A transthalamic pathway crucial for perception.

Perception arises from activity between cortical areas, first primary cortex and then higher order cortices. This communication is served in part by transthalamic (cortico-thalamo-cortical) pathways, which ubiquitously parallel direct corticocortical pathways, but their role in sensory processing has largely remained unexplored. Here, we show that the transthalamic pathway linking somatosensory cortices propagates task-relevant information required for correct sensory decisions. Using optogenetics, we specifically inhibited the pathway at its synapse in higher order somatosensory thalamus of mice performing a texture-based discrimination task. We concurrently monitored the cellular effects of inhibition in primary or secondary cortex using two-photon calcium imaging. Inhibition severely impaired performance despite intact direct corticocortical projections, thus challenging the purely corticocentric map of perception. Interestingly, the inhibition did not reduce overall cell responsiveness to texture stimulation in somatosensory cortex, but rather disrupted the texture selectivity of cells, a discriminability that develops over task learning. This discriminability was more disrupted in the secondary than primary somatosensory cortex, emphasizing the feedforward influence of the transthalamic route. Transthalamic pathways thus appear critical in delivering performance-relevant information to higher order cortex and are critical hierarchical pathways in perceptual decision-making.

COVID-19 vaccination acceptability in the UK at the start of the vaccination programme: a nationally representative cross-sectional survey (CoVAccS - wave 2).

OBJECTIVES: Investigate factors associated with the intention to have the COVID-19 vaccination following initiation of the UK national vaccination programme. STUDY DESIGN: An online cross-sectional survey completed by 1500 adults (13th-15th January 2021). METHODS: Linear regression analyses were used to investigate associations between intention to be vaccinated for COVID-19 and sociodemographic factors, previous influenza vaccination, attitudes and beliefs about COVID-19 and COVID-19 vaccination and vaccination in general. Participants' main reasons for likely vaccination (non-)uptake were also solicited. RESULTS: 73.5% of participants (95% CI 71.2%, 75.7%) reported being likely to be vaccinated against COVID-19, 17.3% (95% CI 15.4%, 19.3%) were unsure, and 9.3% (95% CI 7.9%, 10.8%) reported being unlikely to be vaccinated. The full regression model explained 69.8% of the variance in intention. Intention was associated with: having been/intending to be vaccinated for influenza last winter/this winter; stronger beliefs about social acceptability of a COVID-19 vaccine; the perceived need for vaccination; adequacy of information about the vaccine; and weaker beliefs that the vaccine is unsafe. Beliefs that only those at serious risk of illness should be vaccinated and that the vaccines are just a means for manufacturers to make money were negatively associated with vaccination intention. CONCLUSIONS: Most participants reported being likely to get the COVID-19 vaccination. COVID-19 vaccination attitudes and beliefs are a crucial factor underpinning vaccine intention. Continued engagement with the public with a focus on the importance and safety of vaccination is recommended.

Atypical presentations of intracranial dysgerminoma mimicking central nervous system inflammatory or demyelinating disease.

OBJECTIVES: The aim of this study is to report a case series of atypical presentations of intracranial dysgerminoma in which the diagnosis was delayed due to clinical and radiographic findings initially suggestive of CNS inflammatory or demyelinating diseases, such as MS. METHODS: This study is a case series detailing the history, clinical presentations, radiographic and laboratory results, and management of three patients with biopsy-proven intracranial dysgerminoma. RESULTS: All three patients demonstrated hyperintense lesions on MRI that were more suggestive of demyelinating or inflammatory diseases, including lesions involving the midbrain and corpus callosum. All three patients were serum positive for oligoclonal bands and negative for both AFP and beta-hCG (these two markers are commonly seen in dysgerminoma cases). One case involved a steroid-responsive tumor whereas the other two cases either did not respond to steroids or steroids were withheld due to uncertainty of etiology. Following biopsy, all three results were consistent with dysgerminoma. CONCLUSION: Clinicians should be aware that dysgerminoma may mimic the clinical and radiographic presentations of demyelinating diseases such as MS. These lesions can cause acute visual loss or diplopia, have MRI and CSF findings that might mimic MS, and have been shown to respond to steroids. Atypical clinical (e.g., headache, dorsal midbrain syndrome, bilateral optic neuropathy) or atypical radiographic features (e.g., mass effect, hydrocephalus) should prompt consideration for repeat imaging and possible biopsy even if serum or CSF tumor markers (beta-hCG and AFP) are negative for dysgerminoma.

Knowledge, attitudes and awareness of the human papillomavirus amongst primary care practice nurses: an evaluation of current training in England.

Background: The incorporation of Human papillomavirus (HPV) testing into the English cervical screening programme has been met with fear and anxiety. Healthcare professionals need to be adequately informed about HPV to help alleviate patient concerns. The aim of this study was to evaluate the HPV training provided to practice nurses (PNs) and determine their level of HPV knowledge. Method: A web-based survey was distributed to 147 General Practice surgeries in the Leicester, Leicestershire and Rutland regions, between May and July 2015. The survey explored four broad areas; demographics/level of experience, HPV knowledge, attitudes towards the HPV vaccine and self-perceived adequacy of HPV knowledge. Results: A total of 128 surveys were completed, with 94 complete responses. Overall awareness of basic HPV facts was adequate; however, detailed, and in some cases basic, knowledge was lacking. 9.6% failed to identify that HPV can cause cervical cancer and 62.8% believed that HPV requires treatment. Not all PNs felt adequately informed about HPV and a need to improve the provision of training was identified. Conclusion: PNs play a key role in increasing public awareness of HPV and implementing cervical cancer screening. The provision of education to PNs needs to be a priority and current methods of training need to be re-evaluated.

Disclosing the results of the invasive cervical cancer review to patients: a survey of lead colposcopists across England.

OBJECTIVE: To survey lead colposcopists to explore the extent to which patients are currently being invited to discuss the results of their invasive cervical cancer review, the reasons why this might not be happening and the clinician experience. METHODS: An online survey was sent to lead colposcopists across England. They were asked whether they offered the review to patients, if they did how they did so and what their experience was and if they did not, why not. RESULTS: There was a 68.5% (N = 122) response rate, with 53% of respondents currently offering the review meetings. Patients were predominantly invited to the review meeting face to face and clinicians' experiences were mixed with a variety of positive and negative aspects of the meetings given. For those clinicians not currently offering a review meeting, there were a variety of reasons: 25% cited a lack of awareness of the guidelines, 19% time constraints, 12% a fear of causing additional distress and 2% a fear of litigation. Open-ended responses demonstrated a considerable amount of misunderstanding about the process. CONCLUSION: Despite National Health Service Cervical Screening Programme guidelines, not all clinicians offer review meetings to patients and those who do offer them do not always offer them to all women. Patient research needs to be conducted to explore the value of the meetings further, and there is a need to do more to engage clinicians in the process.

Awareness and knowledge of HPV and cervical cancer in female students: A survey (with a cautionary note).

We conducted a survey to explore levels of awareness and knowledge of human papillomavirus (HPV) and cervical cancer in 170 female students and whether mode of data collection (online vs. paper) affected the results. 27% of women named HPV as a cause of cervical cancer with online respondents more likely to do so. 75% of women had heard of HPV. More online respondents had heard of HPV than paper respondents. 127 women reported having heard of HPV, with a mean knowledge score of 2.989 (standard deviation [SD] 1.599). Online respondents scored higher (3.57, SD 1.316) than paper respondents (2.688, SD 1.591). Knowledge and awareness of HPV and its link to cervical cancer appear to have increased which may be related to the HPV vaccination programme. However, there is still a considerable number of women with little to no knowledge of HPV. Online surveys may result in an inflated estimation of awareness and knowledge.

Cloud-assisted mobile-access of health data with privacy and auditability.

Motivated by the privacy issues, curbing the adoption of electronic healthcare systems and the wild success of cloud service models, we propose to build privacy into mobile healthcare systems with the help of the private cloud. Our system offers salient features including efficient key management, privacy-preserving data storage, and retrieval, especially for retrieval at emergencies, and auditability for misusing health data. Specifically, we propose to integrate key management from pseudorandom number generator for unlinkability, a secure indexing method for privacy-preserving keyword search which hides both search and access patterns based on redundancy, and integrate the concept of attribute-based encryption with threshold signing for providing role-based access control with auditability to prevent potential misbehavior, in both normal and emergency cases.

Activation of both Group I and Group II metabotropic glutamatergic receptors suppress retinogeniculate transmission.

Relay cells of dorsal lateral geniculate nucleus (LGN) receive a Class 1 glutamatergic input from the retina and a Class 2 input from cortical layer 6. Among the properties of Class 2 synapses is the ability to activate metabotropic glutamate receptors (mGluRs), and mGluR activation is known to affect thalamocortical transmission via regulating retinogeniculate and thalamocortical synapses. Using brain slices, we studied the effects of Group I (dihydroxyphenylglycine) and Group II ((2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine) mGluR agonists on retinogeniculate synapses. We showed that both agonists inhibit retinogeniculate excitatory postsynaptic currents (EPSCs) through presynaptic mechanisms, and their effects are additive and independent. We also found high-frequency stimulation of the layer 6 corticothalamic input produced a similar suppression of retinogeniculate EPSCs, suggesting layer 6 projection to LGN as a plausible source of activating these presynaptic mGluRs.

The invasive cervical cancer review: psychological issues surrounding disclosure.

An audit of the screening history of all new cervical cancer cases has been a requirement since April 2007. While NHS cervical screening programmes (NHSCSP) guidance requires that women diagnosed with cervical cancer are offered the findings of the audit, as yet there has been no research to investigate the psychological impact that meeting to discuss the findings might have on patients. This is in spite of the fact that cytological under-call may play a role in as many as 20% of cervical cancer cases. This review draws on the literature concerning breaking bad news, discussing cancer and disclosing medical errors, in order to gain insight into both the negative and positive consequences that may accompany a cervical screening review meeting. We conclude that while patients are likely to experience some distress at disclosure, there are also likely to be positive aspects, such as greater trust and improved perception of care.

Sacroiliac joint vacuum phenomenon--underreported finding.

BACKGROUND AND PURPOSE: Vacuum phenomenon (VP) is commonly found in sacroiliac joints, and its significance in patients with back pain has been debated. We investigated the prevalence of sacroiliac joint vacuum phenomenon (SJVP) and the rate at which it is reported on abdominopelvic and lumbosacral spine computed tomography (CT) images by body imagers and neuroradiologists. We hypothesized that it would be more common than not and that neuroradiologists would identify it more frequently than body imagers and on spine images more commonly than abdominopelvic studies due to the search for the source of back pain in the former. MATERIALS AND METHODS: CT images of the pelvis and lumbar spine from January to February 2009 were retrospectively reviewed. Six hundred fifty-two patients were studied during this period. Axial thin-section images were reviewed under default lung and bone window settings. Age, sex, and radiologist reports were assessed from electronic medical records. RESULTS: The prevalence of SJVP on CT imaging was 34%, with higher rates found in female (41%, P<.001) and older (39%, P<.05) patients. Eighty-five percent of the phenomena were present bilaterally. Among the 223 patients with SJVP, only 17% were reported. There were no statistically significant differences between reporting rates for body radiologists and neuroradiologists. CONCLUSION: SJVP is a prevalent condition with higher rates among older and female individuals. The phenomenon is underreported on CT images whether the studies performed are abdominopelvic scans or spine studies and whether they are interpreted by body imagers or neuroradiologists.

Different distributions of calbindin and calretinin immunostaining across the medial and dorsal divisions of the mouse medial geniculate body.

We studied the distributions of calretinin and calbindin immunoreactivity in subdivisions of the mouse medial geniculate body and the adjacent paralaminar nuclei. We found that the vast majority of labeled cells in the dorsal division of the medial geniculate body were immunoreactive for calbindin-only, whereas most of the remaining labeled cells were double-labeled. Very few calretinin+ only cells were observed. By contrast, we observed significant proportions of calbindin+ only, calretinin+ only and double-labeled cells in the medial division of the medial geniculate body. Further, the distributions of calbindin-only, calretinin-only and double-labeled cells did not differ between the medial division of the medial geniculate body, the suprageniculate nucleus, the peripeduncular nucleus and the posterior intralaminar nucleus. We found essentially no somatic staining for either calbindin or calretinin in the ventral division of the medial geniculate body. These data suggest that there are distinct neurochemical differences between the two non-lemniscal auditory thalamic nuclei. In addition, these data extend previous observations that the medial division of the medial geniculate body shares many properties with the paralaminar group of nuclei.

Rapid and sensitive mapping of long-range connections in vitro using flavoprotein autofluorescence imaging combined with laser photostimulation.

We investigated the use of flavoprotein autofluorescence (FA) as a tool to map long-range neural connections and combined FA with laser-uncaging of glutamate to facilitate rapid long-range mapping in vitro. Using the somatosensory thalamocortical slice, we determined that the spatial resolution of FA is >or=100-200 microm and that the sensitivity for detecting thalamocortical synaptic activity approximates that of whole cell recording. Blockade of ionotropic glutamate receptors with DNQX and AP5 abolished cortical responses to electrical thalamic stimulation. The combination of FA with photostimulation using caged glutamate revealed robust long-distance connectivity patterns that could be readily assessed in slices from the somatosensory, auditory, and visual systems that contained thalamocortical, corticothalamic, or corticocortical connections. We mapped the projection from the ventral posterior nucleus of thalamus (VPM) to the primary somatosensory cortex-barrel field and confirmed topography that had been previously described using more laborious methods. We also produced a novel map of the projections from the VPM to the thalamic reticular nucleus, showing precise topography along the dorsoventral axis. Importantly, only about 30 s were needed to generate the connectivity map (six stimulus locations). These data suggest that FA is a sensitive tool for exploring and measuring connectivity and, when coupled with glutamate photostimulation, can rapidly map long-range projections in a single animal.

Fewer driver synapses in higher order than in first order thalamic relays.

We used electron microscopy to determine the relative numbers of the three synaptic terminal types, RL (round vesicle, large terminal), RS (round vesicles, small terminal), and F (flattened vesicles), found in several representative thalamic nuclei in cats chosen as representative examples of first and higher order thalamic nuclei, where the first order nuclei relay subcortical information mainly to primary sensory cortex, and the higher order nuclei largely relay information from one cortical area to another. The nuclei sampled were the first order ventral posterior nucleus (somatosensory) and the ventral portion of the medial geniculate nucleus (auditory), and the higher order posterior nucleus (somatosensory) and the medial portion of the medial geniculate nucleus (auditory). We found that the relative percentage of synapses from RL terminals varied significantly among these nuclei, these values being higher for first order nuclei (12.6% for the ventral posterior nucleus and 8.2% for the ventral portion of the medial geniculate nucleus) than for the higher order nuclei (5.4% for the posterior nucleus, and 3.5% for the medial portion of the medial geniculate nucleus). This is consistent with a similar analysis of first and higher order nuclei for the visual system (the lateral geniculate nucleus and pulvinar, respectively). Since synapses from RL terminals represent the main information to be relayed, whereas synapses from F and RS terminals are modulatory in function, we conclude that there is relatively more modulation of the thalamic relay in the cortico-thalamo-cortical higher order pathway than in first order relays.

Higher-order thalamic relays burst more than first-order relays.

There is a strong correlation between the behavior of an animal and the firing mode (burst or tonic) of thalamic relay neurons. Certain differences between first- and higher-order thalamic relays (which relay peripheral information to the cortex versus information from one cortical area to another, respectively) suggest that more bursting might occur in the higher-order relays. Accordingly, we recorded bursting behavior in single cells from awake, behaving rhesus monkeys in first-order (the lateral geniculate nucleus, the ventral posterior nucleus, and the ventral portion of the medial geniculate nucleus) and higher-order (pulvinar and the medial dorsal nucleus) thalamic relays. We found that the extent of bursting was dramatically greater in the higher-order than in the first-order relays, and this increased bursting correlated with lower spontaneous activity in the higher-order relays. If bursting effectively signals the introduction of new information to a cortical area, as suggested, this increased bursting may be more important in corticocortical transmission than in transmission of primary information to cortex.

The thalamus as a monitor of motor outputs.

Many of the ascending pathways to the thalamus have branches involved in movement control. In addition, the recently defined, rich innervation of 'higher' thalamic nuclei (such as the pulvinar) from pyramidal cells in layer five of the neocortex also comes from branches of long descending axons that supply motor structures. For many higher thalamic nuclei the clue to understanding the messages that are relayed to the cortex will depend on knowing the nature of these layer five motor outputs and on defining how messages from groups of functionally distinct output types are combined as inputs to higher cortical areas. Current evidence indicates that many and possibly all thalamic relays to the neocortex are about instructions that cortical and subcortical neurons are contributing to movement control. The perceptual functions of the cortex can thus be seen to represent abstractions from ongoing motor instructions.

Synaptic targets of thalamic reticular nucleus terminals in the visual thalamus of the cat.

A major inhibitory input to the dorsal thalamus arises from neurons in the thalamic reticular nucleus (TRN), which use gamma-aminobutyric acid (GABA) as a neurotransmitter. We examined the synaptic targets of TRN terminals in the visual thalamus, including the A lamina of the dorsal lateral geniculate nucleus (LGN), the medial interlaminar nucleus (MIN), the lateral posterior nucleus (LP), and the pulvinar nucleus (PUL). To identify TRN terminals, we injected biocytin into the visual sector of the TRN to label terminals by anterograde transport. We then used postembedding immunocytochemical staining for GABA to distinguish TRN terminals as biocytin-labeled GABA-positive terminals and to distinguish the postsynaptic targets of TRN terminals as GABA-negative thalamocortical cells or GABA-positive interneurons. We found that, in all nuclei, the TRN provides GABAergic input primarily to thalamocortical relay cells (93-100%). Most of this input seems targeted to peripheral dendrites outside of glomeruli. The TRN does not appear to be a significant source of GABAergic input to interneurons in the visual thalamus. We also examined the synaptic targets of the overall population of GABAergic axon terminals (F1 profiles) within these same regions of the visual thalamus and found that the TRN contacts cannot account for all F1 profiles. In addition to F1 contacts on the dendrites of thalamocortical cells, which presumably include TRN terminals, another population of F1 profiles, most likely interneuron axons, provides input to GABAergic interneuron dendrites. Our results suggest that the TRN terminals are ideally situated to modulate thalamocortical transmission by controlling the response mode of thalamocortical cells.

Thalamic relay functions.

The lateral geniculate nucleus is the best understood thalamic relay. Only 5-10% of the inputs to geniculate relay cells derive from retina, which is the driving input. The rest, being modulatory, derive from local inhibitory inputs, descending inputs from visual cortex, and ascending inputs from brainstem. The nonretinal, modulatory inputs, which form the vast majority, dynamically control the nature of the geniculate relay. Among other actions, these modulatory inputs regulate membrane properties of relay cells and thereby control their mode of response to retinal inputs, and this dramatically affects the nature of information relayed to cortex. Our studies of the lateral geniculate nucleus of the cat lead to the speculation that this dynamic control depends on the animal's behavioral state and represents the neuronal substrate for many forms of visual attention. The lateral geniculate nucleus is a first-order relay, because it relays subcortical (i.e. retinal) information to cortex for the first time. In contrast, the other main thalamic relay of visual information, the pulvinar (and lateral posterior nucleus in carnivores), is largely a higher-order relay, since much of it seems to relay information from one cortical area to another. Much more corticocortical processing may involve these 're-entry' routes than has been hitherto appreciated. If so, the thalamus sits at an indispensable position for corticocortical processing.

The effects of saccadic eye movements on the activity of geniculate relay neurons in the monkey.

Saccadic suppression is the reduced visibility that occurs during saccadic eye movements. Recent psychophysical studies have suggested that this is due to a reduction in responsiveness of magnocellular (M), but not parvocellular (P), cells of the lateral geniculate nucleus. To address this and other phenomena of responsiveness during saccades, we recorded from geniculate neurons in the behaving monkey before, during, and after saccades. Specifically, we measured neuronal responses to a flashing, whole-field illumination. Contrary to the prediction, most M neurons showed pronounced enhancement of visual activity during saccades, whereas such responsiveness of parvocellular (P) neurons was not significantly affected by saccades. We also analyzed the extent to which saccades affected burst firing, which results from activation of a voltage-dependent Ca2+ conductance. We found that both M and P cells displayed a significant suppression of burst firing during saccades. These results do not support the idea that saccadic suppression has an obvious substrate in reduced responsiveness of geniculate cells, but this suppression may be related to an increased visual threshold for detection associated with reduced burst firing.

Visual response properties of neurons in the LGN of normally reared and visually deprived macaque monkeys.

It is now well appreciated that parallel retino-geniculo-cortical pathways exist in the monkey as in the cat, the species in which parallel visual pathways were first and most thoroughly documented. What remains unclear is precisely how many separate pathways pass through the parvo- and magnocellular divisions of the macaque lateral geniculate nucleus (LGN), what relationships-homologous or otherwise-these pathways have to the cat's X, Y, and W pathways, and whether these are affected by visual deprivation. To address these issues of classification and trans-species comparison, we used achromatic stimuli to obtain an extensive set of quantitative measurements of receptive field properties in the parvo- and magnocellular laminae of the LGN of nine macaque monkeys: four normally reared and five monocularly deprived of vision by lid suture near the time of birth. In agreement with previous studies, we find that on average magnocellular neurons differ from parvocellular neurons by having shorter response latencies to optic chiasm stimulation, greater sensitivity to luminance contrast, and better temporal resolution. Magnocellular laminae are also distinguished by containing neurons that summate luminance over their receptive fields nonlinearly (Y cells) and whose temporal response phases decrease with increasing stimulus contrast (indicative of a contrast gain control mechanism). We found little evidence for major differences between magno- and parvocellular neurons on the basis of most spatial parameters except that at any eccentricity, the neurons with the smallest receptive field centers tended to be parvocellular. All parameters were distributed unimodally and continuously through the parvo- and magnocellular populations, giving no indications of subpopulations within each division. Monocular deprivation led to clear anatomical effects: cells in deprived-eye laminae were pale and shrunken compared with those in nondeprived eye laminae, and Cat-301 immunoreactivity in deprived laminae was essentially uniformly abolished. However, deprivation had only subtle effects on the response properties of LGN neurons. Neurons driven by the deprived eye in both magno- and parvocellular laminae had lower nonlinearity indices (i.e., summed signals across their receptive fields more linearly) and were somewhat less responsive. In magnocellular laminae driven by the deprived eye, neuronal response latencies to stimulation of the optic chiasm were slightly shorter than those in the nondeprived laminae, and receptive field surrounds were a bit stronger. No other response parameters were affected by deprivation, and there was no evidence for loss of a specific cell class as in the cat.