Executive function in schizophrenia and autism in adults shares common components separating high and low performance groups.

The profile of executive function (EF) in adults with Schizophrenia (SCZ) and autism spectrum disorder (ASD) remains unclear. This study aims to ascertain if distinct EF patterns can be identified between each clinical condition by comparing the neuropsychological profile of adults with SCZ and ASD, for whom the differential diagnosis is still highly challenging. Forty-five individuals (15 SCZ, 15 ASD, 15 controls) matched for age, sex, education level, and handedness underwent intelligence evaluation and neuropsychological testing for working memory, inhibition, planning and set-shifting, and verbal fluency subdomains. Principal component analysis (2D-PCA) using variables representing 4 domains was employed to identify patterns in neuropsychological profiles. The ASD group had lower scores on the Digits Forward subtest compared to the SCZ group (7.2 ± 2.1 vs. 9.3 ± 1.9, p = 0.003; Cohen's d: 1.05). ASD also performed significantly worse on the Stroop Word Test compared to the control group (77.7± 17.9 vs. 98.0 ± 12.7, p = 0.009; Cohen's d: 1.31). No significant differences were observed between ASD and SCZ on other EF measures. The larger contributors for the dimensions in 2D-PCA were the Digits Forward subtest and Stroop Word Test. Still, there was substantial overlap between the clinical groups. This study suggests a high degree of similarity of EF between SCZ and ASD. Through four EF measures, the discrimination of low and high-functioning EF groups spanning both diagnostic categories may help to identify the individuals who could better benefit from cognitive rehabilitation strategies.

Neurochemical differences in core regions of the autistic brain: a multivoxel 1H-MRS study in children.

Autism spectrum disorder (ASD) is a neurodevelopmental condition which compromises various cognitive and behavioural domains. The understanding of the pathophysiology and molecular neurobiology of ASD is still an open critical research question. Here, we aimed to address ASD neurochemistry in the same time point at key regions that have been associated with its pathophysiology: the insula, hippocampus, putamen and thalamus. We conducted a multivoxel proton magnetic resonance spectroscopy (1H-MRS) study to non-invasively estimate the concentrations of total choline (GPC + PCh, tCho), total N-acetyl-aspartate (NAA + NAAG, tNAA) and Glx (Glu + Gln), presenting the results as ratios to total creatine while investigating replication for ratios to total choline as a secondary analysis. Twenty-two male children aged between 10 and 18 years diagnosed with ASD (none with intellectual disability, in spite of the expected lower IQ) and 22 age- and gender-matched typically developing (TD) controls were included. Aspartate ratios were significantly lower in the insula (tNAA/tCr: p = 0.010; tNAA/tCho: p = 0.012) and putamen (tNAA/tCr: p = 0.015) of ASD individuals in comparison with TD controls. The Glx ratios were significantly higher in the hippocampus of the ASD group (Glx/tCr: p = 0.027; Glx/tCho: p = 0.011). Differences in tNAA and Glx indices suggest that these metabolites might be neurochemical markers of region-specific atypical metabolism in ASD children, with a potential contribution for future advances in clinical monitoring and treatment.

The evolution of blood-brain barrier permeability changes after stroke and its implications on clinical outcome: A systematic review and meta-analysis.

BACKGROUND: Blood-brain barrier permeability (BBBp) is a key process involved in ischemic stroke pathophysiology. However, there is a lack of consensus on how BBBp evolves after the ischemia injury, and its clinical relevance at different timepoints post stroke. AIMS: The main objective of this study is to assess BBBp evolution through stroke phases and its implications on patient outcomes. METHODS: We screened PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials up to 31 December 2021. We included research quantitatively using neuroimaging to assess BBBp in stroke patients. BBBp in the different phases was evaluated by a random-effect model based on the standardized mean difference (SMD) between the ipsilateral and contralateral sides of the brain. We performed a subgroup analysis on clinical outcome, reperfusion treatment, haemorrhagic transformation, and imaging method. RESULTS: We identified 3761 studies, of which 22 (1592 patients and 1787 evaluations) were included in our study. Overall, 17 studies reported BBBp for the hyperacute phase, 8 for the acute, 5 for the subacute, and 2 for the chronic phase. All phases were associated with increased BBBp: 0.74 (0.48-0.99), 1.68 (0.94-2.42), 1.98 (0.96-3.00), and 1.00 (0.45-1.55), respectively. An increase in BBBp was associated with hemorrhagic transformation in the hyperacute phase and with improved functional outcomes in the late subacute phase. CONCLUSION: BBBp is persistently increased after stroke, peaking in the acute and subacute phases. The degree of BBBp influences patient outcomes depending on stroke phase. Our findings support the clinical relevance of BBBp dynamics in stroke care.

Regular physical activity moderates the adverse impact of type 2 diabetes on brain atrophy independently from HbA1c.

Objective: Brain atrophy has been consistently associated with type 2 diabetes, beginning in early stages of dysglycemia, independently from micro and macrovascular complications. On the contrary, physical activity relates with larger brain volumes. Our aim is to assess the influence of regular physical activity on brain volumes in people with type 2 diabetes. Methods: A cross-sectional multimodal evaluation with 3T MRI was performed on 170 individuals: 85 individuals with type 2 diabetes and 85 controls. They underwent clinical examination, blood sampling and 3T MRI. Brain volumes (mm3) were estimated using FreeSurfer 7. Physical activity duration was self-reported by the participants as the number of hours of physical activity per week for at least the previous 6 months. Statistical analysis was performed with IBM SPSS 27. Results: People with type 2 diabetes had significantly lower cortical and subcortical volumes, adjusted for age and individual intracranial volume, comparing to controls. Regression analysis showed that within type 2 diabetes group, lower gray matter volumes were associated with lesser physical activity duration (hours/week), independently from HbA1c. Moreover, there were significant moderate positive correlations between regular physical activity duration and gray matter volumes of cortical and subcortical subregions, specifically in the diabetes group. Conclusions: This study reveals a putative beneficial effect of regular physical activity independently of glycemic control, as assessed by HbA1c, which might contribute to reduce the negative impact of type 2 diabetes in the brain.

Simultaneous changes in visual acuity, cortical population receptive field size, visual field map size, and retinal thickness in healthy human aging.

Healthy human aging is associated with a deterioration of visual acuity, retinal thinning, visual field map shrinkage and increasing population receptive field sizes. Here we ask how these changes are related to each other in a cross-sectional sample of fifty healthy adults aged 20-80 years. We hypothesized that age-related loss of macular retinal ganglion cells may lead to decreased visual field map sizes, and both may lead to increased pRF sizes in the cortical central visual field representation. We measured our participants' perceptual corrected visual acuity using standard ophthalmological letter charts. We then measured their early visual field map (V1, V2 and V3) functional population receptive field (pRF) sizes and structural surface areas using fMRI, and their retinal structure using high-definition optical coherence tomography. With increasing age visual acuity decreased, pRF sizes increased, visual field maps surface areas (but not whole-brain surface areas) decreased, and retinal thickness decreased. Among these measures, only functional pRF sizes predicted perceptual visual acuity, and Bayesian statistics support a null relationship between visual acuity and cortical or retinal structure. However, pRF sizes were in turn predicted by cortical structure only (visual field map surface areas), which were only predicted by retinal structure (thickness). These results suggest that simultaneous disruptions of neural structure and function throughout the early visual system may underlie the deterioration of perceptual visual acuity in healthy aging.

Protective effects of cognitive and brain reserve in multiple sclerosis: Differential roles on social cognition and 'classic cognition'.

BACKGROUND: According to cognitive reserve (CR) and brain reserve (BR) theories, lifetime intellectual enrichment and maximal brain volume protect against cognitive decline. OBJECTIVE: To examine the effects of CR and BR on social cognition in multiple sclerosis (MS), and compare it with 'classic cognition'. METHODS: We included 60 MS patients and 60 healthy controls matched on age, sex, and education. Education was used has a proxy of CR and intracranial volume (ICV) as a proxy of BR. Participants underwent Theory of Mind (ToM) testing (Eyes Test, Videos Test), comprehensive neuropsychological assessment and 3Tesla brain MRI. Cortical and subcortical grey matter (GM) volumes were calculated. RESULTS: We found positive effects of education and ICV on general cognitive status and ToM performance, respectively. Higher education moderated the impact of subcortical GM atrophy on 'classic' cognitive status (R2=0.219, p=<0.001). Conversely, greater ICV attenuated the impact of cortical GM atrophy on Eyes Test (R2=0.158, p=0.002) and Videos Test (R2=0.198, p=0.001). Stratification for disease duration showed that the protective effect of education/ICV occurred in early stages of disease (<10 years). CONCLUSION: CR and BR have differential protective roles in MS, with BR having a positive effect on social cognition and CR on 'classic' cognitive domains.

The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes.

Glucose metabolism is pivotal for energy and neurotransmitter synthesis and homeostasis, particularly in Glutamate and GABA systems. In turn, the stringent control of inhibitory/excitatory tonus is known to be relevant in neuropsychiatric conditions. Glutamatergic neurotransmission dominates excitatory synaptic functions and is involved in plasticity and excitotoxicity. GABAergic neurochemistry underlies inhibition and predicts impaired psychophysical function in diabetes. It has also been associated with cognitive decline in people with diabetes. Still, the relation between metabolic homeostasis and neurotransmission remains elusive. Two 3T proton MR spectroscopy studies were independently conducted in the occipital cortex to provide insight into inhibitory/excitatory homeostasis (GABA/Glutamate) and to evaluate the impact of chronic metabolic control on the levels and regulation (as assessed by regression slopes) of the two main neurotransmitters of the CNS in type 2 diabetes (T2DM) and type 1 diabetes (T1DM). Compared to controls, participants with T2DM showed significantly lower Glutamate, and also GABA. Nevertheless, higher levels of GABA/Glx (Glutamate+Glutamine), and lower levels of Glutamate were associated with poor metabolic control in participants with T2DM. Importantly, the relationship between GABA/Glx and HbA1c found in T2DM supports a relationship between inhibitory/excitatory balance and metabolic control. Interestingly, this neurometabolic profile was undetected in T1DM. In this condition we found strong evidence for alterations in MRS surrogate measures of neuroinflammation (myo-Inositol), positively related to chronic metabolic control. Our results suggest a role for Glutamate as a global marker of T2DM and a sensitive marker of glycemic status. GABA/Glx may provide a signature of cortical metabolic state in poorly controlled patients as assessed by HbA1c levels, which indicate long-term blood Glucose control. These findings are consistent with an interplay between abnormal neurotransmission and metabolic control in particular in type 2 diabetes thereby revealing dissimilar contributions to the pathophysiology of neural dysfunction in both types of diabetes.

Headache intensity is associated with increased white matter lesion burden in CADASIL patients.

OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cause of vascular dementia in adults. Migraine is a major symptom of the disease. We aimed to identify clinical and demographical features of the headache associated with increased cerebral lesion burden in a cohort of CADASIL patients. METHODS: Thirty-two patients with CADASIL were enrolled in this cross-sectional study. Demographics data, vascular risk factors and headache characteristics were collected through a structured questionnaire. MRI (3-T) was used to determine white matter hyperintensities burden evaluated by its volume (WMH-V). RESULTS: Regression analysis showed that age (ß = 1.266, 95%CI = [0.805, 1.726], p < 0.001), headache intensity (ß = 5.143, 95%CI = [2.362, 7.924], p = 0.001) and female sex (ß = 19.727, 95%CI = [8.750, 30.075], p = 0.001) were the main predictors of WMH-V. DISCUSSION: Age, female sex and headache intensity are associated with increased white matter lesion volume in CADASIL.

The neural basis of fatigue in multiple sclerosis: A multimodal MRI approach.

BACKGROUND: Fatigue is a frequent disabling symptom in multiple sclerosis (MS), but its pathophysiology remains incompletely understood. This study aimed to explore the underlying neural basis of fatigue in patients with MS. METHODS: We enrolled 60 consecutive patients with MS and 60 healthy controls (HC) matched on age, sex, and education. Fatigue was assessed using the Portuguese version of the Modified Fatigue Impact Scale (MFIS). All participants underwent 3T brain MRI (conventional and diffusion tensor imaging [DTI] sequences). White matter (WM) focal lesions were identified and T1/T2 lesion volumes were computed. Tract-based spatial statistics were applied for voxel-wise analysis of DTI metrics fractional anisotropy and mean diffusivity (MD) on normal-appearing WM (NAWM). Using Freesurfer software, total and regional volumes of cortical and subcortical gray matter (GM) were calculated. RESULTS: Compared to HC, patients with MS scored significantly higher on MFIS (33.8 ± 19.7 vs 16.5 ± 15.1, p < 0.001). MFIS scores were not significantly correlated with T1/T2 lesion volumes, total GM volume, or any regional volume of cortical and subcortical GM. Significant correlations were found between global scores of MFIS and MD increase of the NAWM skeleton, including corona radiata, internal capsule, external capsule, corticospinal tract, cingulum, corpus callosum, fornix, superior longitudinal fasciculus, superior fronto-occipital fasciculus, sagittal stratum, posterior thalamic radiation, cerebral peduncle, and uncinate fasciculus. CONCLUSIONS: In this study, fatigue was associated with widespread NAWM damage but not with lesion load or GM atrophy. Functional disconnection, caused by diffuse microstructural WM damage, might be the main neural basis of fatigue in MS.

Mitochondrial pathophysiology beyond the retinal ganglion cell: occipital GABA is decreased in autosomal dominant optic neuropathy.

PURPOSE: It has remained a mystery why some genetic mitochondrial disorders affect predominantly specific cell types such as the retinal ganglion cell. This is particularly intriguing concerning retinal and cortical function since they are tightly linked in health and disease. Autosomal dominant optic neuropathy (ADOA) is a mitochondrial disease that affects the ganglion cell. However, it is unknown whether alterations are also present in the visual cortex, namely in excitation/inhibition balance. METHODS: In this study, we performed in vivo structural and biochemical proton magnetic resonance imaging in 14 ADOA and 11 age-matched control participants focusing on the visual cortex, with the aim of establishing whether in this genetically determined disease an independent cortical neurochemical phenotype could be established irrespective of a putative structural phenotype. Cortical thickness of anatomically defined visual areas was estimated, and a voxel-based morphometry approach was used to assess occipital volumetric changes in ADOA. Neurochemical measurements were focused on γ-aminobutyric acid (GABA) and glutamate, as indicators of the local excitatory/inhibitory balance. RESULTS: We found evidence for reduced visual cortical GABA and preserved glutamate concentrations in the absence of cortical or subcortical atrophy. These changes in GABA levels were explained by neither structural nor functional measures of visual loss, suggesting a developmental origin. CONCLUSIONS: These results suggest that mitochondrial disorders that were previously believed to only affect retinal function may also affect cortical physiology, especially the GABAergic system, suggesting reduced brain inhibition vs. excitation. This GABA phenotype, independent of sensory loss or cortical atrophy and in the presence of preserved glutamate levels, suggests a neurochemical developmental change at the cortical level, leading to a pathophysiological excitation/inhibition imbalance.

The retinal ganglion cell layer predicts normal-appearing white matter tract integrity in multiple sclerosis: A combined diffusion tensor imaging and optical coherence tomography approach.

We investigated the relationship between retinal layers and normal-appearing white matter (WM) integrity in the brain of patients with relapsing-remitting multiple sclerosis (MS), using a combined diffusion tensor imaging and high resolution optical coherence tomography approach. Fifty patients and 62 controls were recruited. The patients were divided into two groups according to presence (n = 18) or absence (n = 32) of optic neuritis. Diffusion tensor data were analyzed with a voxel-wise whole brain analysis of diffusion metrics in WM with tract-based spatial statistics. Thickness measurements were obtained for each individual retinal layer. Partial correlation and multivariate regression analyses were performed, assessing the association between individual retinal layers and diffusion metrics across all groups. Region-based analysis was performed, by focusing on tracts associated with the visual system. Receiver operating characteristic (ROC) curves were computed to compare the biomarker potential for the diagnosis of MS, using the thickness of each retinal layer and diffusion metrics. In patients without optic neuritis, both ganglion cell layer (GCL) and inner plexiform layer thickness correlated with the diffusion metrics within and outside the visual system. GCL thickness was a significant predictor of diffusion metrics in the whole WM skeleton, unlike other layers. No association was observed for either controls or patients with a history of optic neuritis. ROC analysis showed that the biomarker potential for the diagnosis of MS based on the GCL was high when compared to other layers. We conclude that GCL integrity is a predictor of whole-brain WM disruption in MS patients without optic neuritis.

Disconnection as a mechanism for social cognition impairment in multiple sclerosis.

OBJECTIVE: To assess the contribution of microstructural normal-appearing white matter (NAWM) damage to social cognition impairment, specifically in the theory of mind (ToM), in multiple sclerosis (MS). METHODS: We enrolled consecutively 60 patients with MS and 60 healthy controls (HC) matched on age, sex, and education level. All participants underwent ToM testing (Eyes Test, Videos Test) and 3T brain MRI including conventional and diffusion tensor imaging sequences. Tract-based spatial statistics (TBSS) were applied for whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on NAWM. RESULTS: Patients with MS performed worse on both tasks of ToM compared to HC (Eyes Test 58.7 ± 13.8 vs 81.9 ± 10.4, p < 0.001, Hedges g -1.886; Videos Test 75.3 ± 9.3 vs 88.1 ± 7.1, p < 0.001, Hedges g -1.537). Performance on ToM tests was correlated with higher values of FA and lower values of MD across widespread white matter tracts. The largest effects (≥90% of voxels with statistical significance) for the Eyes Test were body and genu of corpus callosum, fornix, tapetum, uncinate fasciculus, and left inferior cerebellar peduncle, and for the Videos Test genu and splenium of corpus callosum, fornix, uncinate fasciculus, left tapetum, and right superior fronto-occipital fasciculus. CONCLUSIONS: These results indicate that a diffuse pattern of NAWM damage in MS contributes to social cognition impairment in the ToM domain, probably due to a mechanism of disconnection within the social brain network. Gray matter pathology is also expected to have an important role; thus further research is required to clarify the neural basis of social cognition impairment in MS.

Diabetic brain or retina? Visual psychophysical performance in diabetic patients in relation to GABA levels in occipital cortex.

Visual impairment is one of the most feared complications of Type 2 Diabetes Mellitus. Here, we aimed to investigate the role of occipital cortex γ-aminobutyric acid (GABA) as a predictor of visual performance in type 2 diabetes. 18 type 2 diabetes patients were included in a longitudinal prospective one-year study, as well as 22 healthy age-matched controls. We collected demographic data, HbA1C and used a novel set of visual psychophysical tests addressing color, achromatic luminance and speed discrimination in both groups. Psychophysical tests underwent dimension reduction with principle component analysis into three synthetic variables: speed, achromatic luminance and color discrimination. A MEGA-PRESS magnetic resonance brain spectroscopy sequence was used to measure occipital GABA levels in the type 2 diabetes group. Retinopathy grading and retinal microaneurysms counting were performed in the type 2 diabetes group for single-armed correlations. Speed discrimination thresholds were significantly higher in the type 2 diabetes group in both visits; mean difference (95% confidence interval), [0.86 (0.32-1.40) in the first visit, 0.74 (0.04-1.44) in the second visit]. GABA from the occipital cortex predicted speed and achromatic luminance discrimination thresholds within the same visit (r = 0.54 and 0.52; p = 0.02 and 0.03, respectively) in type 2 diabetes group. GABA from the occipital cortex also predicted speed discrimination thresholds one year later (r = 0.52; p = 0.03) in the type 2 diabetes group. Our results suggest that speed discrimination is impaired in type 2 diabetes and that occipital cortical GABA is a novel predictor of visual psychophysical performance independently from retinopathy grade, metabolic control or disease duration in the early stages of the disease.

Impairment of social cognition in multiple sclerosis: Amygdala atrophy is the main predictor.

BACKGROUND: Patients with multiple sclerosis (MS) frequently reveal social behavior disturbance. Nevertheless, little is known regarding the impact of MS on social cognition, particularly theory of mind (ToM), and its neural basis. OBJECTIVES: To explore how ToM is affected in MS and its neural correlates. METHODS: Enrolled 60 consecutive MS patients and 60 healthy controls (HC) matched on age, sex, and education. Participants underwent ToM testing (Eyes Test, Videos Test) and 3 T brain magnetic resonance imaging (MRI). Using Freesurfer software, cortical and subcortical gray matter (GM) volumes were calculated. RESULTS: MS patients performed worse on Eyes Test (58.7% ± 13.8% vs 81.9% ± 10.4%, p < 0.001) and Videos Test (75.3% ± 9.3% vs 88.1% ± 7.1%, p < 0.001). Eyes Test performance in MS was positively correlated with the volume of subcortical structures (amygdala, putamen) and cortical regions (entorhinal cortex, fusiform gyrus, superior temporal gyrus, superior parietal gyrus, supramarginal gyrus, medial orbitofrontal cortex, anterior and posterior cingulate gyrus). In regression analysis, amygdala volume was the single predictor of performance ( R2 change = 0.064, p = 0.031), and a mediation analysis indicated that it contributes for the differences observed between MS and HC. CONCLUSION: Patients with MS have impairment on social cognition. Amygdala atrophy was the main predictor probably due to its central position within the "social brain" network.

Genetically induced impairment of retinal ganglion cells at the axonal level is linked to extrastriate cortical plasticity.

Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder, which leads to initially silent visual loss due to retinal ganglion cell (RGC) degeneration. We aimed to establish a link between features of retinal progressive impairment and putative cortical changes in a cohort of 15 asymptomatic patients harboring the 11778G>A mutation with preserved visual acuity and normal ocular examination. To study plasticity evoked by clinically silent degeneration of RGC we only studied mutation carriers. We phenotyped pre-clinical silent degeneration from the psychophysical, neurophysiological and structural points of view to understand whether retinal measures could be related to cortical reorganization, using pattern electrophysiology, chromatic contrast sensitivity and high-resolution optical coherence tomography to measure macular, RGC nerve fiber layer as well as inner/outer retinal layer thickness. We then performed correlation analysis of these measures with cortical thickness estimates in functionally mapped retinotopic visual cortex. We found that compensatory cortical plasticity occurring in V2/V3 is predicted by the swelling (indicating deficits of axonal transport and intracellular edema) of the macular RGC axonal layer. Increased cortical thickness (CT) in V2 and V3 was observed in peripheral regions, like visual field loss, in these mutation carriers. CT was a very discriminative measure between carriers and controls, as revealed by ROC analysis. Importantly, the substantial cortical reorganization that occurs in the carrier state can be used to provide statistical discrimination between carriers and controls to a level that is similar to measures of retinal dysfunction. We conclude that peripheral cortical compensatory plasticity in early visual areas V2/V3 may be triggered by pathology in peripheral RGC axons in combination with potential developmental changes.

Development and aging of visual hemifield asymmetries in contrast sensitivity.

The relation of development and aging with models of visual anisotropies and their influence on low-level visual processing remain to be established. Our main goal was to explore visual performance asymmetries in development and normal aging using low-level contrast sensitivity behavioral tasks [probing two distinct spatiotemporal frequency channels, (a) intermediate spatial and null temporal frequency (3.5 cycles per degree (cpd) and 0 Hz); and (b) low spatial and high temporal frequency (0.25 cpd undergoing 25 Hz counterphase flicker)]. Different patterns of functional asymmetries were investigated within four (two neurodevelopmental and two adult) age groups (N = 258 participants; 8-65 years). We found a left visual hemifield/right hemisphere advantage for only the intermediate spatial frequency channel that was present early in life and remained stable throughout adulthood. In contrast, inferior/superior visual hemifield asymmetries, with a direct ecological meaning, were found for both spatiotemporal frequency channels. This inferior visual hemifield advantage emerged early in life and persisted throughout aging. These findings show that both right hemispheric and dorsal retinotopic patterns of dominance in low-level vision emerge early in childhood, maintaining during aging.

Abnormal late visual responses and alpha oscillations in neurofibromatosis type 1: a link to visual and attention deficits.

BACKGROUND: Neurofibromatosis type 1 (NF1) affects several areas of cognitive function including visual processing and attention. We investigated the neural mechanisms underlying the visual deficits of children and adolescents with NF1 by studying visual evoked potentials (VEPs) and brain oscillations during visual stimulation and rest periods. METHODS: Electroencephalogram/event-related potential (EEG/ERP) responses were measured during visual processing (NF1 n = 17; controls n = 19) and idle periods with eyes closed and eyes open (NF1 n = 12; controls n = 14). Visual stimulation was chosen to bias activation of the three detection mechanisms: achromatic, red-green and blue-yellow. RESULTS: We found significant differences between the groups for late chromatic VEPs and a specific enhancement in the amplitude of the parieto-occipital alpha amplitude both during visual stimulation and idle periods. Alpha modulation and the negative influence of alpha oscillations in visual performance were found in both groups. CONCLUSIONS: Our findings suggest abnormal later stages of visual processing and enhanced amplitude of alpha oscillations supporting the existence of deficits in basic sensory processing in NF1. Given the link between alpha oscillations, visual perception and attention, these results indicate a neural mechanism that might underlie the visual sensitivity deficits and increased lapses of attention observed in individuals with NF1.

Long term cortical plasticity in visual retinotopic areas in humans with silent retinal ganglion cell loss.

Visual cortical plasticity induced by overt retinal lesions (scotomas) has remained a controversial phenomenon. Here we studied cortical plasticity in a silent model of retinal ganglion cell loss, documented by in vivo optical biopsy using coherence tomography. The cortical impact of non-scotomatous subtle retinal ganglion cell functional and structural loss was investigated in carriers of the mitochondrial DNA 11778G>A mutation causing Leber's hereditary optic neuropathy. We used magnetic resonance imaging (MRI) to measure cortical thickness and fMRI to define retinotopic cortical visual areas V1, V2 and V3 in silent carriers and matched control groups. Repeated Measures analysis of variance revealed a surprising increase in cortical thickness in the younger carrier group (below 21 years of age). This effect dominated in extrastriate cortex, and notably V2. This form of structural plasticity suggests enhanced plastic developmental mechanisms in extrastriate retinotopic regions close to V1 and not receiving direct retinocortical input.