A 3D convolutional neural network to classify subjects as Alzheimer's disease, frontotemporal dementia or healthy controls using brain 18F-FDG PET.

With the arrival of disease-modifying drugs, neurodegenerative diseases will require an accurate diagnosis for optimal treatment. Convolutional neural networks are powerful deep learning techniques that can provide great help to physicians in image analysis. The purpose of this study is to introduce and validate a 3D neural network for classification of Alzheimer's disease (AD), frontotemporal dementia (FTD) or cognitively normal (CN) subjects based on brain glucose metabolism. Retrospective [18F]-FDG-PET scans of 199 CE, 192 FTD and 200 CN subjects were collected from our local database, Alzheimer's disease and frontotemporal lobar degeneration neuroimaging initiatives. Training and test sets were created using randomization on a 90 %-10 % basis, and training of a 3D VGG16-like neural network was performed using data augmentation and cross-validation. Performance was compared to clinical interpretation by three specialists in the independent test set. Regions determining classification were identified in an occlusion experiment and Gradient-weighted Class Activation Mapping. Test set subjects were age- and sex-matched across categories. The model achieved an overall 89.8 % accuracy in predicting the class of test scans. Areas under the ROC curves were 93.3 % for AD, 95.3 % for FTD, and 99.9 % for CN. The physicians' consensus showed a 69.5 % accuracy, and there was substantial agreement between them (kappa = 0.61, 95 % CI: 0.49-0.73). To our knowledge, this is the first study to introduce a deep learning model able to discriminate AD and FTD based on [18F]-FDG PET scans, and to isolate CN subjects with excellent accuracy. These initial results are promising and hint at the potential for generalization to data from other centers.

Increased network centrality of the anterior insula in early abstinence from alcohol.

Abnormal resting-state functional connectivity, as measured by functional magnetic resonance imaging (MRI), has been reported in alcohol use disorders (AUD), but findings are so far inconsistent. Here, we exploited recent developments in graph-theoretical analyses, enabling improved resolution and fine-grained representation of brain networks, to investigate functional connectivity in 35 recently detoxified alcohol dependent patients versus 34 healthy controls. Specifically, we focused on the modular organization, that is, the presence of tightly connected substructures within a network, and on the identification of brain regions responsible for network integration using an unbiased approach based on a large-scale network composed of more than 600 a priori defined nodes. We found significant reductions in global connectivity and region-specific disruption in the network topology in patients compared with controls. Specifically, the basal brain and the insular-supramarginal cortices, which form tightly coupled modules in healthy subjects, were fragmented in patients. Further, patients showed a strong increase in the centrality of the anterior insula, which exhibited stronger connectivity to distal cortical regions and weaker connectivity to the posterior insula. Anterior insula centrality, a measure of the integrative role of a region, was significantly associated with increased risk of relapse. Exploratory analysis suggests partial recovery of modular structure and insular connectivity in patients after 2 weeks. These findings support the hypothesis that, at least during the early stages of abstinence, the anterior insula may drive exaggerated integration of interoceptive states in AUD patients with possible consequences for decision making and emotional states and that functional connectivity is dynamically changing during treatment.

Resting-State Functional Connectivity in Frontostriatal and Posterior Cortical Subtypes in Parkinson's Disease-Mild Cognitive Impairment.

BACKGROUND: The "dual syndrome hypothesis" distinguished two subtypes in mild cognitive impairment (MCI) in Parkinson's disease: frontostriatal, characterized by attentional and executive deficits; and posterior cortical, characterized by visuospatial, memory, and language deficits. OBJECTIVE: The aim was to identify resting-state functional modifications associated with these subtypes. METHODS: Ninety-five nondemented patients categorized as having normal cognition (n = 31), frontostriatal (n = 14), posterior cortical (n = 20), or mixed (n = 30) cognitive subtype had a 3 T resting-state functional magnetic resonance imaging scan. Twenty-four age-matched healthy controls (HCs) were also included. A group-level independent component analysis was performed to identify resting-state networks, and the selected components were subdivided into 564 cortical regions in addition to 26 basal ganglia regions. Global intra- and inter-network connectivity along with global and local efficiencies was compared between groups. The network-based statistics approach was used to identify connections significantly different between groups. RESULTS: Patients with posterior cortical deficits had increased intra-network functional connectivity (FC) within the basal ganglia network compared with patients with frontostriatal deficits. Patients with frontostriatal deficits had reduced inter-network FC between several networks, including the visual, default-mode, sensorimotor, salience, dorsal attentional, basal ganglia, and frontoparietal networks, compared with HCs, patients with normal cognition, and patients with a posterior cortical subtype. Similar results were also found between patients with a mixed subtype and HCs. CONCLUSION: MCI subtypes are associated with specific changes in resting-state FC. Longitudinal studies are needed to determine the predictive potential of these markers regarding the risk of developing dementia. © 2021 International Parkinson and Movement Disorder Society.

Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease.

Objective: Predicted age difference (PAD) is a score computed by subtracting chronological age from "brain" age, which is estimated using neuroimaging data. The goal of this study was to evaluate the PAD as a marker of phenotypic heterogeneity and severity among early-onset Alzheimer's disease (EOAD) patients. Methods: We first used 3D T1-weighted (3D-T1) magnetic resonance images (MRI) of 3,227 healthy subjects aged between 18 and 85 years to train, optimize, and evaluate the brain age model. A total of 123 participants who met the criteria for early-onset (<65 years) sporadic form of probable Alzheimer's disease (AD) and presented with two distinctive clinical presentations [an amnestic form (n = 74) and a non-amnestic form (n = 49)] were included at baseline and followed-up for a maximum period of 4 years. All the participants underwent a work-up at baseline and every year during the follow-up period, which included clinical examination, neuropsychological testing and genotyping, and structural MRI. In addition, cerebrospinal fluid biomarker assay was recorded at baseline. PAD score was calculated by applying brain age model to 3D-T1 images of the EOAD patients and healthy controls, who were matched based on age and sex. At baseline, between-group differences for neuropsychological and PAD scores were assessed using linear models. Regarding longitudinal analysis of neuropsychological and PAD scores, differences between amnestic and non-amnestic participants were analyzed using linear mixed-effects modeling. Results: PAD score was significantly higher for non-amnestic patients (2.35 ± 0.91) when compared to amnestic patients (2.09 ± 0.74) and controls (0.00 ± 1). Moreover, PAD score was linearly correlated with the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Sum of Boxes (CDR-SB), for both amnestic and non-amnestic sporadic forms. Longitudinal analyses showed that the gradual development of the disease in patients was accompanied by a significant increase in PAD score over time, for both amnestic and non-amnestic patients. Conclusion: PAD score was able to separate amnestic and non-amnestic sporadic forms. Regardless of the clinical presentation, as PAD score was a way of quantifying an early brain age acceleration, it was an appropriate method to detect the development of AD and follow the evolution of the disease as a marker of severity as MMSE and CDR-SB.

A multimodal, longitudinal study of cognitive heterogeneity in early-onset Alzheimer's disease.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is a heterogeneous pathology. Young patients with AD are particularly likely to have an atypical presentation. The objectives of the present cluster analysis were to determine whether patients with early-onset AD (EOAD) had several distinct cognitive profiles and to compare the resulting clusters with regard to clinical, neuroimaging, and laboratory characteristics. METHODS: We collected cognitive, behavioural, functional, neuroimaging, and laboratory data on 72 patients meeting the criteria for probable mild EOAD. The patients were first classified into clinical phenotype groups by a multidisciplinary board of clinicians. The patients' cognitive and functional decline was monitored for 24 months. A k-means clustering analysis was then used to determine clusters on the basis of the patients' neuropsychological test results. RESULTS: Two distinct clusters were identified: the patients in the first cluster (C1, n = 38) had a predominant memory impairment, whereas patients in the second (C2, n = 34) did not. Dyslipidaemia and the presence of ɛ4 apolipoprotein E allele were more frequent in C1, whereas the cognitive and functional decline was faster in the patients in C2. Moreover, posterior brain abnormalities were more severe in patients in C2 than in patients in C1. CONCLUSIONS: By applying a k-means clustering analysis, we identified two clusters of patients in an EOAD cohort. The clusters differed with regard to certain clinical, imaging, and laboratory characteristics. This clustering procedure might be of value for managing patients with EOAD in general and for identifying those at risk of more rapid decline in particular.

Apomorphine-induced reorganization of striato-frontal connectivity in patients with tremor-dominant Parkinson's disease.

INTRODUCTION: Apomorphine is a dopamine agonist used in Parkinson's disease (PD), which matches levodopa in terms of the magnitude of effect on the cardinal motor features, such as tremor and bradykinesia. The beneficial effect of this treatment on PD patients with tremor-dominant has widely been demonstrated, although the underlying neural correlates are unknown. We sought to examine the effects of apomorphine on topological characteristics of resting-state functional connectivity networks in tremor-dominant PD (tdPD) patients. METHODS: Sixteen tdPD patients were examined using a combined electromyography-functional magnetic resonance imaging approach. Patients were scanned twice following either placebo (subcutaneous injection of 1 mL saline solution) or 1 mg of apomorphine injection. Graph analysis methods were employed to investigate the modular organization of functional connectivity networks before and after drug treatment. RESULTS: After injection of apomorphine, evident reduction of tremor symptoms was mirrored by a significant increase in overall connectivity strength and reorganization of the modular structure of the basal ganglia and of the fronto-striatal module. Moreover, we found an increase in the centrality of motor and premotor regions. No differences were found between pre- and post-placebo sessions. CONCLUSION: These results provide new evidence about the effects of apomorphine at a large-scale neural network level showing that drug treatment modifies the brain functional organization of tdPD, increasing the overall resting-state functional connectivity strength, the segregation of striato-frontal regions and the integrative role of motor areas.

Large-Scale Brain Networks Underlying Successful and Unsuccessful Encoding, Maintenance, and Retrieval of Everyday Scenes in Visuospatial Working Memory.

Recent research on working memory (WM) identified the contribution of several large-scale brain networks operating during WM tasks, such as the frontoparietal attention network (AN), the default mode network (DMN), and the salience network (SN). To date, however, the dynamical interplay among these networks is largely unexplored during successful or unsuccessful WM performance, especially with complex and ecological stimuli. Here we systematically characterized the selective contribution of these networks during a visuospatial WM task requiring the encoding, maintenance and retrieval of real-life scenes. While undergoing fMRI scans, participants were presented with everyday life visual scenes for 4 s (encoding phase). After a delay of 8 s (maintenance phase), participants were presented with a target-object extracted from the previous scene. Participants had to judge whether the target-object was presented at the same or in a different location compared to the original scene (retrieval phase) and then provide a confidence judgment. Using the independent component analysis (ICA), we found that subsequent remembering was associated with the activity of the AN at encoding, the attention and SN at maintenance, plus the visual network at retrieval. Conversely, subsequent forgetting was associated with the activity of the DMN at maintenance, and the SN at retrieval. Overall, these findings reveal a dynamical interplay between large-scale brain networks during visuospatial WM performance related to complex, real-life stimuli.

Disrupted modular organization of primary sensory brain areas in schizophrenia.

Abnormal brain resting-state functional connectivity has been consistently observed in patients affected by schizophrenia (SCZ) using functional MRI and other neuroimaging techniques. Graph theoretical methods provide a framework to investigate these defective functional interactions and their effects on the organization of brain connectivity networks. A few studies have shown altered distribution of connectivity within and between functional modules in SCZ patients, an indication of imbalanced functional segregation ad integration. However, no major alterations of modular organization have been reported in patients, and unambiguous identification of the neural substrates affected remains elusive. Recently, it has been demonstrated that current modularity analysis methods suffer from a fundamental and severe resolution limit, as they fail to detect features that are smaller than a scale determined by the size of the entire connectivity network. This resolution limit is likely to have hampered the ability to resolve differences between patients and controls in previous studies. Here, we apply Surprise, a novel resolution limit-free approach, to study the modular organization of resting state functional connectivity networks in a large cohort of SCZ patients and in matched healthy controls. Leveraging these important methodological advances we find new evidence of substantial fragmentation and reorganization involving primary sensory, auditory and visual areas in SCZ patients. Conversely, frontal and prefrontal areas, typically associated with higher cognitive functions, appear to be largely unaffected, with changes selectively involving language and speech processing areas. Our findings support the hypothesis that cognitive dysfunction in SCZ may involve deficits occurring already at early stages of sensory processing.

Graph Analysis and Modularity of Brain Functional Connectivity Networks: Searching for the Optimal Threshold.

Neuroimaging data can be represented as networks of nodes and edges that capture the topological organization of the brain connectivity. Graph theory provides a general and powerful framework to study these networks and their structure at various scales. By way of example, community detection methods have been widely applied to investigate the modular structure of many natural networks, including brain functional connectivity networks. Sparsification procedures are often applied to remove the weakest edges, which are the most affected by experimental noise, and to reduce the density of the graph, thus making it theoretically and computationally more tractable. However, weak links may also contain significant structural information, and procedures to identify the optimal tradeoff are the subject of active research. Here, we explore the use of percolation analysis, a method grounded in statistical physics, to identify the optimal sparsification threshold for community detection in brain connectivity networks. By using synthetic networks endowed with a ground-truth modular structure and realistic topological features typical of human brain functional connectivity networks, we show that percolation analysis can be applied to identify the optimal sparsification threshold that maximizes information on the networks' community structure. We validate this approach using three different community detection methods widely applied to the analysis of brain connectivity networks: Newman's modularity, InfoMap and Asymptotical Surprise. Importantly, we test the effects of noise and data variability, which are critical factors to determine the optimal threshold. This data-driven method should prove particularly useful in the analysis of the community structure of brain networks in populations characterized by different connectivity strengths, such as patients and controls.

Community detection in weighted brain connectivity networks beyond the resolution limit.

Graph theory provides a powerful framework to investigate brain functional connectivity networks and their modular organization. However, most graph-based methods suffer from a fundamental resolution limit that may have affected previous studies and prevented detection of modules, or "communities", that are smaller than a specific scale. Surprise, a resolution-limit-free function rooted in discrete probability theory, has been recently introduced and applied to brain networks, revealing a wide size-distribution of functional modules (Nicolini and Bifone, 2016), in contrast with many previous reports. However, the use of Surprise is limited to binary networks, while brain networks are intrinsically weighted, reflecting a continuous distribution of connectivity strengths between different brain regions. Here, we propose Asymptotical Surprise, a continuous version of Surprise, for the study of weighted brain connectivity networks, and validate this approach in synthetic networks endowed with a ground-truth modular structure. We compare Asymptotical Surprise with leading community detection methods currently in use and show its superior sensitivity in the detection of small modules even in the presence of noise and intersubject variability such as those observed in fMRI data. We apply our novel approach to functional connectivity networks from resting state fMRI experiments, and demonstrate a heterogeneous modular organization, with a wide distribution of clusters spanning multiple scales. Finally, we discuss the implications of these findings for the identification of connector hubs, the brain regions responsible for the integration of the different network elements, showing that the improved resolution afforded by Asymptotical Surprise leads to a different classification compared to current methods.

Time-resolved detection of stimulus/task-related networks, via clustering of transient intersubject synchronization.

Several methods are available for the identification of functional networks of brain areas using functional magnetic resonance imaging (fMRI) time-series. These typically assume a fixed relationship between the signal of the areas belonging to the same network during the entire time-series (e.g., positive correlation between the areas belonging to the same network), or require a priori information about when this relationship may change (task-dependent changes of connectivity). We present a fully data-driven method that identifies transient network configurations that are triggered by the external input and that, therefore, include only regions involved in stimulus/task processing. Intersubject synchronization with short sliding time-windows was used to identify if/when any area showed stimulus/task-related responses. Next, a first clustering step grouped together areas that became engaged concurrently and repetitively during the time-series (stimulus/task-related networks). Finally, for each network, a second clustering step grouped together all the time-windows with the same BOLD signal. The final output consists of a set of network configurations that show stimulus/task-related activity at specific time-points during the fMRI time-series. We label these configurations: "brain modes" (bModes). The method was validated using simulated datasets and a real fMRI experiment with multiple tasks and conditions. Future applications include the investigation of brain functions using complex and naturalistic stimuli.

Quantitative evaluation of fMRI retinotopic maps, from V1 to V4, for cognitive experiments.

FMRI retinotopic mapping is a non-invasive technique for the delineation of low-level visual areas in individual subjects. It generally relies upon the analysis of functional responses to periodic visual stimuli that encode eccentricity or polar angle in the visual field. This technique is used in vision research when the precise assignation of brain activation to retinotopic areas is an issue. It involves processing steps computed with different algorithms and embedded in various software suites. Manual intervention may be needed for some steps. Although the diversity of the available processing suites and manual interventions may potentially introduce some differences in the final delineation of visual areas, no documented comparison between maps obtained with different procedures has been reported in the literature. To explore the effect of the processing steps on the quality of the maps obtained, we used two tools, BALC, which relies on a fully automated procedure, and BrainVoyager, where areas are delineated "by hand" on the brain surface. To focus on the mapping procedures specifically, we used the same SPM pipeline for pretreatment and the same tissue segmentation tool. We document the consistency and differences of the fMRI retinotopic maps obtained from "routine retinotopy" experiments on 10 subjects. The maps obtained by skilled users are never fully identical. However, the agreement between the maps, around 80% for low-level areas, is probably sufficient for most applications. Our results also indicate that assigning cognitive activations, following a specific experiment (here, color perception), to individual retinotopic maps is not free of errors. We provide measurements of this error, that may help for the cautious interpretation of cognitive activation projection onto fMRI retinotopic maps. On average, the magnitude of the error is about 20%, with much larger differences in a few subjects. More variability may even be expected with less trained users or using different acquisition parameters and preprocessing chains.

Audio-visual perception of 3D cinematography: an fMRI study using condition-based and computation-based analyses.

The use of naturalistic stimuli to probe sensory functions in the human brain is gaining increasing interest. Previous imaging studies examined brain activity associated with the processing of cinematographic material using both standard "condition-based" designs, as well as "computational" methods based on the extraction of time-varying features of the stimuli (e.g. motion). Here, we exploited both approaches to investigate the neural correlates of complex visual and auditory spatial signals in cinematography. In the first experiment, the participants watched a piece of a commercial movie presented in four blocked conditions: 3D vision with surround sounds (3D-Surround), 3D with monaural sound (3D-Mono), 2D-Surround, and 2D-Mono. In the second experiment, they watched two different segments of the movie both presented continuously in 3D-Surround. The blocked presentation served for standard condition-based analyses, while all datasets were submitted to computation-based analyses. The latter assessed where activity co-varied with visual disparity signals and the complexity of auditory multi-sources signals. The blocked analyses associated 3D viewing with the activation of the dorsal and lateral occipital cortex and superior parietal lobule, while the surround sounds activated the superior and middle temporal gyri (S/MTG). The computation-based analyses revealed the effects of absolute disparity in dorsal occipital and posterior parietal cortices and of disparity gradients in the posterior middle temporal gyrus plus the inferior frontal gyrus. The complexity of the surround sounds was associated with activity in specific sub-regions of S/MTG, even after accounting for changes of sound intensity. These results demonstrate that the processing of naturalistic audio-visual signals entails an extensive set of visual and auditory areas, and that computation-based analyses can track the contribution of complex spatial aspects characterizing such life-like stimuli.

Retinotopic and lateralized processing of spatial frequencies in human visual cortex during scene categorization.

Using large natural scenes filtered in spatial frequencies, we aimed to demonstrate that spatial frequency processing could not only be retinotopically mapped but could also be lateralized in both hemispheres. For this purpose, participants performed a categorization task using large black and white photographs of natural scenes (indoors vs. outdoors, with a visual angle of 24° × 18°) filtered in low spatial frequencies (LSF), high spatial frequencies (HSF), and nonfiltered scenes, in block-designed fMRI recording sessions. At the group level, the comparison between the spatial frequency content of scenes revealed first that, compared with HSF, LSF scene categorization elicited activation in the anterior half of the calcarine fissures linked to the peripheral visual field, whereas, compared with LSF, HSF scene categorization elicited activation in the posterior part of the occipital lobes, which are linked to the fovea, according to the retinotopic property of visual areas. At the individual level, functional activations projected on retinotopic maps revealed that LSF processing was mapped in the anterior part of V1, whereas HSF processing was mapped in the posterior and ventral part of V2, V3, and V4. Moreover, at the group level, direct interhemispheric comparisons performed on the same fMRI data highlighted a right-sided occipito-temporal predominance for LSF processing and a left-sided temporal cortex predominance for HSF processing, in accordance with hemispheric specialization theories. By using suitable method of analysis on the same data, our results enabled us to demonstrate for the first time that spatial frequencies processing is mapped retinotopically and lateralized in human occipital cortex.

Sensory processing during viewing of cinematographic material: computational modeling and functional neuroimaging.

The investigation of brain activity using naturalistic, ecologically-valid stimuli is becoming an important challenge for neuroscience research. Several approaches have been proposed, primarily relying on data-driven methods (e.g. independent component analysis, ICA). However, data-driven methods often require some post-hoc interpretation of the imaging results to draw inferences about the underlying sensory, motor or cognitive functions. Here, we propose using a biologically-plausible computational model to extract (multi-)sensory stimulus statistics that can be used for standard hypothesis-driven analyses (general linear model, GLM). We ran two separate fMRI experiments, which both involved subjects watching an episode of a TV-series. In Exp 1, we manipulated the presentation by switching on-and-off color, motion and/or sound at variable intervals, whereas in Exp 2, the video was played in the original version, with all the consequent continuous changes of the different sensory features intact. Both for vision and audition, we extracted stimulus statistics corresponding to spatial and temporal discontinuities of low-level features, as well as a combined measure related to the overall stimulus saliency. Results showed that activity in occipital visual cortex and the superior temporal auditory cortex co-varied with changes of low-level features. Visual saliency was found to further boost activity in extra-striate visual cortex plus posterior parietal cortex, while auditory saliency was found to enhance activity in the superior temporal cortex. Data-driven ICA analyses of the same datasets also identified "sensory" networks comprising visual and auditory areas, but without providing specific information about the possible underlying processes, e.g., these processes could relate to modality, stimulus features and/or saliency. We conclude that the combination of computational modeling and GLM enables the tracking of the impact of bottom-up signals on brain activity during viewing of complex and dynamic multisensory stimuli, beyond the capability of purely data-driven approaches.

A BOLD signature of eyeblinks in the visual cortex.

We are usually unaware of the brief but large illumination changes caused by blinks, presumably because of blink suppression mechanisms. In fMRI however, increase of the BOLD signal was reported in the visual cortex, e.g. during blocks of voluntary blinks (Bristow, Frith and Rees, 2005) or after spontaneous blinks recorded during the prolonged fixation of a static stimulus (Tse, Baumgartner and Greenlee, 2010). We tested whether such activation, possibly related to illumination changes, was also present during standard fMRI retinotopic and visual experiments and was large enough to contaminate the BOLD signal we are interested in. We monitored in a 3T scanner the eyeblinks of 14 subjects who observed three different types of visual stimuli, including periodic rotating wedges and contracting/expanding rings, event-related Mondrians and graphemes, while fixating. We performed event-related analyses on the set of detected spontaneous blinks. We observed large and widespread BOLD responses related to blinks in the visual cortex of every subject and whatever the visual stimulus. The magnitude of the modulation was comparable to visual stimulation. However, blink-related activations lay mostly in the anterior parts of retinotopic visual areas, coding the periphery of the visual field well beyond the extent of our stimuli. Blinks therefore represent an important source of BOLD variations in the visual cortex and a troublesome source of noise since any correlation, even weak, between the distribution of blinks and a tested protocol could trigger artifactual activities. However, the typical signature of blinks along the anterior calcarine and the parieto-occipital sulcus allows identifying, even in the absence of eyetracking, fMRI protocols possibly contaminated by a heterogeneous distribution of blinks.

The neural bases of grapheme-color synesthesia are not localized in real color-sensitive areas.

The subjective experience of color by synesthetes when viewing achromatic letters and numbers supposedly relates to real color experience, as exemplified by the recruitment of the V4 color center observed in some brain imaging studies. Phenomenological reports and psychophysics tests indicate, however, that both experiences are different. Using functional magnetic resonance imaging, we tried to precise the degree of coactivation by real and synesthetic colors, by evaluating each color center individually, and applying adaptation protocols across real and synesthetic colors. We also looked for structural differences between synesthetes and nonsynesthetes. In 10 synesthetes, we found that color areas and retinotopic areas were not activated by synesthetic colors, whatever the strength of synesthetic associations measured objectively for each subject. Voxel-based morphometry revealed no white matter (WM) or gray matter difference in those regions when compared with 25 control subjects. But synesthetes had more WM in the retrosplenial cortex bilaterally. The joint coding of real and synesthetic colors, if it exists, must therefore be distributed rather than localized in the visual cortex. Alternatively, the key to synesthetic color experience might not lie in the color system.

Influence of background on image recognition in normal vision and age-related macular degeneration.

PURPOSE: The influence of background attenuation on the spatial frequency bandwidth requirements for image recognition was assessed in normal young and older groups and in a group with age-related macular degeneration (AMD). Bandwidth requirements were also assessed in the visual periphery of young normal observers. METHODS: In Experiment 1, each observer was presented with 20 series of images. Each series consisted of a sequence of progressively low-pass filtered images, presented in an order of increasing bandwidth, i.e., according to an ascending method of limits. For half of the series, the background of the base image was selectively darkened by 80% of its original luminance. Three measures were analyzed: (1) the critical bandwidth defined as the bandwidth in cycles/image (cpi) at which 50% of the images were recognized, (2) the minimal bandwidth, defined as the minimal bandwidth at which images were recognized and (3) the proportion of images recognized at full bandwidth. In Experiment 2, young normal observers were similarly tested in central vision and at 5.5° eccentricity (superior or inferior visual field). A third background attenuation condition was included, as well, in which the background was low-pass filtered. RESULTS: The critical bandwidth for image recognition was significantly reduced by darkening the image background for normal young and old and the AMD groups. This improvement was found to be contrast dependent for the darkened background. In addition, AMD observers tended to recognize more images at full bandwidth if the background was darkened. For normal young observers, making the background low-pass was ineffective in lowering the critical bandwidth in the fovea. Fewer images were recognized at full bandwidth at 5.5° eccentricity for a low-pass background and marginally fewer for a darkened background. CONCLUSIONS: Selective attenuation of the image background can lead to reductions in the bandwidth requirements for image recognition in AMD. However, performance of young normal observers for images presented in the periphery was unlike AMD performance under the conditions investigated. These results have interesting implications for the design of image enhancement algorithms to aid low vision observers.

fMRI retinotopic mapping at 3 T: benefits gained from correcting the spatial distortions due to static field inhomogeneity.

fMRI retinotopic mapping usually relies upon Fourier analysis of functional responses to periodic visual stimuli that encode eccentricity or polar angle in the visual field. Generally, phase estimations are assigned to a surface model of the cerebral cortex and borders between retinotopic areas are eventually determined following ad hoc phase analysis on the surface model. Assigning functional responses to a surface model of the cortex is particularly sensitive to geometric distortions of the 3D functional data due to static field inhomogeneity. Here, we assess and document the benefits gained from correcting the fMRI data for these effects, under standard experimental conditions (echo-planar imaging, 3.0-T field strength) and with well-chosen acquisition parameters (regarding slice orientation and phase-encoding direction). While it appears that, in the absence of correction, errors in the estimates of the borders between low-order visual areas do not then significantly exceed the variance of statistical origin, about half of the functional responses in a retinotopic experiment are misassigned to neighboring functional areas. Therefore, correction of the effects due to geometric distortions is important in any retinotopic mapping experiment and by extension in any fMRI experiment on the visual system.