Summary of my talk. Cerebellum means little brain but a huge neural resource. Studying the cerebellum in. Chris Miall

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Studying the cerebellum in sensory motor control Chris Miall Behavioural Brain Sciences School of Psychology University of Birmingham Summary of my talk Cerebellum means little brain but a huge neural resource 1. Cerebellum: Unique structure unique function? 2. How do we study the cerebellum? 3. The idea of the cerebellum as a predictor 4. What next? maybe 30% of the total brain area more than 50% of all nerve cells highly conserved architecture across vertebrate species expanded in primates in parallel p p p with neocortex

Cerebellar cortical sheet One role: Motor sensory-motor control is hard prediction? Purkinje cells 1 mm Section though bird cerebellar cortex (Cajal 1905) Length of cerebellar cortex related to body mass Width may be related to cognitive properties 5of 27 Experiments with animals Neuronal recording Inactivation studies Theoretical models Experiments with normal volunteers Brain stimulation Brain imaging How do we study the cerebellum? Experiments with patients Behavioural measurements - eyes and limbs Brain imaging Effects of physiotherapy Roxana Burciu and Dagmar Timmann Department of Neurology, University Clinic Essen, Germany Our aims: - To show that training improves ataxia - To understand how training helps Postural training: - Move cursor on the screen by changing center of gravity - One hour per day - 14 days Assessments: - Clinical ataxia scores and various postural measures - Brain scans to show changes in gray matter density SMART Equitest NeuroCom

Cerebellar nuclei in health and disease Roxana Stefanescu and ddagmar Timmann Department of Neurology, University Clinic Essen, Germany Our aims: - To better understand function and malfunction of the deep cerebellar nuclei Why is the cerebellum so active? Imaging the cerebellum Cerebellar nuclei Structural MRI Functional MRI Finger tapping Movement tasks.. left right Potential roles in cognitive tasks (planning, attention, language) Experiments: - Use a very strong magnet (7 Tesla) to do magnetic resonance imaging (MRI) of the cerebellum - Measure size and activation of deep cerebellar nuclei - Compare findings in participants with SCA3, SCA6, Friedreich ataxia and no ataxia Links with affective disorders, autism, dyslexia). 10 of 27 Joern Diedrichsen, UCL London Cerebellar maps of the digits Cerebellum plays a prominent role in motor learning. Are there finger representations in the cerebellum? How are they different from the neocortical counterparts? How is sensory and motor integrated here?

Cerebellar resting activity and motor memory Patients with focal cerebellar damage recruit cerebral cognitive resources The cerebellum may be active at rest to consolidate previous learning experiences into memories (skills) 1. Visuomotor adaptation Albert, Robinson & Miall, Curr Biol 2009 Resting-state fmri to investigate changes in functional connectivity patterns in cerebellar stroke patients and normal age/gender-matched controls Default Mode Network and a cerebellar network are weaker in patients than in controls Fig. 1. Co-activation between sub-regions of the DMN (p < 0.001, n=26) is significantly reduced in patients relative to controls (p < 005) 0.05). Fig. 2. Co-activation across L&R cerebellar hemispheres (p < 0.01, n=26), is also reduced significantly in patients relative to controls (p < 0.05). MNI coordinates: x=6, y=-38, y=4 mm 2. Serial Reaction Time Task Interaction between the anterior cingulate cortex and the cerebellum is stronger in patients than controls Fig. 3. The cerebellum is more strongly correlated with the anterior cingulate cortex in patients relative to controls. This may suggest a greater use of cognitive resources in this group after stroke. MNI coordinates: x=16, y=-62, y=-22 mm MNI coordinates: x=-0, y=16, y=32 mm Transcranial magnetic stimulation TMS disruption of state estimation Miall, Christensen, Cain & Stanley PLoS Biology 2007 16 : 17

A predictive role for the cerebellum in language processing Transcranial direct current stimulation The right cerebellum is involved in language tasks Visual World Task Subjects look at scenes and listened to sentences Target (object) can (or cannot) be predicted from the verb (predictive vs(non-predictive condition) eye-movements are recorded Target is fixated earlier in the predictive condition Paradigm can be used to study prediction in language Hypothesis: cerebellum is involved in predictive language processing rtms will perturb predictive eye gaze shift predictive effect will decrease or disappear predictive effect will decrease or disappear the letter Predictive: The girl will write the letter Non-predictive: The girl will receive the letter Visual World task TBS Visual World task Polarity-specific effect of cerebellar TDCS in a novel motor task tdcs can modulate in a focal and polarity-specific manner cerebellar excitability How does tdcs affects learning? The task + Results: Anodal tdcs slowed down performance Cathodal tdcs enhanced performance 0.36 0.34 0.32 Anodal tdcs Cathodal 0.3 = Sham AV VERAGE SPK 0.28 0.26 AVERAGE SPK PER BLOCK & EXPONENTIAL FITTED CURVES ANODAL ANODAL_fit CATHODAL CATHODAL _ fit SHAM SHAM_fit 1 2 3 4 5 6 7 BLOCKS The cerebellum sends and receives information from areas of the prefrontal cortex that are involved in cognition Paced Auditory Serial Addition Task (PASAT) versus Paced Auditory Serial Subtraction Task (PASST) The PASAT and PASST share 15.0 14.0 the same covert speech operations but require different levels of cognitive skill - 70 7.0 subtraction is more difficult than 6.0 addition Cerebellar stimulation & working memory in tasks with high cognitive demand 1+4 8 1 5 1 3 7 2 6 9 5 12 9 6 6 4 10 9 8 15 4 7 3 5 3 6 8 2 5 1 13 11 10 8 8 9 14 10 7 6 5 4 6 3 8 1 7 4 9 3 6 9 10 9 11 9 8 11 13 12 7 2 6 9 5 2 4 8 3 1 10 9 8 15 14 7 6 12 11 4 8 5 7 1 8 2 4 9 7 9 9 13 12 8 9 10 6 13 16 16 3 1 5 7 4 8 1 3 8 2 12 4 6 12 11 12 9 4 11 10 nt correct Percen Results: Cathodal stimulation enhances WM performance more than anodal stimulation during the subtraction task, but not during the addition task. 13.0 12.0 11.0 10.0 9.0 8.0 5.0 4.0 3.0 2.0 1.0 0.0 Difference pre-post post tdcs Difference pre-post post tdcs (addition task) (subtraction task) Anodal 9.2 6.3 Cathodal 8.9 10.8

Motor role(s) of the cerebellum The cerebro-cerebellar challenges Coordination of eye & hand modulates cerebellar activity it signal Skilful movement depends on prediction Cerebellum provides a forward prediction of movement outcome Spatial pattern of cerebellar activation suggests a modular arrangement Cerebellum is brain s virtual reality machine M1 PMv PPC CB VIS Does the cerebellum predict cognitive processes? How does the cerebellum perform these calculations? What are the effects of cerebellar disease on the cerebral cortex? How does the brain reorganize after cerebellum damage? DLPFC Cog PPC CB