Impact of Anatomical Variability on Sensitivity Profile in fNIRS-MRI Integration

Functional near-infrared spectroscopy (fNIRS) is an important non-invasive technique used to monitor cortical activity. However, a varying sensitivity of surface channels vs. cortical structures may suggest integrating the fNIRS with the subject-specific anatomy (SSA) obtained from routine MRI. Actual processing tools permit the computation of the SSA forward problem (i.e., cortex to channel sensitivity) and next, a regularized solution of the inverse problem to map the fNIRS signals onto the cortex. The focus of this study is on the analysis of the forward problem to quantify the effect of inter-subject variability. Thirteen young adults (six males, seven females, age 29.3 +/- 4.3) underwent both an MRI scan and a motor grasping task with a continuous wave fNIRS system of 102 measurement channels with optodes placed according to a 10/5 system. The fNIRS sensitivity profile was estimated using Monte Carlo simulations on each SSA and on three major atlases (i.e., Colin27, ICBM152 and FSAverage) for comparison. In each SSA, the average sensitivity curves were obtained by aligning the 102 channels and segmenting them by depth quartiles. The first quartile (depth < 11.8 (0.7) mm, median (IQR)) covered 0.391 (0.087)% of the total sensitivity profile, while the second one (depth < 13.6 (0.7) mm) covered 0.292 (0.009)%, hence indicating that about 70% of the signal was from the gyri. The sensitivity bell-shape was broad in the source-detector direction (20.953 (5.379) mm FWHM, first depth quartile) and steeper in the transversal one (6.082 (2.086) mm). The sensitivity of channels vs. different cortical areas based on SSA were analyzed finding high dispersions among subjects and large differences with atlas-based evaluations. Moreover, the inverse cortical mapping for the grasping task showed differences between SSA and atlas based solutions. In conclusion, integration with MRI SSA can significantly improve fNIRS interpretation

Multistimulation Group Therapy in Alzheimer’s Disease Promotes Changes in Brain Functioning

Background The growing social emergency represented by Alzheimer’s disease (AD) and the lack of medical treatments able to modify the disease course have kindled the interest in nonpharmacological therapies. Objective We introduced a novel nonpharmacological approach for people with AD (PWA) named Multidimensional Stimulation group Therapy (MST) to improve PWA condition in different disease domains: cognition, behavior, and motor functioning. Methods. Enrolling 60 PWA in a mild to moderate stage of the disease, we evaluated the efficacy of MST with a randomized-controlled study. Neuropsychological and neurobehavioral measures and functional magnetic resonance imaging (fMRI) data were considered as outcome measures. Results The following significant intervention-related changes were observed: reduction in Neuropsychiatric Inventory scale score, improvement in language and memory subscales of Alzheimer’s Disease Assessment Scale–Cognitive subscale, and increased fMRI activations in temporal brain areas, right insular cortex, and thalamus. Conclusions Cognitive-behavioral and fMRI results support the notion that MST has significant effects in improving PWA cognitive-behavioral status by restoring neural functioning

High-Dimensional ICA Analysis Detects Within-Network Functional Connectivity Damage of Default-Mode and Sensory-Motor Networks in Alzheimer’s Disease

High-dimensional independent component analysis (ICA), compared to low-dimensional ICA, allows to conduct a detailed parcellation of the resting-state networks. The purpose of this study was to give further insight into functional connectivity (FC) in Alzheimer's disease (AD) using high-dimensional ICA. For this reason, we performed both low- and high-dimensional ICA analyses of resting-state fMRI data of 20 healthy controls and 21 patients with AD, focusing on the primarily altered default-mode network (DMN) and exploring the sensory-motor network. As expected, results obtained at low dimensionality were in line with previous literature. Moreover, high-dimensional results allowed us to observe either the presence of within-network disconnections and FC damage confined to some of the resting-state subnetworks. Due to the higher sensitivity of the high-dimensional ICA analysis, our results suggest that high-dimensional decomposition in subnetworks is very promising to better localize FC alterations in AD and that FC damage is not confined to the DMN

Surface-based integration approach for fNIRS-fMRI reliability assessment

Introduction: Studies integrating functional near-infrared spectroscopy (fNIRS) with functional MRI (fMRI) employ heterogeneous methods in defining common regions of interest in which similarities are assessed. Therefore, spatial agreement and temporal correlation may not be reproducible across studies. In the present work, we address this issue by proposing a novel method for integration and analysis of fNIRS and fMRI over the cortical surface. Materials and methods: Eighteen healthy volunteers (age mean±SD 30.55 ± 4.7, 7 males) performed a motor task during non-simultaneous fMRI and fNIRS acquisitions. First, fNIRS and fMRI data were integrated by projecting subject- and group-level source maps over the cortical surface mesh to define anatomically constrained functional ROIs (acfROI). Next, spatial agreement and temporal correlation were quantified as Dice Coefficient (DC) and Pearson's correlation coefficient between fNIRS-fMRI in the acfROIs. Results: Subject-level results revealed moderate to substantial spatial agreement (DC range 0.43 - 0.64), confirmed at the group-level only for blood oxygenation level-dependent (BOLD) signal vs. HbO2 (0.44 - 0.69), while lack of agreement was found for BOLD vs. HbR in some instances (0.05 - 0.49). Subject-level temporal correlation was moderate to strong (0.79 - 0.85 for BOLD vs. HbO2 and -0.62 to -0.72 for BOLD vs. HbR), while an overall strong correlation was found for group-level results (0.95 - 0.98 for BOLD vs. HbO2 and -0.91 to -0.94 for BOLD vs. HbR). Conclusion: The proposed method directly compares fNIRS and fMRI by projecting individual source maps to the cortical surface. Our results indicate spatial and temporal correspondence between fNIRS and fMRI, and promotes the use of fNIRS when more ecological acquision settings are required, such as longitudinal monitoring of brain activity before and after rehabilitation

Real-Time Phase-Contrast MRI to Monitor Cervical Blood and Cerebrospinal Fluid Flow Beat-by-Beat Variability

Beat-by-beat variability (BBV) rhythms are observed in both cardiovascular (CV) and intracranial (IC) compartments, yet interactions between the two are not fully understood. Real-Time Phase-Contrast (RT-PC) MRI sequence was acquired for 30 healthy volunteers at 1st cervical level on a 3T scanner. The arterial (AF), venous (VF), and cerebrospinal fluid (CSF) flow (CSFF) were computed as velocity integrals over the internal carotid artery, internal jugular vein, and CSF. AF, VF, and CSFF signals were segmented in inspiration and expiration beats, to assess the respiration influence. Systolic and diastolic BBV, and heart period series underwent autoregressive power spectral density analysis, to evaluate the low-frequency (LF, Mayer waves) and high frequency (HF, respiratory waves) components. The diastolic VF had the largest BBV. LF power was high in the diastolic AF series, poor in all CSFF series. The pulse wave analyses revealed higher mean amplitude during inspiration. Findings suggests a possible role of LF modulation of IC resistances and propagation of HF waves from VF to AF and CCSF. PC-RT-MRI could provide new insight into the interaction between CV and IC regulation and pave the way for a detailed analysis of the cerebrovascular effects of varied respiration patterns due to exercise and rehabilitation

Social Mind and Long-Lasting Disease: Focus on Affective and Cognitive Theory of Mind in Multiple Sclerosis

The role of social cognition, including theory of mind (ToM), in affecting quality of life (QoL) along the course of diseases has been reported. This is a considerable aspect in chronic pathologies, such as multiple sclerosis (MS), in which supporting and maintaining QoL is of crucial importance. We aimed to investigate the relation between ToM, clinical variables and neuropsychological profile in a cohort of adults with long lasting disease, such as different clinical MS phenotypes (Relapsing Remitting -RR- versus Progressive -Pr). In particular, our study focuses on (1) how (affective and cognitive) ToM impairment occurs in different phenotypes, (2) whether MS ToM impairment is secondary to or independent from cognitive deficit and (3) whether ToM deficit impacts QoL. 42 adults with MS (18 M: 24 F, 52.38 10.31 mean age, 21.24 10.94 mean disease duration, 26 RR and 16 Pr) and 26 matched healthy controls (HC) (7 M: 19 F, 51.35 12.42 mean age) were screened with a neuropsychological and ToM battery, assessing both affective and cognitive components. We found statistically significant groups differences in cognitive but not affective ToM, with a lower performance in PrMS than those with a RRMS disease course. Also, significant predictive effects of neuropsychological tests on ToM were identified in MS group. Finally, MS people with different level of affective ToM differed significantly in QoL. ToM deficit in moderately disabled people with MS involves cognitive but not affective ToM components with implications on QoL. It also appears to be related to cognitive performance. As neurological and neurocognitive profiles influence mentalizing in MS, ToM evaluation should be considered for inclusion in clinical screening

SNAP-25 Single Nucleotide Polymorphisms, Brain Morphology and Intelligence in Children With Borderline Intellectual Functioning: A Mediation Analysis

Borderline intellectual functioning (BIF) is a multifactorial condition in which both genetic and environmental factors are likely to contribute to the clinical outcome. Abnormal cortical development and lower IQ scores were shown to be correlated in BIF children, but the genetic components of this condition and their possible connection with intelligence and brain morphology have never been investigated in BIF. The synaptosomal-associated protein of 25 kD (SNAP-25) is involved in synaptic plasticity, neural maturation, and neurotransmission, affecting intellectual functioning. We investigated SNAP-25 polymorphisms in BIF and correlated such polymorphisms with intelligence and cortical thickness, using socioeconomic status and environmental stress as covariates as a good proxy of the variables that determine intellectual abilities. Thirty-three children with a diagnosis of BIF were enrolled in the study. SNAP-25 polymorphisms rs363050, rs363039, rs363043, rs3746544, and rs1051312 were analyzed by genotyping; cortical thickness was studied by MRI; intelligence was measured using the WISC-III/IV subscales; environmental stressors playing a role in neuropsychiatric development were considered as covariate factors. Results showed that BIF children carrying the rs363043(T) minor allele represented by (CT C TT) genotypes were characterized by lower performance Perceptual Reasoning Index and lower full-scale IQ scores (p = 0.04) compared to those carrying the (CC) genotype. This association was correlated with a reduced thickness of the left inferior parietal cortex (direct effect = 0.44) and of the left supramarginal gyrus (direct effect = 0.56). These results suggest a link between SNAP-25 polymorphism and intelligence with the mediation role of brain morphological features in children with BIF

Italian adaptation of the Edinburgh Social Cognition Test (ESCoT):A new tool for the assessment of theory of mind and social norm understanding

The relevance of social cognition assessment has been formally described in the Diagnostic and Statistical Manual of Mental Disorders-5. However, social cognition tools evaluating different socio-cognitive components for Italian-speaking populations are lacking. The Edinburgh Social Cognition Test (ESCoT) is a new social cognition measure that uses animations of everyday social interactions to assess (i) cognitive theory of mind, (ii) affective theory of mind, (iii) interpersonal social norm understanding, and (iv) intrapersonal social norm understanding. Previous studies have shown that the ESCoT is a sensitive measure of social cognition in healthy and clinical populations in the United Kingdom. This work aimed to adapt and validate the ESCoT in an Italian population of healthy adults. A translation-back-translation procedure was followed to create and refine the Italian version. Then, 94 healthy adults (47 females, mean age  35 ± 15.9) completed the ESCoT, a battery of conventional social cognition tests (Yoni; Reading the Mind in the Eyes Strange Stories, and Social Norm Questionnaire, SNQ) and measures of intelligence and executive functions. Reliability, convergent validity, and predictors of performance on the ESCoT were examined. Results demonstrated good reliability of the ESCoT and an association between the ESCoT scores and some traditional social cognition tests (Yoni cognitive subscale, SNQ). Hierarchical regression results showed that the ESCoT total score was associated with age. Also, the ESCoT subscore (intrapersonal social norm understanding) was associated with education. These findings support the ESCoT as a valid tool testing social norm understanding, a reliable measure of social cognition for an adult Italian population, and provides further evidence that the ESCoT is sensitive to age- and education-related changes in social cognition, and it is a task not affected by general cognitive functioning