Region Of Primary Visual Cortex Research Articles

Persistent Brain Connectivity Changes in Healthy Volunteers Following Nitrous Oxide Inhalation

BackgroundNitrous oxide holds promise in the treatment of major depressive disorder. Its psychotropic effects and NMDA receptor antagonism have led to comparisons with ketamine. Despite longstanding use, persistent effects of nitrous oxide on the brain have not been characterized. MethodsSixteen healthy volunteers were recruited in a double-blind crossover study. In randomized order, individuals underwent a 1-hour inhalation of either 50% nitrous oxide/oxygen or air/oxygen mixtures. At least two 7.5-minute echo-planar resting-state functional magnetic resonance imaging scans were obtained before and at 2 and 24 hours after each inhalation (average 130 min/participant). Using the time series of preprocessed, motion artifact–scrubbed, and nuisance covariate–regressed imaging data, interregional signal correlations were measured and converted to T scores. Hierarchical clustering and linear mixed-effects models were employed. ResultsNitrous oxide inhalation produced changes in global brain connectivity that persisted in the occipital cortex at 2 and 24 hours postinhalation (p < .05, false discovery rate–corrected). Analysis of resting-state networks demonstrated robust strengthening of connectivity between regions of the visual network and those of the dorsal attention network, across 2 and 24 hours after inhalation (p < .05, false discovery rate–corrected). Weaker changes in connectivity were found between the visual cortex and regions of the frontoparietal and default mode networks. Parallel analyses following air/oxygen inhalation yielded no significant changes in functional connectivity. ConclusionsNitrous oxide inhalation in healthy volunteers revealed persistent increases in global connectivity between regions of primary visual cortex and dorsal attention network. These findings suggest that nitrous oxide inhalation induces neurophysiological cortical changes that persist for at least 24 hours.

Chronic Monocular Deprivation Reveals MMP9-Dependent and -Independent Aspects of Murine Visual System Plasticity.

The deletion of matrix metalloproteinase MMP9 is combined here with chronic monocular deprivation (cMD) to identify the contributions of this proteinase to plasticity in the visual system. Calcium imaging of supragranular neurons of the binocular region of primary visual cortex (V1b) of wild-type mice revealed that cMD initiated at eye opening significantly decreased the strength of deprived-eye visual responses to all stimulus contrasts and spatial frequencies. cMD did not change the selectivity of V1b neurons for the spatial frequency, but orientation selectivity was higher in low spatial frequency-tuned neurons, and orientation and direction selectivity were lower in high spatial frequency-tuned neurons. Constitutive deletion of MMP9 did not impact the stimulus selectivity of V1b neurons, including ocular preference and tuning for spatial frequency, orientation, and direction. However, MMP9−/− mice were completely insensitive to plasticity engaged by cMD, such that the strength of the visual responses evoked by deprived-eye stimulation was maintained across all stimulus contrasts, orientations, directions, and spatial frequencies. Other forms of experience-dependent plasticity, including stimulus selective response potentiation, were normal in MMP9−/− mice. Thus, MMP9 activity is dispensable for many forms of activity-dependent plasticity in the mouse visual system, but is obligatory for the plasticity engaged by cMD.

Functional MRI of visual cortex predicts training-induced recovery in stroke patients with homonymous visual field defects

Post-chiasmatic damage to the visual system leads to homonymous visual field defects (HVDs), which can severely interfere with daily life activities. Visual Restitution Training (VRT) can recover parts of the affected visual field in patients with chronic HVDs, but training outcome is variable. An untested hypothesis suggests that training potential may be largest in regions with ‘neural reserve’, where cortical responses to visual stimulation do not lead to visual awareness as assessed by Humphrey perimetry—a standard behavioural visual field test. Here, we tested this hypothesis in a sample of twenty-seven hemianopic stroke patients, who participated in an assiduous 80-hour VRT program. For each patient, we collected Humphrey perimetry and wide-field fMRI-based retinotopic mapping data prior to training. In addition, we used Goal Attainment Scaling to assess whether personal activities in daily living improved. After training, we assessed with a second Humphrey perimetry measurement whether the visual field was improved and evaluated which personal goals were attained. Confirming the hypothesis, we found significantly larger improvements of visual sensitivity at field locations with neural reserve. These visual field improvements implicated both regions in primary visual cortex and higher order visual areas. In addition, improvement in daily life activities correlated with the extent of visual field enlargement. Our findings are an important step toward understanding the mechanisms of visual restitution as well as predicting training efficacy in stroke patients with chronic hemianopia.

Individual variation in patterns of task focused, and detailed, thought are uniquely associated within the architecture of the medial temporal lobe

Understanding the neural processes that support different patterns of ongoing thought is an important goal of contemporary cognitive neuroscience. Early accounts assumed the default mode network (DMN) was especially important for conscious attention to task-irrelevant/personally relevant materials. However, simple task-negative accounts of the DMN are incompatible with more recent evidence that neural patterns within the system can be related to ongoing processing during active task states. To better characterise the contribution of the DMN to ongoing thought, we conducted a cross-sectional analysis of the relationship between the structural organisation of the brain, as indexed by cortical thickness, and patterns of experience, identified using experience sampling in the cognitive laboratory. In a sample of 181 healthy individuals (mean age 20 years, 117 females) we identified an association between cortical thickness in the anterior parahippocampus and patterns of task focused thought, as well as an adjacent posterior region in which cortical thickness was associated with experiences with higher levels of subjective detail. Both regions fell within regions of medial temporal lobe associated with the DMN, yet varied in their functional connectivity: the time series of signals in the ‘on-task’ region were more correlated with systems important for external task-relevant processing (as determined by meta-analysis) including the dorsal and ventral attention, and fronto-parietal networks. In contrast, connectivity within the region linked to subjective ‘detail’ was more correlated with the medial core of the DMN (posterior cingulate and the medial pre-frontal cortex) and regions of primary visual cortex. These results provide cross-sectional evidence that confirms a role of the DMN in how detailed experiences are and so provide further evidence that the role of this system in experience is not simply task-irrelevant. Our results also highlight processes within the medial temporal lobe, and their interactions with other regions of cortex, as important in determining multiple aspects of how human cognition unfolds.

The impact of bilateral ongoing activity on evoked responses in mouse cortex.

In the absence of external stimuli or overt behavior, the activity of the left and right cortical hemispheres shows fluctuations that are largely bilateral. Here, we show that these fluctuations are largely responsible for the variability observed in cortical responses to sensory stimuli. Using widefield imaging of voltage and calcium signals, we measured activity in the cortex of mice performing a visual detection task. Bilateral fluctuations invested all areas, particularly those closest to the midline. Activity was less bilateral in the monocular region of primary visual cortex and, especially during task engagement, in secondary motor cortex. Ongoing bilateral fluctuations dominated unilateral visual responses, and interacted additively with them, explaining much of the variance in trial-by-trial activity. Even though these fluctuations occurred in regions necessary for the task, they did not affect detection behavior. We conclude that bilateral ongoing activity continues during visual stimulation and has a powerful additive impact on visual responses.

No evidence for altered up- and downregulation of brain activity in visual cortex during illusory shape perception in autism

Autism spectrum disorder (ASD) may be marked by an altered balance between sensory input and prior expectations. Because many illusions rely on integrating sensory input with prior information such as spatial context, individuals with ASD may therefore be less susceptible to visual illusions than typically developing (TD) individuals. Yet empirical evidence on the matter is rather divergent, varying depending on the type of illusion, study procedure, and population.Visual illusions lead to neural activity alterations in the visual system. In the so-called Kanizsa illusion, these are likely caused by top-down feedback to V1. Here we tested the hypothesis that a reduced susceptibility to illusions in ASD would manifest as diminished modulation of V1 activity by illusions, using functional magnetic resonance imaging (fMRI). We presented 22 adolescents with ASD and 22 age-, gender-, and intelligence-matched TD controls with displays that consisted of three circular inducers. These either formed an illusory triangle (Kanizsa illusion) or not. We identified regions in primary visual cortex (V1) that corresponded to (the visual field locations of) the illusory triangle and its inducers, and recorded their visual response.Previous research in healthy volunteers has shown a specific pattern of up- and down-regulation in regions of V1 that process the shape and inducers, respectively. Here, we replicated this pattern of up- and downregulation in V1, in both the TD and ASD groups, with no differences between groups. This suggests that illusory shape processing in primary visual cortex is equally present in ASD, suggesting unimpaired processing of spatial context.

Detailed Visual Cortical Responses Generated by Retinal Sheet Transplants in Rats with Severe Retinal Degeneration.

To combat retinal degeneration, healthy fetal retinal sheets have been successfully transplanted into both rodent models and humans, with synaptic connectivity between transplant and degenerated host retina having been confirmed. In rodent studies, transplants have been shown to restore responses to flashes of light in a region of the superior colliculus corresponding to the location of the transplant in the host retina. To determine the quality and detail of visual information provided by the transplant, visual responsivity was studied here at the level of visual cortex where higher visual perception is processed. For our model, we used the transgenic Rho-S334ter line-3 rat (both sexes), which loses photoreceptors at an early age and is effectively blind at postnatal day 30. These rats received fetal retinal sheet transplants in one eye between 24 and 40 d of age. Three to 10 months following surgery, visually responsive neurons were found in regions of primary visual cortex matching the transplanted region of the retina that were as highly selective as normal rat to stimulus orientation, size, contrast, and spatial and temporal frequencies. Conversely, we found that selective response properties were largely absent in nontransplanted line-3 rats. Our data show that fetal retinal sheet transplants can result in remarkably normal visual function in visual cortex of rats with a degenerated host retina and represents a critical step toward developing an effective remedy for the visually impaired human population.SIGNIFICANCE STATEMENT Age-related macular degeneration and retinitis pigmentosa lead to profound vision loss in millions of people worldwide. Many patients lose both retinal pigment epithelium and photoreceptors. Hence, there is a great demand for the development of efficient techniques that allow for long-term vision restoration. In this study, we transplanted dissected fetal retinal sheets, which can differentiate into photoreceptors and integrate with the host retina of rats with severe retinal degeneration. Remarkably, we show that transplants generated visual responses in cortex similar in quality to normal rats. Furthermore, transplants preserved connectivity within visual cortex and the retinal relay from the lateral geniculate nucleus to visual cortex, supporting their potential application in curing vision loss associated with retinal degeneration.

Individual variation in the propensity for prospective thought is associated with functional integration between visual and retrosplenial cortex

It is well recognized that the default mode network (DMN) is involved in states of imagination, although the cognitive processes that this association reflects are not well understood. The DMN includes many regions that function as cortical “hubs”, including the posterior cingulate/retrosplenial cortex, anterior temporal lobe and the hippocampus. This suggests that the role of the DMN in cognition may reflect a process of cortical integration. In the current study we tested whether functional connectivity from uni-modal regions of cortex into the DMN is linked to features of imaginative thought. We found that strong intrinsic communication between visual and retrosplenial cortex was correlated with the degree of social thoughts about the future. Using an independent dataset, we show that the same region of retrosplenial cortex is functionally coupled to regions of primary visual cortex as well as core regions that make up the DMN. Finally, we compared the functional connectivity of the retrosplenial cortex, with a region of medial prefrontal cortex implicated in the integration of information from regions of the temporal lobe associated with future thought in a prior study. This analysis shows that the retrosplenial cortex is preferentially coupled to medial occipital, temporal lobe regions and the angular gyrus, areas linked to episodic memory, scene construction and navigation. In contrast, the medial prefrontal cortex shows preferential connectivity with motor cortex and lateral temporal and prefrontal regions implicated in language, motor processes and working memory. Together these findings suggest that integrating neural information from visual cortex into retrosplenial cortex may be important for imagining the future and may do so by creating a mental scene in which prospective simulations play out. We speculate that the role of the DMN in imagination may emerge from its capacity to bind together distributed representations from across the cortex in a coherent manner.

Parallel pathways from whisker and visual sensory cortices to distinct frontal regions of mouse neocortex.

The spatial organization of mouse frontal cortex is poorly understood. Here, we used voltage-sensitive dye to image electrical activity in the dorsal cortex of awake head-restrained mice. Whisker-deflection evoked the earliest sensory response in a localized region of primary somatosensory cortex and visual stimulation evoked the earliest responses in a localized region of primary visual cortex. Over the next milliseconds, the initial sensory response spread within the respective primary sensory cortex and into the surrounding higher order sensory cortices. In addition, secondary hotspots in the frontal cortex were evoked by whisker and visual stimulation, with the frontal hotspot for whisker deflection being more anterior and lateral compared to the frontal hotspot evoked by visual stimulation. Investigating axonal projections, we found that the somatosensory whisker cortex and the visual cortex directly innervated frontal cortex, with visual cortex axons innervating a region medial and posterior to the innervation from somatosensory cortex, consistent with the location of sensory responses in frontal cortex. In turn, the axonal outputs of these two frontal cortical areas innervate distinct regions of striatum, superior colliculus, and brainstem. Sensory input, therefore, appears to map onto modality-specific regions of frontal cortex, perhaps participating in distinct sensorimotor transformations, and directing distinct motor outputs.

An individual differences analysis of the neurocognitive architecture of the semantic system at rest

Efficient semantic cognition depends on accessing and selecting conceptual knowledge relevant to the current task or context. This study explored the neurocognitive architecture that supports this function by examining how individual variation in functional brain organisation predicts comprehension and semantic generation. Participants underwent resting state functional magnetic resonance imaging (fMRI) and, on separate days, performed written synonym judgement, and letter and category fluency tasks. We found that better synonym judgement for high frequency items was linked to greater functional coupling between posterior fusiform and anterior superior temporal cortex (aSTG), which might index orthographic-to-semantic access. However, stronger coupling between aSTG and ventromedial prefrontal cortex was associated with poor performance on the same trials, potentially reflecting greater difficulty in focussing retrieval on relevant features for high frequency items that appear in a greater range of contexts. Fluency performance was instead linked to variations in the functional coupling of the inferior frontal gyrus (IFG); anterior IFG was more coupled to regions of primary visual cortex for individuals who were good at category fluency, while poor letter fluency was predicted by stronger coupling between posterior IFG and retrosplenial cortex. These results show that individual differences in functional connectivity at rest predict semantic performance and are consistent with a component process account of semantic cognition in which representational information is shaped by control processes to fit the current requirements, in both comprehension and fluency tasks.

Object-Centered Shifts of Receptive Field Positions in Monkey Primary Visual Cortex

Stimuli that project the same retinal visual angle can appear to occupy very different proportions of the visual field if they are perceived to be at different distances [1-8]. Previous research shows that perceived angular size alters the spatial distribution of activity in early retinotopic visual cortex [7, 9-11]. For example, a sphere superimposed on the far end of a corridor scene appears to occupy a larger visual angle and activates a larger region of primary visual cortex (V1) compared with the same sphere superimposed on the near end of the corridor [7]. These previous results, however, were obtained from human subjects using psychophysics and fMRI, a fact that fundamentally limits our understanding of the underlying neuronal mechanisms. Here, we present an animal model that allows for a finer examination of size perception at the level of single neurons. We first show that macaque monkeys perceive a size-distance illusion similarly to humans. Then, using extracellular recordings, we test the specific hypothesis [12] that neurons in V1 shift the position of their receptive fields (RFs) in response to complex monocular depth cues. Consistent with this hypothesis, we found that when ring-shaped stimuli appeared at the back of the corridor, RFs of V1 neurons shifted toward the center of the rings. When the same stimuli appeared at the front of the corridor, RFs shifted outward. Thus, our results show for the first time that V1 RFs can shift, potentially serving as the neural basis for the perception of angular size.

Large-Scale Axonal Reorganization of Inhibitory Neurons following Retinal Lesions

The functional properties of adult cortical neurons are subject to alterations in sensory experience. Retinal lesions lead to remapping of cortical topography in the region of primary visual cortex representing the lesioned part of the retina, the lesion projection zone (LPZ), with receptive fields shifting to the intact parts of the retina. Neurons within the LPZ receive strengthened input from the surrounding region by growth of the plexus of excitatory long-range horizontal connections. Here, by combining cell type-specific labeling with a genetically engineered recombinant adeno-associated virus and in vivo two-photon microscopy in adult macaques, we showed that the remapping was also associated with alterations in the axonal arbors of inhibitory neurons, which underwent a parallel process of pruning and growth. The axons of inhibitory neurons located within the LPZ extended across the LPZ border, suggesting a mechanism by which new excitatory input arising from the peri-LPZ is balanced by reciprocal inhibition arising from the LPZ.

Distal connectivity causes summation and division across mouse visual cortex

Neurons in different locations across the cortex are connected through polysynaptic networks involving both excitation and inhibition. To probe the functional impact of such networks we used optogenetic stimulation to trigger antidromic spikes in a local region of primary visual cortex. This local activity caused two effects at distal locations: summation and division. The balance between the two depended on visual contrast, and a normalization model precisely captured these effects.

Altered Functional and Structural Connectivity in a Schizophrenia Patient With Complete Agenesis of the Corpus Callosum

Altered Functional and Structural Connectivity in a Schizophrenia Patient With Complete Agenesis of the Corpus Callosum

Activation of SC during electrical stimulation of LGN: retinal antidromic stimulation or corticocollicular activation?

We have recently used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in lateral geniculate nucleus (LGN) increases the fMRI signal in the regions of primary visual cortex receiving input from that site, but suppresses it in the retinotopically matched regions of extrastriate cortex. Intracortical injection experiments showed that such suppression is due to synaptic inhibition. During these experiments, we have consistently observed activation of superior colliculus (SC) following LGN stimulation. Since LGN does not directly project to SC, the current study investigated the origin of SC activation. By examining experimental manipulations inactivating the primary visual cortex, we present here evidence that the robust SC activation, which follows the stimulation of LGN, is due to the activation of corticocollicular pathway.

Local action for global vision

Local action for global vision

Amyloid and glucose imaging in dementia with Lewy bodies and multiple systems atrophy

Background Multiple Systems Atrophy (MSA) and Dementia with Lewy bodies (DLB) can present with both REM behavior disorder and severe autonomic dysfunction. In rare occasions, patients with MSA progress to cognitive impairment and even dementia. Positron emission topography (PET) imaging using both the amyloid ligand Pittsburgh Compound B (11C-PiB) and 18 flurodeoxyglucose (18F-FDG) was used to ascertain the presence of amyloid and pattern of glucose metabolic derangement in both disorders. Methods Patients diagnosed with probable DLB or MSA, with clinical symptoms of either REM Behavior Disorder (RBD), Parkinsonism, or dysautonomia were prospectively identified. All underwent both 11C-PiB and 18F-FDG PET imaging. Statistical comparison between DLB, MSA, and normal controls was performed. Results Six patients, 3 with DLB, 2 with Parkinson predominant MSA (MSA-P), and 1 with cerebellar predominant MSA (MSA-C) were identified. Increased level of PiB retention was noted in all patients diagnosed with DLB, but was absent in MSA. In those with DLB, glucose hypometabolism corresponded with regions of amyloid presence, and included prefrontal, parietotemporal, occipital and primary visual cortex regions. MSA patients were distinguished by cerebellar glucose hypometabolism. Conclusions These findings emphasize the distinguishing characteristics between the alpha-synuclein related disorders of DLB and MSA. The absence of amyloid in the cases of MSA is a possible distinguishing characteristic of the disorder.

Nonstimulated early visual areas carry information about surrounding context

Even within the early sensory areas, the majority of the input to any given cortical neuron comes from other cortical neurons. To extend our knowledge of the contextual information that is transmitted by such lateral and feedback connections, we investigated how visually nonstimulated regions in primary visual cortex (V1) and visual area V2 are influenced by the surrounding context. We used functional magnetic resonance imaging (fMRI) and pattern-classification methods to show that the cortical representation of a nonstimulated quarter-field carries information that can discriminate the surrounding visual context. We show further that the activity patterns in these regions are significantly related to those observed with feed-forward stimulation and that these effects are driven primarily by V1. These results thus demonstrate that visual context strongly influences early visual areas even in the absence of differential feed-forward thalamic stimulation.

The effects of electrical microstimulation on cortical signal propagation

Electrical stimulation has been used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increasing use in electrotherapy and neural prostheses. However, the manner in which electrical stimulation-elicited signals propagate in brain tissues remains unclear. We used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in the lateral geniculate nucleus (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that received input from that site, but suppressed it in the retinotopically matched regions of extrastriate cortex. Consistent with previous observations, intracranial recordings indicated that a short excitatory response occurring immediately after a stimulation pulse was followed by a long-lasting inhibition. Following microinjections of GABA antagonists in V1, LGN stimulation induced positive fMRI signals in all of the cortical areas. Taken together, our findings suggest that electrical stimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated.

Identifying spatially overlapping local cortical networks with MEG

Recent modelling studies (Hadjipapas et al. [2009]: Neuroimage 44:1290‐1303) have shown that it may be possible to distinguish between different neuronal populations on the basis of their macroscopically measured (EEG/MEG) mean field. We set out to test whether the different orientation columns contributing to a signal at a specific cortical location could be identified based on the measured MEG signal. We used 1.5deg square, static, obliquely oriented grating stimuli to generate sustained gamma oscillations in a focal region of primary visual cortex. We then used multivariate classifier methods to predict the orientation (left or right oblique) of the stimuli based purely on the time‐series data from this one location. Both the single trial evoked response (0–300 ms) and induced post‐transient power spectra (300–2,300 ms, 20–70 Hz band) due to the different stimuli were classifiable significantly above chance in 11/12 and 10/12 datasets respectively. Interestingly, stimulus‐specific information is preserved in the sustained part of the gamma oscillation, long after perception has occurred and all neuronal transients have decayed. Importantly, the classification of this induced oscillation was still possible even when the power spectra were rank‐transformed showing that the different underlying networks give rise to different characteristic temporal signatures. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.