Contextual Expectations Shape Cortical Reinstatement of Sensory Representations.

When making a turn at a familiar intersection, we know what items and landmarks will come into view. These perceptual expectations, or predictions, come from our knowledge of the context; however, it is unclear how memory and perceptual systems interact to support the prediction and reactivation of sensory details in cortex. To address this, human participants learned the spatial layout of animals positioned in a cross maze. During fMRI, participants of both sexes navigated between animals to reach a target, and in the process saw a predictable sequence of five animal images. Critically, to isolate activity patterns related to item predictions, rather than bottom-up inputs, one-fourth of trials ended early, with a blank screen presented instead. Using multivariate pattern similarity analysis, we reveal that activity patterns in early visual cortex, posterior medial regions, and the posterior hippocampus showed greater similarity when seeing the same item compared with different items. Further, item effects in posterior hippocampus were specific to the sequence context. Critically, activity patterns associated with seeing an item in visual cortex and posterior medial cortex, were also related to activity patterns when an item was expected, but omitted, suggesting sequence predictions were reinstated in these regions. Finally, multivariate connectivity showed that patterns in the posterior hippocampus at one position in the sequence were related to patterns in early visual cortex and posterior medial cortex at a later position. Together, our results support the idea that hippocampal representations facilitate sensory processing by modulating visual cortical activity in anticipation of expected items.SIGNIFICANCE STATEMENT Our visual world is a series of connected events, where we can predict what we might see next based on our recent past. Understanding the neural circuitry and mechanisms of the perceptual and memory systems that support these expectations is fundamental to revealing how we perceive and act in our world. Using brain imaging, we studied what happens when we expect to see specific visual items, and how such expectations relate to top-down memory signals. We find both visual and memory systems reflect item predictions, and moreover, we show that hippocampal activity supports predictions of future expected items. This demonstrates that the hippocampus acts to predict upcoming items, and reinstates such predictions in cortex.

Neural dynamics of semantic composition.

Human speech comprehension is remarkable for its immediacy and rapidity. The listener interprets an incrementally delivered auditory input, millisecond by millisecond as it is heard, in terms of complex multilevel representations of relevant linguistic and nonlinguistic knowledge. Central to this process are the neural computations involved in semantic combination, whereby the meanings of words are combined into more complex representations, as in the combination of a verb and its following direct object (DO) noun (e.g., "eat the apple"). These combinatorial processes form the backbone for incremental interpretation, enabling listeners to integrate the meaning of each word as it is heard into their dynamic interpretation of the current utterance. Focusing on the verb-DO noun relationship in simple spoken sentences, we applied multivariate pattern analysis and computational semantic modeling to source-localized electro/magnetoencephalographic data to map out the specific representational constraints that are constructed as each word is heard, and to determine how these constraints guide the interpretation of subsequent words in the utterance. Comparing context-independent semantic models of the DO noun with contextually constrained noun models reflecting the semantic properties of the preceding verb, we found that only the contextually constrained model showed a significant fit to the brain data. Pattern-based measures of directed connectivity across the left hemisphere language network revealed a continuous information flow among temporal, inferior frontal, and inferior parietal regions, underpinning the verb's modification of the DO noun's activated semantics. These results provide a plausible neural substrate for seamless real-time incremental interpretation on the observed millisecond time scales.

'They were aware of who I was as a person': Patients' and health professionals' experiences of using the PEGASUS intervention to facilitate decision-making around breast reconstruction.

OBJECTIVE: Many women choose to have breast reconstruction after mastectomy; however, decision-making can be difficult and expectations are often unmet. The PEGASUS intervention (Patient Expectations and Goals: Assisting Shared Understanding of Surgery) was developed to support shared decision-making by helping women and healthcare professionals to clarify and discuss their individual expectations around surgery. This study aimed to explore patients' and health professionals' experiences of using the intervention and its implementation. METHODS: Forty interviews were conducted with participants in a large scale, multi-site trial of the effectiveness of PEGASUS, from 'intervention' (n=16) and 'usual care' groups (n=11), and healthcare professionals (n=13). Data were analysed using thematic analysis. RESULTS: 'Usual care' participants described feeling overwhelmed in decision-making ('bombarded'), often using their own research to break down information ('process of elimination'). In contrast, intervention group participants described PEGASUS providing focus ('focus amongst the frenetic'), and increased connection with clinicians ('more than a number'). Healthcare professionals described increased focus on patient priorities ('shifting focus'), but stressed the need for whole team buy-in ('collective commitment'). CONCLUSIONS: The PEGASUS intervention offered a qualitatively different experience to individuals considering breast reconstruction, with potential to enhance patients' and healthcare professionals' feelings of shared decision-making and patient-centred care. TRIAL REGISTRATION: ISRCTN 18000391 (https://doi.org/10.1186/ISRCTN18000391) 27/01/2016.

The visual and semantic features that predict object memory: Concept property norms for 1,000 object images.

Humans have a remarkable fidelity for visual long-term memory, and yet the composition of these memories is a longstanding debate in cognitive psychology. While much of the work on long-term memory has focused on processes associated with successful encoding and retrieval, more recent work on visual object recognition has developed a focus on the memorability of specific visual stimuli. Such work is engendering a view of object representation as a hierarchical movement from low-level visual representations to higher level categorical organization of conceptual representations. However, studies on object recognition often fail to account for how these high- and low-level features interact to promote distinct forms of memory. Here, we use both visual and semantic factors to investigate their relative contributions to two different forms of memory of everyday objects. We first collected normative visual and semantic feature information on 1,000 object images. We then conducted a memory study where we presented these same images during encoding (picture target) on Day 1, and then either a Lexical (lexical cue) or Visual (picture cue) memory test on Day 2. Our findings indicate that: (1) higher level visual factors (via DNNs) and semantic factors (via feature-based statistics) make independent contributions to object memory, (2) semantic information contributes to both true and false memory performance, and (3) factors that predict object memory depend on the type of memory being tested. These findings help to provide a more complete picture of what factors influence object memorability. These data are available online upon publication as a public resource.

Neural reactivation in parietal cortex enhances memory for episodically linked information.

Remembering is a complex process that involves recalling specific details, such as who you were with when you celebrated your last birthday, as well as contextual information, such as the place where you celebrated. It is well established that the act of remembering enhances long-term retention of the retrieved information, but the neural and cognitive mechanisms that drive memory enhancement are not yet understood. One possibility is that the process of remembering results in reactivation of the broader episodic context. Consistent with this idea, in two experiments, we found that multiple retrieval attempts enhanced long-term retention of both the retrieved object and the nontarget object that shared scene context, compared with a restudy control. Using representational similarity analysis of fMRI data in experiment 2, we found that retrieval resulted in greater neural reactivation of both the target objects and contextually linked objects compared with restudy. Furthermore, this reactivation occurred in a network of medial and lateral parietal lobe regions that have been linked to episodic recollection. The results demonstrate that retrieving a memory can enhance retention of information that is linked in the broader event context and the hippocampus and a posterior medial network of parietal cortical areas (also known as the Default Network) play complementary roles in supporting the reactivation of episodically linked information during retrieval.

Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity.

Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.

Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes.

The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.

Decoding the Cortical Dynamics of Sound-Meaning Mapping.

Comprehending speech involves the rapid and optimally efficient mapping from sound to meaning. Influential cognitive models of spoken word recognition (Marslen-Wilson and Welsh, 1978) propose that the onset of a spoken word initiates a continuous process of activation of the lexical and semantic properties of the word candidates matching the speech input and competition between them, which continues until the point at which the word is differentiated from all other cohort candidates (the uniqueness point, UP). At this point, the word is recognized uniquely and only the target word's semantics are active. Although it is well established that spoken word recognition engages the superior (Rauschecker and Scott, 2009), middle, and inferior (Hickok and Poeppel, 2007) temporal cortices, little is known about the real-time brain activity that underpins the computations and representations that evolve over time during the transformation from speech to meaning. Here, we test for the first time the spatiotemporal dynamics of these processes by collecting MEG data while human participants listened to spoken words. By constructing quantitative models of competition and access to meaning in combination with spatiotemporal searchlight representational similarity analysis (Kriegeskorte et al., 2006) in source space, we were able to test where and when these models produced significant effects. We found early transient effects ∼400 ms before the UP of lexical competition in left supramarginal gyrus, left superior temporal gyrus, left middle temporal gyrus (MTG), and left inferior frontal gyrus (IFG) and of semantic competition in MTG, left angular gyrus, and IFG. After the UP, there were no competitive effects, only target-specific semantic effects in angular gyrus and MTG. SIGNIFICANCE STATEMENT: Understanding spoken words involves complex processes that transform the auditory input into a meaningful interpretation. This effortless transition occurs on millisecond timescales, with remarkable speed and accuracy and without any awareness of the complex computations involved. Here, we reveal the real-time neural dynamics of these processes by collecting data about listeners' brain activity as they hear spoken words. Using novel statistical models of different aspects of the recognition process, we can locate directly which parts of the brain are accessing the stored form and meaning of words and how the competition between different word candidates is resolved neurally in real time. This gives us a uniquely differentiated picture of the neural substrate for the first 500 ms of word recognition.

Oscillatory Dynamics of Perceptual to Conceptual Transformations in the Ventral Visual Pathway.

Object recognition requires dynamic transformations of low-level visual inputs to complex semantic representations. Although this process depends on the ventral visual pathway, we lack an incremental account from low-level inputs to semantic representations and the mechanistic details of these dynamics. Here we combine computational models of vision with semantics and test the output of the incremental model against patterns of neural oscillations recorded with magnetoencephalography in humans. Representational similarity analysis showed visual information was represented in low-frequency activity throughout the ventral visual pathway, and semantic information was represented in theta activity. Furthermore, directed connectivity showed visual information travels through feedforward connections, whereas visual information is transformed into semantic representations through feedforward and feedback activity, centered on the anterior temporal lobe. Our research highlights that the complex transformations between visual and semantic information is driven by feedforward and recurrent dynamics resulting in object-specific semantics.

Neural oscillations during conditional associative learning.

Associative learning requires mapping between complex stimuli and behavioural responses. When multiple stimuli are involved, conditional associative learning is a gradual process with learning based on trial and error. It is established that a distributed network of regions track associative learning, however the role of neural oscillations in human learning remains less clear. Here we used scalp EEG to test how neural oscillations change during learning of arbitrary visuo-motor associations. Participants learned to associative 48 different abstract shapes to one of four button responses through trial and error over repetitions of the shapes. To quantify how well the associations were learned for each trial, we used a state-space computational model of learning that provided a probability of each trial being correct given past performance for that stimulus, that we take as a measure of the strength of the association. We used linear modelling to relate single-trial neural oscillations to single-trial measures of association strength. We found frontal midline theta oscillations during the delay period tracked learning, where theta activity was strongest during the early stages of learning and declined as the associations were formed. Further, posterior alpha and low-beta oscillations in the cue period showed strong desynchronised activity early in learning, while stronger alpha activity during the delay period was seen as associations became well learned. Moreover, the magnitude of these effects during early learning, before the associations were learned, related to improvements in memory seen on the next presentation of the stimulus. The current study provides clear evidence that frontal theta and posterior alpha/beta oscillations play a key role during associative memory formation.

Investigating the Effectiveness, Acceptability and Impact on Healthcare Usage of Providing a Cognitive-Behavioural Based Psychological Therapy Service for Patients with Primary Antibody Deficiency.

PURPOSE: Patients with primary antibody deficiency report poorer quality of life and higher rates of anxiety and depression than the general population. Cognitive-behavioral therapy has been shown to be a valuable treatment for patients with other long-term physical health conditions, improving well-being and enabling them to manage their symptoms more effectively. The aim of this project was to establish the feasibility and effectiveness of providing cognitive-behavioral based therapy to patients with primary antibody deficiency. METHODS: Forty-four patients completed a course of psychological therapy. Participants completed a series of self-report measures examining psychological and physical health, and service usage, prior to starting treatment and following their final session. They also provided feedback on their experience of treatment. RESULTS: Patients showed improvements in anxiety, depression, insomnia and fatigue. There was a high level of acceptability of the service and the potential for long-term cost savings to the NHS. CONCLUSION: Psychological therapy based on the cognitive-behavioral model of treatment appears to be a valuable treatment for patients with primary antibody deficiency and comorbid mental health difficulties.

Theta oscillations promote temporal sequence learning.

Many theoretical models suggest that neural oscillations play a role in learning or retrieval of temporal sequences, but the extent to which oscillations support sequence representation remains unclear. To address this question, we used scalp electroencephalography (EEG) to examine oscillatory activity over learning of different object sequences. Participants made semantic decisions on each object as they were presented in a continuous stream. For three "Consistent" sequences, the order of the objects was always fixed. Activity during Consistent sequences was compared to "Random" sequences that consisted of the same objects presented in a different order on each repetition. Over the course of learning, participants made faster semantic decisions to objects in Consistent, as compared to objects in Random sequences. Thus, participants were able to use sequence knowledge to predict upcoming items in Consistent sequences. EEG analyses revealed decreased oscillatory power in the theta (4-7 Hz) band at frontal sites following decisions about objects in Consistent sequences, as compared with objects in Random sequences. The theta power difference between Consistent and Random only emerged in the second half of the task, as participants were more effectively able to predict items in Consistent sequences. Moreover, we found increases in parieto-occipital alpha (10-13 Hz) and beta (14-28 Hz) power during the pre-response period for objects in Consistent sequences, relative to objects in Random sequences. Linear mixed effects modeling revealed that single trial theta oscillations were related to reaction time for future objects in a sequence, whereas beta and alpha oscillations were only predictive of reaction time on the current trial. These results indicate that theta and alpha/beta activity preferentially relate to future and current events, respectively. More generally our findings highlight the importance of band-specific neural oscillations in the learning of temporal order information.

A study protocol of the effectiveness of PEGASUS: a multi-centred study comparing an intervention to promote shared decision making about breast reconstruction with treatment as usual.

BACKGROUND: Increasingly, women elect breast reconstruction after mastectomy. However, their expectations of surgery are often not met, and dissatisfaction with outcome and ongoing psychosocial concerns and distress are common. We developed a patient-centered intervention, PEGASUS:(Patients' Expectations and Goals: Assisting Shared Understanding of Surgery) which supports shared decision making by helping women clarify their own, individual goals about reconstruction so that they can discuss these with their surgeon. Our acceptability/feasibility work has shown it is well received by patients and health professionals alike. We now need to establish whether PEGASUS improves patients' experiences of breast reconstruction decision making and outcomes. The purpose of this study is, therefore, to examine the effectiveness of PEGASUS, an intervention designed to support shared decision making about breast reconstruction. METHODS: A multi-centered sequential study will compare the impact of PEGASUS with usual care, in terms of patient reported outcomes (self-reported satisfaction with the outcome of surgery, involvement in decision making and in the consultation) and health economics. Initially we will collect data from our comparison (usual care) group (90 women) who will complete standardized measures (Breast-Q, EQ5D -5 L and ICECAP- A) at the time of decision making, 3, 6 and 12 months after surgery. Health professionals will then be trained to use PEGASUS, which will be delivered to the intervention group (another 90 women completing the same measures at the time of decision making, and 3, 6 and 12 months after surgery). Health professionals and a purposefully selected sample of participants will be interviewed about whether their expectations of reconstruction were met, and their experiences of PEGASUS (if appropriate). DISCUSSION: PEGASUS may have the potential to provide health professionals with an easily accessible tool aiming to support shared decision making and improve patients' satisfaction with breast reconstruction. Results of this study will be available at the end of 2019. TRIAL REGISTRATION: ISRCTN 18000391 (DOI 10.1186/ISRCTN18000391) 27/01/2016.

Learning Warps Object Representations in the Ventral Temporal Cortex.

The human ventral temporal cortex (VTC) plays a critical role in object recognition. Although it is well established that visual experience shapes VTC object representations, the impact of semantic and contextual learning is unclear. In this study, we tracked changes in representations of novel visual objects that emerged after learning meaningful information about each object. Over multiple training sessions, participants learned to associate semantic features (e.g., "made of wood," "floats") and spatial contextual associations (e.g., "found in gardens") with novel objects. fMRI was used to examine VTC activity for objects before and after learning. Multivariate pattern similarity analyses revealed that, after learning, VTC activity patterns carried information about the learned contextual associations of the objects, such that objects with contextual associations exhibited higher pattern similarity after learning. Furthermore, these learning-induced increases in pattern information about contextual associations were correlated with reductions in pattern information about the object's visual features. In a second experiment, we validated that these contextual effects translated to real-life objects. Our findings demonstrate that visual object representations in VTC are shaped by the knowledge we have about objects and show that object representations can flexibly adapt as a consequence of learning with the changes related to the specific kind of newly acquired information.

Predicting the Time Course of Individual Objects with MEG.

To respond appropriately to objects, we must process visual inputs rapidly and assign them meaning. This involves highly dynamic, interactive neural processes through which information accumulates and cognitive operations are resolved across multiple time scales. However, there is currently no model of object recognition which provides an integrated account of how visual and semantic information emerge over time; therefore, it remains unknown how and when semantic representations are evoked from visual inputs. Here, we test whether a model of individual objects--based on combining the HMax computational model of vision with semantic-feature information--can account for and predict time-varying neural activity recorded with magnetoencephalography. We show that combining HMax and semantic properties provides a better account of neural object representations compared with the HMax alone, both through model fit and classification performance. Our results show that modeling and classifying individual objects is significantly improved by adding semantic-feature information beyond ∼200 ms. These results provide important insights into the functional properties of visual processing across time.

Promoting lifestyle behaviour change and well-being in hospital patients: a pilot study of an evidence-based psychological intervention.

BACKGROUND: Lifestyle risk behaviours show an inverse social gradient, clustering in vulnerable groups. We designed and piloted an intervention to address barriers to lifestyle behaviour change among hospital patients. METHODS: We designed our intervention using effective components of behaviour change interventions informed by psychological theory. Delivered by a health psychologist based at the Royal Free London NHS Foundation Trust, the 4-week intervention included detailed baseline assessment, personalized goal setting, psychological skills development, motivation support and referral to community services. Primary outcomes were feasibility and patient acceptability. We also evaluated changes to health and well-being. RESULTS: From 1 July 2013 to 31 September 2014, 686 patients were referred, 338 (49.3%) attended a first appointment and 172 (25.1%) completed follow-up. Furthermore, 72.1% of attenders were female with the median age 55 years and poor self-reported baseline health. After 4 weeks, self-efficacy, health and well-being scores significantly improved: 63% of lifestyle goals and 89% of health management goals were fully achieved; 58% of referrals to community lifestyle behaviour change services and 79% of referrals to other services (e.g. Citizen's Advice Bureau) were accepted; 99% were satisfied/very satisfied with the service. CONCLUSIONS: Our hospital-based intervention was feasible, acceptable and showed preliminary health and well-being gains.

Psychological Issues Associated With Absolute Uterine Factor Infertility and Attitudes of Patients Toward Uterine Transplantation.

CONTEXT: Uterine transplantation (UTx). OBJECTIVE: To explore patients' knowledge of and attitudes toward UTx before and after a short educational intervention via a video and question and answer (Q&A) session. DESIGN: Large, in-depth survey investigating patients' motivations, aims, and beliefs on UTx. SETTING: Imperial College London. PARTICIPANTS: Women diagnosed with absolute uterine factor infertility (AUFI) who were seeking information on UTx and had already volunteered to participate in the study. INTERVENTION: A semistructured interview involving a brief baseline questionnaire before a Q&A session and a 20-minute video exploring the main risks and benefits for UTx. MAIN OUTCOME MEASURES: Attitudes of self-referred patients with AUFI toward UTx before and after education focusing on UTx. Rank order of importance of key UTx-related issues. RESULTS: Forty women were interviewed. Following the video presentation and Q&A session, 97.5% (n = 39) would undergo UTx ahead of surrogacy and adoption in full knowledge that the latter 2 options would be ultimately safer for their own well-being and the fact that the graft could fail even prior to conception. All felt that UTx should take place, and 92.5% saw UTx as achievable. CONCLUSION: The study demonstrates a keen interest in UTx, partly because other options seem difficult to access. It is worth noting that people appear to be distancing themselves from the risk. This requires careful assessment in any clinical program. This study is the first to demonstrate a qualitative relationship between patients with AUFI and their curiosity and desire for UTx. It paves the way for forming the introduction into the psychological assessment of a potential patient.

The acceptability of PEGASUS: an intervention to facilitate shared decision-making with women contemplating breast reconstruction.

Good practice guidelines recommend that women who undergo mastectomy are offered reconstructive surgery. However, many who choose this option report a degree of decisional regret and dissatisfaction because their pre-surgical expectations were not met. This paper reports an acceptability study of a new intervention (PEGASUS) that aims to support shared decision-making by eliciting women's pre-surgical expectations and setting patient-centred goals. Eighteen women contemplating breast reconstruction completed the PEGASUS intervention. Semi-structured interviews were conducted with 12 women and 3 health professionals to explore their experiences of using PEGASUS. Interview transcripts were subjected to a thematic analysis, and a content analysis was conducted on 79 goals that the 18 women identified. Feedback was extremely positive--women found that completing PEGASUS alongside a discussion with a specially trained health professional helped them prepare for the surgical consultation and increased their trust in their surgeon. Staff reported that PEGASUS facilitated patient-centred discussions and informed the decisions made about potential surgery. This preliminary study suggests that this novel intervention is acceptable to patients and health professionals alike. Further work is needed to evaluate its efficacy and then its effectiveness with a larger sample of women, and its potential use with other patient groups.