies’s video from min. 1:10). How high resolution fMRI can be used to study such organisation is explained by Rainer with examples of retinotopic mapping (min. 6:30).
In order to be able to spatially localize results from your imaging study to parcellations based on the underlying cortical microstructural profile, findings from detailed postmortem characterisation have to be somehow transformed into usable atlases for in vivo imaging. In his video, Simon Eickhoff explains how probabilistic cytoarchitectonic mapping based on large-scale histology can aid with the spatial identification of MRI findings (from min. 7:28). He also goes into details on how to practically go about the question “Where is my blob?” (from min. 14:00).
But how many brain regions are there now and how should I define them?
How many regions there are depends on how you parcellate the brain (indeed experts often can’t agree on how many lobes there are! To limbic, or not to limbic?). To aid the localisation of findings and the definitions of regions of interest, brain atlases have been created. These atlases represent parcellations of a representative template brain, made to help you define your regions. When using these atlases (described in more detail here), we need to understand where they come from and what their limitations are, to decide which is the best atlas for our purpose.
The different available atlases are based on various features of the brain (e.g. see Paula Croxson’s video on parcellation based on histological and microstructural features or Danilo Bzdok’s video on functional parcellations), and as you will find out there is no simple way of defining ‘brain regions’. There is also no reason to restrict oneself to a single feature of interest. Multimodal parcellations are becoming more popular! In her video, Paula Croxson explains that a robust parcellation of the brain has various advantages, such as help with localisation of function and also for understanding individual variation.
In some contexts, parcellations into individual brain regions may not even be the way to go. For example, higher cognitive functions rely on large-scale networks and a complicated interplay of different regions. Functional connectivity is often done to tap into these networks (also see On Demand post about that). In his talk, Daniel explains how some local changes in functional connectivity even correspond to cytoarchitectonic boundaries (from min. 7:14).
Finally, of course, there is no cortical hegemony in the brain, even though reading the neuroimaging literature seems to imply it. Hence, all the concepts and approaches discussed for cortical parcellations also apply for subcortical parcellation.
We have discussed the cortex and the grey matter, can you tell me something interesting about white matter anatomy?
Of course! Like everything else in anatomy, to speak about white matter deserves a little bit of time travel to the nineteenth century. This is the era where all (or most) of the “great tracts” were first described. We say described rather than discovered because there is nothing intrinsic to a tract that requires it to be so!
This century (and parts of the previous) is the home to German and French giants such as Johann Christian Reil (did you know that the insula is sometimes referred to as the “Island of Reil?”, which is the word for island in Latin), who first described the arcuate and uncinate fasciculus, Karl Friedrich Burdach who identified the inferior longitudinal fasciculus, as well as Joseph and Augusta Dejerine, and Heinrich Sachs who all made contributions to confusing and contorted the white matter lexicon that we all currently know and love. A good resource on white matter tracts is this paper.
In his video, Marco Catani gives an excellent introduction to the different types of white matter tracts that you may encounter during your research (from min. 1:30). He explains that ascending and descending projection fibres connect subcortical with cortical regions, that commissural fibres connect left and right hemisphere, and that association fibres serve feedforward and feedback connections. He also goes into detail about how to evaluate the anatomical plausibility of diffusion MRI tractography, which is currently the only approach that we have to investigate white matter non-invasively (See OHBM How-To Diffusion MRI). If you are specifically interested in the white matter tracts of the occipital lobe, Svenja’s talk guides you through this area of the brain. She goes into details on projection fibres (from min. 1:30), such as the optic radiation, association fibres (from min. 9:27), such as the inferior longitudinal fasciculus, the inferior fronto-occipital fasciculus and the superior longitudinal fasciculus, intralobar association fibres (from min. 16:15) and transcallosal fibres (from min. 21:00).
Can we assign functions to white matter?
No and yes. Tracts are not really thought of primarily as processing regions, therefore the naive labeling of tracts with specific functions may be misguided. However, knowing which tracts tend to be associated with certain functions (particularly their disruption secondary to damage - a disconnection) is crucial for any neurosurgeon’s work. In his video, Hugues Duffau explains this beautifully. He describes the fascinating procedure behind intraoperative direct electrical stimulation of white matter (from min. 3:00) and the way that this is used in neurosurgical mapping. Also check out this paper on disconnections and dysfunctions.
Where is anatomy research heading with MRI developments?
While anatomy seems like an old thing, there is still a lot we haven’t agreed on. With developments in high resolution imaging (described in Noam’s video), we have new ways of understanding how the brain is structured. Noam gives an overview of how moving to high field strength allows to obtain images with higher resolution and more sensitive studying of functional anatomy. Focussing on the visual system, Rainer gives examples for specific developments in ultra-high-resolution functional imaging that allow to study the meso-scopic functional organisation of neurons in vivo.
Rainer Goebel on the latest developments and aims of high resolution MRI.
While many functional imaging findings have been superseded as the resolution and complexity of processing improve over the decades, neuroanatomical findings tend to be less dependent on the specific technique. As Marcel Mesulam said in an interview with the OHBM Blog: “The beauty about neuroanatomy is that it changes over millions of years. So once you discover something, it’s true for a few million years. And I have made some discoveries in neuroanatomy that were published maybe 30 to 35 years ago and are as true today as they were then.”