Mapping the Human Cerebellum Reframes Whole-Brain Functions

New functional topography maps of the human cerebellum could be a game-changer. 

Posted Sep 07, 2018

Courtesy of Viking Adult
Source: Courtesy of Viking Adult

My late father, Richard Bergland, M.D. (1932-2007) published The Fabric of Mind in 1986. For the book cover, dad insisted on a sagittal plane view; he liked how this vantage point elucidates major brain regions within the so-called "cranial globe.” Many people mistakenly think of our “brain” as solely the left and right cerebral hemispheres. Therefore, my father was always eager to put the often-forgotten cerebellum and its cerebellar functions in the spotlight. The sagittal view makes it easy to visualize where the “little brain” fits into a larger framework as part of the whole-brain structure.

Because the cerebellum has long been known for coordinating the timing and precision of fluid muscle movements, it was important for me to position cerebellar motor functions as a central player when I wrote my first book on optimizing athletic mindset and sports performance. Luckily, my father had retired by then and had the time to help me create an original split-brain model geared towards athletes. (For more see, “The Split-Brain: An Ever-Changing Hypothesis”)

In the introduction to The Athlete’s Way: Sweat and the Biology of Bliss (2007) I give some background on the genesis of this split-brain model:

“I owe my successful career as an endurance athlete to my understanding of psychology and neurophysiology, but I am not a scientist. I am an athlete. Even though I haven’t had formal training in the sciences, I grew up with neuroscience since my father is both a neurosurgeon and a neuroscientific researcher. When I was growing up, neuroscience was a constant topic of conversation, and discussions with my father have continued over the years. The Athlete’s Way is based on the hypothesis that humans have two brains: an animal feeling-and-doing athletic brain called the cerebellum (Latin for “little brain”), and a human thinking-and-reasoning brain called the cerebrum (Latin for “brain”). My dad and I refer to this brain model as “down brain-up brain.” The up brain is the cerebrum, based on its position north of the mid-brain, which is midway between the two brains. The cerebellum is the down brain, the southern hemisphere in the cranial globe as it were, based on its position south of the mid-brain. The simple names "down brain-up brain" may sound grammatically incorrect but are a direct and cogent response to the 1970s split-brain model of “left brain-right brain.” I coined the new names in early conversations with my father about the differences between the cerebrum and the cerebellum, and I like the new terminology for its simplicity.”

When laying out the pagination of my manuscript, I asked the book designer at St. Martin's Press to dedicate a full page to the cerebrum-cerebellum brain map (below) from a sagittal view so that general readers could visualize the “upstairs-downstairs” architecture of the whole brain. This brain slice came from my father’s research lab and mirrored The Fabric of Mind book cover to some degree.

 Photo and layout by Christopher Bergland (Circa 2007)
This brain map illustrates the earliest incarnations of the "Bergland Split-Brain Model" and describes various hypothetical roles each brain region might play within an interconnected cerebellar-cerebral cortex system. (From p. 81 of "The Athlete's Way: Sweat and the Biology of Bliss.")
Source: Photo and layout by Christopher Bergland (Circa 2007)

With retrospect, my brain map (above) is embarrassingly hypothetical and clunky. But, its inaccuracies and generalizations serve a historical purpose as part of a timeline: The reason I’m sharing it with you here is to illustrate why I’m so excited by the elegant design and breathtaking detail of the latest human cerebellum maps being created by Xavier Guell at MIT along with Jeremy Schmahmann at Harvard’s Massachusetts General Hospital, Catherine Stoodley at American University, and their colleagues.

That said, before diving into the nitty-gritty neuroscience of the latest cerebellum maps, there is one more first-person narrative story and homemade brain map I want to share with you as part of a timeline that puts their pioneering work in context. 

After my father died in 2007, I made a vow that I’d keep my antennae up for any new cerebellar research and do my best to nibble away at solving the riddle he posited by saying: “We don’t know exactly what the cerebellum is doing. But, whatever it’s doing, it’s doing a lot of it.”

Because I'm not part of academia and don't belong to a scientific community, most of my novel ideas about the cerebellum are based on anecdotal observation and life experience blended with a hodgepodge of empirical evidence. One of these key observations was the link between bipedal motor activities and creative thinking. For example, Albert Einstein famously said of E = mc², “I thought of that while riding my bicycle." Also, countless writers and visionary thinkers throughout history have made daily walks an integral part of their creative process. In my mind, it always seemed that the cerebellum must somehow be involved in the phenomenon of motor activity facilitating divergent thinking and eureka! moments.

As a triathlete who became a writer after retiring from sports competition in midlife, I knew from first-hand experience that running, biking, and swimming helped me process language more fluidly. Whenever I was working out, sentences and various word combinations of whatever I was writing as a rough draft that day seemed to bubble up into conscious awareness like a flow chart. Additionally, whenever I was in a daydreaming state during aerobic exercise, I found myself connecting the dots of seemingly unrelated ideas in ways that didn’t happen when I was sitting still at my desk and not engaged in some form of moderate-to-vigorous physical activity. (For more see, “The Neuroscience of Imagination.”)

One day, back in 2009 (with all of these ideas about a possible link between cerebellar function and the "origins of imagination" floating around in my head), I bumped into a poet friend named Maria on the street. During our conversation about the mysterious link between creative breakthroughs and bipedal motor tasks she said, “Whenever I start moving my arms and legs back and forth on the elliptical trainer, poetry pours out of me.” Suddenly, within milliseconds of Maria uttering those words, I had an “aha!” moment and visualized a brain map that simultaneously showed both hemispheres of the cerebrum and both hemispheres of the cerebellum from a birds’ eye view squished down on to one plane. So, I rushed home and drew the map you see below as quickly as I could. Although this is not a sagittal view, it made it possible for the viewer to simultaneously see both hemispheres of the cerebrum and both hemispheres of the cerebellum as part of our whole-brain architecture. (For more see, "Cerebro-Cerebellar Circuits Reminds Us: To Know Is Not Enough.")

 Photo and illustration by Christopher Bergland (Circa 2009)
This topographical brain map of "cerebro-cerebellar" circuitry illustrates the importance of optimizing the contralateral functional connectivity between both cerebral hemispheres and both cerebellar hemispheres.
Source: Photo and illustration by Christopher Bergland (Circa 2009)

The gist of the whole-brain map above was inspired by my experience-based hypothesis that thoughts and ideas might piggyback on the functional connectivity networks of feedforward and feedback loops between all four brain hemispheres during aerobic motor activities.

Although I drew this map in 2009, I was completely unaware that at the same time, Jeremy Schmahmann and Catherine Stoodley had just published what would turn out to be a landmark paper, “Functional Topography in the Human Cerebellum: A Meta-Analysis of Neuroimaging Studies" (2009), which was followed in 2010 by their paper, "Evidence for Topographic Organization in the Cerebellum of Motor Control Versus Cognitive and Affective Processing."

Through the lens of groundbreaking maps of the human cerebellum, the past few months have been potentially earth-shattering. First, the most recent “Handbook of Clinical Neurology” (volume 154, 3rd Series) includes the cerebellum mapping of Stoodley and Schmahmann: “Chapter Four – Functional Topography of the Human Cerebellum,” which was published online June 11, 2018.

The authors sum up the importance of these brain maps in the study abstract, “Accumulating evidence points to a critical role for the human cerebellum in both motor and nonmotor behaviors. A core tenet of this new understanding of cerebellar function is the existence of functional subregions within the cerebellum that differentially support motor, cognitive, and affective behaviors. The existence of cerebellar connectional and functional topography provides the critical anatomic substrate for a cerebellar role in both motor and nonmotor functions. It also establishes a framework for interpreting cerebellar activation patterns, cognitive and behavioral outcomes following cerebellar damage, and the cerebellar structural and functional differences reported in a range of neurodevelopmental and neuropsychiatric disorders."

 Screenshot by Christopher Bergland (@MINDlinkFound image of Chapter 4 in "The Handbook of Clinical Neurology" Volume 154, Series 3)
Photo caption from @MIINDLinkFound on Twitter July 10, 2018: "New volume on cerebellum by colleagues Mario Manto (Belgium) and Thierry Huisman (Baltimore). Great line up of chapters. Good to write again with former post doc Catherine Stoodley (American University) on cerebellar functional topography."
Source: Screenshot by Christopher Bergland (@MINDlinkFound image of Chapter 4 in "The Handbook of Clinical Neurology" Volume 154, Series 3)

Another recent milestone on the timeline of cerebellum mapping is the publication of a paper by Xavier Guell, John Gabrieli, and Jeremy Schmahmann, "Triple Representation of Language, Working Memory, Social and Emotion Processing in the Cerebellum: Convergent Evidence from Task and Seed-Based Resting-State fMRI Analyses in a Single Large Cohort." This paper was the cover story for the May 2018 issue of NeuroImage seen below. 

The authors summarize the significance of this paper in the study abstract, “Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion.”

NeuroImage/Elsevier (Volume 172, 15 May 2018)
A cerebellum brain map by Xavier Guell and colleagues was featured on the May 2018 cover of NeuroImage.
Source: NeuroImage/Elsevier (Volume 172, 15 May 2018)

In a July 2018 MIT News article, “Charting the Cerebellum,” first author Xavier Guell of MIT's McGovern Institute of Brain Research, describes his team’s state-of-the-art mapping of motor and non-motor functions in the cerebellum, “Neuroscientists in the 1940s and 1950s described a double representation of motor function in the cerebellum, meaning that two regions in each hemisphere of the cerebellum are engaged in motor control. That there are two areas of motor representation in the cerebellum remains one of the most well-established facts of cerebellar macroscale physiology. Our study supports the intriguing idea that while two parts of the cerebellum are simultaneously engaged in motor tasks, three other parts of the cerebellum are simultaneously engaged in non-motor tasks. Our predecessors coined the term "double motor representation,” and we may now have to add “triple non-motor representation” to the dictionary of cerebellar neuroscience.”

Guell participated in yet another recent study that highlights how disrupted functional connectivity between the cerebellum and cerebrum may be linked to high-functioning autism spectrum disorders. This research was led by Sheeba Arnold Anteraper (also of the McGovern Institute for Brain Research at MIT) and published online ahead of print July 31, 2018, in the journal Brain Connectivity.

Anteraper et al. explain the significance of this research in the paper’s conclusion, “The description of functional connectivity abnormalities reported in this study using whole-brain, data-driven analyses has the potential to crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.”  

Additionally, the authors said, “The results of this study support cerebellar involvement in ASD, and thus suggest a potentially relevant position of “Dysmetria of Thought” as a conceptual framework for future studies investigating the nature of ASD symptomatology in psychiatry. This theory holds that motor, cognitive, and affective symptoms that arise from cerebellar abnormalities are a reflection of a singular neurological dysfunction. At a physiological level, Dysmetria of Thought is predicated on the concept of a Universal Cerebellar Transform, which hypothesizes that one single neurological process subserves cerebellar modulation of movement, thought, and emotion (Schmahmann, 1991, 1996; Schmahmann, 2010); see also a recent review in Guell et al. (2018a).”

Lastly, as the final and most recent entry on this timeline, on August 14, 2018, a collaborative team of researchers from Massachusetts Institute of Technology and Massachusetts General Hospital, Harvard Medical School (that included Xavier Guell, Jeremy Schmahmann, John Gabrieli, and Satrajit Ghosh) published a paper, “Functional Gradients of the Cerebellum: A Fundamental Movement-to-Thought Principle."

Again, Guell et al. point out the significance of their radical new “triple non-motor representation” hypothesis, “This is the first study to investigate the progressive, hierarchical organization of the cerebellum. Contrasting with the fundamental and well-established primary-unimodal-transmodal hierarchical organization in the cerebral cortex (Mesulam, 1998, 2008),  the principal axis of cerebellar motor and nonmotor organization remains unknown. We describe for the first time that cerebellar functional regions follow a gradual organization which progresses from primary (motor) to transmodal (DMN, task-unfocused) regions. Further, the relationship between the two principal gradients and the two motor and three nonmotor areas of representation revealed for the first time that there are functional differences not only between the two motor but also between the three nonmotor areas of representation. An initial novel hypothesis regarding the nature of these differences is generated by noting that nonmotor processing in lobules IX/X (third nonmotor representation) might share functional similarities with motor processing in lobule VIII (second motor representation).” 

In closing, below are two of the latest maps of the cerebellum by Guell et al. (2018) with functional gradients. In my opinion, the information held in these maps shifts our worldview of whole-brain functions in ways that could potentially improve lives and help people from all walks of life optimize their full potential. 

Figure One

Xavier Guell et al./eLife 2018 (Creative Commons)
Cerebellum gradients and relationship with discrete task activity maps (from Guell et al., 2018a) and resting-state maps (from Buckner et al., 2011) 
Source: Xavier Guell et al./eLife 2018 (Creative Commons)

Figure Two

 Xavier Guell et al./eLife 2018 (Creative Commons)
Gradient 1 extended from language task/DMN to motor regions. Gradient 2 isolated working memory/frontoparietal network areas. (A) Cerebellum flatmap atlas and gradients 1 and 2. (B) A scatterplot of the first two gradients. Each dot corresponds to a cerebellar voxel, position of each dot along x and y axis corresponds to position along Gradient 1 and Gradient 2 for that cerebellar voxel, and color of the dot corresponds to task activity (top) or resting-state network (bottom) associated with that particular voxel.
Source: Xavier Guell et al./eLife 2018 (Creative Commons)

References

Catherine J. Stoodley and Jeremy D. Schmahmann. "Functional Topography in the Human Cerebellum: A Meta-Analysis of Neuroimaging Studies." NeuroImage (First published: January 2009) DOI: 10.1016/j.neuroimage.2008.08.039 

Catherine J. Stoodley and Jeremy D. Schmahmann. "Evidence for Topographic Organization in the Cerebellum of Motor Control Versus Cognitive and Affective Processing." Cortex (First published: January 2010) DOI: 10.1016/j.cortex.2009.11.008

Randy L. Buckner, Fenna M. Krienen, Angela Castellanos, Julio C. Diaz, and B. T. Thomas Yeo. "The Organization of the Human Cerebellum Estimated by Intrinsic Functional Connectivity." Journal of Neurophysiology (First published: November 1, 2011) DOI: 10.1152/jn.00339.2011

Catherine J. Stoodley and Jeremy D. Schmahmann. "Chapter 4 - Functional Topography of the Human Cerebellum." Handbook of Clinical Neurology (First available online: June 11, 2018) DOI: 10.1016/B978-0-444-63956-1.00004-7

Xavier Guell, John Gabrieli, and Jeremy Schmahmann. "Triple Representation of Language, Working Memory, Social and Emotion Processing in the Cerebellum: Convergent Evidence from Task and Seed-Based Resting-State fMRI Analyses in a Single Large Cohort." NeuroImage (First published online: February 2, 2018 ) DOI: 10.1016/j.neuroimage.2018.01.082

Sheeba Arnold Anteraper, Xavier Guell, Anila D'Mello, Neha Joshi, Susan Whitfield-Gabrieli, and Gagan Joshi. "Disrupted Cerebrocerebellar Intrinsic Functional Connectivity in Young Adults with High-Functioning Autism Spectrum Disorder: A Data-Driven, Whole-Brain, High-Temporal Resolution Functional Magnetic Resonance Imaging Study." Brain Connectivity (First published online: July 31, 2018) DOI: 10.1089/brain.2018.0581

Xavier Guell, Jeremy D. Schmahmann, John D.E. Gabrieli, Satrajit S. Ghosh. "Functional Gradients of the Cerebellum." eLife (First published: August 14, 2018) DOI: 10.7554/eLife.36652

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