Atypical functional connectivity between the amygdala and visual, salience regions in infants with genetic liability for autism.

The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors.

Faster bi-stable visual switching in psychosis.

Bi-stable stimuli evoke two distinct perceptual interpretations that alternate and compete for dominance. Bi-stable perception is thought to be driven at least in part by mutual suppression between distinct neural populations that represent each percept. Abnormal visual perception has been observed among people with psychotic psychopathology (PwPP), and there is evidence to suggest that these visual deficits may depend on impaired neural suppression in the visual cortex. However, it is not yet clear whether bi-stable visual perception is abnormal among PwPP. Here, we examined bi-stable perception in a visual structure-from-motion task using a rotating cylinder illusion in a group of 65 PwPP, 44 first-degree biological relatives, and 43 healthy controls. Data from a 'real switch' task, in which physical depth cues signaled real switches in rotation direction were used to exclude individuals who did not show adequate task performance. In addition, we measured concentrations of neurochemicals, including glutamate, glutamine, and γ-amino butyric acid (GABA), involved in excitatory and inhibitory neurotransmission. These neurochemicals were measured non-invasively in the visual cortex using 7 tesla MR spectroscopy. We found that PwPP and their relatives showed faster bi-stable switch rates than healthy controls. Faster switch rates also correlated with significantly higher psychiatric symptom levels, specifically disorganization, across all participants. However, we did not observe any significant relationships across individuals between neurochemical concentrations and SFM switch rates. Our results are consistent with a reduction in suppressive neural processes during structure-from-motion perception in PwPP, and suggest that genetic liability for psychosis is associated with disrupted bi-stable perception.

Altered functional connectivity strength of primary visual cortex in subjects with thyroid-associated ophthalmopathy.

Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ±â€…4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ±â€…5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.

Cortical dynamics in visual areas induced by the first use of multifocal contact lenses in presbyopes.

A common non-spectacle strategy to correct presbyopia is to provide simultaneous images with multifocal optical designs. Understanding the neuroadaptation mechanisms behind multifocal devices usage would have important clinical implications, such as predicting whether patients will be able to tolerate multifocal optics. The aim of this study was to evaluate the brain correlates during the initial wear of multifocal contact lenses (CLs) using high-density visual evoked potential (VEP) measures. Fifteen presbyopes (mean age 51.8 ±â€¯2.6 years) who had previously not used multifocal CLs were enrolled. VEP measures were achieved while participants looked at arrays of 0.5 logMAR Sloan letters in three different optical conditions arranged with CLs: monofocal condition with the optical power appropriate for the distance viewing; multifocal correction with medium addition; and multifocal correction with low addition. An ANOVA for repeated measures showed that the amplitude of the C1 and N1 components significantly dropped with both multifocal low and medium addition CL conditions compared to monofocal CLs. The P1 and P2 components showed opposite behavior with an increase in amplitudes for multifocal compared to monofocal conditions. VEP data indicated that multifocal presbyopia corrections produce a loss of feedforward activity in the primary visual cortex that is compensated by extra feedback activity in extrastriate areas only, in both early and late visual processing.

Analysis of Immediate Early Gene Expression Levels to Interrogate Changes in Cortical Neuronal Activity Patterns upon Vision Loss.

Mapping immediate early gene (IEG) expression levels to characterize changes in neuronal activity patterns has become a golden standard in neuroscience research. Due to straightforward detection methods such as in situ hybridization and immunohistochemistry, changes in IEG expression can be easily visualized across brain regions and in response to physiological and pathological stimulation. Based on in-house experience and existing literature, zif268 represents itself as the IEG of choice to investigate the neuronal activity dynamics induced by sensory deprivation. In the monocular enucleation mouse model of partial vision loss, zif268 in situ hybridization can be implemented to study cross-modal plasticity by charting the initial decline and subsequent rise in neuronal activity in visual cortical territory deprived of direct retinal visual input. Here, we describe a protocol for high-throughput radioactive zif268 in situ hybridization as a readout for cortical neuronal activity dynamics in response to partial vision loss in mice.

Cross-modal connectivity effects in age-related hearing loss.

Age-related sensorineural hearing loss (HL) leads to localized brain changes in the primary auditory cortex, long-range functional alterations, and is considered a risk factor for dementia. Nonhuman studies have repeatedly highlighted cross-modal brain plasticity in sensorial brain networks other than those primarily involved in the peripheral damage, thus in this study, the possible cortical alterations associated with HL have been analyzed using a whole-brain multimodal connectomic approach. Fifty-two HL and 30 normal hearing participants were examined in a 3T MRI study along with audiological and neurological assessments. Between-regions functional connectivity and whole-brain probabilistic tractography were calculated in a connectome-based manner and graph theory was used to obtain low-dimensional features for the analysis of brain connectivity at global and local levels. The HL condition was associated with a different functional organization of the visual subnetwork as revealed by a significant increase in global efficiency, density, and clustering coefficient. These functional effects were mirrored by similar (but more subtle) structural effects suggesting that a functional repurposing of visual cortical centers occurs to compensate for age-related loss of hearing abilities.

Loss and enhancement of layer-selective signals in geniculostriate and corticotectal pathways of adult human amblyopia.

How abnormal visual experiences early in life influence human subcortical pathways is poorly understood. Using high-resolution fMRI and pathway-selective visual stimuli, we investigate the influence of amblyopia on response properties and the effective connectivity of subcortical visual pathways of the adult human brain. Compared to the normal and fellow eyes, stimuli presented to the amblyopic eye show selectively reduced response in the parvocellular layers of the lateral geniculate nucleus and weaker effective connectivity to V1. Compared to the normal eye, the response of the amblyopic eye to chromatic stimulus decreases in the superficial layers of the superior colliculus, while response of the fellow eye robustly increases in the deep SC with stronger connectivity from the visual cortex. Therefore, amblyopia leads to selective parvocellular alterations of the geniculostriate and corticotectal pathways. These findings provide the neural basis for amblyopic deficits in visual acuity, ocular motor control, and attention.

Complexity Assessment of Chronic Pain in Elderly Knee Osteoarthritis Based on Neuroimaging Recognition Techniques.

The chronic pain of knee osteoarthritis in the elderly is investigated in detail in this paper, as well as the complexity of chronic pain utilising neuroimaging recognition techniques. Chronic pain in knee osteoarthritis (KOA) has a major effect on patients' quality of life and functional activities; therefore, understanding the causes of KOA pain and the analgesic advantages of different therapies is important. In recent years, neuroimaging techniques have become increasingly important in basic and clinical pain research. Thanks to the application and development of neuroimaging techniques in the study of chronic pain in KOA, researchers have found that chronic pain in KOA contains both injury-receptive and neuropathic pain components. The neuropathic pain mechanism that causes KOA pain is complicated, and it may be produced by peripheral or central sensitization, but it has not gotten enough attention in clinical practice, and there is no agreement on how to treat combination neuropathic pain KOA. As a result, using neuroimaging techniques such as magnetic resonance imaging (MRI), electroencephalography (EEG), magnetoencephalography (MEG), and near-infrared spectroscopy (NIRS), this review examines the changes in brain pathophysiology-related regions caused by KOA pain, compares the latest results in pain assessment and prediction, and clarifies the central brain analgesic mechanistic. The capsule network model is introduced in this paper from the perspective of deep learning network structure to construct an information-complete and reversible image low-level feature bridge using isotropic representation, predict the corresponding capsule features from MRI voxel responses, and then, complete the accurate reconstruction of simple images using inverse transformation. The proposed model improves the structural similarity index by about 10%, improves the reconstruction performance of low-level feature content in simple images by about 10%, and achieves feature interpretation and analysis of low-level visual cortical fMRI voxels by visualising capsule features, according to the experimental results.

Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex.

BACKGROUNDA long-held goal of vision therapy is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists.METHODSWe implanted an intracortical microelectrode array consisting of 96 electrodes in the visual cortex of a 57-year-old person with complete blindness for a 6-month period. We measured thresholds and the characteristics of the visual percepts elicited by intracortical microstimulation.RESULTSImplantation and subsequent explantation of intracortical microelectrodes were carried out without complications. The mean stimulation threshold for single electrodes was 66.8 ± 36.5 µA. We consistently obtained high-quality recordings from visually deprived neurons and the stimulation parameters remained stable over time. Simultaneous stimulation via multiple electrodes was associated with a significant reduction in thresholds (P < 0.001, ANOVA) and evoked discriminable phosphene percepts, allowing the blind participant to identify some letters and recognize object boundaries.CONCLUSIONSOur results demonstrate the safety and efficacy of chronic intracortical microstimulation via a large number of electrodes in human visual cortex, showing its high potential for restoring functional vision in the blind.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02983370.FUNDINGThe Spanish Ministerio de Ciencia Innovación y Universidades, the Generalitat Valenciana (Spain), the Europan Union's Horizon 2020 programme, the Bidons Egara Research Chair of the University Miguel Hernández (Spain), and the John Moran Eye Center of the University of Utah.

Visual Cortex Engagement in Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a family of inherited disorders caused by the progressive degeneration of retinal photoreceptors. There is no cure for RP, but recent research advances have provided promising results from many clinical trials. All these therapeutic strategies are focused on preserving existing photoreceptors or substituting light-responsive elements. Vision recovery, however, strongly relies on the anatomical and functional integrity of the visual system beyond photoreceptors. Although the retinal structure and optic pathway are substantially preserved at least in early stages of RP, studies describing the visual cortex status are missing. Using a well-established mouse model of RP, we analyzed the response of visual cortical circuits to the progressive degeneration of photoreceptors. We demonstrated that the visual cortex goes through a transient and previously undescribed alteration in the local excitation/inhibition balance, with a net shift towards increased intracortical inhibition leading to improved filtering and decoding of corrupted visual inputs. These results suggest a compensatory action of the visual cortex that increases the range of residual visual sensitivity in RP.

Excitatory Contribution to Binocular Interactions in Human Visual Cortex Is Reduced in Strabismic Amblyopia.

Binocular summation in strabismic amblyopia is typically reported as being absent or greatly reduced in behavioral studies and is thought to be because of a preferential loss of excitatory interactions between the eyes. Here, we studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with strabismic and anisometropic amblyopia in both sexes, using source-imaged steady-state visual evoked potentials (SSVEP) over a wide range of relative contrast between the two eyes. Dichoptic parallel grating stimuli modulated at unique temporal frequencies in each eye allowed us to quantify spectral response components associated with monocular inputs (self-terms) and the response components because of interaction of the inputs of the two eyes [intermodulation (IM) terms]. Although anisometropic amblyopes revealed a similar pattern of responses to normal-vision observers, strabismic amblyopes exhibited substantially reduced IM responses across cortical regions of interest (V1, V3a, hV4, hMT+ and lateral occipital cortex), indicating reduced interocular interactions in visual cortex. A contrast gain control model that simultaneously fits self- and IM-term responses within each cortical area revealed different patterns of binocular interactions between individuals with normal and disrupted binocularity. Our model fits show that in strabismic amblyopia, the excitatory contribution to binocular interactions is significantly reduced in both V1 and extra-striate cortex, whereas suppressive contributions remain intact. Our results provide robust electrophysiological evidence supporting the view that disruption of binocular interactions in strabismus or amblyopia is because of preferential loss of excitatory interactions between the eyes.SIGNIFICANCE STATEMENT We studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with normal and amblyopic vision, using source-imaged SSVEP and frequency-domain analysis of dichoptic stimuli over a wide range of relative contrast between the two eyes. A dichoptic contrast gain control model was used to characterize these interactions in amblyopia and provided a quantitative comparison to normal vision. Our model fits revealed different patterns of binocular interactions between normal and amblyopic vision. Strabismic amblyopia significantly reduced excitatory contributions to binocular interactions, whereas suppressive contributions remained intact. Our results provide robust evidence supporting the view that the preferential loss of excitatory interactions disrupts binocular interactions in strabismic amblyopia.

Cortical Visual Mapping following Ocular Gene Augmentation Therapy for Achromatopsia.

The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. CNGA3-achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of gray. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two CNGA3-achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI-based measurements to assess participants' early visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed, including reduction in photoaversion, marginal improvement in acuity, and a new ability to detect red color. No improvement was observed in color arrangement tests. Cortically, pretreatment, patients' population-receptive field sizes of early visual areas were untypically large, but were decreased following treatment specifically in the treated eye. We suggest that this demonstrates cortical ability to encode new input, even at adulthood. On the other hand, no activation of color-specific cortical regions was demonstrated in these patients either before or up to 1 year post-treatment. The source of this deficiency might be attributed either to insufficient recovery of cone function at the retinal level or to challenges that the adult cortex faces when computing new cone-derived input to achieve color perception.SIGNIFICANCE STATEMENT The possibility that the adult human brain may regain or develop function following correction of congenital deafferentation has fired the imagination of scientists over the years. In the visual domain, cases of recovery from congenital deficits are rare. Gene therapy visual restoration for congenital CNGA3-achromatopsia, a disease caused by cone photoreceptor dysfunction, gave us the opportunity to examine cortical function, to the best of our knowledge for the first time, both before and after restorative treatment. While behaviorally only minor improvements were observed post-treatment, fMRI analysis, including size algorithms of population-receptive fields, revealed cortical changes, specifically receptive field size decrease in the treated eyes. This suggests that, at least to some degree, the adult cortex is able to encode new input.

Effect of regulation of the NRG1/ErbB4 signaling pathway on the visual cortex synaptic plasticity of amblyopic adult rats.

This study aimed to investigate the effect of the neuregulin-1/epidermal growth factor 4 (NRG1/ErbB4) signaling pathway on visual cortex synaptic plasticity in adult amblyopic rats with monocular deprivation (MD). Compared with the control group, the P wave latency and amplitude of the MD group were prolonged and low, respectively, with reduced synaptic plasticity-related protein expression, lower number of visual cortex neurons, and increased apoptosis of visual cortex neurons. Recombinant neuregulin-1 (rNRG1) administration activated the NRG1/ErbB4 signaling pathway and improved the visual cortex synaptic plasticity in MD amblyopic rats. However, the effects of rNRG1 were reversed by AG1478 (ErbB4 receptor blockers). The NRG1/ErbB4 signaling pathway in the parvalbumin neurons from MD rats was also inactivated. Amblyopic rats had significantly low cell activity and downregulated expression of synaptic plasticity-related proteins. Thus, exogenous administration of NRG1 can activate ErbB4 signal transduction and improve the damaged synaptic plasticity of the visual cortex among amblyopic rats. Further studies are warranted to explore the potential for clinical management of amblyopia.

Visual gamma oscillations predict sensory sensitivity in females as they do in males.

Gamma oscillations are driven by local cortical excitatory (E)-inhibitory (I) loops and may help to characterize neural processing involving excitatory-inhibitory interactions. In the visual cortex reliable gamma oscillations can be recorded with magnetoencephalography (MEG) in the majority of individuals, which makes visual gamma an attractive candidate for biomarkers of brain disorders associated with E/I imbalance. Little is known, however, about if/how these oscillations reflect individual differences in neural excitability and associated sensory/perceptual phenomena. The power of visual gamma response (GR) changes nonlinearly with increasing stimulation intensity: it increases with transition from static to slowly drifting high-contrast grating and then attenuates with further increase in the drift rate. In a recent MEG study we found that the GR attenuation predicted sensitivity to sensory stimuli in everyday life in neurotypical adult men and in men with autism spectrum disorders. Here, we replicated these results in neurotypical female participants. The GR enhancement with transition from static to slowly drifting grating did not correlate significantly with the sensory sensitivity measures. These findings suggest that weak velocity-related attenuation of the GR is a reliable neural concomitant of visual hypersensitivity and that the degree of GR attenuation may provide useful information about E/I balance in the visual cortex.

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.

Beyond imagination: Hypnotic visual hallucination induces greater lateralised brain activity than visual mental imagery.

Hypnotic suggestions can produce a broad range of perceptual experiences, including hallucinations. Visual hypnotic hallucinations differ in many ways from regular mental images. For example, they are usually experienced as automatic, vivid, and real images, typically compromising the sense of reality. While both hypnotic hallucination and mental imagery are believed to mainly rely on the activation of the visual cortex via top-down mechanisms, it is unknown how they differ in the neural processes they engage. Here we used an adaptation paradigm to test and compare top-down processing between hypnotic hallucination, mental imagery, and visual perception in very highly hypnotisable individuals whose ability to hallucinate was assessed. By measuring the N170/VPP event-related complex and using multivariate decoding analysis, we found that hypnotic hallucination of faces involves greater top-down activation of sensory processing through lateralised neural mechanisms in the right hemisphere compared to mental imagery. Our findings suggest that the neural signatures that distinguish hypnotically hallucinated faces from imagined faces lie in the right brain hemisphere.

Altered Functional Connectivity of the Primary Visual Cortex in Patients With Iridocyclitis and Assessment of Its Predictive Value Using Machine Learning.

Purpose: To explore the intrinsic functional connectivity (FC) alteration of the primary visual cortex (V1) between individuals with iridocyclitis and healthy controls (HCs) by the resting-state functional magnetic resonance imaging (fMRI) technique, and to investigate whether FC findings be used to differentiate patients with iridocyclitis from HCs. Methods: Twenty-six patients with iridocyclitis and twenty-eight well-matched HCs were recruited in our study and underwent resting-state fMRI examinations. The fMRI data were analyzed by Statistical Parametric Mapping (SPM12), Data Processing and Analysis for Brain Imaging (DPABI), and Resting State fMRI Data Analysis Toolkit (REST) software. Differences in FC signal values of the V1 between the individuals with iridocyclitis and HCs were compared using independent two-sample t-tests. Significant differences in FC between two groups were chosen as classification features for distinguishing individuals with iridocyclitis from HCs using a support vector machine (SVM) classifier that involved machine learning. Classifier performance was evaluated using permutation test analysis. Results: Compared with HCs, patients with iridocyclitis displayed significantly increased FC between the left V1 and left cerebellum crus1, left cerebellum 10, bilateral inferior temporal gyrus, right hippocampus, and left superior occipital gyrus. Moreover, patients with iridocyclitis displayed significantly lower FC between the left V1 and both the bilateral calcarine and bilateral postcentral gyrus. Patients with iridocyclitis also exhibited significantly higher FC values between the right V1 and left cerebellum crus1, bilateral thalamus, and left middle temporal gyrus; while they displayed significantly lower FC between the right V1 and both the bilateral calcarine and bilateral postcentral gyrus (voxel-level P<0.01, Gaussian random field correction, cluster-level P<0.05). Our results showed that 63.46% of the participants were correctly classified using the leave-one-out cross-validation technique with an SVM classifier based on the FC of the left V1; and 67.31% of the participants were correctly classified based on the FC of the right V1 (P<0.001, non-parametric permutation test). Conclusion: Patients with iridocyclitis displayed significantly disturbed FC between the V1 and various brain regions, including vision-related, somatosensory, and cognition-related regions. The FC variability could distinguish patients with iridocyclitis from HCs with substantial accuracy. These findings may aid in identifying the potential neurological mechanisms of impaired visual function in individuals with iridocyclitis.

Evidence for Reduced Long-Term Potentiation-Like Visual Cortical Plasticity in Schizophrenia and Bipolar Disorder.

Several lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication. We measured the VEP of patients with SZ spectrum disorders (n = 31), BDI (n = 34), BDII (n = 33), and other BD spectrum disorders (n = 2), and age-matched healthy control (HC) participants (n = 200) before and after prolonged visual stimulation. Compared to HCs, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum (χ 2 = 35.1, P = 3.1 × 10-9) and BD spectrum (χ 2 = 7.0, P = 8.2 × 10-3), including BDI (χ 2 = 6.4, P = .012), but not BDII (χ 2 = 2.2, P = .14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients (χ 2 = 14.2, P = 1.7 × 10-4). N1b modulation was not significantly associated with Positive and Negative Syndrome Scale (PANSS) negative or positive symptoms scores, number of psychotic episodes, Montgomery and Åsberg Depression Rating Scale (MADRS) scores, or Young Mania Rating Scale (YMRS) scores after multiple comparison correction, although a nominal association was observed between N1b modulation and PANSS negative symptoms scores among SZ spectrum patients. These results suggest that LTP-like plasticity is impaired in SZ and BD. Adding to previous genetic, pharmacological, and electrophysiological evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences.

The hippocampus is essential for spatial and episodic memory but is damaged early in Alzheimer's disease and is very sensitive to hypoxia. Understanding how it regulates its oxygen supply is therefore key for designing interventions to preserve its function. However, studies of neurovascular function in the hippocampus in vivo have been limited by its relative inaccessibility. Here we compared hippocampal and visual cortical neurovascular function in awake mice, using two photon imaging of individual neurons and vessels and measures of regional blood flow and haemoglobin oxygenation. We show that blood flow, blood oxygenation and neurovascular coupling were decreased in the hippocampus compared to neocortex, because of differences in both the vascular network and pericyte and endothelial cell function. Modelling oxygen diffusion indicates that these features of the hippocampal vasculature may restrict oxygen availability and could explain its sensitivity to damage during neurological conditions, including Alzheimer's disease, where the brain's energy supply is decreased.

Cerebral Visual Impairment Characterized by Abnormal Visual Orienting Behavior With Preserved Visual Cortical Activation.

Purpose: Children with cerebral visual impairment (CVI) often have abnormal visual orienting behaviors due to impaired or damaged visual cortex. Alternatively, visual-cortical function is intact but visual information is not transformed downstream into an appropriate oculomotor output (visuomotor dysfunction). We examined visual, anatomic, and oculomotor assessments to distinguish visuomotor dysfunction from CVI associated with severely reduced visual-cortical response. Methods: We reviewed the medical records from children with CVI having abnormal visual orienting behaviors, normal ocular examinations, and born near term. Relevant data were visual evoked potentials (VEPs), Teller card acuity, eye movements recorded by video-oculography (VOG), and neuroimaging (magnetic resonance imaging [MRI]) including diffusion tensor imaging (DTI) tractography. Results: Thirty subjects had visuomotor dysfunction based on a normal VEP; of these 33% had a normal MRI and 67% had white matter abnormalities associated with metabolic disease and/or decreased volume of brain parenchyma. VOG recordings showed smooth pursuit gains were uniformly reduced and saccades were dysmetric but followed the main sequence. Ten subjects had severe CVI based on VEPs at noise levels; visual acuities and MRI findings overlapped those of the visuomotor dysfunction group. Developmental delay, seizures, microcephaly, and hypotonia were common across all groups. All subjects with an abnormal conventional MRI had abnormal metrics on DTI tractography from the occipital lobe. Conclusions: A subset of patients with CVI have abnormal visual orienting behaviors despite a normal VEP (visuomotor dysfunction). A majority have abnormal white matter metrics on tractography suggesting a downstream defect in sensorimotor transformation. Clinically, visuomotor dysfunction is indistinguishable from severe CVI.