Task Force Paper on Cerebellum Research Charts Future Course

New 22-year review of Cerebellar Cognitive Affective Syndrome marks a milestone.

Posted Sep 15, 2019

Until the late 1990s, most brain experts thought the human cerebellum (Latin for "little brain") was only involved in motor functions and had nothing to do with non-motor functions or cognition.

Wikimedia/Creative Commons
The human brain viewed from below, showing cerebellum and brainstem with cerebrum above.
Source: Wikimedia/Creative Commons

However, over the past two decades, in one of the most radical paradigm shifts in modern-day neuroscience, hundreds of rigorous scientific studies have established that the cerebellum is also involved in non-motor cognitive functions, which include language processing, visuospatial cognition, emotions, and affective states. (Cerebellar means "relating to or located in the cerebellum.")

Yesterday, an international collaborative of 11 "little brain" thought leaders—who are affiliated with over a dozen world-renowned institutions in five countries—published, "The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper." This monumental review (2019) was published online on September 14 in The Cerebellum journal.

In a Twitter post last night, Schmahmann Lab announced "@TheCerebellum @SpringerNature encouraging sharing [this task force paper] without charge."

Life Sciences Database/Wikimedia Commons
Cerebellum (Latin for "little brain") in red
Source: Life Sciences Database/Wikimedia Commons

Because there is currently little doubt that the human cerebellum plays a role in cognition, emotion, and affect, the task force asserts that the CCAS provides an "ideal clinical entity" to explore the mechanisms that facilitate the cerebellum's role in cognition, psychological disorders, and mental health moving forward.

What is CCAS? Cerebellar cognitive affective syndrome reflects a constellation of cerebellar-induced ripple effects that influence executive function, visuospatial processing, language, and overall emotion/affect. CCAS is also called "Schmahmann's Syndrome."

In their recent task force review (2019), the authors lay out the objective of their multi-faceted paper in the introduction,

"The primary objective of this task force paper is to stimulate further research in this area. After providing an up-to-date overview of the fundamental findings on cerebellar neurocognition, the paper substantiates the concept of cerebellar cognitive affective syndrome (CCAS) with recent evidence from different scientific angles, promotes awareness of CCAS as a clinical entity, and examines our current insight into the therapeutic options available. The paper [also] identifies topics of divergence and outstanding questions for further research."

Before diving into more details about this recent five-part task force paper, below is a brief timeline of Jeremy Schmahmann's maverick role in setting the record straight on long-held misunderstandings about the human cerebellum.

In the late 1990s, Jeremy Schmahmann and colleagues at Harvard Medical School's Massachusetts General Hospital published a handful of game-changing papers that shook up the status quo by questioning the centuries-old assumption by most neuroscientists that the human cerebellum was only involved in motor functions. Schmahmann is a neurologist who specializes in ataxia.

Dysmetria (i.e., lack of coordination) of movement is a classic hallmark of ataxia caused by damage or impairment of the cerebellum. In the early 1990s, Schmahmann was bewildered when he began to notice that damage to certain "microzones" within the cerebellum did not result in motor-coordination-related dysmetria or ataxia; however, these atypical patients with damage to their cerebellum displayed compromising changes in their cognitive functions and affect.

Between 1997 and 1998, Schmahmann had the "hot hand" and published three groundbreaking, peer-reviewed papers that identified a cerebellar role in cognition and affective states for the first time.

In 1997, Jeremy Schmahmann and Deepak Pandya published what would turn out to be a revolutionary paper, "The Cerebocerebellar System." At the time, this paper didn't create a jaw-dropping amount of buzz. But, with 20/20 hindsight, it's clear that this paper marks the beginning of a new era of how neuroscientists would view the cerebellum in the 21st century.

Over two decades ago, Schmahmann and Pandya described their novel, first-of-its-kind concept of a cerebro-cerebellar interconnected system:

"If there is a cerebellar contribution to nonmotor function, particularly to cognitive abilities and affective states, then there must be corresponding anatomic substrates that support this. The cerebellum is strongly interconnected with the cerebral hemispheres in both feed-forward (cerebral hemispheres to cerebellum) and feedback directions. This relationship has long been recognized, particularly with respect to the motor and sensory cortices. Investigations performed over the last decade, however, have demonstrated for the first time the organization and strength of the connections that link the cerebellum with areas of the cerebral cortex known to be concerned with higher-order behavior rather than with motor control."

In April of 1998, Jeremy Schmahmann and Janet Sherman published a landmark paper, "The Cerebellar Cognitive Affective Syndrome," in the journal Brain. This historic paper signifies the first time that constellation of cerebellum-related deficits in executive function, visuospatial cognition, emotion-affect, and language that extend above and beyond speech are classified as a “syndrome” and given a name in a peer-reviewed journal.

Jeremy Schmahmann published another game-changing paper in September of 1998, "Dysmetria of Thought: Clinical Consequences of Cerebellar Dysfunction on Cognition and Affect." The basic premise of Schmahmann's "Dysmetria of Thought" hypothesis (which has stood the test of time) is that disruptions of specific mechanisms within the cerebellum that are part of the nonmotor cerebro-cerebellar circuitry impair someone's coordination of thought, much the same way that cerebellar damage to motor-function regions impairs physical coordination in patients with ataxia.

The Cerebellar Cognitive Affective/Schmahmann Syndrome: A Task Force Paper (2019) Divided into Five Sections:

1. Cerebellar Functional Topography in CCAS: Updates and Challenges: This section by Georgios Argyropoulos and Richard Ivry provides an introduction and overview to functional topography and mapping of the cerebellum. 

2. Cerebellar Neurocognition: Relevance to CCAS: In this section, Catherine Stoodley and Frank Van Overwalle summarize mountains of neuroimaging evidence that illuminates the role that specific regions of the cerebellum play in multiple cognitive domains through the lens of CCAS.

3. Introducing Cognition into Cerebellar Rehabilitation: Facts and Hopes: This section by Michael Adamaszek, Marcella Masciullo, and Marco Molinari addresses practical issues relating to "multimodal deficits in CCAS" and offers some insights on the current landscape regarding therapeutic options.

4. Replication of CCAS: Here, Jeremy Schmahmann and Maria Leggio review replication studies of CCAS over the past 20 years based on research involving children and adults with genetically inherited or otherwise acquired cerebellar diseases.

5. Discussion: Consensus on CCAS and Future Directions: Lastly, in the discussion section of this task force paper, Georgios Argyropoulos, Kim van Dun, and Richard Ivry recap points of convergence from the four above-mentioned sections and identify outstanding questions that require further investigation.

In their conclusion, the 11 co-authors sum up their review and offer guidelines for future research relating to CCAS/Schmahmann Syndrome: 

 

These are exciting times for cerebellar research; our understanding of the enigmatic "little brain" is advancing at breakneck speed.

Based on current trends in neuroscience, it appears that the early-21st century may be an era that goes down in history as the period when non-motor functions of the cerebellum—which were hidden under the radar of 20th-century technology—finally received long-overdue recognition from the mainstream medical establishment and state-of-the-art neuroscience researchers around the globe.

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References

Georgios P. D. Argyropoulos, Kim van Dun, Michael Adamaszek, Maria Leggio, Mario Manto, Marcella Masciullo, Marco Molinari, Catherine J. Stoodley, Frank Van Overwalle, Richard B. Ivry, Jeremy D. Schmahmann. "The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper" The Cerebellum (First published online: September 14, 2019) DOI: 10.1007/s12311-019-01068-8 

Author Affiliations:

1. Georgios P. D. Argyropoulos: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK 

2. Kim van Dun: Rehabilitation Research Center REVAL, UHasselt, Hasselt, Belgium

3. Michael Adamaszek: Clinical and Cognitive Neurorehabilitation, Center of Neurology and Neurorehabilitation, Klinik Bavaria Kreischa, An der Wolfsschlucht1-2, 01703 Kreischa, Germany

4. Maria Leggio: Department of Psychology, Sapienza University of Rome, Italy. Ataxia Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy. Ataxia Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

5. Mario Manto: Department of Neurology, CHU-Charleroi, 6000 Charleroi, Belgium. Department of Neurosciences, University of Mons, 7000 Mons, Belgium

6. Marcella Masciullo: SPInal REhabilitation Lab (SPIRE), IRCCS Fondazione Santa Lucia, Via Ardeatina 306, 00179, Rome, Italy

7. Marco Molinari: Neuro-Robot Rehabilitation Lab, IRCCS Fondazione Santa Lucia, Via Ardeatina 306, 00179, Rome, Italy

8. Catherine J. Stoodley: Department of Psychology, American University, 20016, Washington, DC, USA

9. Frank Van Overwalle: Department of Psychology, Vrije Universiteit Brussel, Brussels, Belgium

10. Richard B. Ivry: Department of Psychology, University of California, Berkeley, CA, USA

11. Jeremy D. Schmahmann: Ataxia Unit, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Jeremy D. Schmahmann "Disorders of the Cerebellum: Ataxia, Dysmetria of Thought, and the Cerebellar Cognitive Affective Syndrome." The Journal of Neuropsychiatry and Clinical Neurosciences (2004) DOI: 10.1176/jnp.16.3.367

Jeremy D. Schmahmann and Janet C. Sherman. "The Cerebellar Cognitive Affective Syndrome." Brain: A Journal of Neurology (1998) DOI: 10.1093/brain/121.4.561

Jeremy D. Schmahmann. "Dysmetria of Thought: Clinical Consequences of Cerebellar Dysfunction on Cognition and Affect." Trends in Cognitive Sciences (1998) DOI: 10.1016/S1364-6613(98)01218-2

Jeremy D. Schmahmann and Deepak N.. Pandya. "The Cerebocerebellar System" International Review of Neurobiology (1997) DOI: 10.1016/S0074-7742(08)60346-3

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