Chiara Cobelli - Academia.edu (original) (raw)

Papers by Chiara Cobelli

Trials

Background Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder that ... more Background Major depressive disorder (MDD) is a common, chronic, debilitating mood disorder that causes serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment option; however, only approximately one third of patients respond to the first treatment because of the ineffectiveness or side effects of antidepressants. Precision medicine in psychiatry might offer clinicians the possibility to tailor treatment according to the best possible evidence of efficacy and tolerability for each subject. In this context, our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with advocacy license independence. Methods Our study is a prospective participant- and rater-blinded, randomized, controlled clinical observational trial enrolling 300 MDD patients who are referred to psychiatric services to receive a new antidepressant due to the failure of their c...

Objective: While the contribution of non-invasive brain stimulation (NIBS) in preventing cognitiv... more Objective: While the contribution of non-invasive brain stimulation (NIBS) in preventing cognitive decline is looked with interest, NIBS empowerment of healthy elderly is understudied. The present research aims at investigating the eff ect of prefrontal transcranial direct current stimulation (tDCS) in empowering executive functions and electrophysiological attention responses in healthy aging. Methods: 22 participants have been assigned to the intervention or control group and underwent a complex assessment at T0 and at T1 \u2013 after three months. The anodal tDCS protocol lasted eight weeks (three sessions per week), with twice-weekly administration of tasks tapping on executive functions. A complete set of standardized cognitive tests and an electroencephalographic recording during a challenging computerized attention task have been integrated in the assessment protocol. Results: T0-T1 comparisons highlighted a signifi cant increase in post-intervention performances for the tDCS...

Cerebral Palsy (CP) refers to non-progressive syndromes resulting from peri-/post-natal injury of... more Cerebral Palsy (CP) refers to non-progressive syndromes resulting from peri-/post-natal injury of the central nervous system. Children suffering from this neurological disorder show limitations in oculomotor control that are often thought to affect the executive functioning. In the present study, we assessed the attentional skills of CP children during the execution of lower-order cognitive tasks. To this end, we recorded ocular movements from 10 CP children (5 females, mean age: 11 years and 4 months \ub1 2 years and 10 months) during the execution of both a simple visually guided saccade task and a spatial cueing paradigm. In the cueing paradigm, 150 ms before the onset of an eye target, one of four placeholder around a central fixation cross briefly flashed (cue). The target randomly occurred at the same location of the cue (valid condition) or at a different one (invalid condition), and subjects had to direct the gaze towards it as fast as possible. Latency and accuracy of saccades recorded from CP subjects were compared with those of 13 children (6 males and 7 females, mean age: 13 years and 1 month \ub1 2 years and 6 months) with Typical Development (TD). Interestingly, the ocular performances during the simple visually guided saccade task did not differ between CP and TD subjects, being both groups quick to react to the onset of the ocular target. In the spatial cueing task, a coupling between cue location and gaze direction emerged, being saccadic latencies faster towards valid targets, both in TD and CP groups. However, CP children often executed gaze movements to the cue, suggesting a difficulty to inhibit an eye shift towards a task-irrelevant visual stimulus. Moreover, CP children frequently executed eye movements during the fixation of the central cross. Interestingly, these intrusive saccades were mostly aimed to one of the placeholder displayed in the visual scene. This behavior clearly suggests a difficulty of CP children to suppress eye movements towards locations exogenously and endogenously activated by visuo-spatial attention. By combining eyetracking techniques and cognitive protocols, the present study offers a new approach for studying executive function in patients suffering from limitations of voluntary motor control

The latency of visually guided saccades executed after a cueing condition was adopted as a more e... more The latency of visually guided saccades executed after a cueing condition was adopted as a more ecological index to explore how spatial attention, usually assessed by manual responses, operates in the visual field. Subjects executed saccades aimed towards one of 4 possible positions, equally distributed around a central fixation cross. Before the onset of the saccadic target, a visual cue was briefly presented at the same or at a different spatial location. The visual cue was non-predictive of the target position. Two experimental sessions were carried out, differing for the onset asynchrony between cue and target. A time-dependent coupling between the task-irrelevant location of the cue and the direction of a following overt shift of attention emerged. Clinical applications of the adopted experimental setting to neurological and psychiatric patients with motor impairments are discussed.

There is increasing evidence that human brain is organised into large-scale networks. Among these... more There is increasing evidence that human brain is organised into large-scale networks. Among these, the Default Mode Network (DMN) and the Salience Network (SN) show abnormal connectivity patterns in Alzheimer\u2019s disease (AD), i.e. reduced connectivity in the DMN and increased connectivity in the SN. In this study, we tested the cognitive/clinical effect of neuromodulation of the above networks in AD through transcranial direct current stimulation (tDCS)

Alzheimer's & Dementia, 2019

Alzheimer's & Dementia, 2017

of dysfunctional networks: anodal stimulation of the DMN (right inferior parietal lobe), cathodal... more of dysfunctional networks: anodal stimulation of the DMN (right inferior parietal lobe), cathodal stimulation of the SN (right dorsolateral prefrontal cortex). Changes from pre-to post-treatment in clinical scales and functional connectivity were defined as outcome measures. Outcomes from clinical scales were compared by using the Wilcoxon signed-rank test, while changes in connectivity were assessed with the Functional Connectivity Toolbox. A seed-to-voxel approach was used to assess connectivity differences between the stimulated node and the other network areas. Results: To date, 16 patients have completed the treatment. 8 patients were allocated to the anodal and 8 to the cathodal arm. Analysis of clinical-neuropsychological scores revealed a beneficial effect of anodal stimulation over cognition (Immediate recall of Rey Word Recognition test, Token test, Clock test and Semantic Fluency test; p<0.05), whereas cathodal stimulation resulted in amelioration of behavioral symptoms (Neuropsychiatric inventory; p<0.05). In the anodal arm, rsfMRI analysis revealed decreased connectivity between the stimulated parietal node and the posterior cingulate (cluster size: 142 voxels; cluster-wise FDR corrected; p<0.05) after tDCS. In the cathodal arm, no change in connectivity was detected between the stimulated node and SN nodes. Conclusions:These data suggest a different effect of the two neuromodulator paradigms over clinical and cognitive outcomes. Our results suggest that anodal tDCS may be more effective than cathodal tDCS in modulating cognition and intra-network connectivity of aberrant networks in AD. Further studies might clarify whether different paradigms or target networks could also be effective interventions in AD.

Frontiers in aging neuroscience, 2017

Episodic memory is critical to daily life functioning. This type of declarative memory declines w... more Episodic memory is critical to daily life functioning. This type of declarative memory declines with age and is the earliest cognitive function to be compromised in Alzheimer's disease (AD). Subjective memory complaints are commonly reported by older adults and have been considered a risk factor for developing AD. The possibilities for prevention of memory disorders in older adults have increased substantially in recent years. Previous studies have shown that anodal transcranial Direct Current Stimulation (tDCS) applied over the left lateral prefrontal cortex (PFC) after a contextual reminder strengthened existing verbal episodic memories, conceivably through reconsolidation, in elderly people. In this study, we hypothesized that anodal tDCS applied over the left lateral PFC after a contextual reminder would improve delayed memory retrieval relative to placebo (sham) stimulation in elderly individuals with SMC. Twenty-two subjects learned a list of words. Twenty-four hour later,...

Journal of Alzheimer's disease : JAD, 2017

The accurate choice of the site of non-invasive brain stimulation (NIBS) is an important factor i... more The accurate choice of the site of non-invasive brain stimulation (NIBS) is an important factor in trial design. Based on the observation that Alzheimer's disease (AD) and behavioral frontotemporal dementia (bvFTD) affect specific large-scale networks, i.e., the default mode network (DMN) and the salience network (SN), respectively, we aimed to identify population-average coordinates of these networks that could be used as potential targets in NIBS trials aiming to modulate these circuits. A systematic literature search of resting-state functional MRI studies reporting DMN and SN stereotactic coordinates was performed according to PRISMA guidelines. Coordinate-based meta-analyses were conducted to identify consistent nodes of the DMN and SN using GingerALE BrainMap software and the activation likelihood estimation method. DMN coordinates mapped primarily to mesial areas (posterior cingulate cortex/precuneus [Brodmann Area - BA 23/31] and medial prefrontal cortex [BA 9/10/32]). M...

Scientific Reports, 2016

Emotional deficits are part of the non-motor features of Parkinson’s disease but few attention ha... more Emotional deficits are part of the non-motor features of Parkinson’s disease but few attention has been paid to specific aspects such as subjective emotional experience and autonomic responses. This study aimed to investigate the mechanisms of emotional recognition in Parkinson’s Disease (PD) using the following levels: explicit evaluation of emotions (Self-Assessment Manikin) and implicit reactivity (Skin Conductance Response; electromyographic measure of facial feedback of the zygomaticus and corrugator muscles). 20 PD Patients and 34 healthy controls were required to observe and evaluate affective pictures during physiological parameters recording. In PD, the appraisal process on both valence and arousal features of emotional cues were preserved, but we found significant impairment in autonomic responses. Specifically, in comparison to healthy controls, PD patients revealed lower Skin Conductance Response values to negative and high arousing emotional stimuli. In addition, the el...

Clinical Neurophysiology, 2016

follow-up P300 latencies and choice reaction time in stroke patients and evaluate their changes o... more follow-up P300 latencies and choice reaction time in stroke patients and evaluate their changes over a prospective 1-year follow-up period. Methods: The study included 60 patients (mean age 57.1 ± 7.2 years, range 45-72 years) with acute first-ever brain infarction. The control group consisted of 30 age-and sex-matched healthy volunteers (mean age 56.2 ± 6.3 years, range 42-72 years). We recorded the P300 wave using an auditory oddball paradigm. Results: The P300 latencies in stroke patients were significantly longer (Fz 423.5 ± 37.6 Cz 429.9 ± 40.6 Pz 433.8 ± 35.0) than those of the control group (Fz 359.5 ± 34.7 Cz 363.4 ± 33.1 Pz 367.4 ± 35.0). The latency of P300 showed a highly significant average improvement 12 months after the stroke compared to the baseline.The reaction time was significantly longer in stroke patients than those of the control group. Conclusion: The P3 latency stands out as a marker for cognitive function recovery after the stroke.

Movement Disorders, 2016

Parkinson&amp;amp;amp;#39;s disease (PD) is characterized by both motor and cognitive def... more Parkinson&amp;amp;amp;#39;s disease (PD) is characterized by both motor and cognitive deficits. In PD, physical exercise has been found to improve physical functioning. Recent studies demonstrated that repeated sessions of transcranial direct current stimulation led to an increased performance in cognitive and motor tasks in patients with PD. The present study investigated the effects of anodal transcranial direct current stimulation applied over the dorsolateral prefrontal cortex and combined with physical therapy in PD patients. A total of 20 patients with PD were assigned to 1 of 2 study groups: group 1, anodal transcranial direct current stimulation plus physical therapy (n = 10) or group 2, placebo transcranial direct current stimulation plus physical therapy (n = 10). The 2 weeks of treatment consisted of daily direct current stimulation application for 25 minutes during physical therapy. Long-term effects of treatment were evaluated on clinical, neuropsychological, and motor task performance at 3-month follow-up. An improvement in motor abilities and a reduction of depressive symptoms were observed in both groups after the end of treatment and at 3-month follow-up. The Parkinson&amp;amp;amp;#39;s Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. The application of anodal transcranial direct current stimulation may be a relevant tool to improve cognitive abilities in PD and might be a novel therapeutic strategy for PD patients with mild cognitive impairment. © 2016 International Parkinson and Movement Disorder Society.

Neurobiology of Aging, 2016

Episodic memory displays the largest degree of age-related decline, a process that is accelerated... more Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer's disease. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation (tDCS) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen's d effect size = 1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design-specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as mild cognitive impairment.

Neuroscience, Jan 26, 2015

The present research explored the cortical correlates of emotional memories in response to words ... more The present research explored the cortical correlates of emotional memories in response to words and pictures. Subjects' performance (Accuracy Index, AI; response times, RTs; RTs/AI) was considered when a repetitive Transcranial Magnetic Stimulation (rTMS) was applied on the left dorsolateral prefrontal cortex (LDLPFC). Specifically, the role of LDLPFC was tested by performing a memory task, in which old (previously encoded targets) and new (previously not encoded distractors) emotional pictures/words had to be recognized. Valence (positive vs. negative) and arousing power (high vs. low) of stimuli were also modulated. Moreover, subjective evaluation of emotional stimuli in terms of valence/arousal was explored. We found significant performance improving (higher AI, reduced RTs, improved general performance) in response to rTMS. This "better recognition effect" was only related to specific emotional features, that is positive high arousal pictures or words. Moreover no...

Brain and language, 2014

The present research addressed the question of where memories for emotional words could be repres... more The present research addressed the question of where memories for emotional words could be represented in the brain. A second main question was related to the effect of personality traits, in terms of the Behavior Activation System (BAS), in emotional word recognition. We tested the role of the left DLPFC (LDLPFC) by performing a memory task in which old (previously encoded targets) and new (previously not encoded distractors) positive or negative emotional words had to be recognized. High-BAS and low-BAS subjects were compared when a repetitive TMS (rTMS) was applied on the LDLPFC. We found significant differences between high-BAS vs. low-BAS subjects, with better performance for high-BAS in response to positive words. In parallel, an increased left cortical activity (alpha desynchronization) was observed for high-BAS in the case of positive words. Thus, we can conclude that the left approach-related hemisphere, underlying BAS, may support faster recognition of positive words.