Role of Broca's Area in Implicit Motor Skill Learning: Evidence from Continuous Theta-burst Magnetic Stimulation

Complex actions can be regarded as a concatenation of simple motor acts, arranged according to specific rules. Because the caudal part of the Broca's region (left Brodmann's area 44, BA 44) is involved in processing hierarchically organized behaviors, we aimed to test the hypothesis that this area may also play a role in learning structured motor sequences. To address this issue, we investigated the inhibitory effects of a continuous theta-burst TMS (cTBS) applied over left BA 44 in healthy subjects, just before they performed a serial RT task (SRTT). SRTT has been widely used to study motor skill learning and is also of interest because, for complex structured sequences, subjects spontaneously organize them into smaller subsequences, referred to as chunks. As a control, cTBS was applied over the vertex in another group, which underwent the same experiment. Control subjects showed both a general practice learning effect, evidenced by a progressive decrease in RT across blocks and a sequence-specific learning effect, demonstrated by a significant RT increase in a pseudorandom sequence. In contrast, when cTBS was applied over left BA 44, subjects lacked both the general practice and sequence-specific learning effects. However, surprisingly, their chunking pattern was preserved and remained indistinguishable from controls. The present study indicates that left BA 44 plays a role in motor sequence learning, but without being involved in elementary chunking. This dissociation between chunking and sequence learning could be explained if we postulate that left BA 44 intervenes in high hierarchical level processing, possibly to integrate elementary chunks together.

[1]  O. Hikosaka,et al.  Learning of sequential movements in the monkey: process of learning and retention of memory. , 1995, Journal of neurophysiology.

[2]  Alvaro Pascual-Leone,et al.  The time course of off-line motor sequence learning. , 2005, Brain research. Cognitive brain research.

[3]  Etienne Olivier,et al.  Role of Broca’s area in motor sequence programming: a cTBS study , 2011, Neuroreport.

[4]  I Koch,et al.  Patterns, chunks, and hierarchies in serial reaction-time tasks , 2000, Psychological research.

[5]  Scott T. Grafton,et al.  Attention and stimulus characteristics determine the locus of motor-sequence encoding. A PET study. , 1997, Brain : a journal of neurology.

[6]  R. C. Oldfield THE ASSESSMENT AND ANALYSIS OF HANDEDNESS , 1971 .

[7]  E. Robertson The Serial Reaction Time Task: Implicit Motor Skill Learning? , 2007, The Journal of Neuroscience.

[8]  Luis Jiménez,et al.  Taking patterns for chunks: is there any evidence of chunk learning in continuous serial reaction-time tasks? , 2008, Psychological research.

[9]  G. Novembre,et al.  Syntax in a pianist's hand: ERP signatures of “embodied” syntax processing in music , 2013, Cortex.

[10]  Joan Y. Chiao,et al.  An Event-related fMRI Study of Artificial Grammar Learning in a Balanced Chunk Strength Design , 2004, Journal of Cognitive Neuroscience.

[11]  Luciano Fadiga,et al.  Role of Broca's area in encoding sequential human actions: a virtual lesion study , 2009, Neuroreport.

[12]  Benoit M. Macq,et al.  Registration and real-time visualization of transcranial magnetic stimulation with 3-D MR images , 2004, IEEE Transactions on Biomedical Engineering.

[13]  Mark Hallett,et al.  The role of the dorsolateral prefrontal cortex in implicit procedural learning , 2004, Experimental Brain Research.

[14]  Sabrina M. Tom,et al.  The Neural Correlates of Motor Skill Automaticity , 2005, The Journal of Neuroscience.

[15]  I. Koch,et al.  Learning hierarchically structured action sequences is unaffected by prefrontal-cortex lesion , 2006, Experimental Brain Research.

[16]  A. Nobre,et al.  Dissociating Linguistic Processes in the Left Inferior Frontal Cortex with Transcranial Magnetic Stimulation , 2022 .

[17]  L. Craighero,et al.  Broca's Area in Language, Action, and Music , 2009, Annals of the New York Academy of Sciences.

[18]  Thomas Goschke,et al.  On the modularity of implicit sequence learning: Independent acquisition of spatial, symbolic, and manual sequences , 2012, Cognitive Psychology.

[19]  J. Rothwell,et al.  Theta Burst Stimulation of the Human Motor Cortex , 2005, Neuron.

[20]  Stefan Knecht,et al.  Electrical Stimulation of Broca's Area Enhances Implicit Learning of an Artificial Grammar , 2010, Journal of Cognitive Neuroscience.

[21]  P. Hagoort,et al.  The inferior frontal cortex in artificial syntax processing: An rTMS study , 2008, Brain Research.

[22]  John C. Rothwell,et al.  The Contribution of Primary Motor Cortex is Essential for Probabilistic Implicit Sequence Learning: Evidence from Theta Burst Magnetic Stimulation , 2010, Journal of Cognitive Neuroscience.

[23]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[24]  R. Passingham,et al.  The Time Course of Changes during Motor Sequence Learning: A Whole-Brain fMRI Study , 1998, NeuroImage.

[25]  J. Edwards,et al.  Motor sequence chunking is impaired by basal ganglia stroke , 2009, Neurobiology of Learning and Memory.

[26]  Ahmed,et al.  Hierarchical Chunking during Learning of Visuomotor Sequences , 2006, The 2006 IEEE International Joint Conference on Neural Network Proceedings.

[27]  Daniel Bullock,et al.  Learning and production of movement sequences: behavioral, neurophysiological, and modeling perspectives. , 2004, Human movement science.

[28]  David L. Wright,et al.  Contextual Interference: A Response Planning Account , 1998 .

[29]  J. W. Aldridge,et al.  Coding of Serial Order by Neostriatal Neurons: A “Natural Action” Approach to Movement Sequence , 1998, The Journal of Neuroscience.

[30]  J. Doyon,et al.  Reorganization and plasticity in the adult brain during learning of motor skills , 2005, Current Opinion in Neurobiology.

[31]  Walter Senn,et al.  Repetitive TMS over the human oculomotor cortex: Comparison of 1-Hz and theta burst stimulation , 2006, Neuroscience Letters.

[32]  P. Rossini,et al.  Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. , 1994, Electroencephalography and clinical neurophysiology.

[33]  K. Berridge,et al.  Cortex, striatum and cerebellum: control of serial order in a grooming sequence , 2004, Experimental Brain Research.

[34]  D. Wright,et al.  Motor programming during practice conditions high and low in contextual interference. , 2001, Journal of experimental psychology. Human perception and performance.

[35]  Maxime J Parent,et al.  Movement chunking during sequence learning is a dopamine-dependant process: a study conducted in Parkinson’s disease , 2010, Experimental Brain Research.

[36]  Ivan Toni,et al.  Parieto-Frontal Connectivity during Visually Guided Grasping , 2007, The Journal of Neuroscience.

[37]  A. Anwander,et al.  Connectivity-Based Parcellation of Broca's Area. , 2006, Cerebral cortex.

[38]  Karl Magnus Petersson,et al.  Artificial syntactic violations activate Broca's region , 2004 .

[39]  M. Nissen,et al.  Attentional requirements of learning: Evidence from performance measures , 1987, Cognitive Psychology.

[40]  Scott T. Grafton,et al.  Neural Substrates of Response-based Sequence Learning using fMRI , 2004, Journal of Cognitive Neuroscience.

[41]  D A Rosenbaum,et al.  Hierarchical control of rapid movement sequences. , 1983, Journal of experimental psychology. Human perception and performance.

[42]  A. Reber Implicit learning and tacit knowledge , 1993 .

[43]  Angela D. Friederici,et al.  Neural circuits of hierarchical visuo-spatial sequence processing , 2009, Brain Research.

[44]  Kenji Doya,et al.  fMRI investigation of cortical and subcortical networks in the learning of abstract and effector-specific representations of motor sequences , 2006, NeuroImage.

[45]  A. Reber Implicit learning of artificial grammars , 1967 .

[46]  Angela D. Friederici,et al.  Hierarchical artificial grammar processing engages Broca's area , 2008, NeuroImage.

[47]  Axel Cleeremans,et al.  Can sequence learning be implicit? New evidence with the process dissociation procedure , 2001, Psychonomic bulletin & review.

[48]  Kae Nakamura,et al.  Emergence of rhythm during motor learning , 2004, Trends in Cognitive Sciences.

[49]  Joachim Hoffmann,et al.  RT patterns and chunks in SRT tasks: a reply to Jiménez (2008) , 2010, Psychological research.

[50]  E. Koechlin,et al.  Broca's Area and the Hierarchical Organization of Human Behavior , 2006, Neuron.

[51]  L. A. Jeffress,et al.  Cerebral Mechanisms in Behavior , 1953 .

[52]  M. Lévesque,et al.  Raclopride-induced motor consolidation impairment in primates: role of the dopamine type-2 receptor in movement chunking into integrated sequences , 2007, Experimental Brain Research.

[53]  Yosef Grodzinsky,et al.  Neuroimaging of syntax and syntactic processing , 2006, Current Opinion in Neurobiology.

[54]  S. Bookheimer,et al.  Dissociating Neural Mechanisms of Temporal Sequencing and Processing Phonemes , 2003, Neuron.

[55]  Howard Eichenbaum,et al.  Essential Role of the Hippocampal Formation in Rapid Learning of Higher-Order Sequential Associations , 2006, The Journal of Neuroscience.

[56]  Alice C. Roy,et al.  Encoding of human action in Broca's area. , 2009, Brain : a journal of neurology.

[57]  C. I. Connolly,et al.  Building neural representations of habits. , 1999, Science.

[58]  Simon B. Eickhoff,et al.  Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space—The roles of Brodmann areas 44 and 45 , 2004, NeuroImage.

[59]  J. Gabrieli,et al.  Direct comparison of neural systems mediating conscious and unconscious skill learning. , 2002, Journal of neurophysiology.

[60]  Tao Liu,et al.  Differential Effect of Reward and Punishment on Procedural Learning , 2009, The Journal of Neuroscience.

[61]  R. Passingham,et al.  Learning Arbitrary Visuomotor Associations: Temporal Dynamic of Brain Activity , 2001, NeuroImage.

[62]  M. Tommerdahl,et al.  Continuous theta-burst stimulation modulates tactile synchronization , 2013, BMC Neuroscience.

[63]  Alan Cowey,et al.  Transcranial magnetic stimulation and cognitive neuroscience , 2000, Nature Reviews Neuroscience.

[64]  Angela D. Friederici,et al.  Procedural Learning in Broca's Aphasia: Dissociation between the Implicit Acquisition of Spatio-Motor and Phoneme Sequences , 2001, Journal of Cognitive Neuroscience.

[65]  V. Penhune,et al.  Specific Increases within Global Decreases: A Functional Magnetic Resonance Imaging Investigation of Five Days of Motor Sequence Learning , 2010, The Journal of Neuroscience.

[66]  William B Verwey,et al.  Evidence for Lasting Sequence Segmentation in the Discrete Sequence-Production Task , 2003, Journal of motor behavior.

[67]  Heidi Johansen-Berg,et al.  White matter integrity in the vicinity of Broca's area predicts grammar learning success , 2009, NeuroImage.

[68]  Masako Okamoto,et al.  Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10–20 system oriented for transcranial functional brain mapping , 2004, NeuroImage.

[69]  O. Hikosaka,et al.  Chunking during human visuomotor sequence learning , 2003, Experimental Brain Research.

[70]  S Dehaene,et al.  A hierarchical neuronal network for planning behavior. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[71]  M. Corballis From mouth to hand: Gesture, speech, and the evolution of right-handedness , 2003, Behavioral and Brain Sciences.

[72]  E. Koechlin,et al.  The Architecture of Cognitive Control in the Human Prefrontal Cortex , 2003, Science.

[73]  Paul J. Reber,et al.  Neural Correlates of Artificial Grammar Learning , 2002, NeuroImage.

[74]  J. Ashe,et al.  Neural correlates of encoding and expression in implicit sequence learning , 2005, Experimental Brain Research.

[75]  M. Tettamanti,et al.  Broca's Area: a Supramodal Hierarchical Processor? , 2006, Cortex.

[76]  Scott T. Grafton,et al.  Functional Mapping of Sequence Learning in Normal Humans , 1995, Journal of Cognitive Neuroscience.

[77]  T. J. Grabowski Re-examining the Brain Regions Crucial for Orchestrating Speech Articulation , 2006 .

[78]  Morten H. Christiansen,et al.  Sequential learning in non-human primates , 2001, Trends in Cognitive Sciences.

[79]  Peter Ford Dominey,et al.  Neurological basis of language and sequential cognition: Evidence from simulation, aphasia, and ERP studies , 2003, Brain and Language.

[80]  Tim Curran,et al.  Higher-Order Associative Learning in Amnesia: Evidence from the Serial Reaction Time Task , 1997, Journal of Cognitive Neuroscience.

[81]  Guillén Fernández,et al.  Neural correlates of artificial syntactic structure classification , 2006, NeuroImage.

[82]  S. Keele,et al.  Modularity of Sequence Learning Systems in Humans , 1995 .

[83]  A. Graybiel The Basal Ganglia and Chunking of Action Repertoires , 1998, Neurobiology of Learning and Memory.

[84]  E. Soetens,et al.  Sequence learning and sequential effects , 2004, Psychological research.

[85]  C. Stern,et al.  An fMRI Study of the Role of the Medial Temporal Lobe in Implicit and Explicit Sequence Learning , 2003, Neuron.

[86]  K. Lashley The problem of serial order in behavior , 1951 .

[87]  Morten H. Christiansen,et al.  Impaired artificial grammar learning in agrammatism , 2010, Cognition.

[88]  K. Berridge,et al.  Implementation of Action Sequences by a Neostriatal Site: A Lesion Mapping Study of Grooming Syntax , 1996, The Journal of Neuroscience.

[89]  Kirrie J. Ballard,et al.  Motor programming in apraxia of speech , 2008, Brain and Language.

[90]  Carol A. Seger,et al.  Neural activity differs between explicit and implicit learning of artificial grammar strings: An fMRI study , 2000, Psychobiology.

[91]  P. Greenfield,et al.  Language, tools and brain: The ontogeny and phylogeny of hierarchically organized sequential behavior , 1991, Behavioral and Brain Sciences.

[92]  Scott T. Grafton,et al.  Abstract and Effector-Specific Representations of Motor Sequences Identified with PET , 1998, The Journal of Neuroscience.

[93]  Tony Ro,et al.  Transcranial Magnetic Stimulation: Disrupting Neural Activity to Alter and Assess Brain Function , 2010, The Journal of Neuroscience.

[94]  G. A. Miller THE PSYCHOLOGICAL REVIEW THE MAGICAL NUMBER SEVEN, PLUS OR MINUS TWO: SOME LIMITS ON OUR CAPACITY FOR PROCESSING INFORMATION 1 , 1956 .

[95]  Karl J. Friston,et al.  Learning-related neuronal responses in prefrontal cortex studied with functional neuroimaging. , 1999, Cerebral cortex.

[96]  Willem B Verwey,et al.  Motor Learning and Chunking in Dyslexia , 2009, Journal of motor behavior.

[97]  E. Wassermann Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. , 1998, Electroencephalography and clinical neurophysiology.

[98]  Robert F. Port,et al.  Neural Representation of Temporal Patterns , 1995, Springer US.