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Uptake of horseradish peroxidase by geniculo-cortical axons in the golden hamster: analysis by computer reconstruction.

Micro-injections of horseradish peroxidase (HRP) were made into the visual cortex of the golden hamster. The "projection lines" of labelled neurons in the dorsal lateral geniculate nucleus (LGNd) were three-dimensionally reconstructed, using a computer graphics technique. The lines run rostrally and medially from their origins at the lateral surface of the nucleus. Using an anatomically determined retinotopic map of the LGNd, the positions of all labelled cells near the lateral surface were converted into equivalent visual field co-ordinates and displayed on a physiologically determined retinotopic map of the primary visual cortex. Comparison between the scatter of these equivalent retinotopic loci and an actual reconstruction of the injection site revealed that: 1. there was general agreement between the independent retinotopic maps of LGNd and visual cortex; 2. there was greater retinotopic scatter of labelled LGNd cells than could be accounted for by the area of tissue injury in the cortex; 3. the retinotopic scatter matched more closely the total visible halo of HRP staining in the grey matter; 4. HRP can be taken up from a cytoarchitectonic field into which it diffuses after injection into a neighbouring area; 5. HRP is probably not taken up by undamaged axons in the white matter. These results are compared with those obtained in other animals and other systems. No general rules emerge, but the possibility of uptake from wide areas of diffusion must be considered when interpreting results of HRP injection.

Animals↗

Linear aspects of transformation from interictal epileptic discharges to BOLD fMRI signals in an animal model of occipital epilepsy.

Epileptic disorders manifest with seizures and interictal epileptic discharges (IEDs). The hemodynamic changes that accompany IEDs are poorly understood and may be critical for understanding epileptogenesis. Despite a known linear coupling of the neurovascular elements in normal brain tissues, previous simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) studies have shown variable correlations between epileptic discharges and blood oxygenation level-dependent (BOLD) response, partly because most previous studies assumed particular hemodynamic properties in normal brain tissue. The occurrence of IEDs in human subjects is unpredictable. Therefore, an animal model with reproducible stereotyped IEDs was developed by the focal injection of penicillin into the right occipital cortex of rats anesthetized with isoflurane. Simultaneous EEG-fMRI was used to study the hemodynamic changes during IEDs. A hybrid of temporal independent component analysis (ICA) of EEG and spatial ICA of fMRI data was used to correlate BOLD fMRI signals with IEDs. A linear autoregression with exogenous input (ARX) model was used to estimate the hemodynamic impulse response function (HIRF) based on the data from simultaneous EEG-fMRI measurement. Changes in the measured BOLD signal from the right primary visual cortex and bilateral visual association cortices were consistently coupled to IEDs. The linear ARX model was applied here to confirm that a linear transform can be used to study the correlation between BOLD signal and its corresponding neural activity in this animal model of occipital epilepsy.

Animals↗

Dynamics of neuronal sensitivity in visual cortex and local feature discrimination.

A striking aspect of natural scenes is that image features such as line orientation are strongly correlated at neighboring spatial locations but not at distant locations. Thus, during the viewing of a scene, eye movements are often accompanied by a change in the orientation structure of the image. How does this behavior influence the discrimination of local features and their encoding by visual cortical neurons? Here we examined the perceived changes in orientation induced by brief exposure to oriented image patterns in monkeys and humans, and then used reverse correlation to investigate dynamic changes in neuronal sensitivity in the primary visual cortex (V1) of behaving monkeys. Whereas brief adaptation to an oriented grating impaired identification of nearby orientations by broadening orientation selectivity and changing the preferred orientation of individual V1 neurons, it actually enhanced the identification of orthogonal orientations by sharpening neuronal selectivity. Hence, successive exposure to image patches of dissimilar spatial structure enhances both the ability to discriminate local features and the encoding of these features by V1 neurons.

Action Potentials↗

Pattern of neuronal activity associated with conscious and unconscious processing of visual signals.

Following striate cortex damage in monkeys and humans there can be residual function mediated by parallel visual pathways. In humans this can sometimes be associated with a "feeling" that something has happened, especially with rapid movement or abrupt onset. For less transient events, discriminative performance may still be well above chance even when the subject reports no conscious awareness of the stimulus. In a previous study we examined parameters that yield good residual visual performance in the "blind" hemifield of a subject with unilateral damage to the primary visual cortex. With appropriate parameters we demonstrated good discriminative performance, both with and without conscious awareness of a visual event. These observations raise the possibility of imaging the brain activity generated in the "aware" and the "unaware" modes, with matched levels of discrimination performance, and hence of revealing patterns of brain activation associated with visual awareness. The intact hemifield also allows a comparison with normal vision. Here we report the results of a functional magnetic resonance imaging study on the same subject carried out under aware and unaware stimulus conditions. The results point to a shift in the pattern of activity from neocortex in the aware mode, to subcortical structures in the unaware mode. In the aware mode prestriate and dorsolateral prefrontal cortices (area 46) are active. In the unaware mode the superior colliculus is active, together with medial and orbital prefrontal cortical sites.

Brain↗

Combined activation and deactivation of visual cortex during tactile sensory processing.

The involvement of occipital cortex in sensory processing is not restricted solely to the visual modality. Tactile processing has been shown to modulate higher-order visual and multisensory integration areas in sighted as well as visually deprived subjects; however, the extent of involvement of early visual cortical areas remains unclear. To investigate this issue, we employed functional magnetic resonance imaging in normally sighted, briefly blindfolded subjects with well-defined visuotopic borders as they tactually explored and rated raised-dot patterns. Tactile task performance resulted in significant activation in primary visual cortex (V1) and deactivation of extrastriate cortical regions V2, V3, V3A, and hV4 with greater deactivation in dorsal subregions and higher visual areas. These results suggest that tactile processing affects occipital cortex via two distinct pathways: a suppressive top-down pathway descending through the visual cortical hierarchy and an excitatory pathway arising from outside the visual cortical hierarchy that drives area V1 directly.

Adult↗

Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys.

Explorations of learning and memory, other long-term plastic changes, and additional cognitive functions in the behaving primate brain would greatly benefit from the ability to image the functional architecture within the same patch of cortex, at the columnar level, for a long period of time. We developed methods for long-term optical imaging based on intrinsic signals and repeatedly visualized the same functional domains in behaving macaque cortex for a period extending over 1 year. Using optical imaging and imaging spectroscopy, we first explored the relationship between electrical activity and hemodynamic events in the awake behaving primate and compared it with anesthetized preparations. We found that, whereas the amplitude of the intrinsic signal was much larger in the awake animal, its temporal pattern was similar to that observed in the anesthetized animals. In both groups, deoxyhemoglobin concentration reached a peak 2-3 sec after stimulus onset. Furthermore, the early activity-dependent increase in deoxyhemoglobin concentration (the "initial dip") was far more tightly colocalized with electrical activity than the delayed increase in oxyhemoglobin concentration, known to be associated with an increase in blood flow. The implications of these results for improvement of the spatial resolution of blood oxygenation level-dependent functional magnetic resonance imaging are discussed. After the characterization of the intrinsic signal in the behaving primate, we used this new imaging method to explore the stability of cortical maps in the macaque primary visual cortex. Functional maps of orientation and ocular dominance columns were found to be stable for a period longer than 1 year.

Anesthesia↗

Reciprocal projections of cat extrastriate cortex: I. Distribution and morphology of neurons projecting from posterior medial lateral suprasylvian sulcus to area 17.

Reciprocal projections between cortical areas have been subdivided into two functionally distinct component, "feedforward" and "feedback" (for review, see Felleman and Van Essen [1991] Cereb. Cortex 1:1-47). Some anatomical evidence, such as differences in the laminar distribution of the neurons of origin and of the terminations of their axons, has supported this division. However, very little is actually known about the distribution and morphology of the neurons of the feedback projections. In order to contribute further to our understanding of these two components of the corticocortical projections, I studied the distribution and morphology of a feedback projection, the reciprocal projection from the posterior medial lateral suprasylvian sulcus (PMLS), to primary visual cortex (area 17). Retrograde transport of horseradish peroxidase and fluorescent tracers in vivo combined with intracellular dye injections in lightly fixed cortical slices revealed many similarities between the feedforward and feedback projections: 1) They both emanate from all layers but layer 1; 2) each layer of origin contains a wide variety of standard and/or inverted pyramidal neurons; and 3) all of these, with the exception of a rare, large layer 5 neuron, have dendritic fields restricted principally to their layers of origin. There was, however, one major difference between the feedforward and feedback projections: In contrast to the projection from area 17 to PMLS, the projection from PMLS had a dense projection from layer 6 that compromised a striking abundance of spiny fusiform and inverted pyramidal neurons. These were morphologically distinct from other layer 6 neurons that project to the thalamus. Taken together, these data suggest that the reciprocal projections between area 17 and area PMLS, although not completely equivalent, share essential features that form a distinct population of neurons differing in morphology from corticothalamic projection neurons.

Animals↗

Region-specific distribution of catecholamine afferents in primate cerebral cortex: a fluorescence histochemical analysis.

The density, laminar distribution, spatial orientation, and intrahemispheric pathways of norepinephrine (NE)- and dopamine (DA)- containing axons were analyzed in a wide range of cytoarchitectonically distinct areas of cerebral cortex in the adult rhesus monkey by fluorescence histochemistry. Although the boundaries between most areas were rarely sharp, there were marked regional differences in density and distribution of monoamine afferents in different cortical regions. Fibers exhibiting typical DA-like morphology were found only in the temporal and frontal lobes including motor and premotor areas as well as anterior cingulate and prefrontal cortices. In contrast, NE-containing axons were present in all cerebral lobes, with notably high density in the somatosensory area and low numbers in primary visual cortex. Intracerebral distribution was characterized by a network of large preterminal axons coursing both anteroposteriorly and mediolaterally in layer VI and in the subjacent white matter. In most cytoarchitectonic regions examined, catecholamine (CA)-containing axons exhibited a bilaminar distribution into one superficial and one deep fiber band. The location and width of the two dense bands, as well as the orientation and relative density of fibers within them, was region specific. Although fluorescent axons were found at all cortical depths, layers I, and IV usually contained relatively few fluorescent axons while layers II-III and IV-V were often densely innervated. An observation that may reflect a specialization in gyrencephalic brains is the particularly dense CA innervation around sulcal invaginations in all cerebral lobes. The present results confirm previous biochemical evidence of regional heterogeneity in the concentration of DA and NE in the primate neocortex (Brown and Goldman, '77:Brain Res. 124:576-550) an provide the first anatomical demonstration of corresponding differences in the pattern and density of CA innervation in diverse cytoarchitectonic areas in rhesus monkey. These findings raise the possibility of selective targets and functions for CA fibers in different layers and regions of the primate cortex.

Animals↗

A quantitative approach to cytoarchitectonics. VIII. The areal pattern of the cortex of the albino mouse.

The cerebral cortex of the albino mouse was examined by means of a quantitative method. An image analyzer was used in conjunction with an automatic scanning procedure to determine the grey level index in Nissl-stained sections. Computer plots of various ranges of grey level indices enabled delineation of cortical areas, from which cortical maps were graphically reconstructed. The cortical areal pattern is, in some regions, similar to the commonly used map of Caviness (1975) but differs considerably in other regions, especially in the temporal one. Furthermore, the primary visual cortex of the mouse was shown to be composed of two distinct cytoarchitectonic areas. The results of the study are discussed with respect to the literature on anatomical and functional localizations in the mouse cerebral cortex.

Animals↗

An fMRI version of the Farnsworth-Munsell 100-Hue test reveals multiple color-selective areas in human ventral occipitotemporal cortex.

Studies of patients with cerebral achromatopsia have suggested that ventral occipitotemporal cortex is important for color perception. We created a functional magnetic resonance imaging (fMRI) version of a clinical test commonly used to assess achromatopsia, the Farnsworth-Munsell 100-Hue test. The test required normal subjects to use color information in the visual stimulus to perform a color sequencing task. A modification of the test requiring ordering by luminance was used as a control task. Subjects were also imaged as they passively viewed colored stimuli. A limited number of areas responded more to chromatic than achromatic stimulation, including primary visual cortex. Most color-selective activity was concentrated in ventral occipitotemporal cortex. Several areas in ventral cortex were identified. The most posterior, located in posterior fusiform gyrus, corresponded to the area activated by passive viewing of colored stimuli. More anterior and medial color-selective areas were located in the collateral sulcus and fusiform gyrus. These more anterior areas were not identified in previous imaging studies which used passive viewing of colored stimuli, and were most active in our study when visual color information was behaviorally relevant, suggesting that attention influences activity in color-selective areas. The fMRI version of the Farnsworth-Munsell test may be useful in the study of achromatopsia.

Adaptation, Physiological↗

Brain metabolism in the cerebellum and visual cortex correlates with neuropsychological testing in patients with Alzheimer's disease.

This study was designed to measure glucose metabolic deficits in areas not typically recognized as abnormal on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans in patients with Alzheimer's disease (AD), and to correlate such findings with subtle neuropsychological impairment. FDG-PET scans on 38 AD patients with no clinical evidence of visual, spatial or motor deficits were acquired on the PET HEAD scanner 40 min following the intravenous administration of 115 microCi.kg-1 of FDG. All FDG-PET scans were analysed blindly using a region of interest (ROI) template with regions for the primary visual cortex (PVC), secondary visual cortex (SVC) and cerebellum. Counts from the ROIs of these regions were normalized to whole brain activity and the results were compared with psychometric and neuropsychological measures. A number of significant correlations were found between these structures and various neuropsychological measures (P<0.05). Specifically, there were significant correlations between clock drawing and the cerebellum activity; memory and activity in the PVC, SVC and cerebellum; social score and activity in the PVC and left cerebellum; judgement and activity in the right SVC and right PVC; and the overall Mini-Mental State Examination and activity in the PVC, SVC and cerebellum. The results of this study suggest that metabolism in areas not typically recognized as abnormal on FDG-PET scans in AD, such as the PVC, SVC and cerebellum, is correlated with deficits in neuropsychological function. This may have important clinical and pathophysiological implications in the study of AD and other illnesses of dementia.

Aged↗

A model for the development of simple cell receptive fields and the ordered arrangement of orientation columns through activity-dependent competition between ON- and OFF-center inputs.

Neurons in the primary visual cortex of higher mammals respond selectively to light/dark borders of a particular orientation. The receptive fields of simple cells, a type of orientation-selective cell, consist of adjacent, oriented regions alternately receiving ON-center and OFF-center excitatory input. I show that this segregation of inputs within receptive fields can occur through an activity-dependent competition between ON-center and OFF-center inputs, just as segregation of inputs between different postsynaptic cells into ocular dominance columns appears to occur through activity-dependent competition between left-eye and right-eye inputs. These different outcomes are proposed to result, not from different mechanisms, but from different spatial structures of the correlations in neural activity among the competing inputs in each case. Simple cells result if ON-center inputs are best correlated with other ON-center inputs, and OFF with OFF, at small retinotopic separations, but ON-center inputs are best correlated with OFF-center inputs at larger separations. This hypothesis leads robustly to development of simple cell receptive fields selective for orientation and spatial frequency, and to the continuous and periodic arrangement of preferred orientation across the cortex. Input correlations determine the mean preferred spatial frequency and degree of orientation selectivity. Estimates of these correlations based on measurements in adult cat retina (Mastronarde, 1983a,b) produce quantitative predictions for the mean preferred spatial frequencies of cat simple cells across eccentricities that agree with experiments (Movshon et al., 1978b). Intracortical interactions are the primary determinant of cortical organization. Simple cell spatial phases can play a key role in this organization, so arrangements of spatial phases and preferred orientations may need to be studied together to understand either alone. Possible origins for other cortical features including spatial frequency clusters, afferent ON/OFF segregation, blobs, pinwheels, and opponent inhibition within simple cell receptive fields are suggested. A number of strong experimental tests of the hypothesis are proposed.

Algorithms↗

Spatial and temporal dependencies of cross-orientation suppression in human vision.

A well-known property of orientation-tuned neurons in the visual cortex is that they are suppressed by the superposition of an orthogonal mask. This phenomenon has been explained in terms of physiological constraints (synaptic depression), engineering solutions for components with poor dynamic range (contrast normalization) and fundamental coding strategies for natural images (redundancy reduction). A common but often tacit assumption is that the suppressive process is equally potent at different spatial and temporal scales of analysis. To determine whether it is so, we measured psychophysical cross-orientation masking (XOM) functions for flickering horizontal Gabor stimuli over wide ranges of spatio-temporal frequency and contrast. We found that orthogonal masks raised contrast detection thresholds substantially at low spatial frequencies and high temporal frequencies (high speeds), and that small and unexpected levels of facilitation were evident elsewhere. The data were well fit by a functional model of contrast gain control, where (i) the weight of suppression increased with the ratio of temporal to spatial frequency and (ii) the weight of facilitatory modulation was the same for all conditions, but outcompeted by suppression at higher contrasts. These results (i) provide new constraints for models of primary visual cortex, (ii) associate XOM and facilitation with the transient magno- and sustained parvostreams, respectively, and (iii) reconcile earlier conflicting psychophysical reports on XOM.

Adult↗

Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Regional and diagnostic specificity.

BACKGROUND: Multiple lines of evidence indicate that the prefrontal cortex is a site of dysfunction in schizophrenia. However, the apparent absence of gross structural abnormalities in this area suggests that the pathophysiological characteristics of schizophrenia may involve more subtle disturbances in prefrontal cortical circuitry, such as alterations in synaptic connectivity and transmission. In this study, immunoreactivity for synaptophysin, an integral membrane protein of small synaptic vesicles, was used to assess the integrity of cortical synaptic circuitry in schizophrenia. METHODS: Using immunocytochemical techniques and adjusted optical density measurements, we examined synaptophysin immunoreactivity in prefrontal cortical areas 9 and 46 and in area 17 (the primary visual cortex) from 10 pairs of case subjects with schizophrenia and control subjects. matched on a pairwise basis for age, sex, race, and postmortem interval, and in 5 matched pairs of nonschizophrenic psychiatric case subjects and normal control subjects. RESULTS: Compared with levels found in matched control subjects, synaptophysin immunoreactivity in areas 46 and 9 was significantly decreased (P < .001 and P < .008, respectively) across all cortical layers in the case subjects with schizophrenia. In contrast, no differences were observed in area 17. In addition, levels of synaptophysin immunoreactivity in areas 46, 9, and 17 did not differ between 5 nonschizophrenic psychiatric case subjects and their matched controls, suggesting that decreased synaptophysin levels in the prefrontal cortex of patients with schizophrenia may be specific to that disorder. CONCLUSION: Additional studies are required to determine if the decrease in levels of synaptophysin immunoreactivity is caused by a decrease in the number or size of presynaptic terminals, a decrease in the number of synaptic vesicle per terminal, or a decrease in the expression of synaptophysin. However, all of these potential explanations are consistent with a disturbance in synaptic transmission in the prefrontal cortex of patients with schizophrenia.

Adult↗

Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Regional and diagnostic specificity.

BACKGROUND: Multiple lines of evidence indicate that the prefrontal cortex is a site of dysfunction in schizophrenia. However, the apparent absence of gross structural abnormalities in this area suggests that the pathophysiological characteristics of schizophrenia may involve more subtle disturbances in prefrontal cortical circuitry, such as alterations in synaptic connectivity and transmission. In this study, immunoreactivity for synaptophysin, an integral membrane protein of small synaptic vesicles, was used to assess the integrity of cortical synaptic circuitry in schizophrenia. METHODS: Using immunocytochemical techniques and adjusted optical density measurements, we examined synaptophysin immunoreactivity in prefrontal cortical areas 9 and 46 and in area 17 (the primary visual cortex) from 10 pairs of case subjects with schizophrenia and control subjects matched on a pairwise basis for age, sex, race, and postmortem interval, and in 5 matched pairs of nonschizophrenic psychiatric case subjects and normal control subjects. RESULTS: Compared with levels found in matched control subjects, synaptophysin immunoreactivity in areas 46 and 9 was significantly decreased (P < .001 and P < .008, respectively) across all cortical layers in the case subjects with schizophrenia. In contrast, no differences were observed in area 17. In addition, levels of synaptophysin immunoreactivity in areas 46, 9, and 17 did not differ between 5 nonschizophrenic psychiatric case subjects and their matched controls, suggesting that decreased synaptophysin levels in the prefrontal cortex of patients with schizophrenia may be specific to that disorder. CONCLUSIONS: Additional studies are required to determine if the decrease in levels of synaptophysin immunoreactivity is caused by a decrease in the number or size of presynaptic terminals, a decrease in the number of synaptic vesicles per terminal, or a decrease in the expression of synaptophysin. However, all of these potential explanations are consistent with a disturbance in synaptic transmission in the prefrontal cortex of patients with schizophrenia.

Adult↗

Posterior cortical atrophy in Alzheimer's disease: analysis of a new case and re-evaluation of a historical report.

Disturbances of visual function are not uncommon in Alzheimer's disease and several cases with complex impairment of visuospatial abilities have been described. For instance, posterior cortical atrophy has been demonstrated in cases displaying Balint's syndrome as the first symptom of the dementing illness. Such cases showed very high lesion counts in the occipital cortex, as well as in visual association regions in the posterior parietal and posterior cingulate cortex, whereas the prefrontal cortex was consistently less severely involved than usually observed in Alzheimer's disease. This suggests that the distribution of the lesions had been shifted to specific elements of the visual system. In the present study, we report the quantitative analysis of a new case of Alzheimer's disease with possible Balint's syndrome and re-evaluate a case originally described in 1945. The distribution of lesion in these two cases parallels previous observations of Alzheimer's disease cases with early visual impairment. Both cases displayed very high densities of neurofibrillary tangles and senile plaques in the primary visual cortex, secondary visual cortex, visual association areas of the dorsal occipital and posterior parietal lobe and in the posterior cingulate cortex, whereas the prefrontal and inferior temporal regions were comparatively less affected. These cases may define clinical subgroups of Alzheimer's disease and suggest that the breakdown of corticocortical projections that is known to occur in dementia may involve select components of specific functional systems in certain cases. In particular, pathways that subserve motion detection and visuospatial analysis appear to be dramatically affected in these cases presenting with Balint's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characteristics of human luminance discrimination and modeling a neural network based on the response properties of the visual cortex.

Reaction time (RT) and error rate that depend on stimulus duration were measured in a luminance-discrimination reaction time task. Two patches of light with different luminance were presented to participants for 'short' (150 ms) or 'long' (1 s) period on each trial. When the stimulus duration was 'short', the participants responded more rapidly with poorer discrimination performance than they did in the longer duration. The results suggested that different sensory responses in the visual cortices were responsible for the dependence of response speed and accuracy on the stimulus duration during the luminance-discrimination reaction time task. It was shown that the simple winner-take-all-type neural network model receiving transient and sustained stimulus information from the primary visual cortex successfully reproduced RT distributions for correct responses and error rates. Moreover, temporal spike sequences obtained from the model network closely resembled to the neural activity in the monkey prefrontal or parietal area during other visual decision tasks such as motion discrimination and oddball detection tasks.

Adult↗

Dynamic characteristics of oxygenation-sensitive MRI signal in different temporal protocols for imaging human brain activity.

The temporal characteristics of cerebral blood oxygenation during human brain activation were monitored with dynamic echo-planar imaging (EPI) using the blood oxygenation level dependent (BOLD) fMRI. We investigated oxygenation-sensitive signal changes: 1. during repetitive block stimuli, to determine the latency of the activation-induced signal change in the primary visual cortex; 2. on shortening the rest periods between constant stimulated phases, to investigate the limitations that this latency poses in temporal resolution of the technique; and 3. on sustained steady-state stimulation, to characterise oxygenation changes during prolonged brain activation using different stimuli. Delayed intrinsic haemodynamic response and a finite signal-to-noise ratio limit the temporal resolution achieved with BOLD fMRI. Separate activation periods were resolved when the delay between consecutive stimulations was at least 2 s. In this study oxygenation remained elevated throughout sustained activation, suggesting a constant rate of oxygen consumption by the primary cortical neurones during activation. Characterisation of fMRI signal dynamics in dynamic temporal protocols is significant both in terms of optimising stimulation protocols and the potential to gain insight into the physiological mechanisms underlying neuronal activation which could increase the clinical applicability of the technique.

Adult↗