Neural correlates of empathy in mild cognitive impairment.

The occurrence of clinically significant changes in empathy is a matter of debate in Alzheimer's disease (AD). Altered empathic mechanisms observed in AD may be a consequence of cognitive impairment, more specifically of reduced mental flexibility and self-regulation. The present study explored possible changes in empathy for subjects in the prodromal phase of AD, namely mild cognitive impairment (MCI) due to AD, and of their neural substrates. Eighteen MCI patients and 20 healthy controls (HC) were included in the study. The Interpersonal Reactivity Index (IRI) questionnaire was administered to each participant. The IRI encompasses four factors: Perspective Taking; Fantasy; Empathic Concern; Personal Distress. MCI patients underwent a magnetic resonance imaging structural examination and were compared to 30 healthy controls (HC-MRI). A limited number of cortical and subcortical regions involved in social cognition was selected as regions of interest (ROIs). MCI individuals obtained lower scores than HC in the Perspective Taking and Fantasy subscales of the IRI, whereas they obtained higher scores on Empathic Concern. Regarding neuroimaging data, a significant correlation emerged between IRI scores and the neural measurements of different regions involved in empathy, especially covering the temporoparietal junction, which is a critical region engaged in both affective and cognitive dimensions of empathy. The results of the present study suggest that a subtle impairment in regulatory mechanisms of empathy may occur very early during the course of AD, possibly as a consequence of neuropathological changes occurring in brain regions involved in social cognition.

Social cognition in Parkinson's disease and functional movement disorders.

INTRODUCTION: Functional movement disorders (FMD) can overlap with Parkinson's disease (PD), and distinguishing between the two clinical conditions can be complex. Framing social cognition (theory of mind) (TOM) disorder, attention deficit, and psychodynamic features of FMD and PD may improve diagnosis. METHODS: Subjects with FMD and PD and healthy controls (HC) were administered tasks assessing TOM abilities and attention. The psychodynamic hypothesis of conversion disorder was explored by a questionnaire assessing dissociative symptoms. A comprehensive battery of neuropsychological tasks was also administered to FMD and PD. RESULTS: Although both FMD and PD scored lower than HC on all TOM tests, significant correlations between TOM and neuropsychological tasks were found only in PD but not in FMD. Only PD showed a reduction in attentional control. Dissociative symptoms occurred only in FMD. DISCUSSION: Cognitive-affective disturbances are real in FMD, whereas they are largely dependent on cognitive impairment in PD. Attentional control is preserved in FMD compared to PD, consistent with the hypothesis that overload of voluntary attentional orientation may be at the basis of the onset of functional motor symptoms. On a psychodynamic level, the confirmation of dissociative symptoms in FMD supports the conversion disorder hypothesis. CONCLUSION: FMD and PD can be distinguished on an affective and cognitive level. At the same time, however, the objective difficulty often encountered in distinguishing between the two pathologies draws attention to how blurred the boundary between 'organic' and 'functional' can be.

Decision-making under ambiguity and risk and executive functions in Parkinson's disease patients: A scoping review of the studies investigating the Iowa Gambling Task and the Game of Dice.

Evidence shows that patients affected by Parkinson's disease (PD) display the tendency toward making risky choices. This is due, at least in part, to the pathophysiological characteristics of the disease that affects neural areas underlying decision making (DM), in which a pivotal role is played by nonmotor corticostriatal circuits and dopamine. Executive functions (EFs), which can be impaired by PD as well, may sustain optimal choices in DM processes. However, few studies have investigated whether EFs can support PD patients to make good decisions. Adopting the scoping review approach, the present article is designed to deepen the cognitive mechanisms of DM under conditions of ambiguity and risk (that are conditions common to everyday life decisions) in PD patients without impulse control disorders. We focused our attention on the Iowa Gambling Task and the Game of Dice Task, because they are the most commonly used and reliable tasks to assess DM under ambiguity and under risk, respectively, and analyzed the performances in such tasks and their relationships with EFs tests in PD patients. The analysis supported the relationships between EFs and DM performance, especially when a higher cognitive load is required to make optimal decisions, as it happens under conditions of risk. Possible knowledge gaps and further research directions are suggested to better understand DM mechanisms in PD sustaining patients' cognitive functioning and preventing negative consequences in everyday life derived from suboptimal decisions.

Clinical and genetic characteristics of late-onset Huntington's disease in a large European cohort.

BACKGROUND AND PURPOSE: Huntington's disease (HD) is an autosomal dominant condition caused by CAG-triplet repeat expansions. CAG-triplet repeat expansion is inversely correlated with age of onset in HD and largely determines the clinical features. The aim of this study was to examine the phenotypic and genotypic correlates of late-onset HD (LoHD) and to determine whether LoHD is a more benign expression of HD. METHODS: This was a retrospective observational study of 5053 White European HD patients from the ENROLL-HD database. Sociodemographic, genetic and phenotypic variables at baseline evaluation of subjects with LoHD, common-onset HD (CoHD) and young-onset HD (YoHD) were compared. LoHD subjects were compared with healthy subjects (HS) aged ≥60 years. Differences between the CoHD and LoHD groups were also explored in subjects with 41 CAG triplets, a repeat number in the lower pathological expansion range associated with wide variability in age at onset. RESULTS: Late-onset HD presented predominantly as motor-onset disease, with a lower prevalence of both psychiatric history and current symptomatology. Absent/unknown HD family history was significantly more common in the LoHD group (31.2%) than in the other groups. The LoHD group had more severe motor and cognitive deficits than the HS group. Subjects with LoHD and CoHD with 41 triplets in the larger allele were comparable with regard to cognitive impairment, but those with LoHD had more severe motor disorders, less problematic behaviors and more often an unknown HD family history. CONCLUSIONS: It is likely that cognitive disorders and motor symptoms of LoHD are at least partly age-related and not a direct expression of the disease. In addition to CAG-triplet repeat expansion, future studies should investigate the role of other genetic and environmental factors in determining age of onset.

Theory of mind: A clue for the interpretation of functional movement disorders.

OBJECTIVES: Functional movement disorders (FMD) refer to a heterogeneous group of manifestations incongruent with known neurological diseases. Functional neuroimaging studies in FMD indicate the overlap between cerebral regions in which abnormal activation occurs and those considered crucial for theory of mind (ToM), the ability to attribute mental states. The aim of this study was to explore whether FMD might be related to ToM disorders to the extent that they reduce the ability to make inferences about the mental states underlying motor behaviour during social interaction. MATERIALS & METHODS: Eighteen subjects with FMD and 28 matched healthy controls (HC) were given a ToM battery. The severity of FMD was rated by the Simplified-FMD Rating Scale (S-FMDRS). Dissociative symptoms were evaluated by the Dissociative Experiences Scale (DES-II). RESULTS: FMD scored worse than the HC in most ToM tasks: second-order False Beliefs (p = .005), Faux-Pas Recognition Test (p < .001) and Reading the Mind in the Eyes Test (p = .020); control questions elicited normal scores. The DES-II indicated dissociative-borderline psychopathology and negatively correlated with accuracy on the second-order False Belief (Spearman's rho = -.444; p = .032); the positive correlation between DES-II and severity of motor symptoms (S-FMDRS) approached significance (Spearman's rho test = .392; p = .054). ToM disorders were not correlated with S-FMDRS, due to the typical variability in FMD over time with regard to the severity of symptoms and the district of body involved. CONCLUSIONS: Our results are consistent with the hypothesis that FMD are related to ToM deficits, and future studies are needed to define the specific nature of this relationship.

Decision making in Parkinson's disease: An analysis of the studies using the Iowa Gambling Task.

In Parkinson's disease (PD) impairments in decision making can occur, in particular because of the tendency toward risky and rewarding options. The Iowa Gambling Task has been widely used to investigate decision processes involving these options. The task assesses the ability to manage risk and to learn from feedback. The present paper aims at critically examining those studies in which this task has been administered to PD patients, in order to understand possible anomalies in patients' decision processes and which variables are responsible for that. A meta-analysis has been conducted as well. Features of the task, sociodemographic and clinical aspects (including daily drugs intake), cognitive conditions and emotional disorders of the patients have been taken into account. Neural correlates of decision-making competences were considered. It emerged that PD patients show a trend of preference toward risky choices, probably due to an impairment in anticipating the unrewarding consequences or to an insensitiveness to punishment. The possible role played by dopamine medications in decision making under uncertain conditions, affecting basal ganglia and structures involved in the limbic loop, was discussed. Attention has been focused on some aspects that need to be investigated in further research, in order to delve into this issue and promote patients' quality of life.

Contribution of the Cerebellum and the Basal Ganglia to Language Production: Speech, Word Fluency, and Sentence Construction-Evidence from Pathology.

Evidence reported in recent decades increasingly confirms that both the cerebellum and the basal ganglia, which are primarily involved in movement control, also have a significant role in a vast range of cognitive and affective functions. Evidence from pathology indicates that the disorders of some aspects of language production which follow damage of the cerebellum or respectively basal ganglia, i.e., disorders of speech, word fluency, and sentence construction, have identifiable neuropsychological profiles and that most manifestations can be specifically attributed to the dysfunctions of mechanisms supported by one or the other of these structures. The cerebellum and the basal ganglia are reciprocally interconnected. Thus, it is plausible that some disorders observed when damage involves one of these structures could be remote effects of abnormal activity in the other. However, in a purely clinical-neuropsychological perspective, primary and remote effects in the network are difficult to disentangle. Functional neuroimaging and non-invasive brain stimulation techniques likely represent the indispensable support for achieving this goal.

The role of the dorsal striatum in the recognition of emotions expressed by voice in Parkinson's disease.

BACKGROUND AND PURPOSE: Non-motor impairment such as emotion recognition deficit in both facial and vocal expressions has been previously reported in Parkinson's disease (PD). We investigated whether the decoding of emotional prosody is impaired in PD and whether this deficit is related to striatal damage. METHODS: Fifteen PD patients and 15 healthy controls (HCs) were requested to listen to six audio tracks and to recognize the emotions expressed by a professional actor while reading a meaning-neutral sentence. All subjects also received a structural MRI examination. Volumetric measurements were extracted for the striatum, a key region involved in emotional processing and typically impaired in PD. RESULTS: Decoding sadness conveyed by voice was impaired in PD compared with HC and was related to the volume of the dorsal striatum bilaterally. CONCLUSIONS: The dorsal striatum is involved in the decoding of vocal negative emotions in PD.

What about the caregiver? A journey into Parkinson's disease following the burden tracks.

OBJECTIVES: To investigate caregivers and patients characteristics related to different dimensions of burden in Parkinson's disease (PD). METHODS: 55 pairs of PD patients and caregivers were recruited. The burden was evaluated with the Caregiver Burden Inventory (CBI). Multivariate analysis was applied to evaluate the impact of caregivers' and patients' characteristics on the varying aspects of burden. RESULTS: ADL score was the dominant predictor for the total score and all dimensions of CBI, except for the social burden, which is strongly predicted by the motor severity of PD. As one can easily imagine, the Total CBI decreases as the ADL score increases. DISCUSSION: An increased appreciation for characteristics of caregiver burden is a fundamental aspect of the patient's global evaluation. Clinicians may need to directly probe for these factors in the caregiver as they may not be elicited routinely.

Prevalence of Obsessive-Compulsive Symptoms in Elderly Parkinson Disease Patients: A Case-Control Study.

BACKGROUND: The clinical picture of obsessive-compulsive disorder encompasses a broad range of symptoms that are related to multiple psychological domains, including perception, cognition, emotion, and social relatedness. As obsessive-compulsive symptoms (OCS) frequently have an early onset, there are limited data about OCS in older populations (≥65 years) and, in particular, in elderly subjects with Parkinson disease (PD). OBJECTIVE: This study aimed to estimate the prevalence of OCS using a self-report measure (Obsessive-Compulsive Inventory-Revised) and to identify associated sociodemographic and clinical factors in a sample of elderly PD patients compared to a comparison group of similarly aged healthy volunteers. RESULTS: The mean age was 74 ± 6 years in the PD patients and 73 ± 7 years in the comparison group. The mean disease duration was 9.6 ± 5.8 years. Among the PD patients, 30.7% reported at least one OCS or a related disorder compared to 21.1% in the comparison group. Hoarding was significantly more common in PD patients than in the comparison group. CONCLUSIONS: Subclinical OCS were present at a high percentage in both PD patients and comparison group. The OCS phenotype in PD may present differently, as hoarding was more common in PD patients.

Emotional valence may influence memory performance for visual artworks in Parkinson's disease.

BACKGROUND: Non-motor symptoms in Parkinson's disease (PD) include reduced reactivity to emotional stimuli. Visual artworks can evoke emotional responses. Motor, sensorial and cognitive networks implicated in the aesthetic experience and in the emotional-reward domain show a significant overlap with the pathological nigrostriatal, mesocortical and mesolimbic circuitry that characterises PD. METHODS: Memory enhancement by emotional stimuli such as visual artwork-stimuli was explored in 12 right-sided and 12 left-sided non-demented-PD patients, 12 Alzheimer's disease patients (AD) and 13 healthy controls (HC). Ten emotional and 10 non-emotional stimuli were previously identified based on the ratings of the emotional impact provided by 45 non-PD subjects on 82 pictures of paintings. Only figurative artworks were included. Patients and HC were requested to rate on a 7-point scale the emotional impact of 20 pictures; they were then requested to recognise the 20 pictures amongst 20 distractors (incidental memory task). RESULTS AND CONCLUSION: Recognition of emotional stimuli was more accurate compared to non-emotional stimuli in AD, left-sided PD and HC; right-sided PD did not show sensitivity to the emotional valence of the stimuli suggesting the involvement of the nigrostriatal, mesocortical and mesolimbic circuitry of the left hemisphere in the emotional-reward system related to the aesthetic experience.

Degenerative and Vascular Fluent Aphasia: Looking for Differences.

OBJECTIVE: To investigate whether the characteristics of language disorders of degenerative and vascular aphasias depend on the underlying neuropathology. METHODS: Logopenic variant/mixed primary progressive aphasics (lvmPPA; n=18) and poststroke fluent aphasics (PSA; n=11) underwent a neuropsychological examination and an assessment of the macro- and microlinguistic aspects of language. A principal component analysis and a cluster analysis applying a two-group solution were performed on the scores obtained from the neuropsychological and language examination. RESULTS: Global cognition, lexical-semantic, and morphosyntactic components, and two components loading macrolinguistic variables, were extracted by the principal component analysis. A first cluster of 18 participants (14 lvmPPA and 4 PSA) and a second cluster of 11 participants (4 lvmPPA and 7 PSA) were identified. Participants in the first cluster were significantly more impaired than those in the second cluster in global cognition, lexical-semantic, and morphosyntactic components. Macrolinguistic components did not differentiate the two clusters. lvmPPA in the first cluster showed bilateral cortical thinning (greater on the left), whereas lvmPPA in the second cluster showed atrophy only in the left. Participants with PSA in both clusters showed vascular lesions encompassing the posterior left perisylvian regions. Underestimation of the severity of the leukoencephalopathy and damage of the interhemispheric connectivity might be responsible for the inclusion of PSA individuals in the first cluster, despite a unilateral lesion. CONCLUSIONS: Lesion localization is the main factor that determines the characteristics of aphasic deficits. Etiology indirectly acts through a different sensitivity of the brain regions to various pathologies.

The role of cognitive reserve in cognitive aging: what we can learn from Parkinson's disease.

Parkinson's disease (PD) typically occurs in elderly people and some degree of cognitive impairment is usually present. Cognitive reserve (CR) theory was proposed to explain the discrepancy between the degree of brain pathologies and clinical manifestations. We administered a comprehensive neuropsychological battery to 35 non-demented participants affected by PD. All participants underwent also the Cognitive Reserve Index questionnaire and the Brief Intelligence Test as proxies for CR. Relationships between CR and cognitive performance were investigated by linear regression analyses, adjusting for significant confounding factors. At linear regression analyses, higher CR scores were independently associated with a better performance on Word Fluency (p ≤ 0.04) and Digit Span (backward) (p ≤ 0.02); no associations were observed between CR and other cognitive tests. Our data provide empirical support to the relation between CR and cognitive impairment in PD. In particular, this study suggests that CR may have greater effects on the cognitive areas mostly affected in PD as executive functions.

Lexical-semantic deficits in processing food and non-food items.

The study of category specific deficits in brain-damaged patients has been instrumental in explaining how knowledge about different types of objects is organized in the brain. Much of this research focused on testing putative semantic sensory/functional subsystems that could explain the observed dissociations in performance between living things (e.g., animals and fruits/vegetables) and non-living things (e.g., tools). As neuropsychological patterns that did not fit the original living/non-living distinction were observed, an alternative organization of semantic memory in domains constrained by evolutionary pressure was hypothesized. However, the category of food, that contains both living-natural items, such as an apple, and nonliving-manufactured items as in the case of a hamburger, has never been systematically investigated. As such, food category could turn out to be very useful to test whether the brain organizes the knowledge about food in sensory/functional subsystems, in a specific domain, or whether both approaches might need to be integrated. In the present study we tested the ability of patients with Alzheimer dementia (AD) and with Primary Progressive Aphasias (PPA) as well as healthy controls to perform a confrontation naming task, a categorization task, and a comprehension of edible (natural and manufactured food) and non edible items (tools and non-edible natural things) task (Tasks 1-3). The same photographs of natural and manufactured food were presented together with a description of food's sensory or functional property that could be either congruent or incongruent with that particular food (Task 4). Patients were overall less accurate than healthy individuals, and PPA patients were generally more impaired than AD patients, especially on the naming task. Food tended to be processed better than non-food in two out of three tasks (categorization and comprehension tasks). Patient groups showed no difference in naming food and non-food items, while controls were more accurate with non-food than food (controlling for the linguistic variables and calorie content). AD patients named manufactured food more accurately than natural food (with PPA and controls showing no difference). Recognition of food and, to some extent, of manufactured food seems to be more resilient to brain damage, possibly by virtue of its survival relevance. Furthermore, on Task 4 patients showed an advantage for the sensory-natural pairs over sensory-manufactured combination. Overall, findings do not fit an existing model of semantic memory and suggest that properties intrinsic to the food items (such as the level of transformation and the calorie content) or even to the participants like the Body Mass Index (as shown in another study reviewed here) should be considered.

On the Relationship Between Semantic Knowledge and Prejudice About Social Groups in Patients with Dementia.

OBJECTIVE AND BACKGROUND: Patterns of brain-damaged individuals' deficits in categorizing living versus non-living things indicate separation of semantic knowledge categories in the brain. Recent work in patients with dementia suggested that semantic knowledge about social groups differs from knowledge about living and non-living things. In this study we analyzed patients' social appraisal by testing whether their degree of impairment in social-group knowledge predicted their social-group evaluative reactions (prejudice). We hypothesized that impaired knowledge about social groups would correlate with either heightened or reduced prejudice. METHODS: In Rumiati et al, Cogn Neurosci (2014) http://dx.doi.org/10.1080/17588928.2013.876981, we had given a sorting task to 21 patients with frontotemporal dementia or dementia of the Alzheimer type and 23 healthy controls, to test their knowledge of social groups and living and non-living things. In this study we asked the same participants to evaluate social groups. We used controls' evaluations to rank 20 social groups from extremely negative to extremely positive. We used patients' severity of deficit in sorting social groups to predict the patients' evaluations of the groups, controlling for their levels of deficit in sorting living and non-living items. We also compared the evaluations by patients±deficits in social-group sorting to controls' evaluations. RESULTS: The patients with impaired social-group knowledge evaluated the less-admired groups more positively than did controls, and the more-admired groups less positively. CONCLUSIONS: Impaired social-group knowledge, not a general semantic loss, predicts reduced evaluative bias. Our findings are consistent with neuroimaging evidence for a relationship between semantic and evaluative social-group processes.

Clinical and MRI characterization of apraxic syndrome in corticobasal degeneration: A single-case study.

Objective: To identify the cortical and subcortical distribution of atrophy and the disorganization of white matter bundles underlying the apraxic disorders in a patient with corticobasal degeneration (CBD). Method: Patient underwent appropriate neuropsychological tasks aimed at identifying the nature of the apraxic disorder and morphometric structural MRI with whole-brain voxel-wise analysis. Results: Progressive limbkinetic apraxia (LKA) with onset in the right upper limb with subsequent extension to the limbs, trunk, orofacial district, and eye movements was documented, associated with element of ideomotor apraxia (IMA). The MRI study showed grey matter atrophy extending to much of the frontal cortex bilaterally, including the precentral cortex, and into the inferior parietal regions. Caudate and putamen were involved on the left. Significant clusters of white matter atrophy were found in the bilateral superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and corpus callosum (CC). Sensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were normal. Conclusion: Previous observations in CBD indicate lack of inhibitory control from the sensory to the primary motor cortex with dysfunctional frontoparietal and cortico-motoneuron projections. Our neuroimaging data are partially consistent with these observations suggesting that the apraxic disorder in our patient might be produced by the disconnection of the primary motor cortex from the parietal areas that prevents selection and control of muscle movements, in the presence of preserved cortico-motoneuron as demonstrated by normal PEM. Apraxic disorders in CBD are high-level deficits of movement control that spare the motoneuron.

Cognitive Reserve proxies can modulate motor and non-motor basal ganglia circuits in early Parkinson's Disease.

Parkinson's Disease (PD) is hallmarked by dysfunctional circuitry between the basal ganglia and dorsolateral-prefrontal cortex. Recently progress has been made in understanding factors contributing to differential susceptibility to pathology mitigating disease-related cognitive decline. Cognitive reserve, the brain processing resources accumulated throughout life while engaged in mentally stimulating activities, can play an important protective role in cognitive performance. We tested the hypothesis that Cognitive Reserve proxies may exert an impact on the basal ganglia and dorsolateral-prefrontal atrophy in early PD. Forty-five early patients with PD and 20 age-gender-matched healthy controls (HC) completed the Cognitive Reserve Index questionnaire to quantify Cognitive Reserve proxies by three indexes (CRI-Education, CRI-Working Activity, CRI-Leisure Time) and a structural MRI examination (3T). Morphometrical indexes for basal ganglia (bilateral putamen, caudate, pallidum volume) and dorsolateral-prefrontal cortex (cortical thickness) were computed. Significant differences between HC and PD were tested by direct comparisons in demographics, cognitive level, and cognitive reserve proxies indexes. Then two multiple regression analyses were performed to identify predictors of the basal ganglia and dorsolateral-prefrontal cortex structural integrity. Regression analysis revealed that basal ganglia volume was significantly predicted by CRI-Education (pFDR = 0.029), sex (pFDR = 0.029), and Total Intracranial Volume (pFDR < 0.001). Instead, the dorsolateral-prefrontal thickness was predicted by CRI-Leisure Time (pFDR = 0.030) and age (pFDR = 0.010). Cognitive Reserve proxies, especially education and leisure-time activities, can play a protective role on the structural integrity of the basal ganglia and dorsolateral-prefrontal cortex, respectively, critical regions hallmarking brain status of early phases of PD.

Exploring cognitive reserve's influence: unveiling the dynamics of digital telerehabilitation in Parkinson's Disease Resilience.

Telerehabilitation is emerging as a promising digital method for delivering rehabilitation to Parkinson's Disease (PD) patients, especially in the early stages to promote brain resilience. This study explores how cognitive reserve (CR), the brain's ability to withstand aging and disease, impacts the effectiveness of telerehabilitation. It specifically examines the influence of lifelong cognitive activities on the relationship between neural reserve and improved functional abilities following rehabilitation. In the study, 42 PD patients underwent a 4-month neuromotor telerehabilitation program. CR proxies were assessed using the Cognitive Reserve Index questionnaire (CRIq), brain changes via 3T-MRI, and functional response through changes in the 6-Minute Walk Distance (6MWD). Participants were divided into responders (n = 23) and non-responders (n = 19) based on their 6MWD improvement. A multiple regression model was run to test significant predictors of 6MWD after treatment in each group. The results revealed a significant correlation between 6MWD and CRIq scores, but only among responders. Notably, the CRIq Leisure-Time sub-index, along with baseline 6MWD, were predictors of post-treatment 6MWD. These findings highlight CR's role in enhancing the benefits of telerehabilitation on PD patients' neuromotor functions. Clinically, these results suggest that neurologists and clinicians should consider patients' lifestyles and cognitive engagement as important factors in predicting and enhancing the outcomes of telerehabilitation. The study underscores the potential of CR as both a predictor and booster of telerehabilitation's effects, advocating for a personalized approach to PD treatment that takes into account individual CR levels.

The rising role of cognitive reserve and associated compensatory brain networks in spinocerebellar ataxia type 2.

Pre-existing or enhanced cognitive abilities influence symptom onset and severity in neurodegenerative diseases, which improve an individual's ability to deal with neurodegeneration. This process is named cognitive reserve (CR), and it has acquired high visibility in the field of neurodegeneration. However, the investigation of CR has been neglected in the context of cerebellar neurodegenerative disorders. The present study assessed CR and its impact on cognitive abilities in spinocerebellar ataxia type 2 (SCA2), which is a rare cerebellar neurodegenerative disease. We investigated the existence of CR networks in terms of compensatory mechanisms and neural reserve driven by increased cerebello-cerebral functional connectivity. The CR of 12 SCA2 patients was assessed using the Cognitive Reserve Index Questionnaire (CRIq), which was developed for appraising life-span CR. Patients underwent several neuropsychological tests to evaluate cognitive functioning and a functional MRI examination. Network based statistics analysis was used to assess functional brain networks. The results revealed significant correlations of CRIq measures with cognitive domains and patterns of increased connectivity in specific cerebellar and cerebral regions, which likely indicated CR networks. This study showed that CR may influence disease-related cognitive deficits, and it was related to the effective use of specific cerebello-cerebral networks that reflect a CR biomarker.

Resting-state functional connectivity is modulated by cognitive reserve in early Parkinson's disease.

Background: Fronto-striatal disconnection is thought to be at the basis of dysexecutive symptoms in patients with Parkinson's disease (PD). Multiple reserve-related processes may offer resilience against functional decline. Among these, cognitive reserve (CR) refers to the adaptability of cognitive processes. Objective: To test the hypothesis that functional connectivity of pathways associated with executive dysfunction in PD is modulated by CR. Methods: Twenty-six PD patients and 24 controls underwent resting-state functional magnetic resonance imaging. Functional connectivity was explored with independent component analysis and seed-based approaches. The following networks were selected from the outcome of the independent component analysis: default-mode (DMN), left and right fronto-parietal (l/rFPN), salience (SalN), sensorimotor (SMN), and occipital visual (OVN). Seed regions were selected in the substantia nigra and in the dorsolateral and ventromedial prefrontal cortex for the assessment of seed-based functional connectivity maps. Educational and occupational attainments were used as CR proxies. Results: Compared with their counterparts with high CR, PD individuals with low CR had reduced posterior DMN functional connectivity in the anterior cingulate and basal ganglia, and bilaterally reduced connectivity in fronto-parietal regions within the networks defined by the dorsolateral and ventrolateral prefrontal seeds. Hyper-connectivity was detected within medial prefrontal regions when comparing low-CR PD with low-CR controls. Conclusion: CR may exert a modulatory effect on functional connectivity in basal ganglia and executive-attentional fronto-parietal networks. In PD patients with low CR, attentional control networks seem to be downregulated, whereas higher recruitment of medial frontal regions suggests compensation via an upregulation mechanism. This upregulation might contribute to maintaining efficient cognitive functioning when posterior cortical function is progressively reduced.