New Psychometric Evidence of the Grief Impairment Scale (GIS) in People Who Have Experienced the Death of a Loved One From a Network Psychometric Approach in Two Latin American Countries.

This study aimed to evaluate the psychometric properties of the Grief Impairment Scale (GIS) using a network psychometric model. A total of 1048 individuals from Peru and El Salvador participated. A network psychometric model was used to determine internal structure, reliability, and cross-country invariance. The results indicate that the GIS items were grouped into a single network structure through Exploratory Graph Analysis. Reliability was estimated by structural consistency, and it was found that when replicating the network structure within an empirical dimension, a single network structure was consistently obtained, and all items remained stable. Furthermore, the network structure was invariant, thus functioning similarly across the different country groups. In conclusion, the GIS presented solid psychometric evidence of validity based on its internal structure, reliability, and cross-country invariance. Therefore, the GIS is a psychometrically sound measure of functional impairment symptoms due to grief for Peruvian and Salvadoran individuals.

Assessment of Obsessive Thoughts About COVID-19 in 7 Latin American Countries: Structure and Measurement Invariance of the Obsession With COVID-19 Scale.

The present study aimed to evaluate the measurement invariance of the Obsession with COVID-19 Scale (OCS) among seven Latin American countries: Bolivia, Brazil, Cuba, El Salvador, Guatemala, Paraguay, and Uruguay. Although the OCS has been used in several countries and languages, there is a need for approaches that better integrate the cross-cultural equivalence of the scale. A total of 3185 people participated in the study. The results indicated the presence of a unidimensional structure and good reliability indices for the OCS in each country. The alignment method indicated that the OCS is an invariant measure of COVID-19 obsession among the populations of seven Latin American countries. The findings based on IRT analysis indicated that all OCS items had adequate discrimination and difficulty parameters. The findings contribute to the understanding of the internal structure of the scale in different countries at the same time, something that has been pending evaluation.

Topical NSAIDs, intravitreal dexamethasone and peribulbar triamcinolone for pseudophakic macular edema.

BACKGROUND: The purpose of this study is to assess the effectiveness of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids (intravitreal dexamethasone and peribulbar triamcinolone) in treating pseudophakic macular edema (PME). METHODS: Retrospective study of 33 eyes. Variables included best corrected visual acuity (BCVA; logMAR scale) and central retinal thickness (CRT) and central choroidal thickness (CCT) assessed with swept-source OCT. All patients were initially prescribed topical NSAIDs and reevaluated after 2 months. If improvement in BCVA or CRT was noted, topical NSAIDs were continued until resolution. If no improvement was observed at 2 months or subsequent visits, intravitreal dexamethasone implant was performed. Patients who refused intravitreal treatment were offered peribulbar triamcinolone. RESULTS: After treatment with topical NSAIDs for a median of 2 months, BCVA increased significantly from 0.5 to 0.3 while CRT decreased significantly from 435 to 316 µm. PME resolved in 19 of the 33 eyes (57.6%). Of the 14 recalcitrant cases, 13 were treated with corticosteroids. Of these 13 cases, 9 (69.2%) resolved. BCVA increased non-significantly from 0.7 to 0.4. CRT and CCT decreased significantly from 492 to 317 µm and from 204 to 182 µm respectively. CONCLUSIONS: The overall success rate of the treatment algorithm was greater than 80%, a remarkable finding considering that no randomized study has yet been conducted to determine the optimal therapeutic protocol for PME. This is the first study to evaluate choroidal thickness in PME using SS-OCT, which could play a key role in its pathophysiology and provide useful information to improve the management of PME.

Survival in small choroidal melanocytic lesions with risk factors managed by initial observation until detection of tumour growth.

BACKGROUND: The main objective was to describe metastatic and survival rates in patients with small choroidal melanocytic lesions initially managed by observation. METHODS: Retrospective, observational study of consecutive cases recruited from 2001 through 2018, followed for a median (mean, range) of 81.0 (89.3, 10-204) months in a tertiary referral centre for ocular oncology. Seventy-five consecutive patients diagnosed with small choroidal melanocytic lesions with risk factors for growth initially observed and who showed progression during follow-up. Treatment was performed (plaque radiotherapy or enucleation in 96% and 4% of cases, respectively) at detection of tumour growth. RESULTS: Median (mean, range) tumour thickness was 2.2 (2.23, 1.08-3.40) mm, and median maximum basal diameter was 8.5 (8.16, 4-12) mm. At diagnosis, a median (mean, range) of 5 (5.48, 1-8) risk factors for progression were present. Lesions grew at a median (mean, range) rate of 0.42 mm/y (1.12, 0-7.68) in thickness and 1.05 mm/y (3.14, 0-4.8) in maximum diameter. Median (mean, range) time until growth was 17.00 (32.6, 1-161) months post-diagnosis, at which time tumours were treated. Five patients developed local recurrence after brachytherapy requiring enucleation. Four patients developed hepatic metastasis. Melanoma-specific survival was 98% at 5 years (95% CI, 94.2-100%) and 91.6% (95% CI, 82-100%) at 10 and 15 years. CONCLUSION: In small melanocytic lesions with risk factors for growth, initial observation until detection of tumour growth results in a seemingly low risk of metastasis, suggesting that this may be an initial approach to consider in tumours with indeterminate malignant potential.

INTERNAL LIMITING MEMBRANE PEELING VERSUS NONPEELING TO PREVENT EPIRETINAL MEMBRANE DEVELOPMENT IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: A Swept-Source Optical Coherence Tomography Study With a New Postoperative Classification System.

PURPOSE: To determine whether internal limiting membrane peeling in primary rhegmatogenous retinal detachment prevents epiretinal membrane (ERM) development. Secondarily, we propose a classification system for postoperative ERMs. METHODS: Retrospective, interventional, comparative case series. Consecutive eyes with primary rhegmatogenous retinal detachment (n = 140) treated by a single surgeon. The presence of postoperative ERMs was assessed with swept-source optical coherence tomography. RESULTS: An ERM was detected in 26 eyes (46.4%) in the nonpeeling group and in one eye (1.8%) in the internal limiting membrane peeling group (P ≤ 0.001). The median visual acuity significantly improved in both groups (P ≤ 0.001). Inner retinal dimples were observed in 41.1% of eyes in the internal limiting membrane peeling group versus 0% in the nonpeeling group (P ≤ 0.001), and they were not correlated with visual acuity (r = 0.011; P = 0.941). Based on swept-source optical coherence tomography findings, we identified three different types of ERMs: 7 (26.9%) were classified as Type 1, 12 (46.1%) as Type 2, and 7 (26.9%) as Type 3. Superficial retinal plexus deformations observed on optical coherence tomography angiography and en face images were detected in 100% of Type 3 ERMs, 41.6% of Type 2, and 0% of Type 1 (χ = 14.3; P = 0.001). Interestingly, all of the patients who presented these alterations also had metamorphopsia. CONCLUSION: Internal limiting membrane peeling in primary rhegmatogenous retinal detachment seems to prevent postoperative ERM development. Swept-source optical coherence tomography analysis is helpful to define and classify different types of ERMs and to establish the surgical indication for their removal.

Automatic classification of major depression disorder using arterial spin labeling MRI perfusion measurements.

AIM: Neuroimaging-based multivariate pattern-recognition methods have been successfully used to develop diagnostic algorithms to distinguish patients with major depressive disorder (MDD) from healthy controls (HC). We developed and evaluated the accuracy of a multivariate classification method for the differentiation of MDD and HC using cerebral blood flow (CBF) features measured by non-invasive arterial spin labeling (ASL) MRI. METHODS: Twenty-two medication-free patients with the diagnosis of MDD based on DSM-IV criteria and 22 HC underwent pseudo-continuous 3-D-ASL imaging to assess CBF. Using an atlas-based approach, regional CBF was determined in various brain regions and used together with sex and age as classification features. A linear kernel support vector machine was used for feature ranking and selection as well as for the classification of patients with MDD and HC. Permutation testing was used to test for significance of the classification results. RESULTS: The automatic classifier based on CBF features showed a statistically significant accuracy of 77.3% (P = 0.004) with a specificity of 80% and sensitivity of 75% for classification of MDD versus HC. The features that contributed to the classification were sex and regional CBF of the cortical, limbic, and paralimbic regions. CONCLUSION: Machine-learning models based on CBF measurements are capable of differentiating MDD from HC with high accuracy. The use of larger study cohorts and inclusion of other imaging measures may improve the performance of the classifier to achieve the accuracy required for clinical application.

Phytochemical Findings Evidencing Botanical Origin of New Propolis Type from North-West Argentina.

Propolis samples from north-west Argentina (Amaicha del Valle, Tucumán) were evaluated by palynology, FT-IR spectra, and RP-HPTLC. In addition, the volatile fraction was studied by HS-SPME-GC/MS. The botanical species most visited by Apis mellifera L. near the apiaries were collected and their RP-HPTLC extracts profiles were compared with propolis samples. In addition, GC/MS was performed for volatile compounds from Zuccagnia punctata Cav. (Fabaceae). FT-IR spectra and RP-HPTLC fingerprints of propolis samples showed similar profiles. In RP-HPTLC analyses, only Z. punctata presented a similar fingerprint to Amaicha propolis. The major volatile compounds present in both were trans-linalool oxide (furanoid), 6-camphenone, linalool, trans-pinocarveol, p-cymen-8-ol, and 2,3,6-trimethylbenzaldehyde. Potential variations for the Amaicha del Valle propolis volatile fraction as consequence of propolis sample preparation were demonstrated.

Dysregulation of energy metabolism in multiple sclerosis measured in vivo with diffusion-weighted spectroscopy.

OBJECTIVE: We employed diffusion-weighted magnetic resonance spectroscopy (DW-MRS), which allows to measure in vivo the diffusion properties of metabolites, to explore the functional neuro-axonal damage and the ongoing energetic dysregulation in multiple sclerosis (MS). METHODS: Twenty-five patients with MS and 18 healthy controls (HC) underwent conventional magnetic resonance imaging (MRI) and DW-MRS. The apparent diffusion coefficient (ADC) of total N-acetyl-aspartate (tNAA) and creatine-phosphocreatine (tCr) were measured in the parietal normal-appearing white matter (NAWM) and in the thalamic grey matter (TGM). Multiple regressions were used to compare metabolite ADCs between groups and to explore clinical correlations. RESULTS: In patients compared with HCs, we found a reduction in ADC(tNAA) in the TGM, reflecting functional and structural neuro-axonal damage, and in ADC(tCr) in both NAWM and TGM, possibly reflecting a reduction in energy supply in neurons and glial cells. Metabolite ADCs did not correlate with tissue atrophy, lesional volume or metabolite concentrations, while in TGM metabolite ADCs correlated with clinical scores. CONCLUSION: DW-MRS showed a reduction in tCr diffusivity in the normal-appearing brain of patients with MS, which might reflect a state of ongoing energy dysregulation affecting neurons and/or glial cells. Reversing this energy dysregulation before neuro-axonal degeneration arises may become a key objective in future neuroprotective strategies.

Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis.

BACKGROUND: Quantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) is essential to understand the pathogenesis of the disease and to evaluate promyelinating therapies. Selectively binding myelin in the central nervous system white matter, Pittsburgh compound B ([11 C]PiB) can be used as a positron emission tomography (PET) tracer to explore myelin dynamics in MS. METHODS: Patients with active relapsing-remitting MS (n = 20) and healthy controls (n = 8) were included in a longitudinal trial combining PET with [11 C]PiB and magnetic resonance imaging. Voxel-wise maps of [11 C]PiB distribution volume ratio, reflecting myelin content, were derived. Three dynamic indices were calculated for each patient: the global index of myelin content change; the index of demyelination; and the index of remyelination. RESULTS: At baseline, there was a progressive reduction in [11 C]PiB binding from the normal-appearing white matter to MS lesions, reflecting a decline in myelin content. White matter lesions were characterized by a centripetal decrease in the tracer binding at the voxel level. During follow-up, high between-patient variability was found for all indices of myelin content change. Dynamic remyelination was inversely correlated with clinical disability (p = 0.006 and beta-coefficient = -0.67 with the Expanded Disability Status Scale; p = 0.003 and beta-coefficient = -0.68 with the MS Severity Scale), whereas no significant clinical correlation was found for the demyelination index. INTERPRETATION: [11 C]PiB PET allows quantification of myelin dynamics in MS and enables stratification of patients depending on their individual remyelination potential, which significantly correlates with clinical disability. This technique should be considered to assess novel promyelinating drugs. Ann Neurol 2016;79:726-738.

The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder.

Idiopathic rapid eye movement sleep behaviour disorder is characterized by nocturnal violence, increased muscle tone during rapid eye movement sleep and the lack of any other neurological disease. However, idiopathic rapid eye movement sleep behaviour disorder can precede parkinsonism and dementia by several years. Using 3 T magnetic resonance imaging and neuromelanin-sensitive sequences, we previously found that the signal intensity was reduced in the locus coeruleus/subcoeruleus area of patients with Parkinson's disease and rapid eye movement sleep behaviour disorder. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex with neuromelanin-sensitive imaging in 21 patients with idiopathic rapid eye movement sleep behaviour disorder and compared the results with those from 21 age- and gender-matched healthy volunteers. All subjects underwent a clinical examination, motor, cognitive, autonomous, psychological, olfactory and colour vision tests, and rapid eye movement sleep characterization using video-polysomnography and 3 T magnetic resonance imaging. The patients more frequently had preclinical markers of alpha-synucleinopathies, including constipation, olfactory deficits, orthostatic hypotension, and subtle motor impairment. Using neuromelanin-sensitive imaging, reduced signal intensity was identified in the locus coeruleus/subcoeruleus complex of the patients with idiopathic rapid eye movement sleep behaviour. The mean sensitivity of the visual analyses of the signal performed by neuroradiologists who were blind to the clinical diagnoses was 82.5%, and the specificity was 81% for the identification of idiopathic rapid eye movement sleep behaviour. The results confirm that this complex is affected in idiopathic rapid eye movement sleep behaviour (to the same degree as it is affected in Parkinson's disease). Neuromelanin-sensitive imaging provides an early marker of non-dopaminergic alpha-synucleinopathy that can be detected on an individual basis.

Orthostatic tremor: a cerebellar pathology?

SEE MUTHURAMAN ET AL DOI101093/AWW164 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Primary orthostatic tremor is characterized by high frequency tremor affecting the legs and trunk during the standing position. Cerebellar defects were suggested in orthostatic tremor without direct evidence. We aimed to characterize the anatomo-functional defects of the cerebellar motor pathways in orthostatic tremor. We used multimodal neuroimaging to compare 17 patients with orthostatic tremor and 17 age- and gender-matched healthy volunteers. Nine of the patients with orthostatic tremor underwent repetitive transcranial stimulation applied over the cerebellum during five consecutive days. We quantified the duration of standing position and tremor severity through electromyographic recordings. Compared to healthy volunteers, grey matter volume in patients with orthostatic tremor was (i) increased in the cerebellar vermis and correlated positively with the duration of the standing position; and (ii) increased in the supplementary motor area and decreased in the lateral cerebellum, which both correlated with the disease duration. Functional connectivity between the lateral cerebellum and the supplementary motor area was abnormally increased in patients with orthostatic tremor, and correlated positively with tremor severity. After repetitive transcranial stimulation, tremor severity and functional connectivity between the lateral cerebellum and the supplementary motor area were reduced. We provide an explanation for orthostatic tremor pathophysiology, and demonstrate the functional relevance of cerebello-thalamo-cortical connections in tremor related to cerebellar defects.

DOME-SHAPED MACULA IN MYOPIC EYES: Twelve-Month Follow-up.

PURPOSE: To study the long-term clinical course of dome-shaped macula in myopic eyes and to evaluate treatment efficacy for subretinal fluid (SRF) as a related complication. METHODS: A retrospective, single-center consecutive case series study was conducted. The authors analyzed myopic eyes with dome-shaped macula in patients who presented for evaluation of decreased vision. Dome-shaped macula was defined as a convexity of the retina-choroidal macular complex seen on spectral domain optical coherence tomography images. All patients were followed for at least 12 months (mean, 25 months). Fluorescein angiography and/or indocyanine green angiography were performed in cases with SRF to rule out choroidal neovascularization. RESULTS: A total of 56 dome-shaped macula eyes from 36 patients were included in the study (bilateral in 55% of patients). Mean patient age was 56.9 ± 13.1 years. The mean spherical equivalent was -9.1 ± 6.0 diopters; 53% of eyes were considered highly myopic (>-6 diopters) and 47% of eyes were mildly myopic. In most cases (37 eyes; 66.1%), the dome-shaped macula was detected on vertical spectral domain optical coherence tomography scan patterns. No significant changes (P ≥ 0.1) were observed in mean best-corrected visual acuity or mean central foveal thickness from baseline to final follow-up. Subretinal fluid was present in 29 eyes (51.8%) at baseline, with no differences in best-corrected visual acuity in eyes with and without SRF (P ≥ 0.05). Nineteen of the 29 SRF eyes were treated: 8 underwent low-fluence photodynamic therapy, whereas 7 received bevacizumab, and 4 ranibizumab. No significant differences were found between treated and untreated SRF eyes in best-corrected visual acuity improvement (P ≥ 0.1), or complete resolution of SRF (P ≥ 0.1). Likewise, photodynamic therapy did not yield any significant benefit versus untreated eyes in best-corrected visual acuity or improvement of SRF. CONCLUSION: Dome-shaped macula is a condition associated with myopic eyes that seems to remain stable over time in terms of vision and macular profiles. It is often associated with chronic SRF, for which no effective treatment is current available. However, SRF does not seem to be a significant cause of visual impairment.

The neuronal component of gray matter damage in multiple sclerosis: A [(11) C]flumazenil positron emission tomography study.

OBJECTIVE: Using positron emission tomography (PET) with [(11) C]flumazenil ([(11) C]FMZ), an antagonist of the central benzodiazepine site located within the GABAA receptor, we quantified and mapped neuronal damage in the gray matter (GM) of patients with multiple sclerosis (MS) at distinct disease stages. We investigated the relationship between neuronal damage and white matter (WM) lesions and evaluated the clinical relevance of this neuronal PET metric. METHODS: A cohort of 18 MS patients (9 progressive and 9 relapsing-remitting) was compared to healthy controls and underwent neurological and cognitive evaluations, high-resolution dynamic [(11) C]FMZ PET imaging and brain magnetic resonance imaging. [(11) C]FMZ binding was estimated using the partial saturation protocol providing voxel-wise absolute quantification of GABAA receptor concentration. PET data were evaluated using a region of interest (ROI) approach as well as on a vertex-by-vertex basis. RESULTS: [(11) C]FMZ binding was significantly decreased in the cortical GM of MS patients, compared to controls (-10%). Cortical mapping of benzodiazepine receptor concentration ([(11) C]FMZ Bmax) revealed significant intergroup differences in the bilateral parietal cortices and right frontal areas. ROI analyses taking into account GM volume changes showed extensive decrease in [(11) C]FMZ binding in bilateral parietal, cingulate, and insular cortices as well as in the thalami, amygdalae, and hippocampi. These changes were significant in both progressive and relapsing-remitting forms of the disease and correlated with WM T2-weighted lesion load. [(11) C]FMZ cortical binding correlated with cognitive performance. INTERPRETATION: This pilot study showed that PET with [(11) C]FMZ could be a promising and sensitive quantitative marker to assess and map the neuronal substrate of GM pathology in MS.

Intrinsic signature of essential tremor in the cerebello-frontal network.

Essential tremor is a movement disorder characterized by tremor during voluntary movements, mainly affecting the upper limbs. The cerebellum and its connections to the cortex are known to be involved in essential tremor, but no task-free intrinsic signatures of tremor related to structural cerebellar defects have so far been found in the cortical motor network. Here we used voxel-based morphometry, tractography and resting-state functional MRI at 3 T to compare structural and functional features in 19 patients with essential tremor and homogeneous symptoms in the upper limbs, and 19 age- and gender-matched healthy volunteers. Both structural and functional abnormalities were found in the patients' cerebellum and supplementary motor area. Relative to the healthy controls, the essential tremor patients' cerebellum exhibited less grey matter in lobule VIII and less effective connectivity between each cerebellar cortex and the ipsilateral dentate nucleus. The patient's supplementary motor area exhibited (i) more grey matter; (ii) a lower amplitude of low-frequency fluctuation of the blood oxygenation level-dependent signal; (iii) less effective connectivity between each supplementary motor area and the ipsilateral primary motor hand area, and (iv) a higher probability of connection between supplementary motor area fibres and the spinal cord. Structural and functional changes in the supplementary motor area, but not in the cerebellum, correlated with clinical severity. In addition, changes in the cerebellum and supplementary motor area were interrelated, as shown by a correlation between the lower amplitude of low-frequency fluctuation in the supplementary motor area and grey matter loss in the cerebellum. The structural and functional changes observed in the supplementary motor area might thus be a direct consequence of cerebellar defects: the supplementary motor area would attempt to reduce tremor in the motor output by reducing its communication with M1 hand areas and by directly modulating motor output via its corticospinal projections.See Raethjen and Muthuraman (doi:10.1093/brain/awv238) for a scientific commentary on this article.

Temporal and spatial evolution of grey matter atrophy in primary progressive multiple sclerosis.

Grey matter (GM) atrophy occurs early in primary progressive MS (PPMS), but it is unknown whether its progression involves different brain regions at different rates, as is seen in other neurodegenerative diseases. We aimed to investigate the temporal and regional evolution of GM volume loss over 5years and its relationship with disability progression in early PPMS. We studied 36 patients with PPMS within five years from onset and 19 age and gender-matched healthy controls with clinical and imaging assessments at study entry and yearly for 3years and then at 5years. Patients were scored on the expanded disability status scale (EDSS) and MS Functional Composite (MSFC) at each time-point. An unbiased longitudinal voxel-based morphometry approach, based on high-dimensional spatial alignment within-subject, was applied to the serial imaging data. The rate of local (voxel-wise) volume change per year was compared between groups and its relationship with clinical outcomes was assessed. Patients deteriorated significantly during the five years follow-up. Patients showed a greater decline of GM volume (p<0.05, FWE-corrected) bilaterally in the cingulate cortex, thalamus, putamen, precentral gyrus, insula and cerebellum when compared to healthy controls over five years, although the rate of volume loss varied across the brain, and was the fastest in the cingulate cortex. Significant (p<0.05, FWE-corrected) volume loss was detected in the left insula, left precuneus, and right cingulate cortex in patients at three years, as compared to baseline, whilst the bilateral putamen and the left superior temporal gyrus showed volume loss at five years. In patients, there was a relationship between a higher rate of volume loss in the bilateral cingulate cortex and greater clinical disability, as measured by the MSFC, at five years (Pearson's r=0.49, p=0.003). Longitudinal VBM demonstrated that the progression of GM atrophy in PPMS occurs at different rates in different regions across the brain. The involvement of the cingulate cortex occurs early in the disease course, continues at a steady rate throughout the follow-up period and is associated with patient outcome. These findings provide new insights into the characteristics of GM atrophy across the brain in MS, and have potential consequences for the selection of brain atrophy as an outcome measure in neuroprotective clinical trials.

Brain networks disconnection in early multiple sclerosis cognitive deficits: an anatomofunctional study.

Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large-scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3-5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age-matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage.