Non-visual Brain Research Articles

Convolutional neural network-based classification of glaucoma using optic radiation tissue properties

BackgroundSensory changes due to aging or disease can impact brain tissue. This study aims to investigate the link between glaucoma, a leading cause of blindness, and alterations in brain connections.MethodsWe analyzed diffusion MRI measurements of white matter tissue in a large group, consisting of 905 glaucoma patients (aged 49-80) and 5292 healthy individuals (aged 45-80) from the UK Biobank. Confounds due to group differences were mitigated by matching a sub-sample of controls to glaucoma subjects. We compared classification of glaucoma using convolutional neural networks (CNNs) focusing on the optic radiations, which are the primary visual connection to the cortex, against those analyzing non-visual brain connections. As a control, we evaluated the performance of regularized linear regression models.ResultsWe showed that CNNs using information from the optic radiations exhibited higher accuracy in classifying subjects with glaucoma when contrasted with CNNs relying on information from non-visual brain connections. Regularized linear regression models were also tested, and showed significantly weaker classification performance. Additionally, the CNN was unable to generalize to the classification of age-group or of age-related macular degeneration.ConclusionsOur findings indicate a distinct and potentially non-linear signature of glaucoma in the tissue properties of optic radiations. This study enhances our understanding of how glaucoma affects brain tissue and opens avenues for further research into how diseases that affect sensory input may also affect brain aging.

Contributed Session I: Specific and non-linear effects of glaucoma on optic radiation tissue properties.

Changes in sensory input with aging and disease affect brain tissue properties. To establish the link between glaucoma, the most prevalent cause of irreversible blindness, and changes in major brain connections, we characterized white matter tissue properties in diffusion MRI measurements in a large sample of subjects with glaucoma (N=905; age 49-80) and healthy controls (N=5,292; age 45-80) from the UK Biobank. Confounds due to group differences were mitigated by matching a sub-sample of controls to glaucoma subjects. A convolutional neural network (CNN) accurately classified whether a subject has glaucoma using information from the primary visual connection to cortex (the optic radiations, OR), but not from non-visual brain connections. On the other hand, regularized linear regression could not classify glaucoma, and the CNN did not generalize to classification of age-group or of age-related macular degeneration. This suggests a unique non-linear signature of glaucoma in OR tissue properties.

Abnormal Topological Organization of White Matter Structural Networks in Normal Tension Glaucoma Revealed via Diffusion Tensor Tractography.

Normal tension glaucoma (NTG) is considered a neurodegenerative disease with glaucomatous damage extending to diffuse brain areas. Therefore, this study aims to explore the abnormalities in the NTG structural network to help in the early diagnosis and course evaluation of NTG. The structural networks of 46 NTG patients and 19 age- and sex-matched healthy controls were constructed using diffusion tensor imaging, followed by graph theory analysis and correlation analysis of small-world properties with glaucoma clinical indicators. In addition, the network-based statistical analysis (NBS) method was used to compare structural network connectivity differences between NTG patients and healthy controls. Structural brain networks in both NTG and NC groups exhibited small-world properties. However, the small-world index in the severe NTG group was reduced and correlated with a mean deviation of the visual field (MDVF) and retinal nerve fiber layer (RNFL) thickness. When compared to healthy controls, degree centrality and nodal efficiency in visual brain areas were significantly decreased, and betweenness centrality and nodal local efficiency in both visual and nonvisual brain areas were also significantly altered in NTG patients (all p < 0.05, FDR corrected). Furthermore, NTG patients exhibited increased structural connectivity in the occipitotemporal area, with the left fusiform gyrus (FFG.L) as the hub (p < 0.05). NTG exhibited altered global properties and local properties of visual and cognitive-emotional brain areas, with enhanced structural connections within the occipitotemporal area. Moreover, the disrupted small-world properties of white matter might be imaging biomarkers for assessing NTG progression.

Advances in transcorneal electrical stimulation: From the eye to the brain

The mammalian brain is reported to contain about 106-109 neurons linked together to form complex networks. Physiologically, the neuronal networks interact in a rhythmic oscillatory pattern to coordinate the brain's functions. Neuromodulation covers a broad range of techniques that can alter neuronal network activity through the targeted delivery of electrical or chemical stimuli. Neuromodulation can be used to potentially treat medical conditions and can serve as a research tool for studying neural functions. Typically, the main method of neuromodulation is to electrically stimulate specific structures in both the central and peripheral nervous systems via surgically implanted electrodes. Therefore, it is imperative to explore novel and safer methods for altering neuronal network activity. Transcorneal electrical stimulation (TES) has rapidly emerged as a non-invasive neuromodulatory technique that can exert beneficial effects on the brain through the eyes. There is substantial evidence to show that TES can change the brain oscillations in rodents. Moreover, the molecular data clearly shows that TES can also activate non-visual brain regions. In this review, we first summarize the use of TES in the retina and then discuss its effects in the brain through the eye-brain connection. We then comprehensively review the substantial evidence from electrophysiological, behavioral, and molecular studies on the role of TES on modulating neurons in the brain. Lastly, we discuss the implications and possible future directions of the research on TES as a non-invasive tool for neuromodulation of the brain via directly stimulating the mammalian eye.

Functional connectivity of brain networks with three monochromatic wavelengths: a pilot study using resting-state functional magnetic resonance imaging

Exposure to certain monochromatic wavelengths can affect non-visual brain regions. Growing research indicates that exposure to light can have a positive impact on health-related problems such as spring asthenia, circadian rhythm disruption, and even bipolar disorders and Alzheimer’s. However, the extent and location of changes in brain areas caused by exposure to monochromatic light remain largely unknown. This pilot study (N = 7) using resting-state functional magnetic resonance shows light-dependent functional connectivity patterns on brain networks. We demonstrated that 1 min of blue, green, or red light exposure modifies the functional connectivity (FC) of a broad range of visual and non-visual brain regions. Largely, we observed: (i) a global decrease in FC in all the networks but the salience network after blue light exposure, (ii) a global increase in FC after green light exposure, particularly noticeable in the left hemisphere, and (iii) a decrease in FC on attentional networks coupled with a FC increase in the default mode network after red light exposure. Each one of the FC patterns appears to be best arranged to perform better on tasks associated with specific cognitive domains. Results can be relevant for future research on the impact of light stimulation on brain function and in a variety of health disciplines.

Application of advanced magnetic resonance imaging in glaucoma: a narrative review.

Glaucoma is a group of eye diseases characterized by progressive degeneration of the optic nerve head and retinal ganglion cells and corresponding visual field defects. In recent years, mounting evidence has shown that glaucoma-related damage may not be limited to the degeneration of retinal ganglion cells or the optic nerve head. The entire structure of the visual pathway may be degraded, and the degradation may even extend to some non-visual brain regions. We know that advanced morphological, functional, and metabolic magnetic resonance technologies provide a means to observe quantitatively and in real time the state of brain function. Advanced magnetic resonance imaging (MRI) techniques provide additional diagnostic markers for glaucoma, which are related to known potential histopathological changes. Many researchers in China and globally have conducted clinical and imaging studies on glaucoma. However, they are scattered, and we still need to systematically sort out the advanced MRI related to glaucoma. We reviewed literature published in any language and included all studies that were able to be translated into English from 1 January 1980 to 31 July 2021. Our literature search focused on emerging magnetic resonance neuroimaging techniques for the study of glaucoma. We then identified each functional area of the brain of glaucoma patients through the integration of anatomy, image, and function. The aim was to provide more information about the occurrence and development of glaucoma diseases. From the perspective of neuroimaging, our study provides a research basis to explain the possible mechanism of the occurrence and development of glaucoma. This knowledge gained from these techniques enables us to more clearly observe the damage glaucoma causes to the whole visual pathway. Our study provides new insights into glaucoma-induced changes to the brain. Our findings may enable the progress of these changes to be analyzed and inspire new neuroprotective therapeutic strategies for patients with glaucoma in the future.

Transcorneal Electrical Stimulation Induces Long-Lasting Enhancement of Brain Functional and Directional Connectivity in Retinal Degeneration Mice.

To investigate neuromodulation of functional and directional connectivity features in both visual and non-visual brain cortices after short-term and long-term retinal electrical stimulation in retinal degeneration mice. We performed spontaneous electrocorticography (ECoG) in retinal degeneration (rd) mice following prolonged transcorneal electrical stimulation (pTES) at varying currents (400, 500 and 600 μA) and different time points (transient or day 1 post-stimulation, 1-week post-stimulation and 2-weeks post-stimulation). We also set up a sham control group of rd mice which did not receive any electrical stimulation. Subsequently we analyzed alterations in cross-frequency coupling (CFC), coherence and directional connectivity of the primary visual cortex and the prefrontal cortex. It was observed that the sham control group did not display any significant changes in brain connectivity across all stages of electrical stimulation. For the stimulated groups, we observed that transient electrical stimulation of the retina did not significantly alter brain coherence and connectivity. However, for 1-week post-stimulation, we identified enhanced increase in theta-gamma CFC. Meanwhile, enhanced coherence and directional connectivity appeared predominantly in theta, alpha and beta oscillations. These alterations occurred in both visual and non-visual brain regions and were dependent on the current amplitude of stimulation. Interestingly, 2-weeks post-stimulation demonstrated long-lasting enhancement in network coherence and connectivity patterns at the level of cross-oscillatory interaction, functional connectivity and directional inter-regional communication between the primary visual cortex and prefrontal cortex. Application of electrical stimulation to the retina evidently neuromodulates brain coherence and connectivity of visual and non-visual cortices in retinal degeneration mice and the observed alterations are largely maintained. pTES holds strong possibility of modulating higher cortical functions including pathways of cognition, awareness, emotion and memory.

Dynamic neurogenomic responses to social interactions and dominance outcomes in female paper wasps.

Social interactions have large effects on individual physiology and fitness. In the immediate sense, social stimuli are often highly salient and engaging. Over longer time scales, competitive interactions often lead to distinct social ranks and differences in physiology and behavior. Understanding how initial responses lead to longer-term effects of social interactions requires examining the changes in responses over time. Here we examined the effects of social interactions on transcriptomic signatures at two times, at the end of a 45-minute interaction and 4 hours later, in female Polistes fuscatus paper wasp foundresses. Female P. fuscatus have variable facial patterns that are used for visual individual recognition, so we separately examined the transcriptional dynamics in the optic lobe and the non-visual brain. Results demonstrate much stronger transcriptional responses to social interactions in the non-visual brain compared to the optic lobe. Differentially regulated genes in response to social interactions are enriched for memory-related transcripts. Comparisons between winners and losers of the encounters revealed similar overall transcriptional profiles at the end of an interaction, which significantly diverged over the course of 4 hours, with losers showing changes in expression levels of genes associated with aggression and reproduction in paper wasps. On nests, subordinate foundresses are less aggressive, do more foraging and lay fewer eggs compared to dominant foundresses and we find losers shift expression of many genes in the non-visual brain, including vitellogenin, related to aggression, worker behavior, and reproduction within hours of losing an encounter. These results highlight the early neurogenomic changes that likely contribute to behavioral and physiological effects of social status changes in a social insect.

The effect of congenital blindness on resting-state functional connectivity revisited

Lower resting-state functional connectivity (RSFC) between ‘visual’ and non-‘visual’ neural circuits has been reported as a hallmark of congenital blindness. In sighted individuals, RSFC between visual and non-visual brain regions has been shown to increase during rest with eyes closed relative to rest with eyes open. To determine the role of visual experience on the modulation of RSFC by resting state condition—as well as to evaluate the effect of resting state condition on group differences in RSFC—, we compared RSFC between visual and somatosensory/auditory regions in congenitally blind individuals (n = 9) and sighted participants (n = 9) during eyes open and eyes closed conditions. In the sighted group, we replicated the increase of RSFC between visual and non-visual areas during rest with eyes closed relative to rest with eyes open. This was not the case in the congenitally blind group, resulting in a lower RSFC between ‘visual’ and non-‘visual’ circuits relative to sighted controls only in the eyes closed condition. These results indicate that visual experience is necessary for the modulation of RSFC by resting state condition and highlight the importance of considering whether sighted controls should be tested with eyes open or closed in studies of functional brain reorganization as a consequence of blindness.

Functional, anatomical and diffusion tensor MRI study of radiology expertise.

BackgroundRepeated practice to acquire expertise could result in the structural and functional changes in relevant brain circuits as a result of long-term potentiation, neurogenesis, glial genesis, and remodeling.PurposeThe goal of this study is to use task fMRI to study the brain of expert radiologists performing a diagnosis task where a series of medical images were presented during fMRI acquisition for 12s and participants were asked to choose a diagnosis. Structural and diffusion-tensor MRI were also acquired.MethodsRadiologists (N = 12, 11M, 38.2±10.3 years old) and non-radiologists (N = 17, 15M, 30.6±5.5 years old) were recruited with informed consent. Medical images were presented for 12 s and three multiple choices were displayed and the participants were asked to choose a diagnosis. fMRI, structural and diffusion-tensor MRI were acquired. fMRI analysis used FSL to determine differences in fMRI responses between groups. Voxel-wise analysis was performed to determine if subcortical volume, cortical thickness and fractional anisotropy differed between groups. Correction for multiple comparisons used false discovery rate.ResultsRadiologists showed overall lower task-related brain activation than non-radiologists. Radiologists showed significantly lower activation in the left lateral occipital cortex, left superior parietal lobule, occipital pole, right superior frontal and precentral gyri, lingual gyrus, and the left intraparietal sulcus (p<0.05). There were no significant differences between groups in cortical thickness, subcortical volume and fractional anisotropy (p>0.05).ConclusionsRadiologists and non-radiologists had no significant difference in structural metrics. However, in diagnosis tasks, radiologists showed markedly lower task-related brain activations overall as well as a number of high-order visual and non-visual brain regions than non-radiologists. Some brain circuits appear to be uniquely associated with differential-diagnosis paradigm expertise that are not involved in simpler object-recognition cases. Improved understanding of the brain circuitry involved in acquisition of expertise might be used to design optimal training paradigms.

The relative contributions of visual and semantic information in the neural representation of object categories.

IntroductionHow do multiple sources of information interact to form mental representations of object categories? It is commonly held that object categories reflect the integration of perceptual features and semantic/knowledge‐based features. To explore the relative contributions of these two sources of information, we used functional magnetic resonance imaging (fMRI) to identify regions involved in the representation object categories with shared visual and/or semantic features.MethodsParticipants (N = 20) viewed a series of objects that varied in their degree of visual and semantic overlap in the MRI scanner. We used a blocked adaptation design to identify sensitivity to visual and semantic features in a priori visual processing regions and in a distributed network of object processing regions with an exploratory whole‐brain analysis.ResultsSomewhat surprisingly, within higher‐order visual processing regions—specifically lateral occipital cortex (LOC)—we did not obtain any difference in neural adaptation for shared visual versus semantic category membership. More broadly, both visual and semantic information affected a distributed network of independently identified category‐selective regions. Adaptation was seen a whole‐brain network of processing regions in response to visual similarity and semantic similarity; specifically, the angular gyrus (AnG) adapted to visual similarity and the dorsomedial prefrontal cortex (DMPFC) adapted to both visual and semantic similarity.ConclusionsOur findings suggest that perceptual features help organize mental categories throughout the object processing hierarchy. Most notably, visual similarity also influenced adaptation in nonvisual brain regions (i.e., AnG and DMPFC). We conclude that category‐relevant visual features are maintained in higher‐order conceptual representations and visual information plays an important role in both the acquisition and neural representation of conceptual object categories.

Diffuse brain damage in normal tension glaucoma.

Brain changes within and beyond the visual system have been demonstrated in primary open angle glaucoma (POAG), the most common type of glaucoma. These changes have been often interpreted as a neurodegenerative process due, at least partially, to the raised intraocular pressure (IOP). In this context, normal tension glaucoma (NTG), a form of POAG with IOP <21 mm Hg despite the typical glaucomatous findings, represents the most suitable model of glaucoma to test the validity of this hypothesis. We acquired multimodal brain MRI in NTG patients (n = 17) and compared them with demographically matched groups of POAG patients with raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was performed with nonparametric permutation testing. Both NTG and POAG patients showed, compared to NC, significantly more gray matter atrophy in both the visual system and in nonvisual brain regions and altered diffusion tensor imaging-derived anatomical connectivity (AC; lower fractional anisotropy and/or higher diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with respect to NC was altered in NTG at short-range level [visual network (VN), ventral attention network] and in POAG at long-range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network. This study provides further evidence that diffuse structural and functional abnormalities across glaucoma brain may be, at least partially, independent of raised IOP and the consequent retinal degeneration. This further defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp 39:532-541, 2018. © 2017 Wiley Periodicals, Inc.

Structural brain alterations in primary open angle glaucoma: a 3T MRI study.

Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/2), amygdala and hippocampus. While VBA showed no significant differences in the gray matter volumes of patients, SBA revealed significantly reduced cortical thickness in the right frontal pole and ROI-based analysis volume shrinkage in LGN bilaterally, right V1 and left amygdala. Structural abnormalities were correlated with clinical parameters in a subset of the patients revealing that the left LGN volume was negatively correlated with bilateral cup-to-disk ratio (CDR), the right LGN volume was positively correlated with the mean deviation of the right visual hemifield, and the right V1 cortical thickness was negatively correlated with the right CDR in glaucoma. These results demonstrate that POAG affects both vision-related structures and non-visual cortical regions. Moreover, alterations of the brain visual structures reflect the clinical severity of glaucoma.

Training leads to increased auditory brain–computer interface performance of end-users with motor impairments

ObjectiveAuditory brain–computer interfaces are an assistive technology that can restore communication for motor impaired end-users. Such non-visual brain–computer interface paradigms are of particular importance for end-users that may lose or have lost gaze control. We attempted to show that motor impaired end-users can learn to control an auditory speller on the basis of event-related potentials. MethodsFive end-users with motor impairments, two of whom with additional visual impairments, participated in five sessions. We applied a newly developed auditory brain–computer interface paradigm with natural sounds and directional cues. ResultsThree of five end-users learned to select symbols using this method. Averaged over all five end-users the information transfer rate increased by more than 1800% from the first session (0.17bits/min) to the last session (3.08bits/min). The two best end-users achieved information transfer rates of 5.78bits/min and accuracies of 92%. ConclusionsOur results show that an auditory BCI with a combination of natural sounds and directional cues, can be controlled by end-users with motor impairment. Training improves the performance of end-users to the level of healthy controls. SignificanceTo our knowledge, this is the first time end-users with motor impairments controlled an auditory brain–computer interface speller with such high accuracy and information transfer rates. Further, our results demonstrate that operating a BCI with event-related potentials benefits from training and specifically end-users may require more than one session to develop their full potential.

Visual system plasticity in mammals: the story of monocular enucleation-induced vision loss.

The groundbreaking work of Hubel and Wiesel in the 1960’s on ocular dominance plasticity instigated many studies of the visual system of mammals, enriching our understanding of how the development of its structure and function depends on high quality visual input through both eyes. These studies have mainly employed lid suturing, dark rearing and eye patching applied to different species to reduce or impair visual input, and have created extensive knowledge on binocular vision. However, not all aspects and types of plasticity in the visual cortex have been covered in full detail. In that regard, a more drastic deprivation method like enucleation, leading to complete vision loss appears useful as it has more widespread effects on the afferent visual pathway and even on non-visual brain regions. One-eyed vision due to monocular enucleation (ME) profoundly affects the contralateral retinorecipient subcortical and cortical structures thereby creating a powerful means to investigate cortical plasticity phenomena in which binocular competition has no vote.In this review, we will present current knowledge about the specific application of ME as an experimental tool to study visual and cross-modal brain plasticity and compare early postnatal stages up into adulthood. The structural and physiological consequences of this type of extensive sensory loss as documented and studied in several animal species and human patients will be discussed. We will summarize how ME studies have been instrumental to our current understanding of the differentiation of sensory systems and how the structure and function of cortical circuits in mammals are shaped in response to such an extensive alteration in experience. In conclusion, we will highlight future perspectives and the clinical relevance of adding ME to the list of more longstanding deprivation models in visual system research.

Influence of light on circadian rhythm and alertness

In addition to the role in vision, light also strongly affect human health and well-being. The recent discovery of photoreceptive retinal ganglion cells (pRGCs) provides information on how the non-visual brain centers exert functional control over the circadian and neuroendocrine responses. It is found that light exposure could influence the signals timing and amplitude. Aging limits the photoreception of pRGCs due to age-related influences, which may aggravate variety of common age-associated problems. Extensive research has not only been focused on the effects of light on circadian rhythms but also the subsequent interaction with alertness. In this review, (1) the visual and non-visual pathways were compared and the suprachiasmatic nuclei (SCN)s control over physiological rhythms are summarized; (2) the mechanisms on how circadian rhythms, cognition and alertness influenced by the amplitude, timing and duration of light are analyzed; (3) the effects of ocular aging and cataract surgery on circadian photoreception are summarized; (4) the application of electroencephalogram as an effective way to evaluate alertness are also reviewed.

Reaction time as a measure of enhanced blue-light mediated cognitive function following cataract surgery

Background/aimsSince 2002 the discovery of a novel population of intrinsically photosensitive retinal ganglion cells, expressing the photopigment melanopsin, has attracted broad interest in human blue-light mediated non-visual effects including circadian...

State-Dependent Visual Processing

The temporal dynamics and anatomical correlates underlying human visual cognition are traditionally assessed as a function of stimulus properties and task demands. Any non-stimulus related activity is commonly dismissed as noise and eliminated to extract an evoked signal that is only a small fraction of the magnitude of the measured signal. We review studies that challenge this view by showing that non-stimulus related activity is not mere noise but that it has a well-structured organization which can largely determine the processing of upcoming stimuli. We review recent evidence from human electrophysiology that shows how different aspects of pre-stimulus activity such as pre-stimulus EEG frequency power and phase and pre-stimulus EEG microstates can determine qualitative and quantitative properties of both lower and higher-level visual processing. These studies show that low-level sensory processes depend on the momentary excitability of sensory cortices whereas perceptual processes leading to stimulus awareness depend on momentary pre-stimulus activity in higher-level non-visual brain areas. Also speed and accuracy of stimulus identification have likewise been shown to be modulated by pre-stimulus brain states.

The role of environmental light in sleep and health: Effects of ocular aging and cataract surgery

Environmental illumination profoundly influences human health and well-being. Recently discovered photoreceptive retinal ganglion cells (pRGCs) are primary mediators of numerous circadian, neuroendocrine and neurobehavioral responses. pRGCs provide lighting information to diverse nonvisual (non-image-forming) brain centers including the suprachiasmatic nuclei (SCN) which serve as the body's master biological clock. The SCN exert functional control over circadian aspects of physiology. The timing and strength (amplitude) of SCN rhythmic signals are affected by light exposure. Light deficiency may attenuate SCN function and its control of physiological and hormonal rhythms which in turn can result in a cascade of adverse events. Inadequate pRGC photoreception cannot be perceived consciously, but may aggravate many common age-associated problems including insomnia, depression and impaired cognition. In this review we (1) summarize circadian physiology, emphasizing light's critical role as the most important geophysical timing cue in humans; (2) analyze evidence that typical residential lighting is insufficient for optimal pRGC requirements in youth and even more so with advancing age; (3) show how ocular aging and cataract surgery impact circadian photoreception; and (4) review some of the diverse morbidities associated with chronodisruption in general and those which may be caused by light deficiency in particular.

Circadian photoreception: ageing and the eye’s important role in systemic health

Aim:To analyse how age-related losses in crystalline lens transmittance and pupillary area affect circadian photoreception and compare the circadian performance of phakic and pseudophakic individuals of the same age.Methods:The spectral...