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''Parkinson Disease, Movement Disorders and Dementia''§,§§ Basal Basal Ganglia 2S (2012) e1–e87 Contents lists available at SciVerse ScienceDirect Basal Ganglia journal homepage: www.elsevier.com/locate/baga ‘‘Parkinson Disease, Movement Disorders and Dementia’’§,§§ SESSION 1 ‘‘Connectivity and synaptic plasticity: the contribution amplitudes through functional visuo-motor connectivity (visuo- of neurophysiology and neuroimaging’’ motor integration). Recent observations have found altered responses to Visual-PAS in patients with photoparoxysmal L1 response (PPR) suggesting that abnormal visuo-motor integration may contribute to the pathophysiology of PPR. Exploration of the cortical connectivity by means of transcranial magnetic stimulation References [1] Suppa A, Bologna M, Gilio F, Lorenzano C, Rothwell JC, Antonio Suppa Berardelli A. Preconditioning rTMS of premotor cortex can Department of Neurology and Psychiatry, ‘‘Sapienza’’, University of reduce but not enhance short-term facilitation of primary motor cortex. J Neurophysiol 2008; 99:564-570. Rome, Rome and Neuromed Institute, ‘‘Sapienza’’, University of Rome, [2] Suppa A, Iezzi E, Conte A, Belvisi D, Marsili L, Modugno N, Rome Fabbrini G, Berardelli A. Dopamine influences primary motor Over recent years, an increasing number of studies in humans cortex plasticity and dorsal premotor-to-motor connectivity in have investigated the functional connectivity between the primary Parkinson’s disease. Cereb Cortex 2010; 20:2224-2233. motor cortex (M1) and non-primary motor areas with the [3] Suppa A, Marsili L, Belvisi D, Conte A, Iezzi E, Modugno N, transcranial magnetic stimulation (TMS) technique. One experi- Fabbrini G, Berardelli A. Lack of LTP-like plasticity in primary mental approach consisted of delivering repetitive TMS (rTMS) motor cortex in Parkinson’s disease. Exp Neurol. 2011; over the dorsal premotor cortex (PMd) and measuring post- 227:296-301. intervention changes in motor evoked potential (MEP) amplitude [4] Suppa A, Biasiotta A, Belvisi D, Marsili L, La Cesa S, Truini A, elicited by TMS over M1 [1]. By applying PMd-rTMS in patients Cruccu G, Berardelli A. Heat-evoked experimental pain induces with Parkinson’s Disease (PD), we have demonstrated that altered long-term potentiation-like plasticity in human primary motor M1 responses also reflect abnormal PMd-to-M1 functional cortex. Cereb Cortex 2012; doi:10.1093/cercor/bhs182. connectivity in parkinsonian patients on and off L-dopa therapy [2,3]. The functional connectivity between M1 and non-motor cortical areas has been also investigated by modifying the original L2 paired associative stimulation (PAS) protocol. PAS implies rTMS Plasticity, adaptation and compensation: studies with functional over M1 paired with repetitive electric stimulation of a mixed MRI peripheral nerve at specific interstimulus intervals (ISIs). Accord- ing to the specific ISI used, PAS can increase or decrease MEP Alessandro Tessitore amplitudes through functional sensori-motor connectivity (sen- sori-motor integration). We have recently developed two PAS Dipartimento di Scienze Neurologiche, Seconda Universita` degli Studi protocols able to investigate the functional connectivity between di Napoli, Napoli M1 and sensory areas other than those activated by the original Functional MRI (fMRI), whereby a time series of MRI volumes is PAS. Laser-PAS implies rTMS paired with the nociceptive system collected over several minutes while the patient lies quietly in the activation elicited by the laser evoked potential technique. Laser- scanner or performs a cognitive or motor task, is used to assess PAS is able to induce long-term changes in MEP amplitudes regions of altered activation or functional connectivity between through functional connectivity between brain regions involved in brain regions, or both. Changes in functional connectivity between pain processing and M1 (pain-motor integration) [4]. Laser-PAS brain regions might underlie many of the clinical impairments can be helpful to investigate pain-motor integration processes in seen in PD, such as in the performance of simultaneous move- patients with different types of movement disorders including PD ments. Changes in functional connectivity to or from the and dystonia. Finally, Visual-PAS consists of rTMS paired with the supplementary motor area are associated with impaired motor activation of the visual system as elicited by the visual evoked performance in PD and with difficulties in automatic movement. potential technique. Visual-PAS induces long-term changes in MEP Furthermore, functional connectivity assessed with fMRI might be important for assessing systems-wide compensatory mechanisms in PD. On motor tasks of increasing levels of difficulty, it seems that § Joint Congress LIMPE/DISMOV-SIN. §§ XXXIX LIMPE National Congress VI DISMOV-SIN National Meeting Pisa, Italy, individuals with PD tap into a motor reserve and activate normal November 7-10, 2012. motor networks to a greater degree and at an earlier (simpler) 2210-5336/$ – see front matter http://dx.doi.org/10.1016/j.baga.2012.10.001 e2 Basal Ganglia 2S (2012) e1–e87 stage than healthy controls. fMRI has also shown common of fMRI could help to understand and support the compensatory compensatory activity in the rostral SMA and premotor cortex mechanisms in PD. Depression affects 40-50% PD patients and may in individuals who are heterozygous for mutations in PARK2 and antedate the motor onset. It is long known that depression in PD is PINK1. In recent years, resting-state imaging has been more related to change in monoaminergic systems, and a significant extensively used in the investigation of neurodegenerative reduction of uptake of CTI-32, a PET ligand selective for dopamine disorders. This technique might be useful in PD. The resting-state and noradrenaline, has been observed in the thalamus, ventral motor network is disrupted in PD patients with decreased striatum, locus coeruleus and amigdala in PD with depression with functional connectivity between the posterior putamen and the respects to PD without depression [2]. The correlation of inferior parietal cortex, and an increase in functional connectivity dopaminergic dysfunction with affective disorders has been with the anterior putamen. Assessment of resting-state fMRI is confirmed in some SPECT studies with DATSCAN, even in the closely related to studies examining the default mode network presence of mild affective symptoms. Up to 15% of PD patients may (DMN; including the precuneus, medial, lateral and inferior develop after dopamine replacement therapy impulse control parietal cortex, medial temporal lobe, medial prefrontal, and disorders. An increase of availability and release of dopamine in the posterior cingulate cortex), which is active during wakeful rest. ventral striatum has been consistently demonstrated in PET and However, few studies have addressed the DMN connectivity in PD SPECT studies [3], as well as an hyperactivation of frontal lobes and reporting conflicting results, with some authors detecting reduced anterior cingulate, other than ventral striatum has been reported in deactivation of posterior midline areas (PCC and precuneus) and fMRI studies [4]. The next step will be to define in vivo which mPFC during different cognitive tasks, while others found no neurochemical or functional pattern is related to the risk to altered deactivation during an executive task or a complex visual develop these complications in order to better tailor the therapy scene-encoding task. Such discrepancy across studies may be due since the early phases of PD. to methodological differences in the fMRI analyses or heterogene- ity in patient characteristics. References [1] Helmich RC, Janssen MJ, Oyen WJ, Bloem BR, Toni I. Pallidal References: dysfunction drives a cerebello thalamic circuit into Parkinson [1] Raichle ME, Snyder AZ A default mode of brain function: a brief tremor. Ann Neurol. 2011 Feb;69(2):269-81. history of an evolving idea. Neuroimage. 2007 Oct 1;37(4): [2] Remy P, Doder M, Lees AJ, Turjanski N, Brooks DJ. Depression 1083-90 in Parkinson disease: loss of dopamine and noradrenaline [2] Stoessl AJ, et al. Advances in imaging in Parkinson’s disease. innervation in the limbic system. Brain 2005; 128: Lancet Neurol. 2011 Nov;10(11):987-1001 1314-1322 [3] Wu T et al. Functional connectivity of cortical motor areas in [3] Steeves TD, Miyasaki J, Zurowski M et al. Increased striatal the resting state in Parkinson’s disease. Hum Brain Mapp 2011 dopamine release in Parkinsonian patients with pathological 32:1443-1457 gambling: a 11C-raclopride PET study. Brain 2009; 132: 1376- [4] Van Eimeren T, et al. Dysfunction of the default mode network 1385. in Parkinson disease: a functional magnetic resonance imaging [4] Frosini D, Pesaresi I, Cosottini M. et al. Parkinson’s disease and study. Arch Neurol. 2009 Jul;66(7):877-83. pathological gambling: results from a functional MRI study. Mov Disord. 2010 30;25(14):2449-53. L3 SESSION 2 ‘‘Molecular and clinical markers in Parkinson’s disease: Functional correlates of motor and non-motor symptoms in early preclinical diagnosis and disease progression’’ Parkinson’s disease L4 Roberto Ceravolo Molecular markers in Parkinson’s disease Department of Neuroscience, Azienda Ospedaliero-Universitaria Paolo Calabresi Pisana, Pisa Clinica Neurologica, Universita` degli Studi di Perugia, Perugia The brain functional imaging by means of both functional MRI and PET or SPECT allows to explore the network of synaptic Parkinson’s disease (PD) is a common neurodegenerative connectivity and/or the neurochemical
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