Department of Experimental Medicine, section of Human Physiology Centre for Parkinson s Disease and Movement Disorders - University of Genoa funzioni motorie e cognitive (nella malattia di Parkinson) Laura Avanzino Outline why motor and cognitive functions motor functions cognitive functions motor-cognitive functions 1
Outline why motor and cognitive functions motor functions cognitive functions motor-cognitive functions why motor and cognitive functions The basal ganglia not only are connected to motor cortical areas (that is, the motor cortex, supplementary motor cortex, premotor cortex, cingulate motor area and frontal eye fields) but also have connections with a wide range of non-motor areas of the cortex. 2
why motor and cognitive functions The motor circuit CLINICAL SYMPTOMS Bradykinesia Rigidity Tremor Postural instability Gait disturbances why motor and cognitive functions The cognitive circuit COGNITION Executive functions Top-down attentional dysfunction Visuospatial processing Memory Language 3
motor functions Outline why motor and cognitive functions motor functions cognitive functions motor-cognitive functions motor functions The motor circuit CLINICAL SYMPTOMS Bradykinesia Rigidity Tremor Postural instability Gait disturbances MOTOR CONTROL Aberrant neuroplasticity at subcortical/cortical level Impairment of motor learning (disruption of automatization) 4
motor functions Why tdcs to improve motor functions? tdcs induces LTP-like plasticity LTP is a persistent increase in neuronal transmission tdcs induced changes in neuronal firing are dependant on NMDA., Ca++, and BDNF like LTP Anodal M1 tdcs increased subcortical-cortical functional connectivity Polania 2011, Monte- Silva, 2013 motor functions Why tdcs to improve motor functions? Review Effects of tdcs on motor learning and memory formation: A consensus and critical position paper Ethan R. Buch a, Emiliano Santarnecchi b, Andrea Antal c, Jan Born d,e, Pablo A. Celnik f,g, Joseph Classen h, Christian Gerloff i, Mark Hallett j, Friedhelm C. Hummel i, Michael A. Nitsche k, Alvaro Pascual-Leone b, Walter J. Paulus c, Janine Reis l, Edwin M. Robertson m, John C. Rothw ell n, Marco Sandrini o, Heidi M. Schambra p, Eric M. Wassermann q, Ulf Ziemann r, Leonardo G. Cohen a, tdcs can contribute to the understanding of mechanisms underlying motor learning and motor memory formation. Clinical Neurophysiology, 2017 5
motor functions Why tdcs to improve motor functions? Broeder, 2015 motor functions Motor functions Anodal stimulation of M1 was associated with a significant improvement of motor function compared to sham-stimulation in the UPDRS and simple reaction time (srt). This effect was not observed for cathodal stimulation of M1 or anodal stimulation Fregni, 2006 of DLPFC. 6
motor functions Motor functions Anodal stimulation of M1 significantly increased MEP amplitude and area. There was a trend toward a significant correlation between motor function improvement after M1 anodal tdcs and MEP area increase. Cortical brain stimulation might improve motor function in patients with PD. Fregni, 2006 motor functions Motor functions (single session) Broeder, 2015 7
motor functions Motor functions (multiple sessions) Broeder, 2015 motor functions Motor functions: cerebellum Right deltoid vs Right shoulder Bilateral M1 Bilateral cerebellum 9 PD patients 2 ma, 20 minutes, 5 days UPDRS, BDI, PDQ8, word recall Anodal cerebellar tdcs and M1-tDCS applied daily both improved LIDs in patients with PD but left the other motor and cognitive variables assessed unchanged. Ferrucci, 2016 8
motor functions Motor functions: Take home messages anode cathode M1 montage (contralateral to the more affected side, bilateral, dominant) Scarce or none data on plasticity and motor learning in PD (driving data on healthy) Encouraging data on gait, FOG, upper limb performance Role of the cerebellum on dyskenisias? cognitive functions Outline why motor and cognitive functions motor functions cognitive functions motor-cognitive functions 9
cognitive functions The cognitive circuit COGNITION Executive functions Top-down attentional dysfunction Visuospatial processing Memory Language cognitive functions Why tdcs to improve cognitive functions? 10
cognitive functions Why tdcs to improve cognitive functions in PD? cognitive functions Cognitive functions Effects of transcranial direct current stimulation on working memory in patients with Parkinson' s disease Paulo S. Boggio b,c, Roberta Ferrucci a,e, Sergio P. Rigonatti b, Priscila Covre c, Michael Nitsche d, Alvaro Pascual-Leone a, Felipe Fregni a, vs Left DLPFC M1 18 PD patients 20 minutes, 1 or 2 ma, sham controlled Working memory assessment: three back letter Boggio, 2006 11
cognitive functions Cognitive functions Anodal tdcs of the left DLPFC with a current strength of 2 ma, but not 1 ma, improved accuracy, but not speed of performance. Boggio, 2006 cognitive functions Cognitive functions (single session) Broeder, 2015 12
cognitive functions 16 PD patients Left DLPFC vs TPC 2mA, 20 min Neuropsychological battery A significant main effect of tdcs on phonemic fluency performance, showing that DLPFC stimulation increased the amount of words subjects produced in response to a letter, compared to TPC stimulation Patients produced more words in response to a semantic category cue after DLPFC tdcs compared to TPC stimulation Brain Stimulation, 2013 cognitive functions Significant changes of the BOLDresponse in favor of anodal tdcs over the DLPFC compared to stimulation over the TPC were found in functional networks, involving frontal, parietal and fusiform brain areas Influence in BOLD response in regions of interest 13
cognitive functions Cognitive functions (multiple sessions) 24 PD-MCI 4 week cognitive training + real tdcs (n=12) vs 4 week cognitive training + sham tdcs (n=12) Anodal/ 2mA/ 20 min/ left DLPFC Assessment at 4 weeks and at 16 weeks time points Neuropsychological battery Biundo, 2015 cognitive functions Cognitive functions (multiple sessions) Biundo, 2015 14
cognitive functions 2016 cognitive functions Significant effect of AtDCS plus physical therapy on cognitive performances (PD-CRS frontal-subcortical scale, PD- CRS total scale, and verbal fluency). The absence of any tdcs effect on visual memory tasks and other cognitive abilities suggesting that a learning effect cannot explain the improvements. 15
cognitive functions No significant additional effect of AtDCS on motor performance. Both groups had similar improvements in motor performance. cognitive functions Cognitive functions: take home messages DLPFC montage (left DLPFC) Single session: data on executive functions, BOLD response in the regions of interest Multiple sessions, combined with cognitive or physical training showed interesting findings 16
motor-cognitive functions Outline why motor and cognitive functions motor functions cognitive functions motor-cognitive functions motor-cognitive functions ASSOCIATIVE CIRCUIT Dorso-medial striatum Anterior Putamen & Caudate SENSORIMOTOR CIRCUIT Dorso-lateral striatum Posterior Putamen Prefrontal cortices Sensorimotor cortices Encoding motor and probabilistic associations LATE IMPLICIT LEARNING Response selection and evaluation of outcome or reward EARLY EXPLICIT LEARNING HABITUAL CONTROL GOAL DIRECTED CONTROL Redgrave, 2010 17
motor-cognitive functions motor-cognitive functions The interplay between motor-cognitive functions Dual Task paradigm Dual task performance is also known as concurrent performance and involves the execution of a secondary task, which is the major focus of attention, and a primary (motor) task performed at the same time. Motor Walking + Motor task Motor DT consist in adding another motor task while patients is walking (i.e. transfer coin; carrying a tray with cups of water; avoid obstacles) Cognitive Walking + cognitive task Cognitive DT consist in adding a cognitive working memory task while patients is walking (i.e. serial 3 or 7 subtraction task; word association or generation; task with verbal responses) DT creates competition for attention and allocation of cognitive resources. Thus, one task might be prioritized over the other, depending on the specific circumstances or environmental demands. 18
motor-cognitive functions Dynamic balance It has been extensively demonstrated that gait disorders in people with Parkinson s disease (PD) are accentuated when they perform another task simultaneously. Yogev et al. 2005 motor-cognitive functions Healthy elderly, n=37 20 min of real or sham tdcs targeting the left PFC F3/ right supraorbital margin Outcome measures: 1. Speed and area postural sway (NT/DT) 2. Gait speed and stride duration variability (NT/DT) DT: counting task, verbalized serial subtraction of 7 DT cost = (DT-NT)/NT*100 Manor, 2016 19
motor-cognitive functions The dual-task cost was defined by the percent change in postural sway area between single- and dual-task conditions. For this participant, the cognitive dual-task cost to sway area was noticeably less after real tdcs as compared with the sham condition. Manor, 2016 motor-cognitive functions The dual task cost while walking (speed) improved after real but not sham tdcs. Manor, 2016 20
motor-cognitive functions And what about PD and dual task? Healthy elderly, n=13 Parkinson s disease patients, n=16 20 min of real or sham tdcs targeting the left DLPFC, 2 ma F3/ right supraorbital margin Outcome measures: 1. Dual task gait speed (NT vs DTcognitive vs DTmotor) NT: normal walking DT-cognitive: subtraction of 3 DT-motor: obstacle negotiation motor-cognitive functions 21
motor-cognitive functions Motor-Cognitive functions: take home messages DLPFC montage (left DLPFC) Influence of cognitive areas modulation on motor performance (and viceversa physical therapy has been described to influence cognitive functions) Further studies are needed Conclusions 22
Conclusions 23
motor-cognitive functions motor-cognitive functions anode cathode 20 min of real or sham tdcs targeting the left DlPFC F3/ right suprorbital margin Outcome measures: 1. Berg Balance Scale (BBS), Dynamic Gait Index (DGI) and Timed Up and Go (TUG). Parkinson s disease patients, n=17 Neuroscience letters, 2017 24
motor-cognitive functions a-tdcs on the left DLPFC improves balance and functional mobility in comparison to sham-tdcs. 25