Correction: Spanò et al. Effect of Dual-Task Motor-Cognitive Training in Preventing Falls in Vulnerable Elderly Cerebrovascular Patients: A Pilot Study. Brain Sci. 2022, 12, 168.

In the original publication [...].

The Effect of Dual-Task Motor-Cognitive Training in Adults with Neurological Diseases Who Are at Risk of Falling.

Falls are common in patients with neurological diseases and can be very problematic. Recently, there has been an increase in fall prevention research in people with neurological diseases; however, these studies are usually condition-specific (e.g., only MS, PD or stroke). Here, our aim was to evaluate and compare the efficacy of an advanced and innovative dual-task, motor-cognitive rehabilitation program in individuals with different neurological diseases who are at risk of falling. We recruited 95 consecutive adults with neurological diseases who are at risk of falling and divided them into four groups: 31 with cerebrovascular disease (CVD), 20 with Parkinson's disease (PD), 23 with traumatic brain injury (TBI) and 21 with other neurological diseases (OND). Each patient completed a dual-task, motor-cognitive training program and underwent two test evaluations to assess balance, gait, fear of falling and walking performance at the pre-and post-intervention. We found that our experimental motor-cognitive, dual-task rehabilitation program was an effective method for improving walking balance, gait, walking endurance and speed, and fear of falling, and that it reduced the risk of falls in patients with different neurological diseases. This study presents an alternative approach for people with chronic neurological diseases and provides innovative data for managing this population.

Effect of Early Radial Shock Wave Treatment on Spasticity in Subacute Stroke Patients: A Pilot Study.

Background: Spasticity is a complication that can start immediately after stroke. Radial extracorporeal shock wave therapy (rESWT) is a physical therapy tool used to manage chronic spasticity. However, the effect of rESWT's early use to treat spasticity after stroke is still not clearly investigated. The aim of this study is to evaluate the efficacy of rESWT in improving poststroke spasticity of the upper limb in patients with a recent onset of spasticity compared to conventional physiotherapy alone. Methods: 40 stroke patients were randomly assigned to experimental (EG) or control group (CG). Both groups underwent two daily sessions of conventional rehabilitation therapy (CRT) 5 days per week; the EG underwent one rESWT session a week for 4 weeks. The modified Ashworth scale (MAS) tested at the shoulder, elbow, and wrist was used as outcome measure. MAS was evaluated at baseline, after 2 and 4 rESWT session, and one month after the last session (follow-up). Results: No significant differences between groups were found at baseline in terms of age, days from onset of spasticity after stroke, and MAS at each body segment. The sample lost eight drop-out patients. Except for the shoulder MAS values, the EG showed statistically significant lower MAS values already after the second rESWT session compared to CG. This significant difference was maintained until the follow-up. The CG showed a significant increase of wrist spasticity after the second evaluation, while the EG maintained constant MAS values throughout the observational period. The elbow spasticity was significantly higher in the CG at the follow-up evaluation. Conclusion: The rESWT combined with CRT seems to be effective in avoiding the increasing progression of spasticity after stroke.

Effect of Dual-Task Motor-Cognitive Training in Preventing Falls in Vulnerable Elderly Cerebrovascular Patients: A Pilot Study.

Falling is a frequent and major clinical problem among older adults, as well as in patients with chronic cerebrovascular diseases (CVD). At present, sequential (mixed) and simultaneously (dual-task) motor-cognitive trainings are the best approaches to affording patients more autonomy in their everyday motor independence while reducing fall risks and consequences. The objective of this study was to evaluate the efficacy of an advanced and innovative dual-task motor-cognitive rehabilitation program on fall risks in vulnerable older persons with chronic CVD. To this purpose, 26 consecutive older fallers with chronic CVD were recruited, and completed a mixed motor-cognitive or a dual-task motor-cognitive training program. Each patient also underwent two test evaluations to assess balance, gait, fear of falling, and walking performance at pre-and post-intervention. We found that our experimental motor-cognitive dual-task rehabilitation program could be an effective method to improve walking balance, gait, walking speed, and fear of falling, while reducing the risk of falls in older people with chronic CVD. Furthermore, results show that the simultaneous motor-cognitive training is more effective than the sequential motor-cognitive training. Therefore, our study brings innovative data, which can contribute positively to the management of this population.

Relapsing-remitting and secondary-progressive multiple sclerosis patients differ in decoding others' emotions by their eyes.

BACKGROUND AND PURPOSE: Difficulties in emotion processing and social cognition identified in multiple sclerosis (MS) patients have a potential impact on their adaptation to the social environment. We aimed to explore the neural correlates of emotion recognition in MS and possible differences between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) patients by the Reading the Mind in the Eyes test (RMEt). METHODS: A total of 43 MS patients (27 RRMS, 16 SPMS) and 25 matched healthy controls (HC) underwent clinical assessments, RMEt, and a high-resolution T1-weighted 3-T magnetic resonance imaging (MRI) scan. The number of correct answers on the RMEt was compared between groups. T1-weighted volumes were processed according to an optimized voxel-based morphometry (VBM) protocol to obtain gray matter (GM) maps. Voxelwise analyses were run to assess potential associations between RMEt performance and regional GM volumes. RESULTS: Taken altogether, MS patients reported significantly lower performance on the RMEt compared to HC. When dividing the patients into those with RRMS and those with SPMS, only the latter group was found to perform significantly worse than HC on the RMEt. VBM analysis revealed significant association between RMEt scores and GM volumes in several cortical (temporoparieto-occipital cortex) and subcortical (hippocampus, parahippocampus, and basal ganglia) brain regions, and in the cerebellum in SPMS patients only. CONCLUSIONS: Results suggest that, in addition to other clinical differences between RRMS and SPMS, the ability to recognize others' emotional states may be affected in SPMS more significantly than RRMS patients. This is supported by both behavioral and MRI data.

Left egocentric neglect in early subacute right-stroke patients is related to damage of the superior longitudinal fasciculus.

A typical consequence of stroke in the right hemisphere is unilateral spatial neglect. Distinct forms of neglect have been described, such as space-based (egocentric) and object-based (allocentric) neglect. However, the relationship between these two forms of neglect is still far from being understood, as well as their neural substrates. Here, we further explore this issue by using voxel lesion symptoms mapping (VLSM) analyses on a large sample of early subacute right-stroke patients assessed with the Apples Cancellation Test. This is a sensitive test that simultaneously measures both egocentric and allocentric neglect. Behaviourally, we found no correlation between egocentric and allocentric performance, indicating independent mechanisms supporting the two forms of neglect. This was confirmed by the VLSM analysis that pointed out a link between a damage in the superior longitudinal fasciculus and left egocentric neglect. By contrast, no association was found between brain damage and left allocentric neglect. These results indicate a higher probability to observe egocentric neglect as a consequence of white matter damages in the superior longitudinal fasciculus, while allocentric neglect appears more "globally" related to the whole lesion map. Overall, these findings on early subacute right-stroke patients highlight the role played by white matter integrity in sustaining attention-related operations within an egocentric frame of reference.

Evidence for interhemispheric imbalance in stroke patients as revealed by combining transcranial magnetic stimulation and electroencephalography.

Interhemispheric interactions in stroke patients are frequently characterized by abnormalities, in terms of balance and inhibition. Previous results showed an impressive variability, mostly given to the instability of motor-evoked potentials when evoked from the affected hemisphere. We aim to find reliable interhemispheric measures in stroke patients with a not-evocable motor-evoked potential from the affected hemisphere, by combining transcranial magnetic stimulation (TMS) and electroencephalography. Ninteen stroke patients (seven females; 61.26 ± 9.8 years) were studied for 6 months after a first-ever stroke in the middle cerebral artery territory. Patients underwent four evaluations: clinical, cortical, corticospinal, and structural. To test the reliability of our measures, the evaluations were repeated after 3 weeks. To test the sensitivity, 14 age-matched healthy controls were compared to stroke patients. In stroke patients, stimulation of the affected hemisphere did not result in any inhibition onto the unaffected. The stimulation of the unaffected hemisphere revealed a preservation of the inhibition mechanism onto the affected. This resulted in a remarkable interhemispheric imbalance, whereas this mechanism was steadily symmetric in healthy controls. This result was stable when cortical evaluation was repeated after 3 weeks. Importantly, patients with a better recovery of the affected hand strength were the ones with a more stable interhemispheric balance. Finally, we found an association between microstructural integrity of callosal fibers, suppression of interhemispheric TMS-evoked activity and interhemispheric connectivity. We provide direct and sensitive cortical measures of interhemispheric imbalance in stroke patients. These measures offer a reliable means of distinguishing healthy and pathological interhemispheric dynamics.

Dual-Task Performance in Multiple Sclerosis' Patients: Cerebellum Matters?

OBJECTIVE: Gait, cognitive impairments, and their mutual influence in dual tasking (cognitive-motor dual tasking, CM-DT) are important to address therapeutic approaches in patients with multiple sclerosis (PMS). CM-DT correlates have been widely investigated with variable and dissimilar results, due to differences in methods. However, although the cerebellum has recently shown to be involved in both motor and cognitive functions, few studies have explored its role in the integration of the concurrent execution of gait and cognition. This case-control study aims to explore the effects of adding a cognitive task to walking in PMS and to investigate the role of the cerebellum in the interfering process. METHODS: In total, 20 patients and 18 healthy controls (HC) underwent clinical assessments, dual task (DT), and 3 T magnetic resonance imaging (MRI). DT was composed by three 2-min trials requiring fast walking. In 2 of them 2 different cognitive tasks were added. RESULTS: Both groups evidenced the presence of cognitive-motor interference (CMI) for both cognitive conditions with a greater effect of word list generation task in PMS. Analysis of variance between HC and patients with high or low performances showed a significantly increased volume in Vermis lobules VIIIa and IX of high performers compared with HC. CONCLUSION: Our results show that CMI is also present in healthy individuals but is significantly more disabling in PMS. Furthermore, MRI data point to the existence of an initial mechanism of cerebellar reorganization in PMS with lower interference. Subsequently, the failure of this mechanism due to the progression of disability leads to a more evident expression of symptoms.

Brain Connectivity Changes after Osteopathic Manipulative Treatment: A Randomized Manual Placebo-Controlled Trial.

The effects of osteopathic manipulative treatment (OMT) on functional brain connectivity in healthy adults is missing in the literature. To make up for this lack, we applied advanced network analysis methods to analyze resting state functional magnetic resonance imaging (fMRI) data, after OMT and Placebo treatment (P) in 30 healthy asymptomatic young participants randomized into OMT and placebo groups (OMTg; Pg). fMRI brain activity measures, performed before (T0), immediately after (T1) and three days after (T2) OMT or P were used for inferring treatment effects on brain circuit functional organization. Repeated measures ANOVA and post-hoc analysis demonstrated that Right Precentral Gyrus (F (2, 32) = 5.995, p < 0.005) was more influential over the information flow immediately after the OMT, while decreased betweenness centrality in Left Caudate (F (2, 32) = 6.496, p < 0.005) was observable three days after. Clustering coefficient showed a distinct time-point and group effect. At T1, reduced neighborhood connectivity was observed after OMT in the Left Amygdala (L-Amyg) (F (2, 32) = 7.269, p < 0.005) and Left Middle Temporal Gyrus (F (2, 32) = 6.452, p < 0.005), whereas at T2 the L-Amyg and Vermis-III (F (2, 32) = 6.772, p < 0.005) increased functional interactions. Data demonstrated functional connectivity re-arrangement after OMT.

Rates of depression and anxiety in Italian patients with cystic fibrosis and parent caregivers: Implementation of the Mental Health Guidelines.

BACKGROUND: Individuals with chronic respiratory conditions are at-risk for depression and anxiety. In the largest mental health screening study of over 6000 people with cystic fibrosis (CF) and 4000 parent caregivers (TIDES, 2014), rates of symptomatology were two to three times higher than in the general population. International guidelines recommend annual screening of mental health. This is the first study to implement these guidelines in one of the largest CF Centers in Italy. METHODS: All individuals with CF, 12 and older (n = 167) and caregivers of children with CF (n = 186), birth to 18, were screened. Health outcome data were also collected (i.e FEV1, BMI, pulmonary exacerbations, CF-related diabetes). Prevalence data and associations between psychological symptoms and health outcomes were examined. RESULTS: A high percentage of patients and parent caregivers reported scored above the clinical cut-off for depression and anxiety (37%-48% of adolescents, 45%-46% of adults, 49%-66% of mothers and fathers). Most scores fell in the mild range, however, over 30% were in the moderate to severe range. Elevations in depression and anxiety were correlated. Adolescents who had more pulmonary exacerbations reported higher anxiety. Adults with recent events of hemoptysis reported higher symptoms of depression. CONCLUSIONS: Symptoms of depression and anxiety were elevated in both individuals with CF and parents. Implementation of mental health screening was critical for identifying those in need of psychological interventions. These results strongly suggest that mental health should be integrated into physical health care for those with complex, chronic respiratory conditions, including COPD, PCD.

Cerebral Perfusion Changes After Osteopathic Manipulative Treatment: A Randomized Manual Placebo-Controlled Trial.

Osteopathic Manipulative Treatment (OMT) is a therapeutic approach aimed at enhancing the body's self-regulation focusing on somatic dysfunctions correction. Despite evidence of OMT effectiveness, the underlying neurophysiological mechanisms, as well as blood perfusion effects, are still poorly understood. The study aim was to address OMT effects on cerebral blood flow (CBF) in asymptomatic young volunteers as measured by Magnetic Resonance Arterial Spin Labeling (ASL) method. Thirty blinded participants were randomized to OMT or placebo, and evaluated with an MRI protocol before manual intervention (T0), immediately after (T1), and 3 days later (T2). After T0 MRI, participants received 45 min of OMT, focused on correcting whole body somatic dysfunctions, or placebo manual treatment, consisting of passive touches in a protocolled order. After treatment, participants completed a de-blinding questionnaire about treatment perception. Results show significant differences due to treatment only for the OMT group (OMTg): perfusion decreased (compared to T0) in a cluster comprising the left posterior cingulate cortex (PCC) and the superior parietal lobule, while increased at T2 in the contralateral PCC. Furthermore, more than 60% of participants believed they had undergone OMT. The CBF modifications at T2 suggest that OMT produced immediate but reversible effects on CBF.

Left hemispatial neglect and overt orienting in naturalistic conditions: Role of high-level and stimulus-driven signals.

Deficits of visuospatial orienting in brain-damaged patients affected by hemispatial neglect have been extensively investigated. Nonetheless, spontaneous spatial orienting in naturalistic conditions is still poorly understood. Here, we investigated the role played by top-down and stimulus-driven signals in overt spatial orienting of neglect patients during free-viewing of short videos portraying everyday life situations. In Experiment 1, we assessed orienting when meaningful visual events competed on the left and right side of space, and tested whether sensory salience on the two sides biased orienting. In Experiment 2, we examined whether the spatial alignment of visual and auditory signals modulates orienting. The results of Experiment 1 showed that in neglect patients severe deficits in contralesional orienting were restricted to viewing conditions with bilateral visual events competing for attentional capture. In contrast, orienting towards the contralesional side was largely spared when the videos contained a single event on the left side. In neglect patients the processing of stimulus-driven salience was relatively spared and helped orienting towards the left side when multiple events were present. Experiment 2 showed that sounds spatially aligned with visual events on the left side improved orienting towards the otherwise neglected hemispace. Anatomical scans indicated that neglect patients suffered grey and white matter damages primarily in the ventral frontoparietal cortex. This suggests that the improvement of contralesional orienting associated with visual salience and audiovisual spatial alignment may be due to processing in the relatively intact dorsal frontoparietal areas. Our data show that in naturalistic environments, the presence of multiple meaningful events is a major determinant of spatial orienting deficits in neglect patients, whereas the salience of visual signals and the spatial alignment between auditory and visual signals can counteract spatial orienting deficits. These results open new perspectives to develop novel rehabilitation strategies based on the use of naturalistic stimuli.

Disruption of neurite morphology parallels MS progression.

OBJECTIVES: To apply advanced diffusion MRI methods to the study of normal-appearing brain tissue in MS and examine their correlation with measures of clinical disability. METHODS: A multi-compartment model of diffusion MRI called neurite orientation dispersion and density imaging (NODDI) was used to study 20 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 20 healthy controls. Maps of NODDI were analyzed voxel-wise to assess the presence of abnormalities within the normal-appearing brain tissue and the association with disease severity. Standard diffusion tensor imaging (DTI) parameters were also computed for comparing the 2 techniques. RESULTS: Patients with MS showed reduced neurite density index (NDI) and increased orientation dispersion index (ODI) compared with controls in several brain areas (p < 0.05), with patients with SPMS having more widespread abnormalities. DTI indices were also sensitive to some changes. In addition, patients with SPMS showed reduced ODI in the thalamus and caudate nucleus. These abnormalities were associated with scores of disease severity (p < 0.05). The association with the MS functional composite score was higher in patients with SPMS compared with patients with RRMS. CONCLUSIONS: NODDI and DTI findings are largely overlapping. Nevertheless, NODDI helps interpret previous findings of increased anisotropy in the thalamus of patients with MS and are consistent with the degeneration of selective axon populations.

Whole brain white matter histogram analysis of diffusion tensor imaging data detects microstructural damage in mild cognitive impairment and alzheimer's disease patients.

BACKGROUND: Amnestic mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD). However, the clinical conversion from MCI to AD is unpredictable. Hence, identification of noninvasive biomarkers able to detect early changes induced by dementia is a pressing need. PURPOSE: To explore the added value of histogram analysis applied to measures derived from diffusion tensor imaging (DTI) for detecting brain tissue differences between AD, MCI, and healthy subjects (HS). STUDY TYPE: Prospective. POPULATION/SUBJECTS: A local cohort (57 AD, 28 MCI, 23 HS), and an Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (41 AD, 58 MCI, 41 HS). FIELD STRENGTH: 3T. Dual-echo turbo spin echo (TSE); fluid-attenuated inversion recovery (FLAIR); modified-driven-equilibrium-Fourier-transform (MDEFT); inversion-recovery spoiled gradient recalled (IR-SPGR); diffusion tensor imaging (DTI). ASSESSMENT: Normal-appearing white matter (NAWM) masks were obtained using the T1 -weighted volumes for tissue segmentation and T2 -weighted images for removal of hyperintensities/lesions. From DTI images, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AXD), and radial diffusivity (RD) were obtained. NAWM histograms of FA, MD, AXD, and RD were derived and characterized estimating: peak height, peak location, mean value (MV), and quartiles (C25, C50, C75), which were compared between groups. Receiver operating characteristic (ROC) and area under ROC curves (AUC) were calculated. To confirm our results, the same analysis was repeated on the ADNI dataset. STATISTICAL TESTS: One-way analysis of variance (ANOVA), post-hoc Student's t-test, multiclass ROC analysis. RESULTS: For the local cohort, C25 of AXD had the maximum capability of group discrimination with AUC of 0.80 for "HS vs. patients" comparison and 0.74 for "AD vs. others" comparison. For the ADNI cohort, MV of AXD revealed the maximum group discrimination capability with AUC of 0.75 for "HS vs. patients" comparison and 0.75 for "AD vs. others" comparison. DATA CONCLUSION: AXD of NAWM might be an early marker of microstructural brain tissue changes occurring during the AD course and might be useful for assessing disease progression. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

Introducing axonal myelination in connectomics: A preliminary analysis of g-ratio distribution in healthy subjects.

Microstructural imaging and connectomics are two research areas that hold great potential for investigating brain structure and function. Combining these two approaches can lead to a better and more complete characterization of the brain as a network. The aim of this work is characterizing the connectome from a novel perspective using the myelination measure given by the g-ratio. The g-ratio is the ratio of the inner to the outer diameters of a myelinated axon, whose aggregated value can now be estimated in vivo using MRI. In two different datasets of healthy subjects, we reconstructed the structural connectome and then used the g-ratio estimated from diffusion and magnetization transfer data to characterize the network structure. Significant characteristics of g-ratio weighted graphs emerged. First, the g-ratio distribution across the edges of the graph did not show the power-law distribution observed using the number of streamlines as a weight. Second, connections involving regions related to motor and sensory functions were the highest in myelin content. We also observed significant differences in terms of the hub structure and the rich-club organization suggesting that connections involving hub regions present higher myelination than peripheral connections. Taken together, these findings offer a characterization of g-ratio distribution across the connectome in healthy subjects and lay the foundations for further investigating plasticity and pathology using a similar approach.

Damage to the Frontal Aslant Tract Accounts for Visuo-Constructive Deficits in Alzheimer's Disease.

The frontal aslant tract (FAT) has been described as a bundle connecting the Broca's area to the supplementary motor area (SMA) and the pre-SMA in both hemispheres. The functional properties of this tract and its role in degenerative dementia, such as Alzheimer's disease (AD), still need to be fully clarified. The aim of this study was to explore the microstructural integrity of the FAT in patients with AD and its potential relationship with cognitive functioning. Twenty-three patients with AD and 25 healthy subjects (HS) were enrolled. All subjects underwent cognitive and MRI examination. MRI, including diffusion sequences, was used for probabilistic tractography analysis. We reconstructed individual FATs bilaterally and assessed their microstructural integrity using fractional anisotropy (FA), computed as both mean tract value and voxel-wise using SPM-8. Mean FA values were then used to test for correlations with cognitive measures. Mean tract FA and voxel-wise analyses revealed that patients with AD, compared to HS, had decreased FA in the FAT bilaterally. In addition, positive associations were found between FA in the FATs and patients' performance at tests for constructional praxis and visuospatial logical reasoning. The present results reveal a bilateral damage of FAT in AD patients. The association between FATs' microscopic abnormalities and constructive abilities fits well with the knowledge of a functional involvement of SMA and pre-SMA in movement sequences when executing constructive praxis tasks. The FAT is an associative bundle critically involved in the network sub-serving constructional praxis in patients with AD.

Cognitive reserve and cognitive performance of patients with focal frontal lesions.

The Cognitive reserve (CR) hypothesis was put forward to account for the variability in cognitive performance of patients with similar degrees of brain pathology. Compensatory neural activity within the frontal lobes has often been associated with CR. For the first time we investigated the independent effects of two CR proxies, education and NART IQ, on measures of executive function, fluid intelligence, speed of information processing, verbal short term memory (vSTM), naming, and perception in a sample of 86 patients with focal, unilateral frontal lesions and 142 healthy controls. We fitted multiple linear regression models for each of the cognitive measures and found that only NART IQ predicted executive and naming performance. Neither education nor NART IQ predicted performance on fluid intelligence, processing speed, vSTM or perceptual abilities. Education and NART IQ did not modify the effect of lesion severity on cognitive impairment. We also found that age significantly predicted performance on executive tests and the majority of our other cognitive measures, except vSTM and GNT. Age was the only predictor for fluid intelligence. This latter finding suggests that age plays a role in executive performance over and above the contribution of CR proxies in patients with focal frontal lesions. Overall, our results suggest that the CR proxies do not appear to modify the relationship between cognitive impairment and frontal lesions.

CSF ß-amyloid as a putative biomarker of disease progression in multiple sclerosis.

BACKGROUND: Neurodegeneration plays a major role in determining disability in multiple sclerosis (MS) patients. Hence, there is increasing need to identify reliable biomarkers, which could serve as prognostic measure of disease progression. OBJECTIVES: To assess whether cerebrospinal fluid (CSF) tau and ß-amyloid (Aß) levels were altered in newly diagnosed MS patients and correlated with disability. Moreover, we investigated whether these CSF biomarkers associate with macroscopic brain tissue damage measures. METHODS: CSF Aß and tau levels were determined by enzyme-linked immunosorbent assay in CSF samples from 48 newly diagnosed MS patients, followed-up clinically for 3 years by recording their Expanded Disability Status Scale score at 6-month intervals, and 45 controls. All patients underwent magnetic resonance imaging at baseline and at the end of follow-up to quantify their lesion load (LL). RESULTS: CSF Aß levels were significantly reduced in patients compared to controls ( p < 0.001). Lower CSF Aß levels at baseline were a disability predictor at 3-year follow-up ( p = 0.009). CSF tau levels correlated with T2- and T1-LL ( p < 0.001). CONCLUSION: CSF Aß reduction is a promising biomarker of neurodegeneration and may predict patients' clinical outcome. Therefore, CSF Aß should be considered as a potential biomarker of prognostic value.

Network-Based Substrate of Cognitive Reserve in Alzheimer's Disease.

Cognitive reserve (CR) is known to modulate the clinical features of Alzheimer's disease (AD). This concept may be critical for the development of non-pharmacological interventions able to slow down patients' cognitive decline in the absence of disease-modifying treatments. We aimed at identifying the neurobiological substrates of CR (i.e., neural reserve) over the transition between normal aging and AD, by assessing the underlying brain networks and their topological properties. A cohort of 154 participants (n = 68 with AD, n = 61 with amnestic mild cognitive impairment (aMCI), and 25 healthy subjects) underwent resting-state functional MRI and neuropsychological testing. Within each group, participants were classified as having high or low CR, and functional connectivity measures were compared, within group, between high and low CR individuals. Network-based statistics and topological network properties derived from graph theory were explored. Connectivity differences between high and low CR were evident only for aMCI patients, with participants with high CR showing a significant increase of connectivity in a network involving mainly fronto-parietal nodes. Conversely, they showed significantly decreased connectivity in a network involving fronto-temporo-cerebellar nodes. Consistently, changes to topological measures were observed in either direction, and were associated with measures of global cognitive function. These findings support the hypothesis that CR impacts on neurodegenerative process in the early phase of AD only. In addition, they fit with the existence of a "neural reserve", characterized by specific neural networks and their efficiency. It remains to be demonstrated whether interventions later in life can modulate this "neural reserve".

Inhibition processes are dissociable and lateralized in human prefrontal cortex.

The prefrontal cortex (PFC) is known to make fundamental contributions to executive functions. However, the precise nature of these contributions is incompletely understood. We focused on a specific executive function, inhibition, the ability to suppress a pre-potent response. Functional imaging and animal studies have studied inhibition. However, there are only few lesion studies, typically reporting discrepant findings. For the first time, we conducted cognitive and neuroimaging investigations on patients with focal unilateral PFC lesions across two widely used inhibitory tasks requiring a verbal response: The Hayling Part 2 and Stroop Colour-Word Tests. We systematically explored the relationship between inhibition, fluid intelligence and lesion location using voxel-based lesion symptom mapping (VLSM). We found that PFC patients were significantly impaired compared with healthy comparison group (HC) on both suppression measures of the Hayling and on the Stroop, even when performance on a fluid intelligence test was covaried. No significant relationship was found between patients' performance on each Hayling suppression measure and the Stroop, once fluid intelligence was partialled out, suggesting that the two tests may involve different kinds of inhibition. After accounting for fluid intelligence, we found a significant interaction between tests, Hayling or Stroop, and site, left or right, of PFC damage. This finding suggesting lateralized functional organization was complemented and extended by our VLSM results. We found that performance on both Hayling suppression measures significantly relied on the integrity of a similar and relatively circumscribed region within the right lateral PFC, in the right lateral superior and middle frontal gyri. In stark contrast, performance on the Stroop relies on the integrity of left lateral superior and middle frontal gyri. Thus, lesion location, right or left PFC, is critical in producing impairments on two inhibitory tasks loading similarly on verbal control. This suggests that the two suppression measures of the Hayling and the Stroop are likely to assess dissociable components of executive functions, related to anatomically defined and lateralized PFC circuits. Our findings also suggest that inhibition may actually comprise qualitatively different forms with different neural substrates. This has clinical implications for the diagnosis and treatment of disinhibition impairments, a common behavioural problem caused by PFC lesions. Our results highlight the need to assess inhibition using a variety of tasks and to develop different types of treatments.