Adaptive processing and perceptual learning in visual cortical areas V1 and V4.

Neurons in visual cortical areas primary visual cortex (V1) and V4 are adaptive processors, influenced by perceptual task. This is reflected in their ability to segment the visual scene into task-relevant and task-irrelevant stimulus components and by changing their tuning to task-relevant stimulus properties according to the current top-down instruction. Differences between the information represented in each area were seen. While V1 represented detailed stimulus characteristics, V4 filtered the input from V1 to carry the binary information required for the two-alternative judgement task. Neurons in V1 were activated at locations where the behaviorally relevant stimulus was placed well outside the grating-mapped receptive field. By systematically following the development of the task-dependent signals over the course of perceptual learning, we found that neuronal selectivity for task-relevant information was initially seen in V4 and, over a period of weeks, subsequently in V1. Once the learned information was represented in V1, on any given trial, task-relevant information appeared initially in V1 responses, followed by a 12-ms delay in V4. We propose that the shifting representation of learned information constitutes a mechanism for systems consolidation of memory.

Diagnosis and Treatment of Inguinal Hernias after Surgical Treatment of Prostate Cancer, Current State of the Problem.

(1) Purpose: To compare and evaluate the immediate and long-term results of the use of various hernioplasties for the treatment of inguinal hernias after surgical treatment of prostate cancer; to determine the possibility of performing transabdominal preperitoneal (TAPP) hernioplasty and total extraperitoneal (eTEP) hernioplasty in patients with inguinal hernia during surgical treatment of prostate cancer. (2) Method: This study is a clinical analytical prospective study, without the use of randomization. The study included 220 patients with inguinal hernia, who were randomly divided into two groups (group A (n = 100) and group B (n = 120)). Patients in group A received eTEP, and those in group B received TAPP. The end points of the study were the results associated with the operation itself and the prognosis of the disease in the two groups. (3) Results: Group A: five patients had a scrotal hematoma, in 10 cases nosocomial pneumonia or infectious complications from the postoperative wound. The overall rate of early postoperative complications was 15%. In group B, the following postoperative complications were reported: one case of intestinal injury, six cases of acute urinary retention, eight cases of scrotal hematoma and 12 cases of nosocomial pneumonia or infectious complications from the postoperative wound were admitted. The overall incidence of early postoperative complications was 22.5%. There was no statistically significant difference in the incidence of postoperative complications between the two groups (χ2 (3) = 2.54, p > 0.05). (4) Conclusion: During the analysis of the obtained results, no statistically significant difference was found in the duration of hospitalization, the volume of blood loss, the severity of pain syndrome, postoperative complication incidence and recurrence incidence (p > 0.05); however, the comparison groups differed in the duration of the operation: the operation time in group A was much longer compared to group B (p < 0.05).

Axonal plasticity associated with perceptual learning in adult macaque primary visual cortex.

Perceptual learning is associated with changes in the functional properties of neurons even in primary sensory areas. In macaque monkeys trained to perform a contour detection task, we have observed changes in contour-related facilitation of neuronal responses in primary visual cortex that track their improvement in performance on a contour detection task. We have previously explored the anatomical substrate of experience-dependent changes in the visual cortex based on a retinal lesion model, where we find sprouting and pruning of the axon collaterals in the cortical lesion projection zone. Here, we attempted to determine whether similar changes occur under normal visual experience, such as that associated with perceptual learning. We labeled the long-range horizontal connections in visual cortex by virally mediated transfer of genes expressing fluorescent probes, which enabled us to do longitudinal two-photon imaging of axonal arbors over the period during which animals improve in contour detection performance. We found that there are substantial changes in the axonal arbors of neurons in cortical regions representing the trained part of the visual field, with sprouting of new axon collaterals and pruning of preexisting axon collaterals. Our findings indicate that changes in the structure of axonal arbors are part of the circuit-level mechanism of perceptual learning, and further support the idea that the learned information is encoded at least in part in primary visual cortex.

Interactions between feedback and lateral connections in the primary visual cortex.

Perceptual grouping of line segments into object contours has been thought to be mediated, in part, by long-range horizontal connectivity intrinsic to the primary visual cortex (V1), with a contribution by top-down feedback projections. To dissect the contributions of intraareal and interareal connections during contour integration, we applied conditional Granger causality analysis to assess directional influences among neural signals simultaneously recorded from visual cortical areas V1 and V4 of monkeys performing a contour detection task. Our results showed that discounting the influences from V4 markedly reduced V1 lateral interactions, indicating dependence on feedback signals of the effective connectivity within V1. On the other hand, the feedback influences were reciprocally dependent on V1 lateral interactions because the modulation strengths from V4 to V1 were greatly reduced after discounting the influences from other V1 neurons. Our findings suggest that feedback and lateral connections closely interact to mediate image grouping and segmentation.

Childhood maltreatment as a risk factor for COPD: findings from a population-based survey of Canadian adults.

OBJECTIVE: The aim of this study was to examine the associations between childhood maltreatment (CM) and COPD in adulthood. METHODS: Data were from 15,902 respondents to the 2012 Canadian Community Health Survey - Mental Health. Multiple logistic regression models were used to examine associations between CM and COPD and the role of smoking and mental and substance use variables as mediators in associations. RESULTS: COPD in adulthood was related to CM, with associations differing by sex. Among females, COPD was related to childhood physical abuse (CPA), childhood sexual abuse, and childhood exposure to intimate partner violence, but in the fully adjusted models, the association with CPA did not persist. Among males, COPD was related to childhood exposure to intimate partner violence and severe and frequent CPA, but these associations did not persist in the fully adjusted models. CONCLUSION: Results from this study establish CM as a risk factor for COPD in adulthood. A large part of the association is attributable to cigarette smoking, particularly for males. These findings underscore the importance of interventions to prevent CM as well as programs to assist victims of CM in dealing with tobacco addiction.

A rare case of extremely high counts of circulating tumor cells detected in a patient with an oral squamous cell carcinoma.

BACKGROUND: Despite aggressive regimens, the clinical outcome of head and neck squamous cell carcinoma remains poor. The detection of circulating tumor cells could potentially improve the management of patients with disseminated cancer, including diagnosis, treatment strategies, and surveillance. Currently, CellSearch(®) is the most widely used and the only Food and Drug Administration-cleared system for circulating tumor cells detection in patients with metastatic breast, colorectal, or prostate cancer. In most cases of head and neck squamous cell carcinoma, only low counts of circulating tumor cells have been reported. CASE PRESENTATION: A 56-year-old white male with no particular medical history, was diagnosed with a squamous cell carcinoma of oral cavity. According to the imaging results (computed tomography and (18)F-fluorodeoxyglucose positron emission tomography / computed tomography) and panendoscopy, the TNM staging was classified as T4N2M0. A non-interruptive pelvimandibulectomy was conducted according to the multidisciplinary meeting advices and the postoperative observations were normal. The patient complained of a painful cervical edema and a trismus 6 weeks after the surgery. A relapse was found by computed tomography and the patient died two weeks later. The search for circulating tumor cells in peripheral venous blood by using the CellSearch(®) system revealed a very high count compared with published reports at three time points (pre-operative: 400; intra-operative: 150 and post-operative day 7: 1400 circulating tumor cells). Of note, all detected circulating tumor cells were epidermal growth factor receptor negative. CONCLUSION: We report here for the first time a rare case of oral squamous cell carcinoma with extremely high circulating tumor cells counts using the CellSearch(®) system. The absolute number of circulating tumor cells might predict a particular phase of cancer development as well as a poor survival, potentially contributing to a personalized healthcare.

Physiological role for amyloid precursor protein in adult experience-dependent plasticity.

Changes in neural circuits after experience-dependent plasticity are brought about by the formation of new circuits via axonal growth and pruning. Here, using a combination of electrophysiology, adeno-associated virus-delivered fluorescent proteins, analysis of mutant mice, and two-photon microscopy, we follow long-range horizontally projecting axons in primary somatosensory cortex before and after selective whisker plucking. Whisker plucking induces axonal growth and pruning of horizontal projecting axons from neurons located in the surrounding intact whisker representations. We report that amyloid precursor protein is crucial for axonal pruning and contributes in a cell autonomous way.

Adult cortical plasticity studied with chronically implanted electrode arrays.

The functional architecture of adult cerebral cortex retains a capacity for experience-dependent change. This is seen after focal binocular lesions as rapid changes in receptive field (RF) of the lesion projection zone (LPZ) in the primary visual cortex (V1). To study the dynamics of the circuitry underlying these changes longitudinally, we implanted microelectrode arrays in macaque (Macaca mulatta) V1, eliminating the possibility of sampling bias, which was a concern in previous studies. With this method, we observed a rapid initial recovery in the LPZ and, during the following weeks, 63-89% of the sites in the LPZ showed recovery of visual responses with significant position tuning. The RFs shifted ∼3° away from the scotoma. In the absence of a lesion, visual stimulation surrounding an artificial scotoma did not elicit visual responses, suggesting that the postlesion RF shifts resulted from cortical reorganization. Interestingly, although both spikes and LFPs gave consistent prelesion position tuning, only spikes reflected the postlesion remapping.

Incremental integration of global contours through interplay between visual cortical areas.

The traditional view on visual processing emphasizes a hierarchy: local line segments are first linked into global contours, which in turn are assembled into more complex forms. Distinct from this bottom-up viewpoint, here we provide evidence for a theoretical framework whereby objects and their parts are processed almost concurrently in a bidirectional cortico-cortical loop. By simultaneous recordings from V1 and V4 in awake monkeys, we found that information about global contours in a cluttered background emerged initially in V4, started ∼40 ms later in V1, and continued to develop in parallel in both areas. Detailed analysis of neuronal response properties implicated contour integration to emerge from both bottom-up and reentrant processes. Our results point to an incremental integration mechanism: feedforward assembling accompanied by feedback disambiguating to define and enhance the global contours and to suppress background noise. The consequence is a parallel accumulation of contour information over multiple cortical areas.

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.

Network model of top-down influences on local gain and contextual interactions in visual cortex.

The visual system uses continuity as a cue for grouping oriented line segments that define object boundaries in complex visual scenes. Many studies support the idea that long-range intrinsic horizontal connections in early visual cortex contribute to this grouping. Top-down influences in primary visual cortex (V1) play an important role in the processes of contour integration and perceptual saliency, with contour-related responses being task dependent. This suggests an interaction between recurrent inputs to V1 and intrinsic connections within V1 that enables V1 neurons to respond differently under different conditions. We created a network model that simulates parametrically the control of local gain by hypothetical top-down modification of local recurrence. These local gain changes, as a consequence of network dynamics in our model, enable modulation of contextual interactions in a task-dependent manner. Our model displays contour-related facilitation of neuronal responses and differential foreground vs. background responses over the neuronal ensemble, accounting for the perceptual pop-out of salient contours. It quantitatively reproduces the results of single-unit recording experiments in V1, highlighting salient contours and replicating the time course of contextual influences. We show by means of phase-plane analysis that the model operates stably even in the presence of large inputs. Our model shows how a simple form of top-down modulation of the effective connectivity of intrinsic cortical connections among biophysically realistic neurons can account for some of the response changes seen in perceptual learning and task switching.

Death receptor 6 regulates adult experience-dependent cortical plasticity.

Sensory experience alters cortical circuitry by parallel processes of axon outgrowth and pruning, but the mechanisms that control these rearrangements are poorly understood. Using in vivo 2-photon longitudinal imaging, we found a marked reduction in axonal pruning in somatosensory cortex of mice with a knock-out of the DR6 gene, which codes for Death Receptor 6. This effect was seen for both long-range horizontal excitatory connections and for the axons of inhibitory neurons. These results identify a new pathway governing axonal plasticity associated with experience-dependent changes in cortical maps.

Top-down influences on visual processing.

Re-entrant or feedback pathways between cortical areas carry rich and varied information about behavioural context, including attention, expectation, perceptual tasks, working memory and motor commands. Neurons receiving such inputs effectively function as adaptive processors that are able to assume different functional states according to the task being executed. Recent data suggest that the selection of particular inputs, representing different components of an association field, enable neurons to take on different functional roles. In this Review, we discuss the various top-down influences exerted on the visual cortical pathways and highlight the dynamic nature of the receptive field, which allows neurons to carry information that is relevant to the current perceptual demands.

Top-down modulation of lateral interactions in visual cortex.

The primary visual cortex (V1) changes its computation according to the perceptual task being performed. We propose that this cognitive modulation results from gating of V1 intrinsic connections. To test this idea, using behavioral paradigms that engage top-down modulation of V1 contextual interactions, we recorded from chronically implanted electrode arrays in macaques. We observed task-dependent changes in interactions between V1 sites measured both by correlation between spike trains and by coherence between local field potentials (LFP-LFP coherence). The direction of the changes in aggregate activity, as measured by LFPs, depended on perceptual strategy: perceptual grouping increased LFP coherence between sites crucial for the task, whereas perceptual segregation lowered the LFP coherence. Using spiking activity as a measure, we found that the behaviorally driven changes in correlation structure between neurons dramatically increased the stimulus-related information that they convey; this additional increase in encoded information at the level of neuronal ensembles equals that obtained from task-driven reconfigurations of neural tuning curves. The improvements in information encoding were strongest for stimuli with greatest discrimination difficulty.

Adult visual cortical plasticity.

The visual cortex has the capacity for experience-dependent change, or cortical plasticity, that is retained throughout life. Plasticity is invoked for encoding information during perceptual learning, by internally representing the regularities of the visual environment, which is useful for facilitating intermediate-level vision--contour integration and surface segmentation. The same mechanisms have adaptive value for functional recovery after CNS damage, such as that associated with stroke or neurodegenerative disease. A common feature to plasticity in primary visual cortex (V1) is an association field that links contour elements across the visual field. The circuitry underlying the association field includes a plexus of long-range horizontal connections formed by cortical pyramidal cells. These connections undergo rapid and exuberant sprouting and pruning in response to removal of sensory input, which can account for the topographic reorganization following retinal lesions. Similar alterations in cortical circuitry may be involved in perceptual learning, and the changes observed in V1 may be representative of how learned information is encoded throughout the cerebral cortex.

Adaptive shape processing in primary visual cortex.

The ability to derive meaning from complex sensory input requires the integration of information over space and time, as well as cognitive mechanisms to shape that integration. We studied these processes in the primary visual cortex (V1), where neurons are thought to integrate visual inputs along contours defined by an association field (AF). We recorded extracellularly from single cells in macaque V1 to map the AF, by using an optimization algorithm to find the contours that maximally activated individual cells. We combined the algorithm with a delayed-match-to-sample task, to test how the optimal contours might be molded by the monkey's expectation for particular cue shapes. We found that V1 neurons were selective for complex shapes, a property previously ascribed to higher cortical areas. Furthermore, the shape selectivity was reprogrammed by perceptual task: Over the whole network, the optimal modes of geometric selectivity shifted between distinct subsets of the AF, alternately representing different stimulus features known to predominate in natural scenes. Our results suggest a general model of cortical function, whereby horizontal connections provide a broad domain of potential associations, and top-down inputs dynamically gate these linkages to task switch the function of a network.

Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.

Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.

Experience-dependent gene expression in adult visual cortex.

Experience-dependent plasticity of the adult visual cortex underlies perceptual learning and recovery of function following central nervous system lesions. To reveal the signal transduction cascades involved in adult cortical plasticity, we utilized a model of remapping of cortical topography following binocular retinal lesions. In this model, the lesion projection zone (LPZ) of primary visual cortex (V1) recovers visually driven activity by the sprouting of horizontal axonal connections originating from the cells in the surrounding region. To explore the molecular mechanism underlying this process, we used gene microarrays from an expression library prepared from Macaque V1. By microarray analysis of gene expression levels in the LPZ and the surrounding region, and subsequent confirmation with Quantitative Real-Time polymerase chain reaction and in situ hybridization, the participation of a number of genes was observed, including the Rho GTPase family. Its role in regulation of cytoskeleton assembly provides a possible link between the alteration of neural activity and cortical functional reorganization.

Use of administrative data for the surveillance of mood and anxiety disorders.

OBJECTIVE: There is increasing interest in the use of administrative data for surveillance and research in Australia. The purpose of the present study was to evaluate the usefulness of such data for the surveillance of mood and anxiety disorder using databases from the following Canadian provinces: British Columbia, Ontario, Quebec and Nova Scotia. METHOD: A population-based record-linkage analysis was done using data from physician billings and hospital discharge abstracts, and community-based clinics using a case definition of ICD-9 diagnoses of 296.0-296.9, 311.0, and 300.0-300.9. RESULTS: The prevalence of treated mood and/or anxiety disorder was similar in Nova Scotia, British Columbia, and Ontario at approximately 10%. The prevalence for Quebec was slightly lower at 8%. Findings from the provinces showed consistency across age and sex despite variations in data coding. Women tended to show a higher prevalence overall of mood and anxiety disorder than men. There was considerably more variation, however, when treated anxiety (300.0-300.9) and mood disorders (296.0-296.9, 311.0) were considered separately. Prevalence increased steadily to middle age, declining in the 50s and 60s, and then increased after 70 years of age. CONCLUSIONS: Administrative data can provide a useful, reliable and economical source of information for the surveillance of treated mood and/or anxiety disorder. Due to the lack of specificity, however, in the diagnoses and data capture, it may be difficult to conduct surveillance of mood and anxiety disorders as separate entities. These findings may have implications for the surveillance of mood and anxiety disorders in Australia with the development of a national network for the extraction, linkage and analysis of administrative data.