The pre/parasubiculum: a hippocampal hub for scene-based cognition?

Internal representations of the world in the form of spatially coherent scenes have been linked with cognitive functions including episodic memory, navigation and imagining the future. In human neuroimaging studies, a specific hippocampal subregion, the pre/parasubiculum, is consistently engaged during scene-based cognition. Here we review recent evidence to consider why this might be the case. We note that the pre/ parasubiculum is a primary target of the parieto-medial temporal processing pathway, it receives integrated information from foveal and peripheral visual inputs and it is contiguous with the retrosplenial cortex. We discuss why these factors might indicate that the pre/parasubiculum has privileged access to holistic representations of the environment and could be neuroanatomically determined to preferentially process scenes

Manipulating the temporal locus and content of mind-wandering

The human brain has a tendency to drift into the realm of internally-generated thoughts that are unbound by space and time. The term mind-wandering (MW) is often used describe such thoughts when they are perceptually decoupled. Evidence suggests that exposure to forward and backward illusory motion skews the temporal orientation of MW thoughts to either the future or past respectively. However, little is known about the impact of this manipulation on other features of MW. Here, using a novel experimental paradigm, we first confirmed that our illusory motion method facilitated the generation of MW thoughts congruent with the direction of motion. We then conducted content analyses which revealed that goal orientation and temporal distance were also significantly affected by the direction of illusory motion. We conclude that illusory motion may be an effective means of assaying MW and could help to elucidate this ubiquitous, and likely critical, component of cognition

Decoherence Rates in Large Scale Quantum Computers and Macroscopic Systems

Markovian regime decoherence effects in quantum computers are studied in terms of the fidelity for the situation where the number of qubits N becomes large. A general expression giving the decoherence time scale in terms of Markovian relaxation elements and expectation values of products of system fluctuation operators is obtained, which could also be applied to study decoherence in other macroscopic systems such as Bose condensates and superconductors. A standard circuit model quantum computer involving three-state lambda system ionic qubits is considered, with qubits localised around well-separated positions via trapping potentials. The centre of mass vibrations of the qubits act as a reservoir. Coherent one and two qubit gating processes are controlled by time dependent localised classical electromagnetic fields that address specific qubits, the two qubit gating processes being facilitated by a cavity mode ancilla, which permits state interchange between qubits. With a suitable choice of parameters, it is found that the decoherence time can be made essentially independent of N.Comment: Minor revisions. To be published in J Mod Opt. One figur

Characterising the hippocampal response to perception, construction and complexity

The precise role played by the hippocampus in supporting cognitive functions such as episodic memory and future thinking is debated, but there is general agreement that it involves constructing representations comprised of numerous elements. Visual scenes have been deployed extensively in cognitive neuroscience because they are paradigmatic multi-element stimuli. However, questions remain about the specificity and nature of the hippocampal response to scenes. Here, we devised a paradigm in which we had participants search pairs of images for either colour or layout differences, thought to be associated with perceptual or spatial constructive processes respectively. Importantly, images depicted either naturalistic scenes or phase-scrambled versions of the same scenes, and were either simple or complex. Using this paradigm during functional MRI scanning, we addressed three questions: 1. Is the hippocampus recruited specifically during scene processing? 2. If the hippocampus is more active in response to scenes, does searching for colour or layout differences influence its activation? 3. Does the complexity of the scenes affect its response? We found that, compared to phase-scrambled versions of the scenes, the hippocampus was more responsive to scene stimuli. Moreover, a clear anatomical distinction was evident, with colour detection in scenes engaging the posterior hippocampus whereas layout detection in scenes recruited the anterior hippocampus. The complexity of the scenes did not influence hippocampal activity. These findings seem to align with perspectives that propose the hippocampus is especially attuned to scenes, and its involvement occurs irrespective of the cognitive process or the complexity of the scenes

Segmenting subregions of the human hippocampus on structural magnetic resonance image scans: An illustrated tutorial

BACKGROUND: The hippocampus plays a central role in cognition, and understanding the specific contributions of its subregions will likely be key to explaining its wide-ranging functions. However, delineating substructures within the human hippocampus in vivo from magnetic resonance image scans is fraught with difficulties. To our knowledge, the extant literature contains only brief descriptions of segmentation procedures used to delineate hippocampal subregions in magnetic resonance imaging/functional magnetic resonance imaging studies. // METHODS: Consequently, here we provide a clear, step-by-step and fully illustrated guide to segmenting hippocampal subregions along the entire length of the human hippocampus on 3T magnetic resonance images. // RESULTS: We give a detailed description of how to segment the hippocampus into the following six subregions: dentate gyrus/Cornu Ammonis 4, CA3/2, CA1, subiculum, pre/parasubiculum and the uncus. Importantly, this in-depth protocol incorporates the most recent cyto- and chemo-architectural evidence and includes a series of comprehensive figures which compare slices of histologically stained tissue with equivalent 3T images. // CONCLUSION: As hippocampal subregion segmentation is an evolving field of research, we do not suggest this protocol is definitive or final. Rather, we present a fully explained and expedient method of manual segmentation which remains faithful to our current understanding of human hippocampal neuroanatomy. We hope that this 'tutorial'-style guide, which can be followed by experts and non-experts alike, will be a practical resource for clinical and research scientists with an interest in the human hippocampus

A controlled trial of natalizumab for relapsing multiple sclerosis.

Background: In patients with multiple sclerosis, inflammatory brain lesions appear to arise from autoimmune responses involving activated lymphocytes and monocytes. The glycoprotein (alpha)(sub 4) integrin is expressed on the surface of these cells and plays a critical part in their adhesion to the vascular endothelium and migration into the parenchyma. Natalizumab is an (alpha)(sub 4) integrin antagonist that reduced the development of brain lesions in experimental models and in a preliminary study of patients with multiple sclerosis.Methods: In a randomized, double-blind trial, we randomly assigned a total of 213 patients with relapsing-remitting or relapsing secondary progressive multiple sclerosis to receive 3 mg of intravenous natalizumab per kilogram of body weight (68 patients), 6 mg per kilogram (74 patients), or placebo (71 patients) every 28 days for 6 months. The primary end point was the number of new brain lesions on monthly gadolinium-enhanced magnetic resonance imaging during the six-month treatment period. Clinical outcomes included relapses and self-reported well-being.Results: There were marked reductions in the mean number of new lesions in both natalizumab groups: 9.6 per patient in the placebo group, as compared with 0.7 in the group given 3 mg of natalizumab per kilogram (P<0.001) and 1.1 in the group given 6 mg of natalizumab per kilogram (P<0.001). Twenty-seven patients in the placebo group had relapses, as compared with 13 in the group given 3 mg of natalizumab per kilogram (P=0.02) and 14 in the group given 6 mg of natalizumab per kilogram (P=0.02). The placebo group reported a slight worsening in well-being (a mean decrease of 1.38 mm on a 100-mm visual-analogue scale), whereas the natalizumab groups reported an improvement (mean increase of 9.49 mm in the group given 3 mg of natalizumab per kilogram and 6.21 mm in the group given 6 mg of natalizumab per kilogram).Conclusions: In a placebo-controlled trial, treatment with natalizumab led to fewer inflammatory brain lesions and fewer relapses over a six-month period in patients with relapsing multiple sclerosis

Differences in functional connectivity along the anterior-posterior axis of human hippocampal subfields

There is a paucity of information about how human hippocampal subfields are functionally connected to each other and to neighbouring extra-hippocampal cortices. In particular, little is known about whether patterns of functional connectivity (FC) differ down the anterior-posterior axis of each subfield. Here, using high resolution structural MRI we delineated the hippocampal subfields in healthy young adults. This included the CA fields, separating DG/CA4 from CA3, separating the pre/parasubiculum from the subiculum, and also segmenting the uncus. We then used high resolution resting state functional MRI to interrogate FC. We first analysed the FC of each hippocampal subfield in its entirety, in terms of FC with other subfields and with the neighbouring regions, namely entorhinal, perirhinal, posterior parahippocampal and retrosplenial cortices. Next, we analysed FC for different portions of each hippocampal subfield along its anterior-posterior axis, in terms of FC between different parts of a subfield, FC with other subfield portions, and FC of each subfield portion with the neighbouring cortical regions of interest. We found that intrinsic functional connectivity between the subfields aligned generally with the tri-synaptic circuit but also extended beyond it. Our findings also revealed that patterns of functional connectivity between the subfields and neighbouring cortical areas differed markedly along the anterior-posterior axis of each hippocampal subfield. Overall, these results contribute to ongoing efforts to characterise human hippocampal subfield connectivity, with implications for understanding hippocampal function

Differentiable processing of objects, associations and scenes within the hippocampus

The hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive, with some theories emphasising associative processes and another proposing that scene construction is its primary role. To directly compare these accounts of hippocampal function in human males and females, we devised a novel mental imagery paradigm where different tasks were closely matched for associative processing and mental construction, but either did or did not evoke scene representations, and we combined this with high resolution functional MRI. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. The contrasting patterns of neural engagement could not be accounted for by differences in eye movements, mnemonic processing or the phenomenology of mental imagery. These results inform conceptual debates in the field by showing that the hippocampus does not seem to favour one type of process over another; it is not a story of exclusivity. Rather, there may be different circuits within the hippocampus, each associated with different cortical inputs, which become engaged depending on the nature of the stimuli and the task at hand. Overall, our findings emphasise the importance of considering the hippocampus as a heterogeneous structure, and that a focus on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition.SIGNIFICANCE STATEMENTThe hippocampus is known to be important for a range of cognitive functions including episodic memory, spatial navigation and future-thinking. Wide agreement on the exact nature of its contribution has proved elusive. Here we used a novel mental imagery paradigm and high resolution fMRI to compare accounts of hippocampal function that emphasise associative processes with a theory that proposes scene construction as a primary role. The results were striking in showing that differentiable parts of the hippocampus, along with distinct cortical regions, were recruited for scene construction or non-scene-evoking associative processing. We conclude that a greater emphasis on characterising how specific portions of the hippocampus interact with other brain regions may promote a better understanding of its role in cognition