A role for the fornix in temporal sequence memory.

Converging evidence from studies of human and nonhuman animals suggests that the hippocampus contributes to sequence learning by using temporal context to bind sequentially occurring items. The fornix is a white matter pathway containing the major input and output pathways of the hippocampus, including projections from medial septum and to diencephalon, striatum, lateral septum and prefrontal cortex. If the fornix meaningfully contributes to hippocampal function, then individual differences in fornix microstructure might predict sequence memory. Here, we tested this prediction by performing tractography in 51 healthy adults who had undertaken a sequence memory task. Microstructure properties of the fornix were compared with those of tracts connecting medial temporal lobe regions but not predominantly the hippocampus: the Parahippocampal Cingulum bundle (PHC) (conveying retrosplenial projections to parahippocampal cortex) and the Inferior Longitudinal Fasciculus (ILF) (conveying occipital projections to perirhinal cortex). Using principal components analysis, we combined Free-Water Elimination Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging measures obtained from multi-shell diffusion MRI into two informative indices: the first (PC1) capturing axonal packing/myelin and the second (PC2) capturing microstructural complexity. We found a significant correlation between fornix PC2 and implicit reaction-time indices of sequence memory, indicating that greater fornix microstructural complexity is associated with better sequence memory. No such relationship was found with measures from the PHC and ILF. This study highlights the importance of the fornix in aiding memory for objects within a temporal context, potentially reflecting a role in mediating inter-regional communication within an extended hippocampal system.

Brain-environment alignment during movie watching predicts fluid intelligence and affective function in adulthood.

BOLD fMRI studies have provided compelling evidence that the human brain demonstrates substantial moment-to-moment fluctuations in both activity and functional connectivity (FC) patterns. While the role of brain signal variability in fostering cognitive adaptation to ongoing environmental demands is well-documented, the relevance of moment-to-moment changes in FC patterns is still debated. Here, we adopt a graph theoretical approach in order to shed light on the cognitive-affective implications of FC variability and associated profiles of functional network communication in adulthood. Our goal is to identify brain communication pathways underlying FC reconfiguration at multiple timescales, thereby improving understanding of how faster perceptually bound versus slower conceptual processes shape neural tuning to the dynamics of the external world and, thus, indirectly, mold affective and cognitive responding to the environment. To this end, we used neuroimaging and behavioural data collected during movie watching by the Cambridge Center for Ageing and Neuroscience (N = 642, 326 women) and the Human Connectome Project (N = 176, 106 women). FC variability evoked by changes to both the concrete perceptual and the more abstract conceptual representation of an ongoing situation increased from young to older adulthood. However, coupling between variability in FC patterns and concrete environmental features was stronger at younger ages. FC variability (both moment-to-moment/concrete featural and abstract conceptual boundary-evoked) was associated with age-distinct profiles of network communication, specifically, greater functional integration of the default mode network in older adulthood, but greater informational flow across neural networks implicated in environmentally driven attention and control (cingulo-opercular, salience, ventral attention) in younger adulthood. Whole-brain communication pathways anchored in default mode regions relevant to episodic and semantic context creation (i.e., angular and middle temporal gyri) supported FC reconfiguration in response to changes in the conceptual representation of an ongoing situation (i.e., narrative event boundaries), as well as stronger coupling between moment-to-moment fluctuations in FC and concrete environmental features. Fluid intelligence/abstract reasoning was directly linked to levels of brain-environment alignment, but only indirectly associated with levels of FC variability. Specifically, stronger coupling between moment-to-moment FC variability and concrete environmental features predicted poorer fluid intelligence and greater affectively driven environmental vigilance. Complementarily, across the adult lifespan, higher fluid (but not crystallised) intelligence was related to stronger expression of the network communication profile underlying momentary and event boundary-based FC variability during youth. Our results indicate that the adaptiveness of dynamic FC reconfiguration during naturalistic information processing changes across the lifespan due to the associated network communication profiles. Moreover, our findings on brain-environment alignment complement the existing literature on the beneficial consequences of modulating brain signal variability in response to environmental complexity. Specifically, they imply that coupling between moment-to-moment FC variability and concrete environmental features may index a bias towards perceptually-bound, rather than conceptual processing, which hinders affective functioning and strategic cognitive engagement with the external environment.

Cognitive and White-Matter Compartment Models Reveal Selective Relations between Corticospinal Tract Microstructure and Simple Reaction Time.

The speed of motor reaction to an external stimulus varies substantially between individuals and is slowed in aging. However, the neuroanatomical origins of interindividual variability in reaction time (RT) remain unclear. Here, we combined a cognitive model of RT and a biophysical compartment model of diffusion-weighted MRI (DWI) to characterize the relationship between RT and microstructure of the corticospinal tract (CST) and the optic radiation (OR), the primary motor output and visual input pathways associated with visual-motor responses. We fitted an accumulator model of RT to 46 female human participants' behavioral performance in a simple reaction time task. The non-decision time parameter (Ter) derived from the model was used to account for the latencies of stimulus encoding and action initiation. From multi-shell DWI data, we quantified tissue microstructure of the CST and OR with the neurite orientation dispersion and density imaging (NODDI) model as well as the conventional diffusion tensor imaging model. Using novel skeletonization and segmentation approaches, we showed that DWI-based microstructure metrics varied substantially along CST and OR. The Ter of individual participants was negatively correlated with the NODDI measure of the neurite density in the bilateral superior CST. Further, we found no significant correlation between the microstructural measures and mean RT. Thus, our findings suggest a link between interindividual differences in sensorimotor speed and selective microstructural properties in white-matter tracts.SIGNIFICANCE STATEMENT How does our brain structure contribute to our speed to react? Here, we provided anatomically specific evidence that interindividual differences in response speed is associated with white-matter microstructure. Using a cognitive model of reaction time (RT), we estimated the non-decision time, as an index of the latencies of stimulus encoding and action initiation, during a simple reaction time task. Using an advanced microstructural model for diffusion MRI, we estimated the tissue properties and their variations along the corticospinal tract and optic radiation. We found significant location-specific correlations between the microstructural measures and the model-derived parameter of non-decision time but not mean RT. These results highlight the neuroanatomical signature of interindividual variability in response speed along the sensorimotor pathways.

Neurochemical correlates of scene processing in the precuneus/posterior cingulate cortex: A multimodal fMRI and 1 H-MRS study.

Precuneus/posterior cingulate cortex (PCu/PCC) are key components of a midline network, activated during rest but also in tasks that involve construction of scene or situation models. Despite growing interest in PCu/PCC functional alterations in disease and disease risk, the underlying neurochemical modulators of PCu/PCC's task-evoked activity are largely unstudied. Here, a multimodal imaging approach was applied to investigate whether interindividual differences in PCu/PCC fMRI activity, elicited during perceptual discrimination of scene stimuli, were correlated with local brain metabolite levels, measured during resting-state 1 H-MRS. Forty healthy young adult participants completed an fMRI perceptual odd-one-out task for scenes, objects and faces. 1 H-MRS metabolites N-acetyl-aspartate (tNAA), glutamate (Glx) and γ-amino-butyric acid (GABA+) were quantified via PRESS and MEGA-PRESS scans in a PCu/PCC voxel and an occipital (OCC) control voxel. Whole brain fMRI revealed a cluster in right dorsal PCu/PCC that showed a greater BOLD response to scenes versus faces and objects. When extracted from an independently defined PCu/PCC region of interest, scene activity (vs. faces and objects and also vs. baseline) was positively correlated with PCu/PCC, but not OCC, tNAA. A voxel-wise regression analysis restricted to the PCu/PCC 1 H-MRS voxel area identified a significant PCu/PCC cluster, confirming the positive correlation between scene-related BOLD activity and PCu/PCC tNAA. There were no correlations between PCu/PCC activity and Glx or GABA+ levels. These results demonstrate, for the first time, that scene activity in PCu/PCC is linked to local tNAA levels, identifying a neurochemical influence on interindividual differences in the task-driven activity of a key brain hub.

Ultra-High-Field fMRI Reveals a Role for the Subiculum in Scene Perceptual Discrimination.

Recent "representational" accounts suggest a key role for the hippocampus in complex scene perception. Due to limitations in scanner field strength, however, the functional neuroanatomy of hippocampal-dependent scene perception is unknown. Here, we applied 7 T high-resolution functional magnetic resonance imaging (fMRI) alongside a perceptual oddity task, modified from nonhuman primate studies. This task requires subjects to discriminate highly similar scenes, faces, or objects from multiple viewpoints, and has revealed selective impairments during scene discrimination following hippocampal lesions. Region-of-interest analyses identified a preferential response in the subiculum subfield of the hippocampus during scene, but not face or object, discriminations. Notably, this effect was in the anteromedial subiculum and was not modulated by whether scenes were subsequently remembered or forgotten. These results highlight the value of ultra-high-field fMRI in generating more refined, anatomically informed, functional accounts of hippocampal contributions to cognition, and a unique role for the human subiculum in discrimination of complex scenes from different viewpoints.SIGNIFICANCE STATEMENT There is increasing evidence that the human hippocampus supports functions beyond just episodic memory, with human lesion studies suggesting a contribution to the perceptual processing of navigationally relevant, complex scenes. While the hippocampus itself contains several small, functionally distinct subfields, examining the role of these in scene processing has been previously limited by scanner field strength. By applying ultra-high-resolution 7 T fMRI, we delineated the functional contribution of individual hippocampal subfields during a perceptual discrimination task for scenes, faces, and objects. This demonstrated that the discrimination of scenes, relative to faces and objects, recruits the anterior subicular region of the hippocampus, regardless of whether scenes were subsequently remembered or forgotten.

Evidence for Integrated Visual Face and Body Representations in the Anterior Temporal Lobes.

Research on visual face perception has revealed a region in the ventral anterior temporal lobes, often referred to as the anterior temporal face patch (ATFP), which responds strongly to images of faces. To date, the selectivity of the ATFP has been examined by contrasting responses to faces against a small selection of categories. Here, we assess the selectivity of the ATFP in humans with a broad range of visual control stimuli to provide a stronger test of face selectivity in this region. In Experiment 1, participants viewed images from 20 stimulus categories in an event-related fMRI design. Faces evoked more activity than all other 19 categories in the left ATFP. In the right ATFP, equally strong responses were observed for both faces and headless bodies. To pursue this unexpected finding, in Experiment 2, we used multivoxel pattern analysis to examine whether the strong response to face and body stimuli reflects a common coding of both classes or instead overlapping but distinct representations. On a voxel-by-voxel basis, face and whole-body responses were significantly positively correlated in the right ATFP, but face and body-part responses were not. This finding suggests that there is shared neural coding of faces and whole bodies in the right ATFP that does not extend to individual body parts. In contrast, the same approach revealed distinct face and body representations in the right fusiform gyrus. These results are indicative of an increasing convergence of distinct sources of person-related perceptual information proceeding from the posterior to the anterior temporal cortex.

Interindividual variation in fornix microstructure and macrostructure is related to visual discrimination accuracy for scenes but not faces.

Transection of the nonhuman primate fornix has been shown to impair learning of configurations of spatial features and object-in-scene memory. Although damage to the human fornix also results in memory impairment, it is not known whether there is a preferential involvement of this white-matter tract in spatial learning, as implied by animal studies. Diffusion-weighted MR images were obtained from healthy participants who had completed versions of a task in which they made rapid same/different discriminations to two categories of highly visually similar stimuli: (1) virtual reality scene pairs; and (2) face pairs. Diffusion-MRI measures of white-matter microstructure [fractional anisotropy (FA) and mean diffusivity (MD)] and macrostructure (tissue volume fraction, f) were then extracted from the fornix of each participant, which had been reconstructed using a deterministic tractography protocol. Fornix MD and f measures correlated with scene, but not face, discrimination accuracy in both discrimination tasks. A complementary voxelwise analysis using tract-based spatial statistics suggested the crus of the fornix as a focus for this relationship. These findings extend previous reports of spatial learning impairments after fornix transection in nonhuman primates, critically highlighting the fornix as a source of interindividual variation in scene discrimination in humans.

A critical role for the hippocampus and perirhinal cortex in perceptual learning of scenes and faces: complementary findings from amnesia and FMRI.

It is debated whether subregions within the medial temporal lobe (MTL), in particular the hippocampus (HC) and perirhinal cortex (PrC), play domain-sensitive roles in learning. In the present study, two patients with differing degrees of MTL damage were first exposed to pairs of highly similar scenes, faces, and dot patterns and then asked to make repeated same/different decisions to preexposed and nonexposed (novel) pairs from the three categories (Experiment 1). We measured whether patients would show a benefit of prior exposure (preexposed > nonexposed) and whether repetition of nonexposed (and preexposed) pairs at test would benefit discrimination accuracy. Although selective HC damage impaired learning of scenes, but not faces and dot patterns, broader MTL damage involving the HC and PrC compromised discrimination learning of scenes and faces but left dot pattern learning unaffected. In Experiment 2, a similar task was run in healthy young participants in the MRI scanner. Functional region-of-interest analyses revealed that posterior HC and posterior parahippocampal gyrus showed greater activity during scene pattern learning, but not face and dot pattern learning, whereas PrC, anterior HC, and posterior fusiform gyrus were recruited during discrimination learning for faces, but not scenes and dot pattern learning. Critically, activity in posterior HC and PrC, but not the other functional region-of-interest analyses, was modulated by accuracy (correct > incorrect within a preferred category). Therefore, both approaches revealed a key role for the HC and PrC in discrimination learning, which is consistent with representational accounts in which subregions in these MTL structures store complex spatial and object representations, respectively.

Scene-selectivity in CA1/subicular complex: Multivoxel pattern analysis at 7T.

Prior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g., CA1). Further, as connectivity-based functional gradients in the hippocampus do not respect classical subfield boundary definitions, category selectivity may be distributed across anatomical subfields. Region-of-interest approaches, therefore, may limit our ability to observe category selectivity across discrete subfield boundaries. To address these issues, we applied searchlight multivariate pattern analysis to 7T fMRI data of healthy adults who undertook a simultaneous visual odd-one-out discrimination task for scene and non-scene (including face) visual stimuli, hypothesising that scene classification would be possible in multiple hippocampal regions within, but not constrained to, anteromedial subicular complex and CA1. Indeed, we found that the scene-selective searchlight map overlapped not only with anteromedial subicular complex (distal subiculum, pre/para subiculum), but also inferior CA1, alongside posteromedial (including retrosplenial) and parahippocampal cortices. Probabilistic overlap maps revealed gradients of scene category selectivity, with the strongest overlap located in the medial hippocampus, converging with searchlight findings. This was contrasted with gradients of face category selectivity, which had stronger overlap in more lateral hippocampus, supporting ideas of parallel processing streams for these two categories. Our work helps to map the scene, in contrast to, face processing networks within, and connected to, the human hippocampus.

A role for perirhinal cortex in memory for novel object-context associations.

It is debated whether functional divisions between structures in the medial temporal lobe (MTL), in particular the perirhinal cortex (PrC) and hippocampus (HC), are best conceptualized according to memory process (Diana et al., 2007; Ranganath, 2010; Wixted et al., 2010) or stimulus category (Graham et al., 2010). In the former account, PrC is critical for item familiarity but not recollection of associations between items and their contexts (which is instead dependent upon the HC; Ranganath et al., 2004). In the latter theory, complex object representations in PrC are capable of supporting memory for objects as well as for object-context associations, particularly when there is a demand to discriminate between highly visually similar objects (Cowell et al., 2010). To adjudicate between these accounts, human participants were scanned while making two different judgments about visually presented objects (is the object common or uncommon, or does the object have more edges or curves). In a subsequent, unscanned, retrieval phase, participants made item (old/new) followed by context (encoding task) judgments about previously seen and novel objects. Neural activity at encoding was separated according to the accuracy of the retrieval judgments. PrC activity predicted successful item-context judgments, a result that remained when item-memory strength was equated across objects for which the context was remembered or forgotten. These data imply that the function of PrC goes beyond processing item-based memory information, contributing additionally to memory for item-context associations when the stimuli are objects (Graham et al., 2010).

The interindividual variability of multimodal brain connectivity maintains spatial heterogeneity and relates to tissue microstructure.

Humans differ from each other in a wide range of biometrics, but to what extent brain connectivity varies between individuals remains largely unknown. By combining diffusion-weighted imaging (DWI) and magnetoencephalography (MEG), this study characterizes the inter-subject variability (ISV) of multimodal brain connectivity. Structural connectivity is characterized by higher ISV in association cortices including the core multiple-demand network and lower ISV in the sensorimotor cortex. MEG ISV exhibits frequency-dependent signatures, and the extent of MEG ISV is consistent with that of structural connectivity ISV in selective macroscopic cortical clusters. Across the cortex, the ISVs of structural connectivity and beta-band MEG functional connectivity are negatively associated with cortical myelin content indexed by the quantitative T1 relaxation rate measured by high-resolution 7 T MRI. Furthermore, MEG ISV from alpha to gamma bands relates to the hindrance and restriction of the white-matter tissue estimated by DWI microstructural models. Our findings depict the inter-relationship between the ISV of brain connectivity from multiple modalities, and highlight the role of tissue microstructure underpinning the ISV.

Tract-specific differences in white matter microstructure between young adult APOE ε4 carriers and non-carriers: A replication and extension study.

The parahippocampal cingulum bundle (PHCB) interconnects regions known to be vulnerable to early Alzheimer's disease (AD) pathology, including posteromedial cortex and medial temporal lobe. While AD-related pathology has been robustly associated with alterations in PHCB microstructure, specifically lower fractional anisotropy (FA) and higher mean diffusivity (MD), emerging evidence indicates that the reverse pattern is evident in younger adults at increased risk of AD. In one such study, Hodgetts et al. (2019) reported that healthy young adult carriers of the apolipoprotein-E (APOE) ε4 allele - the strongest common genetic risk factor for AD - showed higher FA and lower MD in the PHCB but not the inferior longitudinal fasciculus (ILF). These results are consistent with proposals claiming that heightened neural activity and intrinsic connectivity play a significant role in increasing posteromedial cortex vulnerability to amyloid-ß and tau spread beyond the medial temporal lobe. Given the implications for understanding AD risk, here we sought to replicate Hodgetts et al.'s finding in a larger sample (N = 128; 40 APOE ε4 carriers, 88 APOE ε4 non-carriers) of young adults (age range = 19-33). Extending this work, we also conducted an exploratory analysis using a more advanced measure of white matter microstructure: hindrance modulated orientational anisotropy (HMOA). Contrary to the original study, we did not observe higher FA or lower MD in the PHCB of APOE ε4 carriers relative to non-carriers. Bayes factors (BFs) further revealed moderate-to-strong evidence in support of these null findings. In addition, we observed no APOE ε4-related differences in PHCB HMOA. Our findings indicate that young adult APOE ε4 carriers and non-carriers do not differ in PHCB microstructure, casting some doubt on the notion that early-life variation in PHCB tract microstructure might enhance vulnerability to amyloid-ß accumulation and/or tau spread.

Perception and conception: temporal lobe activity during complex discriminations of familiar and novel faces and objects.

Recent studies indicate that medial-temporal lobe (MTL) damage, either from focal lesions or neurodegenerative disease (e.g., semantic dementia), impairs perception as well as long-term declarative memory. Notably, however, these two patient groups show different performance for meaningful versus unfamiliar stimuli. In amnesics with nonprogressive MTL lesions, the use of meaningful stimuli, compared with unfamiliar items, boosted discrimination performance. In semantic dementia, a condition characterized by progressive deterioration of conceptual knowledge in the context of anterolateral temporal lobe damage, performance for meaningful stimuli was equivalent to that for unfamiliar items. To further investigate these findings, we scanned healthy volunteers while they performed odd-one-out discriminations involving familiar (i.e., meaningful/famous) and unfamiliar (i.e., novel) objects and faces and a baseline task of size oddity. Outside the scanner, volunteers' recognition memory was assessed. We found above baseline activity in the perirhinal cortex and hippocampus for all object and face discriminations and above baseline activity in the temporal pole for all face discriminations. The comparison of meaningful, relative to novel, faces and objects, revealed increased activity in the perirhinal cortex and hippocampus. In the temporal pole, we also found activity related to meaningfulness for faces but not for objects. Importantly, these meaningfulness effects were evident even for discriminations that were not subsequently well remembered, suggesting that the difference between meaningful and novel stimuli reflects perceptual or conceptual processes rather than solely incidental encoding into long-term memory. The results provide further evidence that the MTL is recruited during complex perceptual discrimination and additionally suggest that these structures are recruited in semantic processing of objects and faces.

Remote memory deficits in transient epileptic amnesia.

Transient epileptic amnesia is a form of temporal lobe epilepsy in which sufferers often complain of irretrievable loss of remote memories. We used a broad range of memory tests to clarify the extent and nature of the remote memory deficits in patients with transient epileptic amnesia. Performance on standard tests of anterograde memory was normal. In contrast, there was a severe impairment of memory for autobiographical events extending across the entire lifespan, providing evidence for the occurrence of 'focal retrograde amnesia' in transient epileptic amnesia. There was a milder impairment of personal semantic memory, most pronounced for midlife years. There were limited deficits of public semantic memory for recent decades. These results may reflect subtle structural pathology in the medial temporal lobes or the effects of the propagation of epileptiform activity through the network of brain regions responsible for long-term memory, or a combination of these two mechanisms.

Influence of conceptual knowledge on visual object discrimination: insights from semantic dementia and MTL amnesia.

Recent evidence suggests that the perirhinal cortex is involved in perception of complex objects with ambiguous features. Anterior regions of the temporal lobes, including the perirhinal cortex as well as lateral cortex, are also thought to play a critical role in semantic memory. To understand how semantic factors might contribute to perceptual discrimination of complex objects, we studied visual object discrimination in patients with semantic dementia (SD)-a neurodegenerative condition characterized by progressive deterioration of semantic knowledge and atrophy to anterior temporal lobes (including perirhinal cortex). In 3 experiments, we assessed discrimination of meaningful (e.g., familiar real-world objects) and novel (e.g., blobs) objects with varying feature ambiguity levels. In a fourth experiment, we compared SD patients with amnesic patients with nonprogressive medial temporal lobe (MTL) lesions and less impaired semantic memory. Across studies, patients with perirhinal damage were impaired at discriminating objects with a high, but not low, degree of feature ambiguity, consistent with previous work indicating a perceptual role for this structure. Stimulus meaningfulness, however, differentially influenced performance in SD patients compared with MTL amnesics, suggesting that perceptual representations of complex objects (dependent upon perirhinal cortex) interact with higher-order abstract conceptual representations, even for tasks with no overt semantic component.

Is knowledge of famous people compromised in mild cognitive impairment?

OBJECTIVE: : This study addressed the issue of whether person naming deficits in mild cognitive impairment (MCI) occurred with deficits in person semantic knowledge and whether person knowledge was more impaired than general semantics. BACKGROUND: : Recent definitions of MCI are beginning to encompass cognitive impairments outside the domain of episodic memory. Increasing evidence suggests that semantic memory may also be compromised in this patient group, including tasks of person naming and identification. METHODS: : Thirteen MCI patients and 14 control subjects matched for age and education performed parallel semantic batteries designed to probe person and general semantic knowledge. RESULTS: : On the person battery, the MCI patients demonstrated impairment relative to controls, on tasks of category fluency, naming, identification, verbal and nonverbal associative and sorting tasks, as well as matching names to faces. By contrast, on the general semantic battery impairments, they were impaired only on category fluency and the nonverbal sorting and associative tasks. A composite measure of person knowledge tasks was also sensitive to disease severity as measured by Mini-Mental State Examination. CONCLUSIONS: : These results support the existence of deficits in MCI across various domains of person knowledge, and the suggestion that deterioration of unique semantic exemplars may be sensitive to incipient Alzheimer disease.

Obstructive sleep apnea syndrome is associated with deficits in verbal but not visual memory.

RATIONALE: Although cognitive deficits are well documented in patients with sleep apnea, the impact on memory remains unclear. OBJECTIVES: To test the hypotheses that (1) patients with obstructive sleep apnea have memory impairment and (2) memory impairment is commensurate with disease severity. METHODS: Patients with obstructive sleep apnea and healthy volunteers (apnea-hypopnea index <5 events/h) completed a test battery specially designed to differentiate between aspects of memory (semantic, episodic, and working) versus attention. Sleepiness was measured on the basis of the Epworth Sleepiness Scale and Oxford Sleep Resistance test. Memory performance in patients versus control subjects was compared (Mann-Whitney U test; P < 0.01, Bonferroni corrected for multiple comparisons) and relationships between performance and disease severity were analyzed by linear regression. MEASUREMENTS AND MAIN RESULTS: Sixty patients and healthy control subjects matched for age (mean +/- SD: patients, 51 +/- 9 yr; control subjects, 50 +/- 9 yr) and education (patients, 14 +/- 3 yr; control subjects, 15 +/- 3 yr) participated. Patients demonstrated impaired Logical Memory Test results (immediate recall: patients, median [range], 36 [9-69]; control subjects, 43 [19-64], P = 0.0004; and delayed recall: patients, 22 [6-42]; control subjects, 27 [10-46]; P = 0.0001). There were minimal differences in attention, visual episodic, semantic, or working memory; patients performed better than control subjects on Spatial Span forward and backward. Regression analysis revealed that Logical Memory Test performance was not significantly related to disease severity after controlling for age, education, and sleepiness. CONCLUSIONS: Obstructive sleep apnea is associated with impairment in verbal, but not visual, memory. The impairment was present across a range of disease severity and was not explained by reduced attention. Such verbal memory impairment may affect daytime functioning and performance.

Pubertal timing and functional neurodevelopmental alterations independently mediate the effect of family conflict on adolescent psychopathology.

This study tested the hypothesis that early life adversity (ELA) heightens psychopathology risk by concurrently altering pubertal and neurodevelopmental timing, and associated gene transcription signatures. Analyses focused on threat- (family conflict/neighbourhood crime) and deprivation-related ELAs (parental inattentiveness/unmet material needs), using longitudinal data from 1514 biologically unrelated youths in the Adolescent Brain and Cognitive Development (ABCD) study. Typical developmental changes in white matter microstructure corresponded to widespread BOLD signal variability (BOLDsv) increases (linked to cell communication and biosynthesis genes) and region-specific task-related BOLDsv increases/decreases (linked to signal transduction, immune and external environmental response genes). Increasing resting-state (RS), but decreasing task-related BOLDsv predicted normative functional network segregation. Family conflict was the strongest concurrent and prospective contributor to psychopathology, while material deprivation constituted an additive risk factor. ELA-linked psychopathology was predicted by higher Time 1 threat-evoked BOLDSV (associated with axonal development, myelination, cell differentiation and signal transduction genes), reduced Time 2 RS BOLDsv (associated with cell metabolism and attention genes) and greater Time 1 to Time 2 control/attention network segregation. Earlier pubertal timing and neurodevelopmental alterations independently mediated ELA effects on psychopathology. Our results underscore the differential roles of the immediate and wider external environment(s) in concurrent and longer-term ELA consequences.

Orbito-frontal cortex is necessary for temporal context memory.

Lesion and neuroimaging studies suggest that orbito-frontal cortex (OFC) supports temporal aspects of episodic memory. However, it is unclear whether OFC contributes to the encoding and/or retrieval of temporal context and whether it is selective for temporal relative to nontemporal (spatial) context memory. We addressed this issue with two complimentary studies: functional magnetic resonance imaging to measure OFC activity associated with successful temporal and spatial context memory during encoding and retrieval in healthy young participants, and a neuropsychological investigation to measure changes in spatial and temporal context memory in OFC lesion patients. Imaging results revealed that OFC contributed to encoding and retrieval of associations between objects and their temporal but not their spatial contexts. Consistent with this, OFC patients exhibited impairments in temporal but not spatial source memory accuracy. These results suggest that OFC plays a critical role in the formation and subsequent retrieval of temporal context.

Medial temporal lobe activity during complex discrimination of faces, objects, and scenes: Effects of viewpoint.

The medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampus and underlying entorhinal, perirhinal and parahippocampal cortex, is traditionally believed to be part of a unitary system dedicated to declarative memory. Recent studies, however, demonstrated perceptual impairments in amnesic individuals with MTL damage, with hippocampal lesions causing scene discrimination deficits, and perirhinal lesions causing object and face discrimination deficits. The degree of impairment on these tasks was influenced by the need to process complex conjunctions of features: discriminations requiring the integration of multiple visual features caused deficits, whereas discriminations that could be solved on the basis of a single feature did not. Here, we address these issues with functional neuroimaging in healthy participants as they performed a version of the oddity discrimination task used previously in patients. Three different types of stimuli (faces, scenes, novel objects) were presented from either identical or different viewpoints. Consistent with studies in patients, we observed increased perirhinal activity when participants distinguished between faces and objects presented from different, compared to identical, viewpoints. The posterior hippocampus, by contrast, showed an effect of viewpoint for both faces and scenes. These findings provide convergent evidence that the MTL is involved in processes beyond long-term declarative memory and suggest a critical role for these structures in integrating complex features of faces, objects, and scenes into view-invariant, abstract representations.