Prognostic Role of Hemispherical Functional Connectivity in Stroke: A Study via Graph Theory Versus Coherence of Electroencephalography Rhythms.

BACKGROUND: The objective of the present study is to explore whether acute stroke may result in changes in brain network architecture by electroencephalography functional coupling analysis and graph theory. METHODS: Ninety acute stroke patients and 110 healthy subjects were enrolled in different clinical centers in Rome, Italy, starting from 2013, and for each one electroencephalographies were recorded within <15 days from stroke onset. All patients were clinically evaluated through National Institutes of Health Stroke Scale, Barthel Index, and Action Research Arm Test in the acute stage and during the follow-up. Functional connectivity was assessed using Total Coherence and Small World (SW) by comparing the affected and the unaffected hemisphere between groups (Stroke versus Healthy). Correlations between connectivity and poststroke recovery scores have been carried out. RESULTS: In stroke patients, network hemispheric asymmetry, in terms of Total Coherence, was mainly detected in the affected hemisphere with lower values in Delta, Theta, Alpha1, and Alpha2 (P=0.000001), whereas the unaffected hemisphere showed lower Total Coherence only in Delta and Theta (P=0.000001). SW revealed a significant difference only in the affected hemisphere in all electroencephalography bands (lower SW in Delta (P=0.000003), Theta (P=0.000003), Alpha1 (P=0.000203), and Alpha2 (P=0.028) and higher SW in Beta2 (P=0.000002) and Gamma (P=0.000002)). We also found significant correlations between SW and improvement in National Institutes of Health Stroke Scale (Theta SW: r=-0.2808), Barthel Index (Delta SW: r=0.3692; Theta SW: r=0.3844, Beta2 SW: r=-0.3589; Gamma SW: r=-04948), and Action Research Arm Test (Beta2 SW: r=-0.4274; Gamma SW: r=-0.4370). CONCLUSIONS: These findings demonstrated changes in global functional connectivity and in the balance of network segregation and integration induced by acute stroke. The findings on the correlations between clinical outcome(s) and poststroke network architecture indicate the possibility to identify a predictive index of recovery useful to address and personalize the rehabilitation program.

Unravelling neurotransmitters impairment in primary progressive aphasias.

Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases mainly characterized by language impairment, and with variably presence of dysexecutive syndrome, behavioural disturbances and parkinsonism. Detailed knowledge of neurotransmitters impairment and its association with clinical features hold the potential to develop new tailored therapeutic approaches. In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of magnetic resonance imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission. We included 103 PPA patients and 80 age-matched healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in PPA patients (relative to HC) are correlated with specific neurotransmitter systems. As compared to HC, voxel-based brain changes in PPA were significantly associated with spatial distribution of serotonin, dopamine, and glutamatergic pathways (p < .05, False Discovery Rate corrected-corrected). Disease severity was negatively correlated with the strength of GMV colocalization of D1 receptors (p = .035) and serotonin transporter (p = .020). Moreover, we observed a significant negative correlation between positive behavioural symptoms, as measured with Frontal Behavioural Inventory, and GMV colocalization of D1 receptors (p = .007) and serotonin transporter (p < .001). This pilot study suggests that JuSpace is a helpful tool to indirectly assess neurotransmitter deficits in neurodegenerative dementias and may provide novel insight into disease mechanisms and associated clinical features.

The Effects of Directional and Non-Directional Stimuli during a Visuomotor Task and Their Correlation with Reaction Time: An ERP Study.

Different visual stimuli can capture and shift attention into different directions. Few studies have explored differences in brain response due to directional (DS) and non-directional visual stimuli (nDS). To explore the latter, event-related potentials (ERP) and contingent negative variation (CNV) during a visuomotor task were evaluated in 19 adults. To examine the relation between task performance and ERPs, the participants were divided into faster (F) and slower (S) groups based on their reaction times (RTs). Moreover, to reveal ERP modulation within the same subject, each recording from the single participants was subdivided into F and S trials based on the specific RT. ERP latencies were analysed between conditions ((DS, nDS); (F, S subjects); (F, S trials)). Correlation was analysed between CNV and RTs. Our results reveal that the ERPs' late components are modulated differently by DS and nDS conditions in terms of amplitude and location. Differences in ERP amplitude, location and latency, were also found according to subjects' performance, i.e., between F and S subjects and trials. In addition, results show that the CNV slope is modulated by the directionality of the stimulus and contributes to motor performance. A better understanding of brain dynamics through ERPs could be useful to explain brain states in healthy subjects and to support diagnoses and personalized rehabilitation in patients with neurological diseases.

Transcranial direct current stimulation applied after encoding facilitates episodic memory consolidation in older adults.

Episodic memory shows the largest degree of age-related memory decline. There is evidence that consolidation, the process that stabilizes memories after encoding, is reduced in older adults. Previous studies have shown that transcranial direct current stimulation (tDCS) applied during intentional encoding or immediately after a contextual reminder enhanced delayed episodic memory performance, suggesting a potential interaction between tDCS and consolidation or reconsolidation processes. The present randomized, double-blind, sham-controlled study addressed the question whether tDCS applied immediately after verbal encoding enhances episodic memory recall through consolidation in healthy older adults. Twenty-eight participants received tDCS (Active or Sham) over the prefrontal cortex (anode over the left dorsolateral prefrontal cortex and cathode over the contralateral supraorbital region), a brain region contributing to episodic memory function. Verbal recall was tested two days and one month later. The results showed that recall performance at one month was enhanced in the Active tDCS group relative to the Sham group. These findings suggest that tDCS applied off-line immediately after encoding over the prefrontal cortex interacts with the processes promoting consolidation of episodic memories in healthy older adults. Targeting consolidation by means of tDCS might be a novel strategy for reducing episodic memory decline.

Enhancing theory of mind in behavioural variant frontotemporal dementia with transcranial direct current stimulation.

Behavioural variant frontotemporal dementia (bvFTD) is a form of frontotemporal degeneration characterized by early changes in personality, emotional blunting, and/or loss of empathy. Recent research has highlighted that these features may be at least partially explained by impairments in the theory of mind (ToM; i.e., the ability to understand and predict other people's behaviour by attributing independent mental states to them). The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that transcranial direct current stimulation (tDCS) over the medial frontal cortex (MFC) selectively enhances communicative intention processing, a specific ToM ability. Using a single-session online design, we administered a ToM task that measures the ability to represent other people's private and communicative intentions during active or sham tDCS to 16 bvFTD patients. To assess the impact of dementia on performance on the ToM task, we included 16 age-matched healthy volunteers who were asked to perform the entire experimental ToM task. BvFTD is characterized by an impairment in the comprehension of both communicative and private intentions relative to a healthy control group and by a disproportional impairment in communicative intention compared with private intention processing. Significant and selective accuracy improvement in the comprehension of communicative intentions after active stimulation was observed in patients with bvFTD. This is the first study that analyses ToM ability in patients with bvFTD using tDCS stimulation. Our findings could potentially contribute to the development of an effective, noninvasive brain stimulation treatment of ToM impairments in patients with bvFTD.

Non-Invasive Brain Stimulation in Dementia: A Complex Network Story.

Non-invasive brain stimulation (NIBS) is emerging as a promising rehabilitation tool for a number of neurodegenerative diseases. However, the therapeutic mechanisms of NIBS are not completely understood. In this review, we will summarize NIBS results in the context of brain imaging studies of functional connectivity and metabolites to gain insight into the possible mechanisms underlying recovery. We will briefly discuss how the clinical manifestations of common neurodegenerative disorders may be related with aberrant connectivity within large-scale neural networks. We will then focus on recent studies combining resting-state functional magnetic resonance imaging with NIBS to delineate how stimulation of different brain regions induce complex network modifications, both at the local and distal level. Moreover, we will review studies combining magnetic resonance spectroscopy and NIBS to investigate how microscale changes are related to modifications of large-scale networks. Finally, we will re-examine previous NIBS studies in dementia in light of this network perspective. A better understanding of NIBS impact on the functionality of large-scale brain networks may be useful to design beneficial treatments for neurodegenerative disorders.

Mild cognitive impairment in Parkinson's disease is improved by transcranial direct current stimulation combined with physical therapy.

BACKGROUND: Parkinson'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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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'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. CONCLUSIONS: 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.

Grey Matter Density Predicts the Improvement of Naming Abilities After tDCS Intervention in Agrammatic Variant of Primary Progressive Aphasia.

Agrammatic variant primary progressive aphasia is a neurodegenerative disorder specifically characterized by language deficits. A recent study has demonstrated a beneficial effect of transcranial direct current stimulation (tDCS) in combination with language training on naming accuracy in these patients. The aim of the study was to evaluate whether the improvement of naming accuracy after tDCS during language training was related to regional grey matter (GM) density. Eighteen avPPA patients underwent a brain magnetic resonance imaging before receiving a treatment that consisted of tDCS over the left dorsolateral prefrontal cortex during individualized language training (10 daily therapy sessions, 5 days per week from Monday to Friday). Performances on neuropsychological tests and naming of objects (treated and untreated) and actions were assessed at baseline, post-treatment  and 3 months after treatment. Correlations between individual changes after treatment on neuropsychological tests and on picture naming task and voxel-based GM volume at baseline were performed. We found that the improvement in the naming of treated objects was positively correlated with GM volume in the left fusiform, left middle temporal, and right inferior temporal gyri whereas action naming change was related to GM density in the left middle temporal gyrus. In conclusion baseline density of GM in these brain regions was associated with greater treatment response on naming performances, suggesting that intervention in early disease stages might be most successful. These findings have implication for designing future rehabilitation protocols in language variants of frontotemporal dementia.

Effects of Intranasal Oxytocin on Long-Term Memory in Healthy Humans: A Systematic Review.

Preclinical Research The neuropeptide oxytocin (Oxt) is implicated in complex emotional and social behaviors and appears to play an important role in learning and memory. Animal studies have shown that the effects of exogenous Oxt on memory vary according to the timing of administration, context, gender, and dose and may improve the memory of social, but not nonsocial stimuli. Oxt is intimately involved in a broad array of neuropsychiatric functions and may therefore be a pharmacological target for several psychiatric disorders. This review summarizes the potential effects of Oxt on long-term memory processes in healthy humans based on a PubMed search over the period 1980-2016. The effects of intranasal Oxt on human memory are controversial and the studies included in this review have applied a variety of learning paradigms, in turn producing variable outcomes. Specifically, data on the long-term memory of nonemotional stimuli found no effect or even worsening in memory, while studies using emotional stimuli showed an improvement of long-term memory performance. In conclusion, this review identified a link between long-term memory performance and exogenous intranasal Oxt in humans, although these results still warrant further confirmation in large, multicenter randomized controlled trials. Drug Dev Res 77 : 479-488, 2016. © 2016 Wiley Periodicals, Inc.

Efficacy of semantic-phonological treatment combined with tDCS for verb retrieval in a patient with aphasia.

Recent studies reported enhanced performance on language tasks induced by transcranial direct current stimulation (tDCS) in patients with aphasia. One chronic patient with non-fluent aphasia received 20 sessions of a verb anomia training combined with off-line bihemispheric tDCS applied to the dorsolateral prefrontal cortex (DLPFC) - anodal tDCS over left DLPFC plus cathodal tDCS over right DLPFC. A significant improvement in verb naming was observed at all testing times (4, 12, 24, and 48 weeks from post-entry/baseline testing) for treated and untreated verbs. Our findings show beneficial effects of verb anomia training in combination with tDCS in chronic aphasic patient, suggesting a long-lasting effect of this treatment.

Cognitive reserve predicts episodic memory enhancement induced by transcranial direct current stimulation in healthy older adults.

Episodic memory shows the largest degree of age-related decline. Anodal transcranial Direct Current Stimulation (tDCS) can enhance episodic memory in aging but there is also evidence of response variability even when using identical stimulation parameters. To explore which inter-individual factors (i.e. age, education, encoding performance, cognitive reserve, tDCS group and timing of tDCS application) may directly and/or indirectly modulate verbal memory recall, we used data from our previous tDCS studies that showed enhanced episodic memory recall in 80 healthy older adults. In these studies we used the same paradigm and stimulation parameters but tDCS was applied during different memory stages. Memory recall was tested 48 hours and 30 days after encoding. Univariate regression models showed that tDCS group (Anodal vs. Sham) predicted memory recall, indicating higher scores in the Anodal group than in the Sham group. Encoding performance predicted memory recall in both tDCS groups. Multiple regression models revealed that cognitive reserve, measured with a life experience questionnaire, predicted memory recall only for the Anodal group. Higher cognitive reserve was linked to better memory recall. Accounting for individual differences in cognitive reserve at baseline helps to explain tDCS responsiveness. This knowledge may contribute to optimize its use in older adults.

Microstructural alterations in the locus coeruleus-entorhinal cortex pathway in Alzheimer's disease and frontotemporal dementia.

INTRODUCTION: We investigated in vivo the microstructural integrity of the pathway connecting the locus coeruleus to the transentorhinal cortex (LC-TEC) in patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD). METHODS: Diffusion-weighted MRI scans were collected for 21 AD, 20 behavioral variants of FTD (bvFTD), and 20 controls. Fractional anisotropy (FA), mean, axial, and radial diffusivities (MD, AxD, RD) were computed in the LC-TEC pathway using a normative atlas. Atrophy was assessed using cortical thickness and correlated with microstructural measures. RESULTS: We found (i) higher RD in AD than controls; (ii) higher MD, RD, and AxD, and lower FA in bvFTD than controls and AD; and (iii) a negative association between LC-TEC MD, RD, and AxD, and entorhinal cortex (EC) thickness in bvFTD (all p < 0.050). DISCUSSION: LC-TEC microstructural alterations are more pronounced in bvFTD than AD, possibly reflecting neurodegeneration secondary to EC atrophy. Highlights: Microstructural integrity of LC-TEC pathway is understudied in AD and bvFTD.LC-TEC microstructural alterations are present in both AD and bvFTD.Greater LC-TEC microstructural alterations in bvFTD than AD.LC-TEC microstructural alterations in bvFTD are associated to EC neurodegeneration.

Long-lasting improvements in episodic memory among subjects with mild cognitive impairment who received transcranial direct current stimulation combined with cognitive treatment and telerehabilitation: a multicentre, randomized, active-controlled study.

Background: In recent years, an increasing number of studies have examined the potential efficacy of cognitive training procedures in individuals with normal ageing and mild cognitive impairment (MCI). Objective: The aims of this study were to (i) evaluate the efficacy of the cognitive Virtual Reality Rehabilitation System (VRRS) combined with anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex compared to placebo tDCS stimulation combined with VRRS and (ii) to determine how to prolong the beneficial effects of the treatment. A total of 109 subjects with MCI were assigned to 1 of 5 study groups in a randomized controlled trial design: (a) face-to-face (FTF) VRRS during anodal tDCS followed by cognitive telerehabilitation (TR) (clinic-atDCS-VRRS+Tele@H-VRRS); (b) FTF VRRS during placebo tDCS followed by TR (clinic-ptDCS-VRRS+Tele@H-VRRS); (c) FTF VRRS followed by cognitive TR (clinic-VRRS+Tele@H-VRRS); (d) FTF VRRS followed by at-home unstructured cognitive stimulation (clinic-VRRS+@H-UCS); and (e) FTF cognitive treatment as usual (clinic-TAU). Results: An improvement in episodic memory was observed after the end of clinic-atDCS-VRRS (p < 0.001). We found no enhancement in episodic memory after clinic-ptDCS-VRRS or after clinic-TAU.Moreover, the combined treatment led to prolonged beneficial effects (clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-ptDCS-VRRS+Tele@H-VRRS: p = 0.047; clinic-atDCS-VRRS+Tele@H-VRRS vs. clinic-VRRS+Tele@H-VRRS: p = 0.06). Discussion: The present study provides preliminary evidence supporting the use of individualized VRRS combined with anodal tDCS and cognitive telerehabilitation for cognitive rehabilitation. Clinical trial registration: https://clinicaltrials.gov/study/NCT03486704?term=NCT03486704&rank=1, NCT03486704.

Clinical validity of the Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB) in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. METHODS: One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. RESULTS: Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. CONCLUSIONS: Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

The combination of hyperventilation test and graph theory parameters to characterize EEG changes in mild cognitive impairment (MCI) condition.

Hyperventilation (HV) is a voluntary activity that causes changes in the neuronal firing characteristics noticeable in the electroencephalogram (EEG) signals. HV-related changes have been scribed to modulation of pO2/pCO2 blood contents. Therefore, an HV test is routinely used for highlighting brain abnormalities including those depending to neurobiological mechanisms at the basis of neurodegenerative disorders. The main aim of the present paper is to study the effectiveness of HV test in modifying the functional connectivity from the EEG signals that can be typical of a prodromal state of Alzheimer's disease (AD), the Mild Cognitive Impairment prodromal to Alzheimer condition. MCI subjects and a group of age-matched healthy elderly (Ctrl) were enrolled and subjected to EEG recording during HV, eyes-closed (EC), and eyes-open (EO) conditions. Since the cognitive decline in MCI seems to be a progressive disconnection syndrome, the approach we used in the present study is the graph theory, which allows to describe brain networks with a series of different parameters. Small world (SW), modularity (M), and global efficiency (GE) indexes were computed among the EC, EO, and HV conditions comparing the MCI group to the Ctrl one. All the three graph parameters, computed in the typical EEG frequency bands, showed significant changes among the three conditions, and more interestingly, a significant difference in the GE values between the MCI group and the Ctrl one was obtained, suggesting that the combination of HV test and graph theory parameters should be a powerful tool for the detection of possible cerebral dysfunction and alteration.

A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia (MAINSTREAM): A Study Protocol.

Primary Progressive Aphasia (PPA) is a syndrome due to different neurodegenerative disorders selectively disrupting language functions. PPA specialist care is underdeveloped. There are very few specialists (neurologists, psychiatrists, neuropsychologists, and speech therapists) and few hospital- or community-based services dedicated to the diagnosis and continuing care of people with PPA. Currently, healthcare systems struggle to provide adequate coverage of care that is too often fragmented, uncoordinated, and unresponsive to the needs of people with PPA and their families. Recently, attention has been gained by non-invasive brain stimulation techniques that allow a personalized treatment approach, such as transcranial Direct Current Stimulation (tDCS). The MAINSTREAM trial looks forward to introducing and evaluating therapeutic innovations such as tDCS coupled with language therapy in rehabilitation settings. A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia, MAINSTREAM (ID: 3430931) was registered in the clinicaltrials.gov database (identifier: NCT05730023) on 15 February 2023.

Brain stimulation improves associative memory in an individual with amnestic mild cognitive impairment.

In patients with cognitive deficits, brain stimulation has been shown to restore cognition ( Miniussi et al., 2008 , Brain Stimulation, 1, 326). The aim of this study was to assess whether repetitive Transcranial Magnetic Stimulation (rTMS) could improve memory performance in an individual with amnestic Mild Cognitive Impairment (aMCI). Stimulation of the left parietal cortex increased accuracy in an association memory task, and this improvement was still significant 24 weeks after stimulation began. These findings indicate that rTMS to the left parietal cortex improved memory performance in aMCI.

tDCS-Induced Memory Reconsolidation Effects: Analysis of Prominent Predicting Factors.

Background: Memory impairment is among one of the greatest cognitive complaints in midlife and in old age. Considering the importance of good memory functioning in everyday life, it is crucial to study interventions that can reduce the natural decline in this cognitive function. Transcranial Magnetic Stimulation (TMS) studies have demonstrated that the lateral prefrontal cortex (PFC) plays a causal role in enhancing episodic memory recall through reconsolidation. Using a similar paradigm with transcranial direct current stimulation (tDCS) over the left lateral PFC, facilitation effects were observed in delayed memory retrieval in older adults with subjective memory complaints (SMCs) and amnestic Mild Cognitive Impairment (aMCI). However, it remains unclear which potential factors (i.e., tDCS group, cognitive reserve, education level, diagnosis and encoding performance) directly and/or indirectly modulate the tDCS-induced memory reconsolidation effects. Methods: We reanalyzed data acquired in our previous tDCS studies with 22 SMC and 18 aMCI participants from the perspective of predicting delayed memory retrieval performance. These studies included a learning session on Day 1, a reactivation by a contextual reminder followed by 15 min of tDCS session on Day 2 (24 h after Day 1), and two retrieval sessions (free recall and recognition) tested on Days 3 and 30 (48 h and 30 Days after Day 1). Results: Univariate models showed that tDCS group (sham vs. active) significantly predicted memory recognition (but not free recall), evidenced by higher scores in the active tDCS group than in sham group, confirming our previous results. Encoding performance and diagnosis (SMC vs. aMCI) significantly predicted memory retrieval, suggesting higher performances in individuals with SMC than in those with aMCI. Regarding cognitive reserve, higher leisure time activity subscores significantly predicted better memory recognition. Finally, multiple models did not show any tDCS group × predictor interaction effects, indicating that the effects of the predictors on retrieval occurred irrespective of tDCS group. Conclusion: Our results shed light on predicting factors of episodic memory retrieval in this reconsolidation paradigm in individuals with SMC and aMCI. The findings suggest that multifactorial interventions program may be most promising to slow cognitive decline and delay the onset of dementia.

The relationship between theory of mind and executive functions in major depressive disorders: A review.

Patients suffering from major depressive disorder (MDD) experience difficulties in multiple cognitive and affective abilities. A large body of literature has argued that MDD patients show impaired executive functions (EFs) and deficits in theory of mind (ToM), the ability to infer the mental states of others. However, the relationship between ToM and EFs has been poorly investigated. The aim of this review is to provide an overview of studies that evaluated the association between ToM and EFs in patients with MDD diagnosis. A literature review was conducted to identify all published studies in which ToM and EFs measures were administered to individuals with MDD and in which the relationship between these two domains was investigated. Eleven studies were included, and for each study, we discussed the findings related to ToM, EFs, and the nature of the link between these two aspects. Most of the studies reported that patients with MDD, compared with healthy controls, showed significant impairments in both ToM and EFs abilities. Moreover, this review indicates the presence of a significant association between these two domains in MDD patients, supporting the evidences that executive functioning is important to perform ToM tasks. Although the results that emerged are interesting, the relationship between ToM and EFs in MDD needs further investigation.

Neuroanatomical correlates of screening for aphasia in NeuroDegeneration (SAND) battery in non-fluent/agrammatic variant of primary progressive aphasia.

Background: Non-fluent/agrammatic variant of Primary Progressive Aphasia (avPPA) is primarily characterized by language impairment due to atrophy of the inferior frontal gyrus and the insula cortex in the dominant hemisphere. The Screening for Aphasia in NeuroDegeneration (SAND) battery has been recently proposed as a screening tool for PPA, with several tasks designed to be specific for different language features. Applying multivariate approaches to neuroimaging data and verbal fluency tasks, Aachener Aphasie Test (AAT) naming subtest and SAND data may help in elucidating the neuroanatomical correlates of language deficits in avPPA. Objective: To investigate the neuroanatomical correlates of language deficits in avPPA using verbal fluency tasks, AAT naming subtest and SAND scores as proxies of brain structural imaging abnormalities. Methods: Thirty-one avPPA patients were consecutively enrolled and underwent extensive neuropsychological assessment and MRI scan. Raw scores of verbal fluency tasks, AAT naming subtest, and SAND subtests, namely living and non-living picture naming, auditory sentence comprehension, single-word comprehension, words and non-words repetition and sentence repetition, were used as proxies to explore structural (gray matter volume) neuroanatomical correlates. We assessed univariate (voxel-based morphometry, VBM) as well as multivariate (source-based morphometry, SBM) approaches. Age, gender, educational level, and disease severity were considered nuisance variables. Results: SAND picture naming (total, living and non-living scores) and AAT naming scores showed a direct correlation with the left temporal network derived from SBM. At univariate analysis, the left middle temporal gyrus was directly correlated with SAND picture naming (total and non-living scores) and AAT naming score. When words and non-words repetition (total score) was considered, a direct correlation with the left temporal network (SBM) and with the left fusiform gyrus (VBM) was also evident. Conclusion: Naming impairments that characterize avPPA are related to specific network-based involvement of the left temporal network, potentially expanding our knowledge on the neuroanatomical basis of this neurodegenerative condition.