Neurofunctional correlates of attention rehabilitation in Parkinson's disease: an explorative study

The effectiveness of cognitive rehabilitation (CR) in Parkinson's disease (PD) is in its relative infancy, and nowadays there is insufficient information to support evidence-based clinical protocols. This study is aimed at testing a validated therapeutic strategy characterized by intensive computer-based attention-training program tailored to attention deficits. We further investigated the presence of synaptic plasticity by means of functional magnetic resonance imaging (fMRI). Using a randomized controlled study, we enrolled eight PD patients who underwent a CR program (Experimental group) and seven clinically/demographically-matched PD patients who underwent a placebo intervention (Control group). Brain activity was assessed using an 8-min resting state (RS) fMRI acquisition. Independent component analysis and statistical parametric mapping were used to assess the effect of CR on brain function. Significant effects were detected both at a phenotypic and at an intermediate phenotypic level. After CR, the Experimental group, in comparison with the Control group, showed a specific enhanced performance in cognitive performance as assessed by the SDMT and digit span forward. RS fMRI analysis for all networks revealed two significant groups (Experimental vs Control) × time (T0 vs T1) interaction effects on the analysis of the attention (superior parietal cortex) and central executive neural networks (dorsolateral prefrontal cortex). We demonstrated that intensive CR tailored for the impaired abilities impacts neural plasticity and improves some aspects of cognitive deficits of PD patients. The reported neurophysiological and behavioural effects corroborate the benefits of our therapeutic approach, which might have a reliable application in clinical management of cognitive defici

Neuropsychological, electrophysiological, and neuroimaging biomarkers for REM behavior disorder

Introduction: Rapid eye movement (REM) sleep behavior disorder (RBD) is a REM sleep parasomnia characterized by dream enacting behaviors allowed by the loss of physiological atonia during REM sleep. This disorder is recognized as a prodromal stage of neurodegenerative disease, in particular Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). Therefore, a timely identification of biomarkers able to predict an early conversion into neurodegeneration is of utmost importance. Areas covered: In this review, the authors provide updated evidence regarding the presence of neuropsychological, electrophysiological and neuroimaging markers in isolated RBD (iRBD) patients when the neurodegeneration is yet to come. Expert opinion: Cognitive profile of iRBD patients is characterized by the presence of impairment in visuospatial abilities and executive function that is observed in α-synucleinopathies. However, longitudinal studies showed that impaired executive functions, rather than visuospatial abilities, augmented conversion risk. Cortical slowdown during wake and REM sleep suggest the presence of an ongoing neurodegenerative process paralleled by cognitive decline. Neuroimaging findings showed that impairment nigrostriatal dopaminergic system might be a good marker to identify those patients at higher risk of short-term conversion. Although a growing body of evidence the identification of biomarkers still represents a critical issue in iRBD

Essential Head Tremor Is Associated with Cerebellar Vermis Atrophy: A Volumetric and Voxel-Based Morphometry MR Imaging Study

BACKGROUND AND PURPOSE: Our aim was to investigate the presence of brain gray matter (GM) abnormalities in patients with different forms of essential tremor (ET). MATERIALS AND METHODS: We used optimized voxel-based morphometry (VBM) and manually traced single region-of-interest analysis in 50 patients with familial ET and in 32 healthy subjects. Thirty patients with ET had tremor of the arms (a-ET), whereas the remaining 20 patients had both arm and head tremor (h-ET). RESULTS: VBM showed marked atrophy of the cerebellar vermis in the patients with h-ET with respect to healthy subjects (Pcorrected < .001). Patients with a-ET showed a trend toward a vermal GM volume loss that did not reach a significant difference with respect to healthy controls (Puncorrected < .01). The region-of-interest analysis showed a reduction of the cerebellar volume (CV) in the h-ET group (98.2 ± 13.6 mm3) compared with healthy controls (110.5 ± 15.5 mm3, P < .012) as well as in the entire vermal area (790.3 ± 94.5 mm2, 898.6 ± 170.6 mm2, P < .04 in h-ET and control groups, respectively). CONCLUSIONS: Atrophy of the cerebellar vermis detected in patients with h-ET strongly supports the evidence for the involvement of the cerebellum in the pathophysiology of ET. The lack of a significant CV loss observed in patients with a-ET suggests that a-ET and h-ET might represent distinct subtypes of the same disease

Impact of pre-sleep habits on adolescent sleep: an Italian population-based study

Objective: Several evidences demonstrate that pre-sleep habits may negatively impact adolescent sleep, yet few data exist on Italian population. This study aimed to investigate the relationship between pre-sleep habits, use of technology/activity and sleep in Italian adolescents. Methods: Self-report questionnaires including Italian version of School Sleep Habits Survey and use of technology/activity (eg smartphone, PC) at bedtime were administered to 972 adolescents (13\u201319 years) from Lombardia. We stratified the sample in five groups according to the age: Group I (13\u201314 years), Group II (15 years), Group III (16 years), Group IV (17 years), Group V (18\u201319 years). Results: Our descriptive analysis reveals a different sleep profile across age-groups: Group III showed highest percentage of bad sleep (26.7%) and frequent nocturnal awakenings (24.1%), Group V had the highest percentage of insufficient sleep (40,4%) and difficulty falling asleep (42.7%) and Group IV presented an elevated difficulty in waking up in the morning (70.1%). A significant negative correlation was found in total group between use of smartphone, internet and studying/doing homework and total sleep time. The use of smartphone, internet videogames, listening to music and studying/doing homework was positively associated with delayed bedtime. Conclusions: This study confirms the great impact of pre-sleep habits, and in particular the use of technology on adolescent sleep. Our results demonstrate that sleep is strongly altered among Italian adolescents using electronic devices in evening. The type of technology may be related to specific sleep profile, emphasizing the importance of stratification analyses to identify associated factors to sleep problems

A network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias

Levodopa-induced dyskinesias are disabling motor complications of long-term dopamine replacement in patients with Parkinson's disease. In recent years, several alternative models have been proposed to explain the pathophysiological mechanisms underlying this hyperkinetic motor disorder. In particular, our group has shed new light on the role of the prefrontal cortex as a key site of interest, demonstrating that, among other areas, the inferior frontal cortex is particularly characterized by altered patterns of anatomical and functional changes. However, how neural activity varies depending on levodopa treatment in patients with dyskinesias and whether the reported prefrontal abnormalities may have a critical role in dyskinesias is debated. To answer these questions we performed independent functional magnetic resonance imaging and repetitive transcranial magnetic stimulation studies. In the first experiment we applied resting state functional magnetic resonance imaging on 12 patients with Parkinson's disease with levodopa-induced dyskinesias and 12 clinically matched patients without dyskinesias, before and after administration of levodopa. Functional connectivity of brain networks in the resting state was assessed in both groups. We chose the right inferior frontal cortex as the seed region given the evidence highlighting the role of this region in motor control. In a second experiment, we applied different forms of repetitive transcranial magnetic stimulation over the right inferior frontal cortex in a new group of dyskinetic patients who were taking a supramaximal dose of levodopa, to verify the clinical relevance of this area in controlling the development of hyperkinetic movements. The resting state functional imaging analysis revealed that in patients with levodopa-induced dyskinesias connectivity of the right inferior frontal cortex was decreased with the left motor cortex and increased with the right putamen when compared to patients without levodopa-induced dyskinesias. This abnormal pattern of connectivity was evident only during the ON phase of levodopa treatment and the degree of such alteration correlated with motor disability. The repetitive TMS experiments showed that a session of continuous but not intermittent or sham theta burst stimulation applied over the inferior frontal cortex was able to reduce the amount of dyskinesias induced by a supramaximal single dose of levodopa, suggesting that this area may play a key role in controlling the development of dyskinesias. Our combined resting state functional magnetic resonance and transcranial magnetic stimulation studies demonstrate that pathophysiological mechanisms underlying levodopa-induced dyskinesias may extend beyond the 'classical' basal ganglia dysfunctions model, including the modulation performed by the neural network centred on the inferior frontal cortex

A network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias

Levodopa-induced dyskinesias are disabling motor complications of long-term dopamine replacement in patients with Parkinson's disease. In recent years, several alternative models have been proposed to explain the pathophysiological mechanisms underlying this hyperkinetic motor disorder. In particular, our group has shed new light on the role of the prefrontal cortex as a key site of interest, demonstrating that, among other areas, the inferior frontal cortex is particularly characterized by altered patterns of anatomical and functional changes. However, how neural activity varies depending on levodopa treatment in patients with dyskinesias and whether the reported prefrontal abnormalities may have a critical role in dyskinesias is debated. To answer these questions we performed independent functional magnetic resonance imaging and repetitive transcranial magnetic stimulation studies. In the first experiment we applied resting state functional magnetic resonance imaging on 12 patients with Parkinson's disease with levodopa-induced dyskinesias and 12 clinically matched patients without dyskinesias, before and after administration of levodopa. Functional connectivity of brain networks in the resting state was assessed in both groups. We chose the right inferior frontal cortex as the seed region given the evidence highlighting the role of this region in motor control. In a second experiment, we applied different forms of repetitive transcranial magnetic stimulation over the right inferior frontal cortex in a new group of dyskinetic patients who were taking a supramaximal dose of levodopa, to verify the clinical relevance of this area in controlling the development of hyperkinetic movements. The resting state functional imaging analysis revealed that in patients with levodopa-induced dyskinesias connectivity of the right inferior frontal cortex was decreased with the left motor cortex and increased with the right putamen when compared to patients without levodopa-induced dyskinesias. This abnormal pattern of connectivity was evident only during the ON phase of levodopa treatment and the degree of such alteration correlated with motor disability. The repetitive TMS experiments showed that a session of continuous but not intermittent or sham theta burst stimulation applied over the inferior frontal cortex was able to reduce the amount of dyskinesias induced by a supramaximal single dose of levodopa, suggesting that this area may play a key role in controlling the development of dyskinesias. Our combined resting state functional magnetic resonance and transcranial magnetic stimulation studies demonstrate that pathophysiological mechanisms underlying levodopa-induced dyskinesias may extend beyond the 'classical' basal ganglia dysfunctions model, including the modulation performed by the neural network centred on the inferior frontal cortex