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Authors: Fasano, Alfonso | Herman, Talia | Tessitore, Alessandro | Strafella, Antonio P. | Bohnen, Nicolaas I.

Article Type: Review Article

Abstract: Functional brain imaging techniques appear ideally suited to explore the pathophysiology of freezing of gait (FOG). In the last two decades, techniques based on magnetic resonance or nuclear medicine imaging have found a number of structural changes and functional disconnections between subcortical and cortical regions of the locomotor network in patients with FOG. FOG seems to be related in part to disruptions in the “executive-attention” network along with regional tissue loss including the premotor area, inferior frontal gyrus, precentral gyrus, the parietal and occipital areas involved in visuospatial functions of the right hemisphere. Several subcortical structures have been also involved …in the etiology of FOG, principally the caudate nucleus and the locomotor centers in the brainstem. Maladaptive neural compensation may present transiently in the presence of acute conflicting motor, cognitive or emotional stimulus processing, thus causing acute network overload and resulting in episodic impairment of stepping. In this review we will summarize the state of the art of neuroimaging research for FOG. We will also discuss the limitations of current approaches and delineate the next steps of neuroimaging research to unravel the pathophysiology of this mysterious motor phenomenon. Show more

Keywords: Freezing of gait, magnetic resonance imaging, Parkinson’s disease, positron emission tomography, single photon emission computed tomography

DOI: 10.3233/JPD-150536

Citation: Journal of Parkinson's Disease, vol. 5, no. 2, pp. 241-254, 2015

Authors: Sierra, María | Carnicella, Sébastien | Strafella, Antonio P. | Bichon, Amélie | Lhommée, Eugénie | Castrioto, Anna | Chabardes, Stephan | Thobois, Stéphane | Krack, Paul

Article Type: Review Article

Abstract: Neuropsychiatric symptoms are common non-motor symptoms in Parkinson’s disease (PD). Apathy and impulse control disorders (ICD) are two opposite motivational expressions of a continuous behavioural spectrum involving hypo- and hyperdopaminergia. Both syndromes share pathological (decreased vs increased) dopamine receptor stimulation states. Apathy belongs to the spectrum of hypodopaminergic symptoms together with anhedonia, anxiety and depression. Apathy is a key symptom of PD which worsens with disease progression. Animal models, imaging and pharmacological studies concur in pointing out dopaminergic denervation in the aetiology of parkinsonian apathy with a cardinal role of decreased tonic D2/D3 receptor stimulation. ICDs are part of the …hyperdopaminergic behavioural spectrum, which also includes punding, and dopamine dysregulation syndrome (DDS), which are all related to non-physiological dopaminergic stimulation induced by antiparkinsonian drugs. According to clinical data tonic D2/D3 receptor stimulation can be sufficient to induce ICDs. Clinical observations in drug addiction and PD as well as data from studies in dopamine depleted rodents provide hints allowing to argue that both pulsatile D1 and D2 receptor stimulation and the severity of dopaminergic denervation are risk factors to develop punding behavior and DDS. Imaging studies have shown that the brain structures involved in drug addiction are also involved in hyperdopaminergic behaviours with increase of bottom-up appetitive drive and decrease in prefrontal top down behavioural control. Show more

Keywords: Apathy, Parkinson’s disease, impulse control disorders, dopamine dysregulation syndrome, punding

DOI: 10.3233/JPD-150535

Citation: Journal of Parkinson's Disease, vol. 5, no. 3, pp. 625-636, 2015

Authors: Fiorenzato, Eleonora | Biundo, Roberta | Cecchin, Diego | Frigo, Anna Chiara | Kim, Jinhee | Weis, Luca | Strafella, Antonio P. | Antonini, Angelo

Article Type: Research Article

Abstract: Background: The pathological processes underlying cognitive impairment in Parkinson’s disease (PD) are heterogeneous and the contribution of cerebral amyloid deposits is poorly defined, particularly in the early stages of the disease. Objective: To investigate regional [18 F]florbetaben binding to amyloid-β (Aβ ) and its contribution to cognitive dysfunction in early stage PD. Methods: A multicenter cohort of 48 PD patients from the Parkinson’s Progression Marker Initiative (PPMI) underwent [18 F]florbetaben positron emission tomography (PET) scanning. Clinical features, including demographic characteristics, motor severity, cerebrospinal fluid (CSF), and cognitive testing were systematically assessed according to the PPMI study protocol. For the purpose …of this study, we analyzed various neuropsychological tests assessing all cognitive functions. Results: There were 10/48 (21%) amyloid positive PD patients (PDAβ +). Increased [18 F]florbetaben uptake in widespread cortical and subcortical regions was associated with poorer performance on global cognition, as assessed by Montreal Cognitive Assessment (MoCA), and impaired performance on Symbol Digit Modality test (SDMT). Further, we found that PDAβ + patients had higher CSF total-tau/Aβ 1 - 42 (p  = 0.001) and phosphorylated-tau/Aβ 1 - 42 in (p  = 0.002) compared to amyloid-negative PD. Conclusion: These findings suggest that multiple disease processes are associated with PD cognitive impairment and amyloid deposits may be observed already in early stages. However, prevalence of amyloid positivity is in the range of literature age-matched control population. Increased cortical and subcortical amyloid is associated with poor performance in attentive-executive domains while cognitive deficits at MoCA and SDMT may identify amyloid-related dysfunction in early PD. Show more

Keywords: Amyloid, cerebrospinal fluid, cognition, cognitive dysfunction, dementia, neuropsychology, Parkinson’s disease, positron emission tomography, synuclein

DOI: 10.3233/JAD-180390

Citation: Journal of Alzheimer's Disease, vol. 66, no. 1, pp. 229-237, 2018

Authors: Criaud, Marion | Poisson, Alice | Thobois, Stéphane | Metereau, Elise | Redouté, Jérôme | Ibarrola, Danièle | Baraduc, Pierre | Broussolle, Emmanuel | Strafella, Antonio P. | Ballanger, Bénédicte | Boulinguez, Philippe

Article Type: Research Article

Abstract: Background: Impairment in initiating movements in PD might be related to executive dysfunction associated with abnormal proactive inhibitory control, a pivotal mechanism consisting in gating movement initiation in uncertain contexts. Objective: Testing this hypothesis on the basis of direct neural-based evidence. Methods: Twelve PD patients on antiparkinsonian medication and fifteen matched healthy controls performed a simple reaction time task during event-related functional MRI scanning. Results: For all subjects, the level of activation of SMA was found to predict RT on a trial-by-trial basis. The increase in movement initiation latency observed in PD patients with regard to controls was associated with …pre-stimulus BOLD increases within several nodes of the proactive inhibitory network (caudate nucleus, precuneus, thalamus). Conclusions: These results provide physiological data consistent with impaired control of proactive inhibition over motor initiation in PD. Patients would be locked into a mode of control maintaining anticipated inhibition over willed movements even when the situation does not require action restraint. The functional and neurochemical bases of brain activity associated with executive settings need to be addressed thoroughly in future studies to better understand disabling symptoms that have few therapeutic options like akinesia. Show more

Keywords: Response inhibition, fMRI, proactive control, reaction time, Parkinson’s disease

DOI: 10.3233/JPD-150750

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 433-440, 2016

Authors: Chung, Jun Ku | Plitman, Eric | Nakajima, Shinichiro | Caravaggio, Fernando | Shinagawa, Shunichiro | Iwata, Yusuke | Gerretsen, Philip | Kim, Julia | Takeuchi, Hiroyoshi | Patel, Raihaan | Chakravarty, M. Mallar | Strafella, Antonio | Graff-Guerrero, Ariel | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Short Communication

Abstract: The clinical and structural trajectories of suspected non-Alzheimer’ pathology (SNAP) remain elusive due to its heterogeneous etiology. Baseline and longitudinal clinical (global cognition, daily functioning, symptoms of dementia, and learning memory) and hippocampal volume trajectories over two years were compared between patients with amnestic mild cognitive impairment (aMCI) with SNAP with reduced hippocampal volumes (SNAP+HIPPO) and aMCI patients with SNAP without reduced hippocampal volumes. SNAP+HIPPO showed overall worse baseline cognitive functions. Longitudinally, SNAP+HIPPO showed faster deterioration of clinical symptoms of dementia. Having both hippocampal atrophy and cortical hypometabolism without amyloid pathology may exacerbate symptoms of dementia in aMCI.

Keywords: Functional decline, hippocampus, mild cognitive impairment, suspected non-Alzheimer’s pathology

DOI: 10.3233/JAD-170098

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 341-347, 2017