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

&NA; Delineation of functional topography is critical to the evolving understanding of the cerebellum's role in a wide range of nervous system functions. We used data from the Human Connectome Project (n = 787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting‐state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohen's d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non‐motor tasks in the same participants, and convergent resting‐state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. 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. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?). HighlightsWe analyzed motor and multiple nonmotor task fMRI activations in the cerebellum.Resting‐state seeds were placed at each task activation peak in the cerebral cortex.We describe cerebellar task topography in the largest single cohort studied to date.Nonmotor cerebellar task activation revealed a pattern of triple representation.Resting‐state analysis revealed an overlapping pattern of triple representation.

[1]  J. Schmahmann,et al.  Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population. , 2000, Brain : a journal of neurology.

[2]  Stephen M Smith,et al.  Correspondence of the brain's functional architecture during activation and rest , 2009, Proceedings of the National Academy of Sciences.

[3]  D. Riva,et al.  The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumours. , 2000, Brain : a journal of neurology.

[4]  D. Schutter,et al.  The Cerebellum in Emotion Regulation: A Repetitive Transcranial Magnetic Stimulation Study , 2009, The Cerebellum.

[5]  J. Schmahmann,et al.  Cerebellar stroke without motor deficit: clinical evidence for motor and non-motor domains within the human cerebellum , 2009, Neuroscience.

[6]  D. Pandya,et al.  Projections to the basis pontis from the superior temporal sulcus and superior temporal region in the rhesus monkey , 1991, The Journal of comparative neurology.

[7]  O. Oscarsson,et al.  FUNCTIONAL ORGANIZATION OF THE SPINO- AND CUNEOCEREBELLAR TRACTS. , 1965, Physiological reviews.

[8]  Christopher L. Asplund,et al.  The organization of the human cerebellum estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[9]  Dennis J L G Schutter,et al.  Rapport sommaire High-frequency repetitive transcranial magnetic stimulation to the cerebellum and implicit processing of happy facial expressions , 2022 .

[10]  Peter Mariën,et al.  Schmahmann’s syndrome - identification of the third cornerstone of clinical ataxiology , 2015, Cerebellum & Ataxias.

[11]  Mark Jenkinson,et al.  The minimal preprocessing pipelines for the Human Connectome Project , 2013, NeuroImage.

[12]  J. Schmahmann From movement to thought: Anatomic substrates of the cerebellar contribution to cognitive processing , 1996, Human brain mapping.

[13]  Frank Van Overwalle,et al.  Social cognition and the cerebellum: A meta-analysis of over 350 fMRI studies , 2014, NeuroImage.

[14]  A. Moustafa,et al.  The Cerebellum and Psychiatric Disorders , 2015, Front. Public Health.

[15]  Catherine J. Stoodley,et al.  Distinct regions of the cerebellum show gray matter decreases in autism, ADHD, and developmental dyslexia , 2014, Front. Syst. Neurosci..

[16]  Ryuta Kawashima,et al.  Remembering with Gains and Losses: Effects of Monetary Reward and Punishment on Successful Encoding Activation of Source Memories , 2013, Cerebral cortex.

[17]  Julie A Fiez,et al.  Cerebellar damage produces selective deficits in verbal working memory. , 2006, Brain : a journal of neurology.

[18]  K. Cheng,et al.  Neural basis of decision making guided by emotional outcomes. , 2015, Journal of neurophysiology.

[19]  A. Berman,et al.  The Effect of Cerebellar Lesions on Emotional Behavior in the Rhesus Monkey , 1974 .

[20]  Katherine E. Prater,et al.  Distinct Cerebellar Contributions to Intrinsic Connectivity Networks , 2009, NeuroImage.

[21]  M. Erb,et al.  Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization , 2001, Human brain mapping.

[22]  H. Mehdorn,et al.  Evidence for distinct cognitive deficits after focal cerebellar lesions , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[23]  J. Polimeni,et al.  Blipped‐controlled aliasing in parallel imaging for simultaneous multislice echo planar imaging with reduced g‐factor penalty , 2012, Magnetic resonance in medicine.

[24]  Jörn Diedrichsen,et al.  A probabilistic MR atlas of the human cerebellum , 2009, NeuroImage.

[25]  Richard F. Thompson,et al.  The role of the cerebellum in classical conditioning of discrete behavioral responses , 2009, Neuroscience.

[26]  Jörn Diedrichsen,et al.  A spatially unbiased atlas template of the human cerebellum , 2006, NeuroImage.

[27]  Mark Jenkinson,et al.  MSM: A new flexible framework for Multimodal Surface Matching , 2014, NeuroImage.

[28]  J. Desmond,et al.  Lobular Patterns of Cerebellar Activation in Verbal Working-Memory and Finger-Tapping Tasks as Revealed by Functional MRI , 1997, The Journal of Neuroscience.

[29]  C. J. Honeya,et al.  Predicting human resting-state functional connectivity from structural connectivity , 2009 .

[30]  Marisa O. Hollinshead,et al.  The organization of the human cerebral cortex estimated by intrinsic functional connectivity. , 2011, Journal of neurophysiology.

[31]  B. Miller,et al.  Neurodegenerative Diseases Target Large-Scale Human Brain Networks , 2009, Neuron.

[32]  S. Kiebel,et al.  Multiple somatotopic representations in the human cerebellum. , 1999, Neuroreport.

[33]  S. White,et al.  Punishing unfairness: Rewarding or the organization of a reactively aggressive response? , 2014, Human brain mapping.

[34]  Jeremy D. Schmahmann,et al.  Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems , 2008, Cortex.

[35]  Peter Mariën,et al.  Cerebellar neurocognition: Insights into the bottom of the brain , 2008, Clinical Neurology and Neurosurgery.

[36]  H. Levinson,et al.  The Cerebellar-Vestibular Predisposition to Anxiety Disorders , 1989, Perceptual and motor skills.

[37]  P. Strick,et al.  Cerebellar output: motor and cognitive channels , 1998, Trends in Cognitive Sciences.

[38]  J Ashe,et al.  Specificity of inferior olive response to stimulus timing. , 2008, Journal of neurophysiology.

[39]  J. Schmahmann,et al.  The cerebellar cognitive affective syndrome. , 1998, Brain : a journal of neurology.

[40]  D. Pandya,et al.  Prelunate, occipitotemporal, and parahippocampal projections to the basis pontis in rhesus monkey , 1993, The Journal of comparative neurology.

[41]  Stephen M. Smith,et al.  Temporal Autocorrelation in Univariate Linear Modeling of FMRI Data , 2001, NeuroImage.

[42]  M. Raichle,et al.  Linguistic processing. , 1997, International review of neurobiology.

[43]  R. Lane,et al.  Neuroanatomical correlates of happiness, sadness, and disgust. , 1997, The American journal of psychiatry.

[44]  Fenna M. Krienen,et al.  Segregated Fronto-Cerebellar Circuits Revealed by Intrinsic Functional Connectivity , 2009, Cerebral cortex.

[45]  Steen Moeller,et al.  Multiband multislice GE‐EPI at 7 tesla, with 16‐fold acceleration using partial parallel imaging with application to high spatial and temporal whole‐brain fMRI , 2010, Magnetic resonance in medicine.

[46]  Stephen M. Smith,et al.  Multiplexed Echo Planar Imaging for Sub-Second Whole Brain FMRI and Fast Diffusion Imaging , 2010, PloS one.

[47]  Peter Mariën,et al.  Cerebellar areas dedicated to social cognition? A comparison of meta-analytic and connectivity results , 2015, Social neuroscience.

[48]  Abraham Z. Snyder,et al.  Function in the human connectome: Task-fMRI and individual differences in behavior , 2013, NeuroImage.

[49]  C. Frith,et al.  Movement and Mind: A Functional Imaging Study of Perception and Interpretation of Complex Intentional Movement Patterns , 2000, NeuroImage.

[50]  Shawn C. Milleville,et al.  Understanding Animate Agents , 2007, Psychological science.

[51]  Jeremy D. Schmahmann,et al.  Chapter 1 Cerebellum and Spinal Cord: Principles of Development, Anatomic Organization, and Functional Relevance , 2007 .

[52]  Masao Ito,et al.  Consensus Paper: The Cerebellum's Role in Movement and Cognition , 2013, The Cerebellum.

[53]  B. Postle,et al.  Superior Parietal Cortex Is Critical for the Manipulation of Information in Working Memory , 2009, The Journal of Neuroscience.

[54]  S. Sakoda,et al.  A functional MRI study of somatotopic representation of somatosensory stimulation in the cerebellum , 2003, Neuroradiology.

[55]  Karl Schilling,et al.  From zebra stripes to postal zones: deciphering patterns of gene expression in the cerebellum , 1998, Trends in Neurosciences.

[56]  Alan C. Evans,et al.  MRI Atlas of the Human Cerebellum , 2000 .

[57]  R. Heath Modulation of emotion with a brain pacemamer. Treatment for intractable psychiatric illness. , 1977, The Journal of nervous and mental disease.

[58]  J. Schmahmann The role of the cerebellum in affect and psychosis , 2000, Journal of Neurolinguistics.

[59]  D. Pandya,et al.  The cerebrocerebellar system. , 1997, International review of neurobiology.

[60]  Narender Ramnani,et al.  Cerebellar contributions to working memory , 2007, NeuroImage.

[61]  Robert S. Dow,et al.  CEREBELLAR ACTION POTENTIALS IN RESPONSE TO STIMULATION OF VARIOUS AFFERENT CONNECTIONS , 1939 .

[62]  Catherine J. Stoodley,et al.  Lateralized cognitive deficits in children following cerebellar lesions , 2001, Developmental medicine and child neurology.

[63]  R. Elliott,et al.  Neuronal correlates of reward and loss in Cluster B personality disorders: A functional magnetic resonance imaging study , 2007, Psychiatry Research: Neuroimaging.

[64]  J. Schmahmann An emerging concept. The cerebellar contribution to higher function. , 1991, Archives of neurology.

[65]  C. Woolsey,et al.  Patterns of localization in precentral and "supplementary" motor areas and their relation to the concept of a premotor area. , 1952, Research publications - Association for Research in Nervous and Mental Disease.

[66]  J. Desmond,et al.  The contributions of cerebro-cerebellar circuitry to executive verbal working memory , 2010, Cortex.

[67]  Dagmar Timmann,et al.  Functional localization in the human cerebellum based on voxelwise statistical analysis: A study of 90 patients , 2006, NeuroImage.

[68]  Jeremy D. Schmahmann,et al.  Metalinguistic Deficits in Patients with Cerebellar Dysfunction: Empirical Support for the Dysmetria of Thought Theory , 2014, The Cerebellum.

[69]  Catherine J. Stoodley,et al.  Consensus Paper: Language and the Cerebellum: an Ongoing Enigma , 2013, The Cerebellum.

[70]  Jeremy D. Schmahmann,et al.  Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies , 2009, NeuroImage.

[71]  Efstathios D. Gennatas,et al.  Predicting Regional Neurodegeneration from the Healthy Brain Functional Connectome , 2012, Neuron.

[72]  Richard B. Ivry,et al.  The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper , 2019, The Cerebellum.

[73]  R. Hawkes,et al.  Zebrin II: A polypeptide antigen expressed selectively by purkinje cells reveals compartments in rat and fish cerebellum , 1990, The Journal of comparative neurology.

[74]  J. Schmahmann The cerebellum and cognition , 2019, Neuroscience Letters.

[75]  Jennifer H. Pfeifer,et al.  Learning to Play It Safe (or Not): Stable and Evolving Neural Responses during Adolescent Risky Decision-making , 2015, Journal of Cognitive Neuroscience.

[76]  Marco Molinari,et al.  The cerebellar cognitive profile. , 2011, Brain : a journal of neurology.

[77]  D. Pandya,et al.  Prefrontal cortex projections to the basilar pons in rhesus monkey: implications for the cerebellar contribution to higher function , 1995, Neuroscience Letters.

[78]  D. Braus,et al.  Lateralized organization of the cerebellum in a silent verbal fluency task: a functional magnetic resonance imaging study in healthy volunteers , 2002, Neuroscience Letters.

[79]  D. V. van Essen,et al.  Mapping Human Cortical Areas In Vivo Based on Myelin Content as Revealed by T1- and T2-Weighted MRI , 2011, The Journal of Neuroscience.

[80]  Jeremy D. Schmahmann,et al.  An fMRI Study of Intra-Individual Functional Topography in the Human Cerebellum , 2010, Behavioural neurology.

[81]  D. Pandya,et al.  Anatomical investigation of projections to the basis pontis from posterior parietal association cortices in rhesus monkey , 1989, The Journal of comparative neurology.

[82]  Masao Ito Movement and thought: identical control mechanisms by the cerebellum , 1993, Trends in Neurosciences.

[83]  F. D’Agata,et al.  Consensus Paper: Cerebellum and Emotion , 2016, The Cerebellum.

[84]  P. Garrard,et al.  Cognitive and social cognitive functioning in spinocerebellar ataxia , 2008, Journal of Neurology.

[85]  Jeremy D. Schmahmann,et al.  Embodied cognition and the cerebellum: Perspectives from the Dysmetria of Thought and the Universal Cerebellar Transform theories , 2017, Cortex.

[86]  Kurt E. Weaver,et al.  Mapping anterior temporal lobe language areas with fMRI: A multicenter normative study , 2011, NeuroImage.

[87]  E. Eldred,et al.  CEREBRO-CEREBELLAR RELATIONSHIPS IN THE MONKEY , 1952 .

[88]  C. Combs,et al.  Electro-anatomical study of cerebellar localization; stimulation of various afferents. , 1954, Journal of neurophysiology.

[89]  H. Johansen-Berg,et al.  Distinct and overlapping functional zones in the cerebellum defined by resting state functional connectivity. , 2010, Cerebral cortex.

[90]  Stephen M. Smith,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[91]  M. Glickstein,et al.  The anatomy of the cerebellum , 1998, Trends in Neurosciences.

[92]  J. Schmahmann The cerebrocerebellar system: anatomic substrates of the cerebellar contribution to cognition and emotion , 2001 .

[93]  Jason B. Mattingley,et al.  Functional topography of primary emotion processing in the human cerebellum , 2012, NeuroImage.

[94]  Karsten Specht,et al.  Evidence of a modality-dependent role of the cerebellum in working memory? An fMRI study comparing verbal and abstract n-back tasks , 2009, NeuroImage.

[95]  P A Turski,et al.  Multiple tactile maps in the human cerebellum , 2001, Neuroreport.

[96]  M. Schwarz,et al.  Working Memory and Verbal Fluency Deficits Following Cerebellar Lesions: Relation to Interindividual Differences in Patient Variables , 2010, The Cerebellum.

[97]  S E Petersen,et al.  A positron emission tomography study of the short-term maintenance of verbal information , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[98]  Y. Shinoda,et al.  Molecular, Topographic, and Functional Organization of the Cerebellar Cortex: A Study with Combined Aldolase C and Olivocerebellar Labeling , 2004, The Journal of Neuroscience.

[99]  Kenneth Hugdahl,et al.  An fMRI study of working memory for schematic facial expressions. , 2007, Scandinavian journal of psychology.

[100]  J. Desmond,et al.  A meta‐analysis of cerebellar contributions to higher cognition from PET and fMRI studies , 2014, Human brain mapping.

[101]  M. Greicius,et al.  Resting-state functional connectivity reflects structural connectivity in the default mode network. , 2009, Cerebral cortex.

[102]  Essa Yacoub,et al.  The WU-Minn Human Connectome Project: An overview , 2013, NeuroImage.

[103]  Richard P. Bagozzi,et al.  fMRI Activities in the Emotional Cerebellum: A Preference for Negative Stimuli and Goal-Directed Behavior , 2011, The Cerebellum.

[104]  W. McMahon,et al.  Superior Temporal Gyrus, Language Function, and Autism , 2007, Developmental neuropsychology.

[105]  Francesco Fera,et al.  The Amygdala Response to Emotional Stimuli: A Comparison of Faces and Scenes , 2002, NeuroImage.

[106]  Jeremy D. Schmahmann,et al.  Cerebellar Contribution to Social Cognition , 2016, The Cerebellum.

[107]  Kalina Christoff,et al.  Localizing the rostrolateral prefrontal cortex at the individual level , 2007, NeuroImage.

[108]  Jeremy D. Schmahmann,et al.  Consensus paper on post-operative pediatric cerebellar mutism syndrome: the Iceland Delphi results , 2016, Child's Nervous System.

[109]  Jörn Diedrichsen,et al.  Surface-Based Display of Volume-Averaged Cerebellar Imaging Data , 2015, PloS one.

[110]  P. Strick,et al.  An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. , 2003, Journal of neurophysiology.

[111]  John E. Desmond,et al.  Load- and practice-dependent increases in cerebro-cerebellar activation in verbal working memory: an fMRI study , 2005, NeuroImage.

[112]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[113]  J. Schmahmann Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. , 2004, The Journal of neuropsychiatry and clinical neurosciences.

[114]  Jeremy D. Schmahmann,et al.  The cerebellum and pain: Passive integrator or active participator? , 2010, Brain Research Reviews.

[115]  Timothy O. Laumann,et al.  Informatics and Data Mining Tools and Strategies for the Human Connectome Project , 2011, Front. Neuroinform..

[116]  Jeremy D. Schmahmann,et al.  Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke , 2016, NeuroImage: Clinical.

[117]  Daniel S. Marcus,et al.  Obscuring Surface Anatomy in Volumetric Imaging Data , 2012, Neuroinformatics.

[118]  E. Eldred,et al.  Cerebrocerebellar relationships in the monkey. , 1952, Journal of neurophysiology.

[119]  Christian Büchel,et al.  A target sample of adolescents and reward processing: same neural and behavioral correlates engaged in common paradigms? , 2012, Experimental Brain Research.

[120]  Jeremy D. Schmahmann,et al.  The Role of the Cerebellum in Cognition and Emotion: Personal Reflections Since 1982 on the Dysmetria of Thought Hypothesis, and Its Historical Evolution from Theory to Therapy , 2010, Neuropsychology Review.

[121]  S. Paradiso,et al.  The cerebellum and emotional experience , 2007, Neuropsychologia.

[122]  Jeremy D. Schmahmann,et al.  Functional topography of the cerebellum for motor and cognitive tasks: An fMRI study , 2012, NeuroImage.

[123]  Catherine J. Stoodley,et al.  Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing , 2010, Cortex.

[124]  J. Bower,et al.  Consensus Paper: The Role of the Cerebellum in Perceptual Processes , 2014, The Cerebellum.

[125]  Brigitte Landeau,et al.  Intrinsic Connectivity Identifies the Hippocampus as a Main Crossroad between Alzheimer’s and Semantic Dementia-Targeted Networks , 2014, Neuron.

[126]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[127]  Jessica A. Collins,et al.  Focal temporal pole atrophy and network degeneration in semantic variant primary progressive aphasia , 2017, Brain : a journal of neurology.

[128]  Jennifer H. Pfeifer,et al.  Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders , 2006, Nature Neuroscience.

[129]  P. Strick,et al.  Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. , 1994, Science.

[130]  P. Strick,et al.  Cerebellum and nonmotor function. , 2009, Annual review of neuroscience.

[131]  N. Gerrits,et al.  Organization of the Vestibulocerebellum , 1996, Annals of the New York Academy of Sciences.

[132]  D. Pandya,et al.  Anatomic Organization of the Basilar Pontine Projections from Prefrontal Cortices in Rhesus Monkey , 1997, The Journal of Neuroscience.

[133]  L. Nystrom,et al.  Tracking the hemodynamic responses to reward and punishment in the striatum. , 2000, Journal of neurophysiology.

[134]  Dwight J. Kravitz,et al.  The ventral visual pathway: an expanded neural framework for the processing of object quality , 2013, Trends in Cognitive Sciences.

[135]  M. Molinari,et al.  Verbal short-term store-rehearsal system and the cerebellum. Evidence from a patient with a right cerebellar lesion. , 1998, Brain : a journal of neurology.

[136]  A. Jansen,et al.  Crossed cerebro–cerebellar language dominance , 2005, Human brain mapping.

[137]  J. Schmahmann,et al.  The neuropsychiatry of the cerebellum — insights from the clinic , 2008, The Cerebellum.

[138]  S. H. A. Chen,et al.  Modality Specific Cerebro-Cerebellar Activations in Verbal Working Memory: An fMRI Study , 2010, Behavioural neurology.

[139]  Xavier Guell,et al.  The cerebellar cognitive affective/Schmahmann syndrome scale , 2017, Brain : a journal of neurology.

[140]  P. Strick,et al.  Cerebellar Loops with Motor Cortex and Prefrontal Cortex of a Nonhuman Primate , 2003, The Journal of Neuroscience.

[141]  M. Seghier The Angular Gyrus , 2013, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[142]  Jesper Andersson,et al.  A multi-modal parcellation of human cerebral cortex , 2016, Nature.

[143]  Gary W Thickbroom,et al.  Dual representation of the hand in the cerebellum: activation with voluntary and passive finger movement , 2003, NeuroImage.