Tracking thoughts: : Exploring the neural architecture of mental time travel during mind-wandering

The capacity to imagine situations that have already happened or fictitious events that may take place in the future is known as mental time travel (MTT). Studies have shown that MTT is an important aspect of spontaneous thought, yet we lack a clear understanding of how the neurocognitive architecture of the brain constrains this element of human cognition. Previous functional magnetic resonance imaging (MRI) studies have shown that MTT involves the coordination between multiple regions that include mesiotemporal structures such as the hippocampus, as well as prefrontal and parietal regions commonly associated with the default mode network (DMN). The current study used a multimodal neuroimaging approach to identify the structural and functional brain organisation that underlies individual differences in the capacity to spontaneously engage in MTT. Using regionally unconstrained diffusion tractography analysis, we found increased diffusion anisotropy in right lateralised temporo-limbic, corticospinal, inferior fronto-occipital tracts in participants who reported greater MTT. Probabilistic connectivity mapping revealed a significantly higher connection probability of the right hippocampus with these tracts. Resting-state functional MRI connectivity analysis using the right hippocampus as a seed region revealed greater functional coupling to the anterior regions of the DMN with increasing levels of MTT. These findings demonstrate that the interactions between the hippocampus and regions of the cortex underlie the capacity to engage in MTT, and support contemporary theoretical accounts that suggest that the integration of the hippocampus with the DMN provides the neurocognitive landscape that allows us to imagine distant times and places

Scene construction impairments in Alzheimer's disease – A unique role for the posterior cingulate cortex

Episodic memory dysfunction represents one of the most prominent and characteristic clinical features of patients with Alzheimer's disease (AD), attributable to the degeneration of medial temporal and posterior parietal regions of the brain. Recent studies have demonstrated marked impairments in the ability to envisage personally relevant events in the future in AD. It remains unclear, however, whether AD patients can imagine fictitious scenes free from temporal constraints, a process that is proposed to rely fundamentally upon the integrity of the hippocampus. The objective of the present study was to investigate the capacity for atemporal scene construction, and its associated neural substrates, in AD. Fourteen AD patients were tested on the scene construction task and their performance was contrasted with 14 age- and education-matched healthy older Control participants. Scene construction performance was strikingly compromised in the AD group, with significant impairments evident for provision of contextual details, spatial coherence, and the overall richness of the imagined experience. Voxel-based morphometry analyses based on structural MRI revealed significant associations between scene construction capacity and atrophy in posterior parietal and lateral temporal brain structures in AD. In contrast, scene construction performance in Controls was related to integrity of frontal, parietal, and medial temporal structures, including the parahippocampal gyrus and posterior hippocampus. The posterior cingulate cortex (PCC) emerged as the common region implicated for scene construction performance across participant groups. Our study highlights the importance of regions specialised for spatial and contextual processing for the construction of atemporal scenes. Damage to these regions in AD compromises the ability to construct novel scenes, leading to the recapitulation of content from previously experienced events

Acute Intoxication Affects Pavlovian Conditioning in Zebrafish (Danio rerio)

The study explored the effects of alcohol on short-term memory in zebrafish. Memory impairments are pervasive in several conditions resulting from long-term alcohol exposure, for example Fetal Alcohol Syndrome (FAS) and Wernicke-Korsakoff Syndrome. Most of the memory effects observed link to abnormal functioning of the hippocampus and frontal lobes. The effects of alcohol on memory are that it acts as a general central nervous system depressant, but it also affects some areas of the brain more than others. In our laboratory we use two variations of Pavlovian conditioning: Delay and Trace, to examine learning and memory with acute alcohol intoxication. The hypothesis was that zebrafish would respond to alcohol in a way similar to humans and other animal models. I used 60 adult zebrafish, half male and half female. The conditioned stimulus (CS) was a red square, while the unconditioned stimulus (US) consisted of zebrafish images that moved around the screen. In Delay conditioning the US immediately followed the offset of the CS. In Trace conditioning a 30-s interval separated CS offset from US onset. The highest concentration of ethanol, 1%, disrupted conditioned approach behavior in both training conditions, but the 0.5% concentration disrupted conditioned approach behavior only in the Trace procedure. This indicates that in the zebrafish, as in mammals, Trace conditioning is more sensitive to alcohol. Although it is unclear what effect of alcohol produces these learning and memory impairments, it is likely that alcohol disrupted activity in the hippocampus. This could occur via several routes—directly, through effects on hippocampal circuitry, or indirectly, by interfering with interactions between the hippocampus and other brain regions. Based on my findings, the zebrafish can be an important model to study both acute and chronic effects of alcohol on memory

Dissociable roles of the inferior longitudinal fasciculus and fornix in face and place perception

We tested a novel hypothesis, generated from representational accounts of medial temporal lobe (MTL) function, that the major white matter tracts converging on perirhinal cortex (PrC) and hippocampus (HC) would be differentially involved in face and scene perception, respectively. Diffusion tensor imaging was applied in healthy participants alongside an odd-one-out paradigm sensitive to PrC and HC lesions in animals and humans. Microstructure of inferior longitudinal fasciculus (ILF, connecting occipital and ventro-anterior temporal lobe, including PrC) and fornix (the main HC input/output pathway) correlated with accuracy on odd-one-out judgements involving faces and scenes, respectively. Similarly, blood oxygen level-dependent (BOLD) response in PrC and HC, elicited during oddity judgements, was correlated with face and scene oddity performance, respectively. We also observed associations between ILF and fornix microstructure and category-selective BOLD response in PrC and HC, respectively. These striking three-way associations highlight functionally dissociable, structurally instantiated MTL neurocognitive networks for complex face and scene perception

Representation of contralateral visual space in the human hippocampus

The initial encoding of visual information primarily from the contralateral visual field is a fundamental organizing principle of the primate visual system. Recently, the presence of such retinotopic sensitivity has been shown to extend well beyond early visual cortex to regions not historically considered retinotopically sensitive. In particular, human scene-selective regions in parahippocampal and medial parietal cortex exhibit prominent biases for the contralateral visual field. Here we used fMRI to test the hypothesis that the human hippocampus, which is thought to be anatomically connected with these scene-selective regions, would also exhibit a biased representation of contralateral visual space. First, population receptive field mapping with scene stimuli revealed strong biases for the contralateral visual field in bilateral hippocampus. Second, the distribution of retinotopic sensitivity suggested a more prominent representation in anterior medial portions of the hippocampus. Finally, the contralateral bias was confirmed in independent data taken from the Human Connectome Project initiative. The presence of contralateral biases in the hippocampus - a structure considered by many as the apex of the visual hierarchy - highlights the truly pervasive influence of retinotopy. Moreover, this finding has important implications for understanding how this information relates to the allocentric global spatial representations known to be encoded therein.SIGNIFICANCE STATEMENT:Retinotopic encoding of visual information is an organizing principle of visual cortex. Recent work demonstrates this sensitivity in structures far beyond early visual cortex, including those anatomically connected to the hippocampus. Here, using population receptive field modelling in two independent sets of data we demonstrate a consistent bias for the contralateral visual field in bilateral hippocampus. Such a bias highlights the truly pervasive influence of retinotopy, with important implications for understanding how the presence of retinotopy relates to more allocentric spatial representations

Distinctive and complementary roles of default mode network subsystems in semantic cognition

The default mode network (DMN) typically deactivates to external tasks, yet supports semantic cognition. It comprises medial temporal (MT), core, and fronto-temporal (FT) subsystems, but its functional organisation is unclear: the requirement for perceptual coupling versus decoupling, input modality (visual/verbal), type of information (social/spatial) and control demands all potentially affect its recruitment. We examined the effect of these factors on activation and deactivation of DMN subsystems during semantic cognition, across four task-based human functional magnetic resonance imaging (fMRI) datasets, and localised these responses in whole-brain state space defined by gradients of intrinsic connectivity. FT showed activation consistent with a central role across domains, tasks and modalities, although it was most responsive to abstract, verbal tasks; this subsystem uniquely showed more ‘tuned’ states characterised by increases in both activation and deactivation when semantic retrieval demands were higher. MT also activated to both perceptually-coupled (scenes) and decoupled (autobiographical memory) tasks, and showed stronger responses to picture associations, consistent with a role in scene construction. Core DMN consistently showed deactivation, especially to externally-oriented tasks. These diverse contributions of DMN subsystems to semantic cognition were related to their location on intrinsic connectivity gradients: activation was closer to sensory-motor cortex than deactivation, particularly for FT and MT, while activation for core DMN was distant from both visual cortex and cognitive control. These results reveal distinctive yet complementary DMN responses: MT and FT support different memory-based representations that are accessed externally and internally, while deactivation in core DMN is associated with demanding, external semantic tasks

Modelling reaction time distribution of fast decision tasks in schizophrenia: Evidence for novel candidate endophenotypes

Increased reaction time (RT) and variability of RT in fast decision tasks is observed in patients with schizophrenia and their first degree relatives. This study used modelling of the RT distribution with the aim of identifying novel candidate endophenotypes for schizophrenia. 20 patients with schizophrenia, 15 siblings of patients and 25 healthy controls performed an oddball task of varying working memory load. Increases in mean and standard deviation (SD) of RT were observed for both patients and siblings compared to controls and they were again independent of working memory load. Ex-Gaussian modelling of the RT distribution confirmed that parameters mu, sigma and tau increased significantly in patients and siblings compared to controls. The Drift Diffusion Model was applied on RT distributions. A decrease in the diffusion drift rate (v) modeling the accumulation of evidence for reaching the decision to choose one stimulus over the other, was observed in patients and siblings compared to controls. The mean time of the non-decisional sensorimotor processes (t0) and it's variance (st0) was also increased in patients and siblings compared to controls. In conclusion modeling of the RT distribution revealed novel potential cognitive endophenotypes in the quest of heritable risk factors for schizophrenia

The Effects of G-Protein-Coupled Estrogen Receptor (GPER) on Cell Signaling, Dendritic Spines, and Memory Consolidation in the Female Mouse Hippocampus

One of the most seminal findings in the literature on hormones and cognition is that the potent estrogen 17β-estradiol (E2) significantly increases the density of dendritic spines on pyramidal neurons in the CA1 region of the dorsal hippocampus (DH). However, the extent to which this E2-induced increase in hippocampal spinogenesis is necessary for memory formation remains unclear. The memory-enhancing effects of E2 in the DH can be mediated by intracellular estrogen receptors (ERs) or by the membrane-bound ER called G-protein coupled estrogen receptor (GPER). We previously reported that infusion of a GPER agonist, G-1, into the DH of ovariectomized female mice mimicked the beneficial effects of E2 on object recognition and spatial memory consolidation in a manner that depended on phosphorylation of the signaling kinase c-Jun N-terminal kinase (JNK). However, the role of CA1 dendritic spines in mediating GPER-induced memory consolidation, as well as the signaling mechanisms that might mediate effects of GPER activation on dendritic spine density, remain unclear. Thus, the present study examined in ovariectomized mice the effects of DH-infused G-1 on dendritic spine density and determined whether such effects are necessary for G-1-induced memory consolidation. We first examined whether object training itself might induce increased CA1 dendritic spine density, and showed that spine density is increased by object training. Next, we found that G-1 significantly increased the density of dendritic spines on apical dendrites of CA1 pyramidal neurons in the DH. We next examined cellular mechanisms regulating G-1 induced spinogenesis by measuring effects of DH G-1 infusion of the phosphorylation of the protein cofilin, which actively regulates actin reorganization. We found that G-1 significantly increased cofilin phosphorylation in the DH, suggesting that activation of GPER may increase dendritic spine morphogenesis through actin polymerization. As with memory consolidation in our previous study, we also found that the effects of G-1 on apical CA1 spine density and cofilin phosphorylation were dependent on JNK phosphorylation in the DH. To verify the importance of actin polymerization in GPER-mediated dendritic spine morphogenesis and hippocampal memory enhancement, we applied an actin polymerization inhibitor, latrunculin A, which prevents actin polymerization and promotes filament disassembly. DH infusion of latrunculin A prevented G-1 from inducing apical CA1 spinogenesis and enhancing both object recognition and spatial memory consolidation. Collectively, these data demonstrate that GPER-mediated hippocampal memory consolidation and spine density changes are dependent on modulating actin dynamics via JNK-Cofilin signaling, supporting a critical role of actin polymerization in the GPER-induced regulation of hippocampal function in female mice