School distress and the school attendance crisis: a story dominated by neurodivergence and unmet need.

Background: The Covid-19 pandemic has brought into sharp focus a school attendance crisis in many countries, although this likely pre-dates the pandemic. Children and young people (CYP) struggling to attend school often display extreme emotional distress before/during/after school. We term this School Distress. Here we sought to elucidate the characteristics of the CYP struggling to attend school in the United Kingdom. Methods: Using a case-control, concurrent embedded mixed-method research design, 947 parents of CYP with experience of School Distress completed a bespoke online questionnaire (February/March 2022), alongside an age-matched control group (n = 149) and a smaller group of parents who electively home-educate (n = 25). Results: In 94.3% of cases, school attendance problems were underpinned by significant emotional distress, with often harrowing accounts of this distress provided by parents. While the mean age of the CYP in this sample was 11.6 years (StDev 3.1 years), their School Distress was evident to parents from a much younger age (7.9 years). Notably, 92.1% of CYP currently experiencing School Distress were described as neurodivergent (ND) and 83.4% as autistic. The Odds Ratio of autistic CYP experiencing School Distress was 46.61 [95% CI (24.67, 88.07)]. Autistic CYP displayed School Distress at a significantly earlier age, and it was significantly more enduring. Multi-modal sensory processing difficulties and ADHD (among other neurodivergent conditions) were also commonly associated with School Distress; with School Distress CYP having an average of 3.62 NDs (StDev 2.68). In addition, clinically significant anxiety symptomology (92.5%) and elevated demand avoidance were also pervasive. Mental health difficulties in the absence of a neurodivergent profile were, however, relatively rare (6.17%). Concerningly, despite the striking levels of emotional distress and disability reported by parents, parents also reported a dearth of meaningful support for their CYP at school. Conclusion: While not a story of exclusivity relating solely to autism, School Distress is a story dominated by complex neurodivergence and a seemingly systemic failure to meet the needs of these CYP. Given the disproportionate number of disabled CYP impacted, we ask whether the United Kingdom is upholding its responsibility to ensure the "right to an education" for all CYP (Human Rights Act 1998).

Characterizing memory loss in patients with autoimmune limbic encephalitis hippocampal lesions.

Since the publication of Scoville and Milner's (1957) seminal paper, the precise functional role played by the hippocampus in support of human memory has been fiercely debated. For instance, the single question of whether the hippocampus plays a time-limited or an indelible role in the recollection of personal memories led to a deep and tenacious schism within the field. Similar polarizations arose between those who debated the precise nature of the role played by the hippocampus in support of semantic relative to episodic memories and in recall/recollection relative to familiarity-based recognition. At the epicenter of these divisions lies conflicting neuropsychological findings. These differences likely arise due to the consistent use of heterogeneous patient populations to adjudicate between these positions. Here we utilized traditional neuropsychological measures in a homogenous patient population with a highly discrete hippocampal lesion (i.e., VGKCC-Ab related autoimmune limbic encephalitis patients). We observed consistent impairment of recent episodic memories, a present but less striking impairment of remote episodic memories, preservation of personal semantic memory, and recall but not recognition memory deficits. We conclude that this increasingly well-characterized patient group may represent an important homogeneous population in which the functional role played by the hippocampus may be more precisely delineated.

Boundary extension is attenuated in patients with ventromedial prefrontal cortex damage.

The ventromedial prefrontal cortex (vmPFC) and hippocampus have been implicated in the mental construction of scenes and events. However, little is known about their specific contributions to these cognitive functions. Boundary extension (BE) is a robust indicator of fast, automatic, and implicit scene construction. BE occurs when individuals who are viewing scenes automatically imagine what might be beyond the view, and consequently later misremember having seen a greater expanse of the scene. Patients with hippocampal damage show attenuated BE because of their scene construction impairment. In the current study, we administered BE tasks to patients with vmPFC damage, brain-damaged control patients, and healthy control participants. We also contrasted the performance of these patients to the previously-published data from patients with hippocampal lesions (Mullally, Intraub, & Maguire, 2012). We found that vmPFC-damaged patients showed reduced BE compared to brain-damaged and healthy controls. Indeed, BE attenuation was similar following vmPFC or hippocampal damage. Notably, however, whereas hippocampal damage seems to particularly impair the spatial coherence of scenes, vmPFC damage leads to a difficulty constructing scenes in a broader sense, with the prediction of what should be in a scene, and the monitoring or integration of the scene elements being particularly compromised. We conclude that vmPFC and hippocampus play important and complementary roles in scene construction.

Scenes, Spaces, and Memory Traces: What Does the Hippocampus Do?

The hippocampus is one of the most closely scrutinized brain structures in neuroscience. While traditionally associated with memory and spatial cognition, in more recent years it has also been linked with other functions, including aspects of perception and imagining fictitious and future scenes. Efforts continue apace to understand how the hippocampus plays such an apparently wide-ranging role. Here we consider recent developments in the field and in particular studies of patients with bilateral hippocampal damage. We outline some key findings, how they have subsequently been challenged, and consider how to reconcile the disparities that are at the heart of current lively debates in the hippocampal literature.

Constructing, Perceiving, and Maintaining Scenes: Hippocampal Activity and Connectivity.

In recent years, evidence has accumulated to suggest the hippocampus plays a role beyond memory. A strong hippocampal response to scenes has been noted, and patients with bilateral hippocampal damage cannot vividly recall scenes from their past or construct scenes in their imagination. There is debate about whether the hippocampus is involved in the online processing of scenes independent of memory. Here, we investigated the hippocampal response to visually perceiving scenes, constructing scenes in the imagination, and maintaining scenes in working memory. We found extensive hippocampal activation for perceiving scenes, and a circumscribed area of anterior medial hippocampus common to perception and construction. There was significantly less hippocampal activity for maintaining scenes in working memory. We also explored the functional connectivity of the anterior medial hippocampus and found significantly stronger connectivity with a distributed set of brain areas during scene construction compared with scene perception. These results increase our knowledge of the hippocampus by identifying a subregion commonly engaged by scenes, whether perceived or constructed, by separating scene construction from working memory, and by revealing the functional network underlying scene construction, offering new insights into why patients with hippocampal lesions cannot construct scenes.

Counterfactual thinking in patients with amnesia.

We often engage in counterfactual (CF) thinking, which involves reflecting on "what might have been." Creating alternative versions of reality seems to have parallels with recollecting the past and imagining the future in requiring the simulation of internally generated models of complex events. Given that episodic memory and imagining the future are impaired in patients with hippocampal damage and amnesia, we wondered whether successful CF thinking also depends upon the integrity of the hippocampus. Here using two nonepisodic CF thinking tasks, we found that patients with bilateral hippocampal damage and amnesia performed comparably with matched controls. They could deconstruct reality, add in and recombine elements, change relations between temporal sequences of events, enabling them to determine plausible alternatives of complex episodes. A difference between the patients and control participants was evident, however, in the patients' subtle avoidance of CF simulations that required the construction of an internal spatial representation. Overall, our findings suggest that mental simulation in the form of nonepisodic CF thinking does not seem to depend upon the hippocampus unless there is the added requirement for construction of a coherent spatial scene within which to play out scenarios.

Learning to remember: the early ontogeny of episodic memory.

Over the past 60 years the neural correlates of human episodic memory have been the focus of intense neuroscientific scrutiny. By contrast, neuroscience has paid substantially less attention to understanding the emergence of this neurocognitive system. In this review we consider how the study of memory development has evolved. In doing so, we concentrate primarily on the first postnatal year because it is within this time window that the most dramatic shifts in scientific opinion have occurred. Moreover, this time frame includes the critical age (∼9 months) at which human infants purportedly first begin to demonstrate rudimentary hippocampal-dependent memory. We review the evidence for and against this assertion, note the lack of direct neurocognitive data speaking to this issue, and question how demonstrations of exuberant relational learning and memory in infants as young as 3-months old can be accommodated within extant models. Finally, we discuss whether current impasses in the infant memory literature could be leveraged by making greater use of neuroimaging techniques, such as magnetic resonance imaging (MRI), which have been deployed so successfully in adults.

Memory, Imagination, and Predicting the Future: A Common Brain Mechanism?

On the face of it, memory, imagination, and prediction seem to be distinct cognitive functions. However, metacognitive, cognitive, neuropsychological, and neuroimaging evidence is emerging that they are not, suggesting intimate links in their underlying processes. Here, we explore these empirical findings and the evolving theoretical frameworks that seek to explain how a common neural system supports our recollection of times past, imagination, and our attempts to predict the future.

Scene construction in developmental amnesia: an fMRI study.

Amnesic patients with bilateral hippocampal damage sustained in adulthood are generally unable to construct scenes in their imagination. By contrast, patients with developmental amnesia (DA), where hippocampal damage was acquired early in life, have preserved performance on this task, although the reason for this sparing is unclear. One possibility is that residual function in remnant hippocampal tissue is sufficient to support basic scene construction in DA. Such a situation was found in the one amnesic patient with adult-acquired hippocampal damage (P01) who could also construct scenes. Alternatively, DA patients' scene construction might not depend on the hippocampus, perhaps being instead reliant on non-hippocampal regions and mediated by semantic knowledge. To adjudicate between these two possibilities, we examined scene construction during functional MRI (fMRI) in Jon, a well-characterised patient with DA who has previously been shown to have preserved scene construction. We found that when Jon constructed scenes he activated many of the regions known to be associated with imagining scenes in control participants including ventromedial prefrontal cortex, posterior cingulate, retrosplenial and posterior parietal cortices. Critically, however, activity was not increased in Jon's remnant hippocampal tissue. Direct comparisons with a group of control participants and patient P01, confirmed that they activated their right hippocampus more than Jon. Our results show that a type of non-hippocampal dependent scene construction is possible and occurs in DA, perhaps mediated by semantic memory, which does not appear to involve the vivid visualisation of imagined scenes.

The hippocampus: a manifesto for change.

We currently lack a unified and mechanistic account of how the hippocampus supports a range of disparate cognitive functions that includes episodic memory, imagining the future, and spatial navigation. Here, we argue that in order to leverage this long-standing issue, traditional notions regarding the architecture of memory should be eschewed. Instead, we invoke the idea that scenes are central to hippocampal information processing. This view is motivated by mounting evidence that the hippocampus is constantly constructing spatially coherent scenes, automatically anticipating and synthesizing representations of the world beyond the immediate sensorium. By characterizing the precise relationship between scenes and the hippocampus, we believe a theoretically enriched understanding of its fundamental role and its breakdown in pathology can emerge.

Exploring the role of space-defining objects in constructing and maintaining imagined scenes.

It has recently been observed that certain objects, when viewed or imagined in isolation, evoke a strong sense of three-dimensional local space surrounding them (space-defining (SD) objects), while others do not (space-ambiguous (SA) objects), and this is associated with engagement of the parahippocampal cortex (PHC). But activation of the PHC is classically associated with scene stimuli. The comparable neural response within PHC to both full scenes and single SD objects, led us to hypothesise that SD objects might play a more critical role in the construction and maintenance of scene representations than SA objects. To test this we used scene construction and deconstruction paradigms, where participants gradually built and maintained scenes using SD, SA and background (wall, floors) items. By examining the order in which each item was added (and later removed) to (and from) a scene, we could estimate the significance of each item type. In two different experiments, participants chose SD over SA objects and background items as the first and most critical item in their constructed scenes and, more generally, selected SD objects earlier than SA objects across the scene construction process. When deconstructing scenes, participants retained significantly more SD objects than SA objects, and the last remaining object across all scenes was highly likely to be an SD object. SD objects therefore enjoy a privileged role in scene construction and maintenance, and appear to be an essential building block of scenes.

The hippocampus extrapolates beyond the view in scenes: an fMRI study of boundary extension.

Boundary extension (BE) is a pervasive phenomenon whereby people remember seeing more of a scene than was present in the physical input, because they extrapolate beyond the borders of the original stimulus. This automatic embedding of a scene into a wider context supports our experience of a continuous and coherent world, and is therefore highly adaptive. BE, whilst occurring rapidly, is nevertheless thought to comprise two stages. The first involves the active extrapolation of the scene beyond its physical boundaries, and is constructive in nature. The second phase occurs at retrieval, where the initial extrapolation beyond the original scene borders is revealed by a subsequent memory error. The brain regions associated with the initial, and crucial, extrapolation of a scene beyond the view have never been investigated. Here, using functional MRI (fMRI) and a classic BE paradigm, we found that this extrapolation of scenes occurred rapidly around the time a scene was first viewed, and was associated with engagement of the hippocampus (HC) and parahippocampal cortex (PHC). Using connectivity analyses we determined that the HC in particular seemed to drive the BE effect, exerting top-down influence on PHC and indeed as far back down the processing stream as early visual cortex (VC). These cortical regions subsequently displayed activity profiles that tracked the trial-by-trial subjective perception of the scenes, rather than physical reality, thereby reflecting the behavioural expression of the BE error. Together our results show that the HC is involved in the active extrapolation of scenes beyond their physical borders. This information is then automatically and rapidly channelled through the scene processing hierarchy as far back as early VC. This suggests that the anticipation and construction of scenes is a pervasive and important aspect of our online perception, with the HC playing a central role.

Suppressing the encoding of new information in memory: a behavioral study derived from principles of hippocampal function.

Cognitive processes do not occur in isolation. Interactions between cognitive processes can be observed as a cost in performance following a switch between tasks, a cost that is greatest when the cognitive requirements of the sequential tasks compete. Interestingly, the long-term mnemonic goals associated with specific cognitive tasks can also directly compete. For example, encoding the sequential order in which stimuli are presented in the commonly-utilised 2-Back working memory (WM) tasks is counter-productive to task performance, as this task requires the continual updating of the contents of one's current mental set. Performance of this task consistently results in reduced activity within the medial temporal lobe (MTL), and this response is believed to reflect the inhibitory mnemonic component of the task. Conversely, there are numerous cognitive paradigms in which participants are explicitly instructed to encode incoming information and performance of these tasks reliably increases MTL activity. Here, we explore the behavioural cost of sequentially performing two tasks with conflicting long-term mnemonic goals and contrasting neural profiles within the MTL. We hypothesised that performing the 2-Back WM prior to a hippocampal-dependent memory task would impair performance on the latter task. We found that participants who performed the 2-Back WM task, prior to the encoding of novel verbal/face-name stimuli, recollected significantly fewer of these stimuli, compared to those who had performed a 0-Back control task. Memory processes believed to be independent of the MTL were unaffected. Our results suggest that the inhibition of MTL-dependent mnemonic function persists beyond the cessation of the 2-Back WM task and can alter performance on entirely separate and subsequently performed memory tasks. Furthermore, they indicate that performance of such tasks may induce a temporarily-sustained, virtual lesion of the hippocampus, which could be used as a probe to explore cognitive processes in the absence of hippocampal involvement.

Retrosplenial cortex codes for permanent landmarks.

Landmarks are critical components of our internal representation of the environment, yet their specific properties are rarely studied, and little is known about how they are processed in the brain. Here we characterised a large set of landmarks along a range of features that included size, visual salience, navigational utility, and permanence. When human participants viewed images of these single landmarks during functional magnetic resonance imaging (fMRI), parahippocampal cortex (PHC) and retrosplenial cortex (RSC) were both engaged by landmark features, but in different ways. PHC responded to a range of landmark attributes, while RSC was engaged by only the most permanent landmarks. Furthermore, when participants were divided into good and poor navigators, the latter were significantly less reliable at identifying the most permanent landmarks, and had reduced responses in RSC and anterodorsal thalamus when viewing such landmarks. The RSC has been widely implicated in navigation but its precise role remains uncertain. Our findings suggest that a primary function of the RSC may be to process the most stable features in an environment, and this could be a prerequisite for successful navigation.

Scene construction in amnesia: an FMRI study.

In recent years, there has been substantial interest in how the human hippocampus not only supports recollection of past experiences, but also the construction of fictitious and future events, and the leverage this might offer for understanding the operating mechanisms of the hippocampus. Evidence that patients with bilateral hippocampal damage and amnesia cannot construct novel or future scenes/events has been influential in driving this line of research forward. There are, however, some patients with hippocampal damage and amnesia who retain the ability to construct novel scenes. This dissociation may indicate that the hippocampus is not required for scene construction, or alternatively, there could be residual function in remnant hippocampal tissue sufficient to support the basic construction of scenes. Resolving this controversy is central to current theoretical debates about the hippocampus. To investigate, we used fMRI and a scene construction task to test patient P01, who has dense amnesia, ∼50% bilateral hippocampal volume loss, and intact scene construction. We found that scene construction in P01 was associated with increased activity in a set of brain areas, including medial temporal, retrosplenial, and posterior parietal cortices, that overlapped considerably with the regions engaged in control participants performing the same task. Most notably, the remnant of P01's right hippocampus exhibited increased activity during scene construction. This suggests that the intact scene construction observed in some hippocampal-damaged amnesic patients may be supported by residual function in their lesioned hippocampus, in accordance with theoretical frameworks that ascribe a vital role to the hippocampus in scene construction.

Exploring the parahippocampal cortex response to high and low spatial frequency spaces.

The posterior parahippocampal cortex (PHC) supports a range of cognitive functions, in particular scene processing. However, it has recently been suggested that PHC engagement during functional MRI simply reflects the representation of three-dimensional local space. If so, PHC should respond to space in the absence of scenes, geometric layout, objects or contextual associations. It has also been reported that PHC activation may be influenced by low-level visual properties of stimuli such as spatial frequency. Here, we tested whether PHC was responsive to the mere sense of space in highly simplified stimuli, and whether this was affected by their spatial frequency distribution. Participants were scanned using functional MRI while viewing depictions of simple three-dimensional space, and matched control stimuli that did not depict a space. Half the stimuli were low-pass filtered to ascertain the impact of spatial frequency. We observed a significant interaction between space and spatial frequency in bilateral PHC. Specifically, stimuli depicting space (more than nonspatial stimuli) engaged the right PHC when they featured high spatial frequencies. In contrast, the interaction in the left PHC did not show a preferential response to space. We conclude that a simple depiction of three-dimensional space that is devoid of objects, scene layouts or contextual associations is sufficient to robustly engage the right PHC, at least when high spatial frequencies are present. We suggest that coding for the presence of space may be a core function of PHC, and could explain its engagement in a range of tasks, including scene processing, where space is always present.

Attenuated boundary extension produces a paradoxical memory advantage in amnesic patients.

BACKGROUND: When we view a scene, we construct an internal representation of the scene that extends beyond its given borders. This cognitive phenomenon is revealed by a subsequent memory error when we confidently misremember the extended scene instead of the original. This effect is known as "boundary extension" and is apparent in adults, children, and babies. RESULTS: Here we show that seven patients with selective bilateral hippocampal damage and amnesia, who cannot imagine spatially coherent scenes, displayed attenuated levels of boundary extension on three separate measures. Paradoxically, this reduced boundary extension resulted in better memory for the stimuli compared with matched control participants, because the patients' recall was less encumbered by the boundary extension error. A further test revealed that although patients could generate appropriate semantic, conceptual, and contextual information about what might be beyond the view in a scene, their representation of the specifically spatial aspect of extended scenes was markedly impoverished. CONCLUSIONS: The patients' superior memory performance betrayed a fundamental deficit in scene processing. Our findings indicate that the hippocampus supports the internal representation of scenes and extended scenes when they are not physically in view, and this may involve providing a spatial framework in scenes. We suggest that interference with the ability to internally represent space may prevent the construction of spatially coherent scenes, with possible consequences for navigation, recollection of the past, and imagination of the future, which depend on this function.

A new role for the parahippocampal cortex in representing space.

The debate surrounding the function of the human posterior parahippocampal cortex (PHC) is currently dominated by two competing theories. The spatial layout hypothesis proposes that PHC processes information about the shape of space embodied in layout-defining scene features. The contextual association hypothesis rejects this notion, proposing instead that PHC responds to highly contextualized, but not necessarily spatial, stimuli. Here we present a novel concept that suggests PHC is primarily concerned with any representation that depicts three-dimensional local space, be it scenes or even single objects. Specifically, we identified space-defining (SD) and space-ambiguous (SA) single objects, where SD objects consistently evoke a strong sense of the surrounding space while SA objects do not, in the absence of any background, spatial layout, or context. We found that participants could easily identify and distinguish between SD and SA objects. This distinction was subsequently affirmed at a neural level, where visualizing or viewing single SD objects compared with SA objects engaged PHC, despite these single SD objects offering no information about the shape or layout of the space. Moreover, this PHC response was robust and not accounted for by other factors, including contextual associations. Instead, it was linked to intrinsic object properties, specifically a combination of perceived object size and portability. By showing that PHC is responsive to the awareness of surrounding local space suggests its role in scene processing is basic and fundamental, such that it is not dependent on complex scene properties such as geometric structure, scene schema, or contextual associations.

Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain.

BACKGROUND: Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. RESULTS: Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho) ratio. CONCLUSION: Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.