Corrigendum: Brain morphological modifications in congenital and acquired auditory deprivation: a systematic review and coordinate-based meta-analysis.

[This corrects the article DOI: 10.3389/fnins.2022.850245.].

Brain structural changes in blindness: a systematic review and an anatomical likelihood estimation (ALE) meta-analysis.

In recent decades, numerous structural brain imaging studies investigated purported morphometric changes in early (EB) and late onset blindness (LB). The results of these studies have not yielded very consistent results, neither with respect to the type, nor to the anatomical locations of the brain morphometric alterations. To better characterize the effects of blindness on brain morphometry, we performed a systematic review and an Anatomical-Likelihood-Estimation (ALE) coordinate-based-meta-analysis of 65 eligible studies on brain structural changes in EB and LB, including 890 EB, 466 LB and 1257 sighted controls. Results revealed atrophic changes throughout the whole extent of the retino-geniculo-striate system in both EB and LB, whereas changes in areas beyond the occipital lobe occurred in EB only. We discuss the nature of some of the contradictory findings with respect to the used brain imaging methodologies and characteristics of the blind populations such as the onset, duration and cause of blindness. Future studies should aim for much larger sample sizes, eventually by merging data from different brain imaging centers using the same imaging sequences, opt for multimodal structural brain imaging, and go beyond a purely structural approach by combining functional with structural connectivity network analyses.

Local networks from different parts of the human cerebral cortex generate and share the same population dynamic.

A major goal of neuroscience is to reveal mechanisms supporting collaborative actions of neurons in local and larger-scale networks. However, no clear overall principle of operation has emerged despite decades-long experimental efforts. Here, we used an unbiased method to extract and identify the dynamics of local postsynaptic network states contained in the cortical field potential. Field potentials were recorded by depth electrodes targeting a wide selection of cortical regions during spontaneous activities, and sensory, motor, and cognitive experimental tasks. Despite different architectures and different activities, all local cortical networks generated the same type of dynamic confined to one region only of state space. Surprisingly, within this region, state trajectories expanded and contracted continuously during all brain activities and generated a single expansion followed by a contraction in a single trial. This behavior deviates from known attractors and attractor networks. The state-space contractions of particular subsets of brain regions cross-correlated during perceptive, motor, and cognitive tasks. Our results imply that the cortex does not need to change its dynamic to shift between different activities, making task-switching inherent in the dynamic of collective cortical operations. Our results provide a mathematically described general explanation of local and larger scale cortical dynamic.

Neural substrates of spatial processing and navigation in blindness: An activation likelihood estimation meta-analysis.

Even though vision is considered the best suited sensory modality to acquire spatial information, blind individuals can form spatial representations to navigate and orient themselves efficiently in space. Consequently, many studies support the amodality hypothesis of spatial representations since sensory modalities other than vision contribute to the formation of spatial representations, independently of visual experience and imagery. However, given the high variability in abilities and deficits observed in blind populations, a clear consensus about the neural representations of space has yet to be established. To this end, we performed a meta-analysis of the literature on the neural correlates of spatial processing and navigation via sensory modalities other than vision, like touch and audition, in individuals with early and late onset blindness. An activation likelihood estimation (ALE) analysis of the neuroimaging literature revealed that early blind individuals and sighted controls activate the same neural networks in the processing of non-visual spatial information and navigation, including the posterior parietal cortex, frontal eye fields, insula, and the hippocampal complex. Furthermore, blind individuals also recruit primary and associative occipital areas involved in visuo-spatial processing via cross-modal plasticity mechanisms. The scarcity of studies involving late blind individuals did not allow us to establish a clear consensus about the neural substrates of spatial representations in this specific population. In conclusion, the results of our analysis on neuroimaging studies involving early blind individuals support the amodality hypothesis of spatial representations.

Brain Morphological Modifications in Congenital and Acquired Auditory Deprivation: A Systematic Review and Coordinate-Based Meta-Analysis.

Neuroplasticity following deafness has been widely demonstrated in both humans and animals, but the anatomical substrate of these changes is not yet clear in human brain. However, it is of high importance since hearing loss is a growing problem due to aging population. Moreover, knowing these brain changes could help to understand some disappointing results with cochlear implant, and therefore could improve hearing rehabilitation. A systematic review and a coordinate-based meta-analysis were realized about the morphological brain changes highlighted by MRI in severe to profound hearing loss, congenital and acquired before or after language onset. 25 papers were included in our review, concerning more than 400 deaf subjects, most of them presenting prelingual deafness. The most consistent finding is a volumetric decrease in gray matter around bilateral auditory cortex. This change was confirmed by the coordinate-based meta-analysis which shows three converging clusters in this region. The visual areas of deaf children is also significantly impacted, with a decrease of the volume of both gray and white matters. Finally, deafness is responsible of a gray matter increase within the cerebellum, especially at the right side. These results are largely discussed and compared with those from deaf animal models and blind humans, which demonstrate for example a much more consistent gray matter decrease along their respective primary sensory pathway. In human deafness, a lot of other factors than deafness could interact on the brain plasticity. One of the most important is the use of sign language and its age of acquisition, which induce among others changes within the hand motor region and the visual cortex. But other confounding factors exist which have been too little considered in the current literature, such as the etiology of the hearing impairment, the speech-reading ability, the hearing aid use, the frequent associated vestibular dysfunction or neurocognitive impairment. Another important weakness highlighted by this review concern the lack of papers about postlingual deafness, whereas it represents most of the deaf population. Further studies are needed to better understand these issues, and finally try to improve deafness rehabilitation.

A quantitative analysis of the retinofugal projections in congenital and late-onset blindness.

Vision loss early in life has dramatic consequences on the organization of the visual system and hence on structural plasticity of its remnant components. Most of the studies on the anatomical changes in the brain following visual deprivation have focused on the re-organization of the visual cortex and its afferent and efferent projections. In this study, we performed a quantitative analysis of the volume and size of the optic chiasm, optic nerve, optic tract and the lateral geniculate nucleus (LGN), the retino recipient thalamic nucleus. Analysis was carried out on structural T1-weighted MRIs from 22 congenitally blind (CB), 14 late blind (LB) and 29 age -and sex-matched sighted control (SC) subjects. We manually segmented the optic nerve, optic chiasm and optic tract, while LGN volumes were extracted using in-house software. We also measured voxel intensity of optic nerve, optic chiasm and optic tract. Mean volumes of the optic nerve, optic tract and optic chiasm were reduced by 50 to 60% in both CB and LB participants. No significant differences were found between the congenitally and late-onset blind participants for any of the measures. Our data further revealed reduced white matter voxel intensities in optic nerve, optic chiasm and optic tract in blind compared to sighted participants, suggesting decreased myelin content in the atrophied white matter. The LGN was reduced by 50% and 44% in CB and LB, respectively. In LB, optic nerve volume correlated negatively with the blindness duration index; no such correlation was found for optic chiasm, optic tract and LGN. The observation that despite the absence of visual input about half of the subcortical retinofugal projections are structurally preserved raises the question of their functional role. One possibility is that the surviving fibers play a role in the maintenance of circadian rhythms in the blind through the intrinsically photosensitive melanopsin-containing retinal ganglion cells.

High-Density EEG in a Charles Bonnet Syndrome Patient during and without Visual Hallucinations: A Case-Report Study.

Charles Bonnet syndrome (CBS) is a rare clinical condition characterized by complex visual hallucinations in people with loss of vision. So far, the neurobiological mechanisms underlying the hallucinations remain elusive. This case-report study aims at investigating electrical activity changes in a CBS patient during visual hallucinations, as compared to a resting-state period (without hallucinations). Prior to the EEG, the patient underwent neuropsychological, ophthalmologic, and neurological examinations. Spectral and connectivity, graph analyses and signal diversity were applied to high-density EEG data. Visual hallucinations (as compared to resting-state) were characterized by a significant reduction of power in the frontal areas, paralleled by an increase in the midline posterior regions in delta and theta bands and by an increase of alpha power in the occipital and midline posterior regions. We next observed a reduction of theta connectivity in the frontal and right posterior areas, which at a network level was complemented by a disruption of small-worldness (lower local and global efficiency) and by an increase of network modularity. Finally, we found a higher signal complexity especially when considering the frontal areas in the alpha band. The emergence of hallucinations may stem from these changes in the visual cortex and in core cortical regions encompassing both the default mode and the fronto-parietal attentional networks.

Blindness and the Reliability of Downwards Sensors to Avoid Obstacles: A Study with the EyeCane.

Vision loss has dramatic repercussions on the quality of life of affected people, particularly with respect to their orientation and mobility. Many devices are available to help blind people to navigate in their environment. The EyeCane is a recently developed electronic travel aid (ETA) that is inexpensive and easy to use, allowing for the detection of obstacles lying ahead within a 2 m range. The goal of this study was to investigate the potential of the EyeCane as a primary aid for spatial navigation. Three groups of participants were recruited: early blind, late blind, and sighted. They were first trained with the EyeCane and then tested in a life-size obstacle course with four obstacles types: cube, door, post, and step. Subjects were requested to cross the corridor while detecting, identifying, and avoiding the obstacles. Each participant had to perform 12 runs with 12 different obstacles configurations. All participants were able to learn quickly to use the EyeCane and successfully complete all trials. Amongst the various obstacles, the step appeared to prove the hardest to detect and resulted in more collisions. Although the EyeCane was effective for detecting obstacles lying ahead, its downward sensor did not reliably detect those on the ground, rendering downward obstacles more hazardous for navigation.

Spatial navigation with horizontally spatialized sounds in early and late blind individuals.

Blind individuals often report difficulties to navigate and to detect objects placed outside their peri-personal space. Although classical sensory substitution devices could be helpful in this respect, these devices often give a complex signal which requires intensive training to analyze. New devices that provide a less complex output signal are therefore needed. Here, we evaluate a smartphone-based sensory substitution device that offers navigation guidance based on strictly spatial cues in the form of horizontally spatialized sounds. The system uses multiple sensors to either detect obstacles at a distance directly in front of the user or to create a 3D map of the environment (detection and avoidance mode, respectively), and informs the user with auditory feedback. We tested 12 early blind, 11 late blind and 24 blindfolded-sighted participants for their ability to detect obstacles and to navigate in an obstacle course. The three groups did not differ in the number of objects detected and avoided. However, early blind and late blind participants were faster than their sighted counterparts to navigate through the obstacle course. These results are consistent with previous research on sensory substitution showing that vision can be replaced by other senses to improve performance in a wide variety of tasks in blind individuals. This study offers new evidence that sensory substitution devices based on horizontally spatialized sounds can be used as a navigation tool with a minimal amount of training.

Metabolic underpinnings of activated and deactivated cortical areas in human brain.

Neuroimaging with functional MRI (fMRI) identifies activated and deactivated brain regions in task-based paradigms. These patterns of (de)activation are altered in diseases, motivating research to understand their underlying biochemical/biophysical mechanisms. Essentially, it remains unknown how aerobic metabolism of glucose to lactate (aerobic glycolysis) and excitatory-inhibitory balance of glutamatergic and GABAergic neuronal activities vary in these areas. In healthy volunteers, we investigated metabolic distinctions of activating visual cortex (VC, a task-positive area) using a visual task and deactivating posterior cingulate cortex (PCC, a task-negative area) using a cognitive task. We used fMRI-guided J-edited functional MRS (fMRS) to measure lactate, glutamate plus glutamine (Glx) and γ-aminobutyric acid (GABA), as indicators of aerobic glycolysis and excitatory-inhibitory balance, respectively. Both lactate and Glx increased upon activating VC, but did not change upon deactivating PCC. Basal GABA was negatively correlated with BOLD responses in both brain areas, but during functional tasks GABA decreased in VC upon activation and GABA increased in PCC upon deactivation, suggesting BOLD responses in relation to baseline are impacted oppositely by task-induced inhibition. In summary, opposite relations between BOLD response and GABAergic inhibition, and increases in aerobic glycolysis and glutamatergic activity distinguish the BOLD response in (de)activated areas.

Organization of the commissural fiber system in congenital and late-onset blindness.

We investigated the effects of blindness on the structural and functional integrity of the corpus callosum and the anterior commissure (AC), which together form the two major components of the commissural pathways. Twelve congenitally blind (CB), 15 late blind (LB; mean onset of blindness of 16.6 ± 8.9 years), and 15 matched normally sighted controls (SC) participated in a multimodal brain imaging study. Magnetic resonance imaging(MRI) data were acquired using a 3T scanner, and included a structural brain scan, resting state functional MRI, and diffusion-weighted imaging. We used tractography to divide the AC into its anterior (aAC) and posterior (pAC) branch. Virtual tract dissection was performed using a deterministic spherical deconvolution tractography algorithm. The corpus callosum was subdivided into five subregions based on the criteria described by Witelson and modified by Bermudez and Zatorre. Our data revealed decreased fractional anisotropy of the pAC in CB and LB compared to SC, together with an increase in the number of streamlines in CB only. In addition, the AC surface area was significantly larger in CB compared to SC and LB, and correlated with the number of streamlines in pAC (rho = 0.55) and tract volume (rho = 0.46). As for the corpus callosum, the splenial part was significantly smaller in CB and LB, and fewer streamlines passed through it. We did not find group differences in functional connectivity of cortical areas connected by fibers crossing any of the five callosal subregions. The present data suggest that the two main components of the commissural system undergo neuroplastic changes, irrespective of the age of onset of blindness, although the alterations observed in the AC are more important in congenital than late-onset blindness.

Reorganization of Sound Location Processing in the Auditory Cortex of Blind Humans.

Auditory spatial tasks induce functional activation in the occipital-visual-cortex of early blind humans. Less is known about the effects of blindness on auditory spatial processing in the temporal-auditory-cortex. Here, we investigated spatial (azimuth) processing in congenitally and early blind humans with a phase-encoding functional magnetic resonance imaging (fMRI) paradigm. Our results show that functional activation in response to sounds in general-independent of sound location-was stronger in the occipital cortex but reduced in the medial temporal cortex of blind participants in comparison with sighted participants. Additionally, activation patterns for binaural spatial processing were different for sighted and blind participants in planum temporale. Finally, fMRI responses in the auditory cortex of blind individuals carried less information on sound azimuth position than those in sighted individuals, as assessed with a 2-channel, opponent coding model for the cortical representation of sound azimuth. These results indicate that early visual deprivation results in reorganization of binaural spatial processing in the auditory cortex and that blind individuals may rely on alternative mechanisms for processing azimuth position.

A thalamocortical pathway for fast rerouting of tactile information to occipital cortex in congenital blindness.

In congenitally blind individuals, the occipital cortex responds to various nonvisual inputs. Some animal studies raise the possibility that a subcortical pathway allows fast re-routing of tactile information to the occipital cortex, but this has not been shown in humans. Here we show using magnetoencephalography (MEG) that tactile stimulation produces occipital cortex activations, starting as early as 35 ms in congenitally blind individuals, but not in blindfolded sighted controls. Given our measured thalamic response latencies of 20 ms and a mean estimated lateral geniculate nucleus to primary visual cortex transfer time of 15 ms, we claim that this early occipital response is mediated by a direct thalamo-cortical pathway. We also observed stronger directed connectivity in the alpha band range from posterior thalamus to occipital cortex in congenitally blind participants. Our results strongly suggest the contribution of a fast thalamo-cortical pathway in the cross-modal activation of the occipital cortex in congenitally blind humans.

Parkinson's disease and changes in the appreciation of art: A comparison of aesthetic and formal evaluations of paintings between PD patients and healthy controls.

Parkinson's disease (PD) is a progressing neurodegenerative disease predominantly involving the loss of dopamine producing neurons with hallmark symptoms of motor disorders and cognitive, motivational, emotional, and perceptual impairments. Intriguingly, PD can also be connected-often anecdotally-with a sudden burst of artistic creativity, motivation, or changed quality/style of produced art. This has led to growing empirical interest, promising a window into brain function and the unique neurological signature of artists. This topic also fits a growing interest from researchers in other areas, including Alzheimer's or other dementia, which have suggested that specific changes in art production/appraisal may provide a unique basis for therapy, diagnosis, or understanding of these diseases. However, whether PD also shows similar impacts on how we perceive and evaluate art has never been systematically addressed. We compared a cohort of PD patients against age-matched healthy controls, asking participants to rate paintings using scales of liking and beauty and terms pertaining to artworks' formal and conceptual qualities previously designed to provide a rubric for symptom identification. We found no evidence for PD-related differences in liking or beauty. However, PD patients showed higher ratings on assessed "emotionality," potentially relating to the tie between PD, dopamine pathways, and emotion/reward.

Resting-state functional connectivity and cortical thickness characterization of a patient with Charles Bonnet syndrome.

Charles Bonnet syndrome (CBS) is a rare condition characterized by visual impairment associated with complex visual hallucinations in elderly people. Although studies suggested that visual hallucinations may be caused by brain damage in the visual system in CBS patients, alterations in specific brain regions in the occipital cortex have not been studied. Functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI; without hallucinations) in CBS patients, has never been explored. We aimed to investigate brain structural and functional changes in a patient with CBS, as compared with late blind (LB) and normally sighted subjects. We employed voxel-based morphometry and cortical thickness analyses to investigate alterations in grey matter characteristics, and rs-fMRI to study changes in functional brain connectivity. Decreased grey matter volume was observed in the middle occipital gyrus and in the cuneus in the CBS patient, and in the middle occipital gyrus and in the lingual gyrus within LB subjects, compared to their respective control groups. Reductions in cortical thickness in associative and multimodal cortices were observed in the CBS patient when comparing with LB subjects. The precuneus exhibited increased functional connectivity with the secondary visual cortex in the CBS patient compared to the controls. In contrast, LB patients showed decreased functional connectivity compared to sighted controls between the DMN and the temporo-occipital fusiform gyrus, a region known to support hallucinations. Our findings suggest a reorganization of the functional connectivity between regions involved in self-awareness and in visual and salience processing in CBS that may contribute to the appearance of visual hallucinations.

Rapid eye movements are reduced in blind individuals.

There is ongoing controversy regarding the role of rapid eye movements (EMs) during rapid eye movement (REM) sleep. One prevailing hypothesis is that EMs during REM sleep are indicative of the presence of visual imagery in dreams. We tested the validity of this hypothesis by measuring EMs in blind subjects and correlating these with visual dream content. Eleven blind subjects, of whom five were congenitally blind (CB) and six late blind (LB), and 11 matched sighted control (SC) subjects participated in this study. All participants underwent full-night polysomnography (PSG) recordings that were staged manually following American Academy of Sleep Medicine (AASM) criteria. Nocturnal EMs were detected automatically using a validated EM detector, and EM activity was represented as "EM coverage" computed as percentage of time with EM in each sleep stage. Frequency of sensory dream elements was measured in dream recall questionnaires over a 30-day period. Both blind groups showed less EM coverage during wakefulness, N1, N2 and REM sleep than did controls. CB and LB subjects did not differ in EM activity. Validation of the detector applied to blind subjects revealed an overall accuracy of 95.6 ± 3.6%. Analysis of dream reports revealed that LB subjects reported significantly more visual dream elements than did CB. Although no specific mechanisms can be revealed in the current study, the quasi absence of nocturnal EMs in LB subjects despite preserved visual dream content does not support the visual scanning of dreams hypothesis. Specifically, results suggest a dissociation between EMs and visual dream content in blind individuals.

Why would Parkinson's disease lead to sudden changes in creativity, motivation, or style with visual art?: A review of case evidence and new neurobiological, contextual, and genetic hypotheses.

Parkinson's disease (PD) is a devastating diagnosis with, however, potential for an extremely intriguing aesthetic component. Despite motor and cognitive deficits, an emerging collection of studies report a burst of visual artistic output and alterations in produced art in a subgroup of patients. This provides a unique window into the neurophysiological bases for why and how we might create and enjoy visual art, as well as into general brain function and the nature of PD or other neurodegenerative diseases. However, there has not been a comprehensive organization of literature on this topic. Nor has there been an attempt to connect case evidence and knowledge on PD with present understanding of visual art making in psychology and neuroaesthetics in order to propose hypotheses for documented artistic changes. Here, we collect the current research on this topic, tie this to PD symptoms and neurobiology, and provide new theories focusing on dopaminergic neuron damage, over-stimulation from dopamine agonist therapy, and context or genetic factors revealing the neurobiological basis of the visual artistic brain.

Impact of Global Mean Normalization on Regional Glucose Metabolism in the Human Brain.

Because the human brain consumes a disproportionate fraction of the resting body's energy, positron emission tomography (PET) measurements of absolute glucose metabolism (CMRglc) can serve as disease biomarkers. Global mean normalization (GMN) of PET data reveals disease-based differences from healthy individuals as fractional changes across regions relative to a global mean. To assess the impact of GMN applied to metabolic data, we compared CMRglc with and without GMN in healthy awake volunteers with eyes closed (i.e., control) against specific physiological/clinical states, including healthy/awake with eyes open, healthy/awake but congenitally blind, healthy/sedated with anesthetics, and patients with disorders of consciousness. Without GMN, global CMRglc alterations compared to control were detected in all conditions except in congenitally blind where regional CMRglc variations were detected in the visual cortex. However, GMN introduced regional and bidirectional CMRglc changes at smaller fractions of the quantitative delocalized changes. While global information was lost with GMN, the quantitative approach (i.e., a validated method for quantitative baseline metabolic activity without GMN) not only preserved global CMRglc alterations induced by opening eyes, sedation, and varying consciousness but also detected regional CMRglc variations in the congenitally blind. These results caution the use of GMN upon PET-measured CMRglc data in health and disease.

Aδ and not C fibers mediate thermal hyperalgesia to short laser stimuli after burn injury in man.

It remains unclear which nerve fibers are responsible for mediating hyperalgesia after skin injury. Here, we examined the role of Aδ and C fibers in inflammatory hyperalgesia after a first-degree burn injury. A CO2 laser delivered ultrafast short constant-temperature heat pulses to the upper part of the lower leg to stimulate selectively the relatively fast-conducting thinly myelinated Aδ and the slowly conducting unmyelinated C fibers. Participants were asked to respond as fast as possible whenever they detected a thermal stimulus. Thresholds and reaction times to selective Aδ and C fiber activations were measured in the conditioned and the surrounding intact skin, at pre-injury, and 1 hour and 24 hours after injury. First-degree burn injury caused a significant decrease in Aδ fiber detection thresholds and a significant increase in the proportion of Aδ-fiber-mediated responses in the inflamed area 24 hours, but not 1 hour, after burn injury. No changes in heat perception were observed in the intact skin surrounding the injury. No group differences in C-fiber-mediated sensations were observed. Our findings indicate that quickly adapting Aδ fibers but not quickly adapting C fibers are sensitized when activated by short and ultrafast heat stimuli after skin burn injury. Our results further show that this change occurs between 1 hour and 24 hours after injury and that it does not extend to the skin surrounding the injury.