Retrospective Inference as a Form of Bounded Rationality, and Its Beneficial Influence on Learning.

Probabilistic models of cognition typically assume that agents make inferences about current states by combining new sensory information with fixed beliefs about the past, an approach known as Bayesian filtering. This is computationally parsimonious, but, in general, leads to suboptimal beliefs about past states, since it ignores the fact that new observations typically contain information about the past as well as the present. This is disadvantageous both because knowledge of past states may be intrinsically valuable, and because it impairs learning about fixed or slowly changing parameters of the environment. For these reasons, in offline data analysis it is usual to infer on every set of states using the entire time series of observations, an approach known as (fixed-interval) Bayesian smoothing. Unfortunately, however, this is impractical for real agents, since it requires the maintenance and updating of beliefs about an ever-growing set of states. We propose an intermediate approach, finite retrospective inference (FRI), in which agents perform update beliefs about a limited number of past states (Formally, this represents online fixed-lag smoothing with a sliding window). This can be seen as a form of bounded rationality in which agents seek to optimize the accuracy of their beliefs subject to computational and other resource costs. We show through simulation that this approach has the capacity to significantly increase the accuracy of both inference and learning, using a simple variational scheme applied to both randomly generated Hidden Markov models (HMMs), and a specific application of the HMM, in the form of the widely used probabilistic reversal task. Our proposal thus constitutes a theoretical contribution to normative accounts of bounded rationality, which makes testable empirical predictions that can be explored in future work.

Specifying a Causal Role for Angular Gyrus in Autobiographical Memory.

Considerable recent evidence indicates that angular gyrus dysfunction in humans does not result in amnesia, but does impair a number of aspects of episodic memory. Patients with parietal lobe lesions have been reported to exhibit a deficit when freely recalling autobiographical events from their pasts, but can remember details of the events when recall is cued by specific questions. In apparent contradiction, inhibitory brain stimulation targeting angular gyrus in healthy volunteers has been found to have no effect on free recall or cued recall of word pairs. The present study sought to resolve this inconsistency by testing free and cued recall of both autobiographical memories and word-pair memories in the same healthy male and female human participants following continuous theta burst stimulation (cTBS) of angular gyrus and a vertex control location. Angular gyrus cTBS resulted in a selective reduction in the free recall, but not cued recall, of autobiographical memories, whereas free and cued recall of word-pair memories were unaffected. Additionally, participants reported fewer autobiographical episodes as being experienced from a first-person perspective following angular gyrus cTBS. The findings add to a growing body of evidence that a function of angular gyrus within the network of brain regions responsible for episodic recollection is to integrate memory features within an egocentric framework into the kind of first-person perspective representation that enables the subjective experience of remembering events from our personal pasts.SIGNIFICANCE STATEMENT In seeking to understand the role played by the angular gyrus region of parietal cortex in human memory, interpreting the often conflicting findings from neuroimaging and neuropsychology studies has been hampered by differences in anatomical specificity and localization between methods. In the present study, we address these limitations using continuous theta burst stimulation in healthy volunteers to disrupt function of angular gyrus and a vertex control region. With this method, we adjudicate between two competing theories of parietal lobe function, finding evidence that is inconsistent with an attentional role for angular gyrus in memory, supporting instead an account in terms of integrating memory features within an egocentric framework into a first-person perspective representation that enables the subjective experience of remembering.

Two years later - Revisiting autobiographical memory representations in vmPFC and hippocampus.

A long-standing question in memory neuroscience concerns how and where autobiographical memories of personal experiences are represented in the brain. In a previous high resolution multivoxel pattern analysis fMRI study, we examined two week old (recent) and ten year old (remote) autobiographical memories (Bonnici et al., 2012, J. Neurosci. 32:16982-16991). We found that remote memories were particularly well represented in ventromedial prefrontal cortex (vmPFC) compared to recent memories. Moreover, while both types of memory were represented within anterior and posterior hippocampus, remote memories were more easily distinguished in the posterior portion. These findings suggested that a change of some kind had occurred between two weeks and ten years in terms of where autobiographical memories were represented in the brain. In order to examine this further, here participants from the original study returned two years later and recalled the memories again. We found that there was no difference in the detectability of memory representations within vmPFC for the now 2 year old and 12 year old memories, and this was also the case for the posterior hippocampus. Direct comparison of the two week old memories (original study) with themselves two years later (present study) confirmed that their representation within vmPFC had become more evident. Overall, this within-subjects longitudinal fMRI study extends our understanding of autobiographical memory representations by allowing us to narrow the window within which their consolidation is likely to occur. We conclude that after a memory is initially encoded, its representation within vmPFC has stablised by, at most, two years later.

Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain.

Increasing research in animals and humans suggests that obesity may be associated with learning and memory deficits, and in particular with reductions in episodic memory. Rodent models have implicated the hippocampus in obesity-related memory impairments, but the neural mechanisms underlying episodic memory deficits in obese humans remain undetermined. In the present study, lean and obese human participants were scanned using fMRI while completing a What-Where-When episodic memory test (the "Treasure-Hunt Task") that assessed the ability to remember integrated item, spatial, and temporal details of previously encoded complex events. In lean participants, the Treasure-Hunt task elicited significant activity in regions of the brain known to be important for recollecting episodic memories, such as the hippocampus, angular gyrus, and dorsolateral prefrontal cortex. Both obesity and insulin resistance were associated with significantly reduced functional activity throughout the core recollection network. These findings indicate that obesity is associated with reduced functional activity in core brain areas supporting episodic memory and that insulin resistance may be a key player in this association.

Goal-directed mechanisms that constrain retrieval predict subsequent memory for new "foil" information.

To remember a previous event, it is often helpful to use goal-directed control processes to constrain what comes to mind during retrieval. Behavioral studies have demonstrated that incidental learning of new "foil" words in a recognition test is superior if the participant is trying to remember studied items that were semantically encoded compared to items that were non-semantically encoded. Here, we applied subsequent memory analysis to fMRI data to understand the neural mechanisms underlying the "foil effect". Participants encoded information during deep semantic and shallow non-semantic tasks and were tested in a subsequent blocked memory task to examine how orienting retrieval towards different types of information influences the incidental encoding of new words presented as foils during the memory test phase. To assess memory for foils, participants performed a further surprise old/new recognition test involving foil words that were encountered during the previous memory test blocks as well as completely new words. Subsequent memory effects, distinguishing successful versus unsuccessful incidental encoding of foils, were observed in regions that included the left inferior frontal gyrus and posterior parietal cortex. The left inferior frontal gyrus exhibited disproportionately larger subsequent memory effects for semantic than non-semantic foils, and significant overlap in activity during semantic, but not non-semantic, initial encoding and foil encoding. The results suggest that orienting retrieval towards different types of foils involves re-implementing the neurocognitive processes that were involved during initial encoding.

Multimodal Feature Integration in the Angular Gyrus during Episodic and Semantic Retrieval.

UNLABELLED: Much evidence from distinct lines of investigation indicates the involvement of angular gyrus (AnG) in the retrieval of both episodic and semantic information, but the region's precise function and whether that function differs across episodic and semantic retrieval have yet to be determined. We used univariate and multivariate fMRI analysis methods to examine the role of AnG in multimodal feature integration during episodic and semantic retrieval. Human participants completed episodic and semantic memory tasks involving unimodal (auditory or visual) and multimodal (audio-visual) stimuli. Univariate analyses revealed the recruitment of functionally distinct AnG subregions during the retrieval of episodic and semantic information. Consistent with a role in multimodal feature integration during episodic retrieval, significantly greater AnG activity was observed during retrieval of integrated multimodal episodic memories compared with unimodal episodic memories. Multivariate classification analyses revealed that individual multimodal episodic memories could be differentiated in AnG, with classification accuracy tracking the vividness of participants' reported recollections, whereas distinct unimodal memories were represented in sensory association areas only. In contrast to episodic retrieval, AnG was engaged to a statistically equivalent degree during retrieval of unimodal and multimodal semantic memories, suggesting a distinct role for AnG during semantic retrieval. Modality-specific sensory association areas exhibited corresponding activity during both episodic and semantic retrieval, which mirrored the functional specialization of these regions during perception. The results offer new insights into the integrative processes subserved by AnG and its contribution to our subjective experience of remembering. SIGNIFICANCE STATEMENT: Using univariate and multivariate fMRI analyses, we provide evidence that functionally distinct subregions of angular gyrus (AnG) contribute to the retrieval of episodic and semantic memories. Our multivariate pattern classifier could distinguish episodic memory representations in AnG according to whether they were multimodal (audio-visual) or unimodal (auditory or visual) in nature, whereas statistically equivalent AnG activity was observed during retrieval of unimodal and multimodal semantic memories. Classification accuracy during episodic retrieval scaled with the trial-by-trial vividness with which participants experienced their recollections. Therefore, the findings offer new insights into the integrative processes subserved by AnG and how its function may contribute to our subjective experience of remembering.

Representations of specific acoustic patterns in the auditory cortex and hippocampus.

Previous behavioural studies have shown that repeated presentation of a randomly chosen acoustic pattern leads to the unsupervised learning of some of its specific acoustic features. The objective of our study was to determine the neural substrate for the representation of freshly learnt acoustic patterns. Subjects first performed a behavioural task that resulted in the incidental learning of three different noise-like acoustic patterns. During subsequent high-resolution functional magnetic resonance imaging scanning, subjects were then exposed again to these three learnt patterns and to others that had not been learned. Multi-voxel pattern analysis was used to test if the learnt acoustic patterns could be 'decoded' from the patterns of activity in the auditory cortex and medial temporal lobe. We found that activity in planum temporale and the hippocampus reliably distinguished between the learnt acoustic patterns. Our results demonstrate that these structures are involved in the neural representation of specific acoustic patterns after they have been learnt.

CA3 size predicts the precision of memory recall.

There is enduring interest in why some of us have clearer memories than others, given the substantial individual variation that exists in retrieval ability and the precision with which we can differentiate past experiences. Here we report novel evidence showing that variation in the size of human hippocampal subfield CA3 predicted the amount of neural interference between episodic memories within CA3, which in turn predicted how much retrieval confusion occurred between past memories. This effect was not apparent in other hippocampal subfields. This shows that subtle individual differences in subjective mnemonic experience can be accurately gauged from measurable variations in the anatomy and neural coding of hippocampal region CA3. Moreover, this mechanism may be relevant for understanding memory muddles in aging and pathological states.

Representations of recent and remote autobiographical memories in hippocampal subfields.

The hippocampus has long been implicated in supporting autobiographical memories, but little is known about how they are instantiated in hippocampal subfields. Using high-resolution functional magnetic resonance imaging (fMRI) combined with multivoxel pattern analysis we found that it was possible to detect representations of specific autobiographical memories in individual hippocampal subfields. Moreover, while subfields in the anterior hippocampus contained information about both recent (2 weeks old) and remote (10 years old) autobiographical memories, posterior CA3 and DG only contained information about the remote memories. Thus, the hippocampal subfields are differentially involved in the representation of recent and remote autobiographical memories during vivid recall.

Assessing hippocampal functional reserve in temporal lobe epilepsy: a multi-voxel pattern analysis of fMRI data.

Assessing the functional reserve of key memory structures in the medial temporal lobes (MTL) of pre-surgical patients with intractable temporal lobe epilepsy (TLE) remains a challenge. Conventional functional MRI (fMRI) memory paradigms have yet to fully convince of their ability to confidently assess the risk of a post-surgical amnesia. An alternative fMRI analysis method, multi-voxel pattern analysis (MVPA), focuses on the patterns of activity across voxels in specific brain regions that are associated with individual memory traces. This method makes it possible to investigate whether the hippocampus and related structures contralateral to any proposed surgery are capable of laying down and representing specific memories. Here we used MVPA-fMRI to assess the functional integrity of the hippocampi and MTL in patients with long-standing medically refractory TLE associated with unilateral hippocampal sclerosis (HS). Patients were exposed to movie clips of everyday events prior to scanning, which they subsequently recalled during high-resolution fMRI. MTL structures were delineated and pattern classifiers were trained to learn the patterns of brain activity across voxels associated with each memory. Predictable patterns of activity across voxels associated with specific memories could be detected in MTL structures, including the hippocampus, on the side contralateral to the HS, indicating their functional viability. By contrast, no discernible memory representations were apparent in the sclerotic hippocampus, but adjacent MTL regions contained detectable information about the memories. These findings suggest that MVPA in fMRI memory studies of TLE can indicate hippocampal functional reserve and may be useful to predict the effects of hippocampal resection in individual patients.

Detecting representations of recent and remote autobiographical memories in vmPFC and hippocampus.

How autobiographical memories are represented in the human brain and whether this changes with time are questions central to memory neuroscience. Two regions in particular have been consistently implicated, the ventromedial prefrontal cortex (vmPFC) and the hippocampus, although their precise contributions are still contested. The key question in this debate, when reduced to its simplest form, concerns where information about specific autobiographical memories is located. Here, we availed ourselves of the opportunity afforded by multivoxel pattern analysis to provide an alternative to conventional neuropsychological and fMRI approaches, by detecting representations of individual autobiographical memories in patterns of fMRI activity. We examined whether information about specific recent (two weeks old) and remote (10 years old) autobiographical memories was represented in vmPFC and hippocampus, and other medial temporal and neocortical regions. vmPFC contained information about recent and remote autobiographical memories, although remote memories were more readily detected there, indicating that consolidation or a change of some kind had occurred. Information about both types of memory was also present in the hippocampus, suggesting it plays a role in the retrieval of vivid autobiographical memories regardless of remoteness. Interestingly, we also found that while recent and remote memories were both represented within anterior and posterior hippocampus, the latter nevertheless contained more information about remote memories. Thus, like vmPFC, the hippocampus too respected the distinction between recent and remote memories. Overall, these findings clarify and extend our view of vmPFC and hippocampus while also informing systems-level consolidation and providing clear targets for future studies.

Multi-voxel pattern analysis in human hippocampal subfields.

A complete understanding of the hippocampus depends on elucidating the representations and computations that exist in its anatomically distinct subfields. High-resolution structural and functional MRI scanning is starting to permit insights into hippocampal subfields in humans. In parallel, such scanning has facilitated the use of multi-voxel pattern analysis (MVPA) to examine information present in the distributed pattern of activity across voxels. The aim of this study was to combine these two relatively new innovations and deploy MVPA in the hippocampal subfields. Delineating subregions of the human hippocampus, a prerequisite for our study, remains a significant challenge, with extant methods often only examining part of the hippocampus, or being unable to differentiate CA3 and dentate gyrus (DG). We therefore devised a new high-resolution anatomical scanning and subfield segmentation protocol that allowed us to overcome these issues, and separately identify CA1, CA3, DG, and subiculum (SUB) across the whole hippocampus using a standard 3T MRI scanner. We then used MVPA to examine fMRI data associated with a decision-making paradigm involving highly similar scenes that had relevance for the computations that occur in hippocampal subfields. Intra- and inter-rater scores for subfield identification using our procedure confirmed its reliability. Moreover, we found that decoding of information within hippocampal subfields was possible using MVPA, with findings that included differential effects for CA3 and DG. We suggest that MVPA in human hippocampal subfields may open up new opportunities to examine how different types of information are represented and processed at this fundamental level.

Decoding information in the human hippocampus: a user's guide.

Multi-voxel pattern analysis (MVPA), or 'decoding', of fMRI activity has gained popularity in the neuroimaging community in recent years. MVPA differs from standard fMRI analyses by focusing on whether information relating to specific stimuli is encoded in patterns of activity across multiple voxels. If a stimulus can be predicted, or decoded, solely from the pattern of fMRI activity, it must mean there is information about that stimulus represented in the brain region where the pattern across voxels was identified. This ability to examine the representation of information relating to specific stimuli (e.g., memories) in particular brain areas makes MVPA an especially suitable method for investigating memory representations in brain structures such as the hippocampus. This approach could open up new opportunities to examine hippocampal representations in terms of their content, and how they might change over time, with aging, and pathology. Here we consider published MVPA studies that specifically focused on the hippocampus, and use them to illustrate the kinds of novel questions that can be addressed using MVPA. We then discuss some of the conceptual and methodological challenges that can arise when implementing MVPA in this context. Overall, we hope to highlight the potential utility of MVPA, when appropriately deployed, and provide some initial guidance to those considering MVPA as a means to investigate the hippocampus.

Decoding representations of scenes in the medial temporal lobes.

Recent theoretical perspectives have suggested that the function of the human hippocampus, like its rodent counterpart, may be best characterized in terms of its information processing capacities. In this study, we use a combination of high-resolution functional magnetic resonance imaging, multivariate pattern analysis, and a simple decision making task, to test specific hypotheses concerning the role of the medial temporal lobe (MTL) in scene processing. We observed that while information that enabled two highly similar scenes to be distinguished was widely distributed throughout the MTL, more distinct scene representations were present in the hippocampus, consistent with its role in performing pattern separation. As well as viewing the two similar scenes, during scanning participants also viewed morphed scenes that spanned a continuum between the original two scenes. We found that patterns of hippocampal activity during morph trials, even when perceptual inputs were held entirely constant (i.e., in 50% morph trials), showed a robust relationship with participants' choices in the decision task. Our findings provide evidence for a specific computational role for the hippocampus in sustaining detailed representations of complex scenes, and shed new light on how the information processing capacities of the hippocampus may influence the decision making process.

Increased prefrontal gyrification in a large high-risk cohort characterizes those who develop schizophrenia and reflects abnormal prefrontal development.

BACKGROUND: In our cohort considered at high risk (HR) of developing schizophrenia, we previously found a significant difference in extent of right prefrontal cortical folding between those who subsequently developed schizophrenia and a matched group who remained well. This study aimed to determine if this preexisting difference distinguished 17 individuals who developed schizophrenia from the 128 HR individuals in the cohort who remained well and to explore possible underlying differences in cortical composition. METHODS: Prefrontal cortical folding was measured by an automated version of the Gyrification Index (A-GI), a ratio reflecting extent of folding. Multivariate logistic regression assessed the probability that prefrontal A-GI predicts diagnostic outcome and subsequently assessed the effect on A-GI of regional cerebrospinal fluid and gray and white matter. RESULTS: High-risk individuals who subsequently developed schizophrenia were distinguished from the remaining cohort by increased right prefrontal cortex (PFC) A-GI. Mean right PFC gray matter volume also differed between groups, but white matter volume did not. Correlations of age with gray and white matter further distinguished groups and a linear regression analysis showed a significant interaction between age and diagnosis on mean volume of right PFC white matter. CONCLUSIONS: Increased A-GI appears to indicate abnormal right prefrontal development in those who develop schizophrenia.

Pre-frontal lobe gyrification index in schizophrenia, mental retardation and comorbid groups: an automated study.

In this paper, we describe the application of an automated method of calculating Gyrification Index (GI) - the Automated GI (A-GI) - to a total of 95 age-matched and sex-matched patients with mental retardation, schizophrenia, comorbid mental retardation and schizophrenia and controls. The results given by the A-GI program show that subjects with mental retardation possessed the lowest GI values in the pre-frontal lobes, with comorbid and schizophrenia groups being midway between this and the controls. The results showed no significant difference in pre-frontal gyrification between the schizophrenia and the comorbid groups. Although the four groups showed a similar pattern of (spatial) differences in terms of pre-frontal lobe volume, this did not solely account for the differences in A-GI. A significant negative correlation between GI and age was also observed across all four groups. These findings suggest that people with schizophrenia have reduced pre-frontal cortical folding regardless of whether or not they have low IQ. Previous studies in the same cohort have suggested that individuals comorbid for schizophrenia and mental retardation may in fact suffer from severe schizophrenia which has led to their low IQ. The pattern of differences observed in the current study supports this view.