Brain Imaging of Motor Learning

BrainBrain ImagingImaging ofof MotorMotor LearningLearning

JulienJulien Doyon,Doyon, Ph.D.Ph.D. Scientific Director Functional Neuroimaging Unit University of Montreal Geriatric Institute University of Montreal MotorMotor SkillSkill LearningLearning

CharacteristicsCharacteristics

 Conceptualized as the acquisition of a specific motor plan (or set) for the effective performance of an intended action.  Acquisition is incremental.  Measured by a reduction in reaction time and errors, and/or by a change in movement synergy and kinematics.  Can be acquired either explicitly or implicitly.  Implicit retrieval.  Long-lasting.  Does not depend on limbic structures. CorticoCortico--StriatalStriatal SystemSystem

SupplementarySupplementary DorsalDorsal andand ventralventral PrimaryPrimary motor motor motormotor areas areas premotorpremotor cortices cortices cortexcortex

VLVLoo

StriatumStriatum

GlobusGlobus palliduspallidus

Carpenter, Core Text of Neuroanatomy, 2ème éd., 1982, Williams & Wilkins Company CorticoCortico--CerebellarCerebellar SystemSystem

SupplementarySupplementary DorsalDorsal andand ventralventral PrimaryPrimary motor motor motormotor areas areas premotorpremotor cortices cortices cortexcortex

XX VLVLcc++ VPLVPLoo

PonsPons

CerebellumCerebellum http://www.braincampus.com AnatomicalAnatomical InteractionsInteractions BetweenBetween thethe CorticoCortico-- StriatalStriatal andand CorticoCortico--CerebellarCerebellar SystemsSystems

Hoshi et al., Nature vol8 (2005), 1491-1493 MotorMotor SkillSkill LearningLearning

Motor, cognitive and physiological factors affecting cerebral plasticity during motor learning :

 Learning phases: fast vs slow vs consolidation vs reconsolidation vs automatization vs retention.

 Sleep, Nap, Interference.

 Type of motor learning: motor sequence vs motor adaptation. MotorMotor Learning:Learning: ExperimentalExperimental ParadigmsParadigms MotorMotor SequenceSequence LearningLearning Tasks:Tasks: IncrementalIncremental acquisitionacquisition ofof aa sequencesequence ofof movementsmovements

Finger Sequence Task Serial Reaction Time Task

1 2 3 4 MotorMotor Learning:Learning: ExperimentalExperimental ParadigmsParadigms

MotorMotor AdaptationAdaptation Tasks:Tasks: CapacityCapacity toto compensatecompensate forfor environmentalenvironmental changeschanges

Visuomotor Adaptation: Kinematic Force Field Adaptation: Dynamic

1 8 2

7 3

6 4 5

Targets appear in a random order: Inversed condition

requires MotorMotor SkillSkill LearningLearning

GoalsGoals ofof thisthis presentationpresentation

 To examine the cerebral plasticity mediating different phases of motor sequence learning (MSL) and motor adaptation (MA) using fMRI.

 To explore the behavioral/functional determinants of cerebral plasticity in both cortico-striatal (CS) and cortico-cerebellar (CC) systems.

 Contribution of sleep versus the simple passage of time to the consolidation of motor memory traces.

 Neural substrates and physiological correlates mediating the consolidation process of motor memory traces. Motor Sequence Learning

Objective

ToTo exploreexplore thethe dynamicdynamic cerebralcerebral changeschanges thatthat occuroccur withinwithin thethe striatumstriatum duringduring thethe fastfast andand slowslow phasesphases ofof learninglearning ofof aa sequencesequence ofof movementsmovements,, asas wellwell asas afterafter performanceperformance hashas becomebecome automatizedautomatized..

Lehéricy et al., (2005), PNAS 102(35) 12566-71 PlasticityPlasticity WithinWithin thethe StriatumStriatum DuringDuring MotorMotor SequenceSequence LearningLearning Method  Subjects : n = 14 (age: 19-34, right handed)  Task : Finger sequence task: 4-keys response box 2 sequences to learn (Trained & Untrained) 8 moves using 4 fingers (left hand)

 Block design :

 Scanning : 5 sessions

TR: 4.5 s TE: 40 ms : 90° bandwidth: 1562Hz/pixel FOV: 192 x 192 mm² Practice done every day for a month matrix size: 128 x 128 5 speed tests performed weekly, as well as before voxel size: 1.5 x 1.5 x 2.5 mm3 and after each scanning session (T1-T3, T4, T5)

Lehéricy et al., (2005), PNAS 102(35) 12566-71 PlasticityPlasticity WithinWithin thethe StriatumStriatum DuringDuring MotorMotor SequenceSequence LearningLearning BehavioralBehavioral results results

Lehéricy et al., (2005), PNAS 102(35) 12566-71 PlasticityPlasticity WithinWithin thethe StriatumStriatum DuringDuring MotorMotor SequenceSequence LearningLearning ImagingImaging resultsresults

Lehéricy et al., (2005), PNAS 102(35) 12566-71 PlasticityPlasticity WithinWithin thethe CerebellumCerebellum DuringDuring MotorMotor SequenceSequence LearningLearning

ImagingImaging resultsresults

Lehéricy et al., (2005), PNAS 102(35) 12566-71 Motor Adaptation

Objective

ToTo exploreexplore thethe cerebralcerebral changeschanges associatedassociated withwith thethe earlyearly andand automatizationautomatization phasesphases ofof anan adaptedadapted movementmovement..

Doyon et al., Behav. Brain Res., 2009 MotorMotor Adaptation:Adaptation: EarlyEarly vsvs AutomatizedAutomatized PhasePhase

Motor Adaptation: Inversed Condition Control Condition: Direct Condition

1 1 8 8 2 2

7 3 7 3

6 4 6 4 5 5

Targets appear in a random order: Targets appear in a random order: Inversed condition Direct condition

requires requires

Doyon et al., Behav. Brain Res., 2009 MotorMotor Adaptation:Adaptation: EarlyEarly vsvs AutomatizedAutomatized PhasePhase

TasksTasks

Primary task:

 Inversed mode (motor adaptation)

 Direct mode (control)

Secondary task:

 Tone discrimination task

Dual tasks:

 Inversed mode & tone discrimination task simultaneously

Doyon et al., Behav. Brain Res., 2009 MotorMotor Adaptation:Adaptation: FastFast vsvs AutomaticAutomatic PhasePhase ExperimentalExperimental ParadigmParadigm

Early Extended Practice Automatic Learning (subject tailored) Execution

Intro Daily Practice fMRI + fMRI Sessions on Tasks

Day 1: Days 2 to 30 : Day 26 15min/day On avg.

Doyon et al., Behav. Brain Res., 2009 MotorMotor adaptation:adaptation: AutomatizationAutomatization

Behavioral results

Doyon et al., Behav. Brain Res., 2009 MotorMotor adaptation:adaptation: AutomatizationAutomatization

Early IM – Early DM

Doyon et al., Behav. Brain Res., 2009 MotorMotor adaptation:adaptation: AutomatizationAutomatization

Automatic IM – Automatic DM

Doyon et al., Behav. Brain Res., 2009 MotorMotor adaptation:adaptation: AutomatizationAutomatization

(Automatic IM – Automatic DM) – (Early IM – Early DM)

Doyon et al., Behav. Brain Res., 2009 NeuralNeural SubstratesSubstrates ofof MotorMotor LearningLearning

Frontal associative regions Motor cortical regions Parietal Cortices Sensorimotor striatum Cerebellar cortices and nuclei

Associative striatum Cerebellar cortices Medial temporal lobe (hippocampus)

Cognitive Cognitive

Fast Learning processes processes

Motor sequence Motor learning adaptation

Doyon & Benali (2005), Current Opinion Neurobiology NeuralNeural SubstratesSubstrates ofof MotorMotor LearningLearning

Motor cortical regions

Striatum Parietal cortex Cerebellum Slow Learning Consolidation

Frontal associative regions Motor cortical regions Parietal Cortices Sensorimotor striatum Cerebellar cortices and nuclei

Associative striatum Cerebellar cortices Medial temporal lobe (hippocampus)

Cognitive Cognitive processes Fast Learning processes Motor sequence Motor learning adaptation Doyon & Benali (2005), Current Opinion Neurobiology NeuralNeural SubstratesSubstrates ofof MotorMotor LearningLearning

Motor cortical regions Motor cortical regions Parietal cortex Parietal cortex Striatum Cerebellum

Automatization

Motor cortical regions Slow Learning Striatum Parietal cortex Cerebellum

Consolidation

Frontal associative regions Motor cortical regions Parietal Cortices Sensorimotor striatum Cerebellar cortices and nuclei Associative striatum Cerebellar cortices Medial temporal lobe (hippocampus) Cognitive Cognitive processes processes Motor sequence Motor Fast Learning learning adaptation

Doyon & Benali (2005), Current Opinion Neurobiology Fast Learning Slow Learning Retention Neural Substrates ofMotorLearning Neural Substrates ofMotorLearning Motor corticalregions aitlcortex Parietal aitlcortex Parietal Motor cortical regions cortical Motor Striatum processes Cognitive Motor corticalregions Sensorimotor striatum Associative striatum Cerebellar cortices Cerebellar striatum Associative Striatum Striatum Motor sequence Motor Medial temporal learning Motor Frontal associativeregions Automatization Time delay Consolidation aitlcortex Parietal cortical lobe (hippocampus) regions oo eai(2005), Current Opinion Neurobiology Doyon & Benali Cerebellar corticesandnuclei Cerebellar adaptation Parietal Cortices Motor aitlcortex Parietal Cerebellum Motor corticalregions Motor cortical regions cortical Motor aitlcortex Parietal Cerebellum processes Cognitive Cerebellum Dissociating Functional Brain Areas Underlying Motor Sequence Learning Versus its Expression

Pierre Orban, Philippe Peigneux, Pierre Maquet, Julien Doyon

Objective

ToTo dissociatedissociate betweenbetween thethe neuralneural substratessubstrates mediatingmediating motormotor sequencesequence learninglearning perper sese,, versusversus performanceperformance (speed)(speed) ofof movementsmovements..

Orban et al., 2010, NeuroImage Dissociating Functional Brain Areas Underlying Motor Sequence Learning Versus its Expression

Experimental Design

3T fMRI study, block design, 32 subjects. -12 blocks

SeqLearn NoSeq/Ctrl Seq/Ctrl -Left hand movements 5-element finger Finger tapping Automatized sequence sequence (2 1 3 4 1) (1, 2, 3 or 4 / (4 3 2 1) at slow, -Nb of movements: slow, medium, medium and fast rate 50/block fast rate)

Parametric fMRI design

1st level – FFX – effects of parametric T modulation for each condition separately i m nd 2 level – RFX – conjunction and between- e condition subtractions Significance: p < 0.001 (uncorrected) Orban et al., 2010, NeuroImage Dissociating Functional Brain Areas Underlying Motor Sequence Learning Versus its Expression

Sequence Automatized Learning: Sequence: Finger tapping SeqLearn Seq/Ctrl NoSeq/Ctrl Conditions

Hz Hz Hz Hz

1121161 32

Orban et al., 2010, NeuroImage Dissociating Functional Brain Areas Underlying Motor Sequence Learning Versus its Expression

Results: fMRI (Parametric analyses)

Finger tapping (NoSeq/Ctrl)

Automatized Sequence (4321) (Seq/Ctrl)

Sequence Learning (SeqLearn) Orban et al., 2010, NeuroImage Dissociating Functional Brain Areas Underlying Motor Sequence Learning Versus its Expression

Results: fMRI (Conjonctions & Contrast analyses)

SeqLearn ∩ Seq/Ctrl ∩ NoSeq/Ctrl

SeqLearn ∩ Seq/Ctrl

SeqLearn –

Seq/Ctrl Orban et al., 2010, NeuroImage Cerebral Correlates of Movement Kinematic Changes Related to Motor Sequence Learning

Pierre Orban, Philippe Peigneux, Marc Barakat, Pierre Maquet, Julien Doyon Montreal, Canada and Liège, Belgium

ObjectiveObjective

ToTo identifyidentify brainbrain regionsregions mediatingmediating thethe changeschanges inin movementmovement kinematicskinematics (i.e.,(i.e., transitions,transitions, velocityvelocity)) associatedassociated withwith thethe learninglearning ofof aa newnew sequencesequence ofof movementsmovements..

Orban et al., Submitted, Eur. J. Neurosci. CerebralCerebral CorrelatesCorrelates ofof MovementMovement KinematicKinematic ChangesChanges RelatedRelated toto MotorMotor SequenceSequence LearningLearning Method

• 12 right-handed subjects (6 males, mean age = 26.5 years).

• Explicitly known 8-element sequence.

• Event-related fMRI design.

• 60 trials with left hand interspersed with rest epochs (mean duration = 12s).

• Finger movements recorded using a custom-made MR compatible keypad.

• Output data: % of maximum displacement reflecting the position of each button as a function of time (sampling rate = 400 Hz).

• 3T MRI scanner (Magnetom Tim Trio, Siemens). (TR = 1000ms, voxel size = 3.4 X 3.4 X 7 mm3, 16 slices).

fMRI Data: Main Effect

fMRI Data:

Vélocity

Transition

Vélocity/ Transition

Orban et al., Submitted, Eur. J. Neurosci. CerebralCerebral PlasticityPlasticity AssociatedAssociated withwith MotorMotor SequenceSequence LearningLearning

ConclusionsConclusions

• The lateral cerebellum (Lobule VI) and putamen (sensorimoteur) contribute critically to experience-dependent learning per se of a new motor sequence.

• Activity in the lateral cerebellum and putamen is mainly associated with improvement in finger movement transitions (co- articulation, chunking). MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects,, NeuralNeural SubstratesSubstrates andand PhysiologicalPhysiological CorrelatesCorrelates

…the memory of a given motor experience is thought to be dynamically re- processed off-line in a time- dependent fashion and transformed into an enduring state. MotorMotor MemoryMemory ConsolidationConsolidation

Parametric design:

 Spontaneous delayed gains in performance without additional practice following an initial training session.

Interference design:

. Time-dependent reduction in interference from a competing task. MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects??

Walker et al., Neuron vol35 (2002), 205-211 MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects??

Walker et al., Neuron Vol. 35 (2002), 205-211 MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects??

Walker et al., Neuron Vol. 35 (2002), 205-211 SleepSleep ContributionContribution toto MotorMotor MemoryMemory ConsolidationConsolidation

Remaining Issues:

• Nature of the motor tasks

• Neural substrates

• Stage(s) of sleep SleepSleep ContributionContribution toto MotorMotor MemoryMemory ConsolidationConsolidation MainMain Objectives:Objectives: .. To study, through behavioral analyses, the effects of sleep versus simple passage of time on the consolidation of motor sequence learning or motor adaptation tasks.

.. To identify, through fMRI studies, the neural substrates mediating the consolidation of both motor sequence and motor adaptation.

.. To identify, with polysomnographic recordings, the sleep feature(s) involved in the motor memory consolidation. MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep vs.vs. SimpleSimple PassagePassage ofof TimeTime -- BehavioralBehavioral StudyStudy ExperimentalExperimental design:design:

NIGHT group (n=26)

Training Retest (12 h after initial 1 2 3 4 1 2 3 or 4 training) SLEEP or PSG

Evening Morning (2 h after 12 hours awakening ) DAY group (n=25) Training Retest (12 h after initial 1 2 3 PASSAGE OF 4 1 2 3 4 training) TIME (withoutnaps ) or or

Morning (2 h after Evening 12 hours awakening ) Doyon et al., 2009, Exp. Brain Res. MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep vs.vs. SimpleSimple PassagePassage ofof TimeTime

BehavioralBehavioral Results:Results: MotorMotor AdaptationAdaptation TaskTask

0,9

significant +2% significant +2.5% 0,89

P O 0,88 A F S S L S T 0,87 E A I E P G M E E 0,86

PI-Speed and precision PI-Speed 0,85

0,84 Post-training Retest Post-training Retest ANOVA 2 sessions X 2 groups= significant session effect:F(1, 24)=27,779, p=0,00002 Doyon et al., 2009, Exp. Brain Res. MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep vs.vs. SimpleSimple PassagePassage ofof TimeTime –– BehavioralBehavioral StudyStudy BehavioralBehavioral Results:Results: SequenceSequence TaskTask 30 24 S P L A NIGHT group E S 23 E S Significant + 14% Non-significant + 2% 24 DAY group P A G 22 O E S P O L R 21 A F 18 O E S E S T F P 20 A I T G M E E

12 I Speed (# sequences per 30s) 19 Speed (#sequences 30s) per M E 18 6 Post-training Retest Post-training Retest 123456789101112 123 Blocks of trials Retest 12h later ANOVA 2 sessions X 2 groups = significant interaction effect: F(1, 23)=10,362 p=0,0038 Fig.1. No significant difference in Fig. 2. In the SEQ task, only the NIGHT learning was observed between group showed significant spontaneous subjects trained in the morning delayed gains at retest in terms of the (DAY group) or in the evening number of correct sequences produced (NIGHT group). in 30-sec trials. Doyon et al., 2009, Exp. Brain Res. MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects??

MotorMotor SequenceSequence Learning:Learning: “““NapNapNap EffectsEffectsEffects”””

120 N=6 nap night sleep nap 100 (90 min) 1 2 3 t 80 4

% improvemen 40

Pre-Test 0hPost-Test 8hPost-Test 22hPost-Test

Korman et al., 2007, Nat. Neurosci.; Doyon et al., 2009, Exp. Brain Res. MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects

Polysomnographic findings

Morin et al., 2008, Sleep MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects??

Fast Spindles (13-15 Hz)

3.5

3 * 2.5

SEQ 2 CTRL Seq 1.5 * * * * ADPT 1 CTRL A dpt densite fuseaux rapides Nb total fuseaux/Durée NREM fuseaux/Durée total Nb 0.5

0 F3 F4 Fz C3 C4 Cz P3 P4 Pz O1 O2 Oz F3 F4 Fz C3 C4 Cz P3 P4 Pz O1 O2 Oz SEQ ADPT MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects??

Slow spindles (11-13 Hz)

3.5

2.5

SEQ 2 CTRL Seq

1.5 ADPT

CTRL Adpt 1 densite fuseaux lents fuseaux densite Nb total fuseaux/Durée NREM 0.5

0 F3 F4 Fz C3 C4 Cz P3 P4 Pz O1 O2 Oz F3 F4 Fz C3 C4 Cz P3 P4 Pz O1 O2 Oz SEQ ADPT NeuronalNeuronal SubstratesSubstrates AssociatedAssociated withwith ConsolidationConsolidation ofof aa MotorMotor MemoryMemory Trace:Trace: MotorMotor SequencSequenc LearningLearning NeuralNeural SubstratesSubstrates ofof MotorMotor LearningLearning

Motor cortical regions Motor cortical regions Parietal cortex Parietal cortex Striatum Cerebellum

Automatization

Motor cortical regions Slow Learning Striatum Parietal cortex Cerebellum

Consolidation

Doyon & Benali (2005), Current Opinion Neurobiology NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory ConsolidationConsolidation

ExperimentalExperimental design:design:

Polysomnographic Recordings

Debas et al., Submitted NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory ConsolidationConsolidation

BehavioralBehavioral ResultsResults:: MotorMotor SequenceSequence TaskTask

*p=.03

Debas et al., Submitted NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: ConjunctionConjunction Analysis:Analysis: ImmediateImmediate PostPost--TrainingTraining fMRIfMRI ResultsResults Results::: MotorMotor SequenceSequence TaskTask Task::: ActivatedActivated AreasAreas CommonCommon toto bothboth NightNight andand DayDay Groups.Groups.

Putamen/Globus Motor cortex Cerebellum: V, VI, VIII Pallidus

y = -30 y = 8 y = -56

Debas et al., Submitted NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: ContrastContrast Analysis:Analysis: RetestRetest SessionSession fMRIfMRI ResultsResults Results::: MotorMotor SequenceSequence TaskTask Task::: NightNight >> DayDay Group.Group. Bilateral Putamen

y = - 5 Debas et al., Submitted NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: GroupGroup xx SessionSession InteractionInteraction fMRIfMRI ResultsResults Results::: MotorMotor SequenceSequence TaskTask Task::: GroupGroup (Night(Night vsvs Day)Day) byby SessionSession (((RetestRetestRetest vsvs ImmediateImmediate PostPost Post-training)--training)training)

Debas et al., Submitted

Debas et al., Submitted NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: ConnectivityConnectivity andand IntegrationIntegration AnalysesAnalyses Identification of functional networks in fMRI data using spatial independent component analysis (ICA). NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: ConnectivityConnectivity andand IntegrationIntegration AnalysesAnalyses Selection of several regions of interest (ROIs) used for the connectivity analyses NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: ConnectivityConnectivity andand IntegrationIntegration AnalysesAnalyses Correlations between ROIS for the two groups (Day and Night) during the “test” and “retest” scanning sessions

Jour - Test Jour – Re-test

Nuit - Test Nuit – Re-test ConnectivityConnectivity andand IntegrationIntegration ofof MotorMotor Networks:Networks: MethodMethod

 Selection of ROI

 Spatial Independent Component Analysis 1

 Used a motor network present in all participants

 Identification of 2 sub- networks (Assoc., Sensori.) (Coynel et al., 2010)

 Within and between networks functional M connectivity quantification B

 Hierarchical integration

 Covariance between ROI’s A BOLD time courses 62 1 Perlbarg et al., ISBI 2008 & HBM 2009 2 Marrelec et al., Med Im An 2008 Coynel et al., In press, NeuroImage ChangesChanges inin FunctionalFunctional IntegrationIntegration FollowingFollowing ConsolidationConsolidation ofof MotorMotor SequenceSequence LearningLearning

Debas et al., OHBM, 2010 ChangesChanges inin FunctionalFunctional IntegrationIntegration FollowingFollowing ConsolidationConsolidation ofof MotorMotor SequenceSequence LearningLearning

Debas et al., OHBM, 2010 MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep EffectsEffects

Spindles detection: an automatic algorithm was used to detect amplitude, duration and number of fast (13.1-14.9 Hz) and slow (11.1-12.9 Hz) spindles on frontal (F3, Fz, F4), central (C3, Cz, C4) and parietal (P3, Pz, P4) derivations during the NREM sleep.

BOLD activity: based on the results of the fMRI analysis, parameter estimates (beta values) for significant voxels in both the right and the left putamen were extracted for every subject of the Night/sleep group.

Statistical analysis: Pearson product-moment correlations were carried out between sleep spindles, changes in BOLD activity in both putamen and overnight gains in performance. Barakat et al., In preparation SlowSlow spindlesspindles amplitudeamplitude

Significant correlations with BOLDboth BOLD changes changes in the in right the putamenright putamen and gains in performance FastFast spindlesspindles amplitudeamplitude

Significant correlationcorrelations with with BOLDboth BOLD changes changes in the in right the putamenright putamen and gains in performance NeuronalNeuronal SubstratesSubstrates AssociatedAssociated withwith ConsolidationConsolidation ofof aa MotorMotor MemoryMemory Trace:Trace: MotorMotor AdaptationAdaptation NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory ConsolidationConsolidation

BehavioralBehavioral ResultsResults:: MotorMotor AdaptationAdaptation TaskTask

300

250

200

150 Test Retest 100

50 0102030405060First 4 blocks Trials No difference between Day and Night Groups Session by Blocks: (p = .034) NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: ConjunctionConjunction Analysis:Analysis: ImmediateImmediate PostPost--TrainingTraining fMRIfMRI ResultsResults Results::: MotorMotor AdaptationAdaptation TaskTaskTask::: ActivatedActivated AreasAreas CommonCommon toto bothboth NightNight andand DayDay Groups.Groups.

Motor cortex Cerebellum: V, VI, VIII

X = 0

X = -27 y = -60 NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: ConjunctionConjunction Analysis:Analysis: RetestRetest vsvs ImmediateImmediate PostPost--TrainingTraining

fMRI Results: Motor Adaptation Task: At Retest: The Night group did not differ from the Day group. Conjunction analysis: Both groups showded greater activity in the cerebellum at retest than during the immediate testing session.

Cerebellum: Lobule VI

Y = -72 SVC 0f 10mm: p = .05 FWE corr. NeuralNeural SubstratesSubstrates ofof MotorMotor MemoryMemory Consolidation:Consolidation: CorrelationCorrelation Analysis:Analysis: fMRIfMRI ResultsResults Results::: MotorMotor AdaptationAdaptation TaskTaskTask::: •• TheThe amountamountof of savingssavingscorrelate correlatewith withactivity activity inin ipsilateralipsilateralCerebellum Cerebellum(Lobule (Lobule VI).VI). 10

-5

-10

Cerebellar (L.VI) BOLD response -15 X = 36 -60 -40 -20 0 20 40 60 Amount of saving between the two sessions (%)

SVC of 10mm: p = .005 FWE corr. MotorMotor MemoryMemory Consolidation:Consolidation: SleepSleep vs.vs. SimpleSimple PassagePassage ofof TimeTime ConclusionsConclusions • Sleep contributes to the consolidation process of a new motor sequence learning task, while the simple passage of time is sufficient to produce a similar effect when using a motor adaptation paradigm.

• The striatum (and the putamen in particular) is involved in the off-line, sleep- dependent, consolidation process of a newly learned motor sequence.

• By contrast, the cerebellum plays a critical role in the consolidation of a new internal model adapted to task demands.

• For the first time, we demonstrate that the amplitude of both fast and slow sleep spindles correlates with previously demonstrated changes of activity in the putamen after motor consolidation, and with behavioural gains of performance in motor sequence learning. AcknowledgementsAcknowledgements

University of Montreal Haifa University, Israël INSERM / U678, Paris

Julie Carrier Avi Karni Habib Benali Rick Hoge Maria korman Stéphane Lehéricy Guillaume Marrelec Marc Barakat Research associate Karen Debas Pierre Orban Vo An Nguyen Geneviève Albouy University of Liège, Ovidiu Lungu Belgium Stuart Fogel Sébastien Proulx Pierre Maquet Samuel Laventure Philippe Peigneux