Storage fidelity for sequence memory in the hippocampal circuit.

Episodic memories have been suggested to be represented by neuronal sequences, which are stored and retrieved from the hippocampal circuit. A special difficulty is that realistic neuronal sequences are strongly correlated with each other since computational memory models generally perform poorly when correlated patterns are stored. Here, we study in a computational model under which conditions the hippocampal circuit can perform this function robustly. During memory encoding, CA3 sequences in our model are driven by intrinsic dynamics, entorhinal inputs, or a combination of both. These CA3 sequences are hetero-associated with the input sequences, so that the network can retrieve entire sequences based on a single cue pattern. We find that overall memory performance depends on two factors: the robustness of sequence retrieval from CA3 and the circuit's ability to perform pattern completion through the feedforward connectivity, including CA3, CA1 and EC. The two factors, in turn, depend on the relative contribution of the external inputs and recurrent drive on CA3 activity. In conclusion, memory performance in our network model critically depends on the network architecture and dynamics in CA3.

Computerized positive mental imagery training versus cognitive control training versus treatment as usual in inpatient mental health settings: study protocol for a randomized controlled feasibility trial.

BACKGROUND: Enhancing the capacity to experience positive affect could help improve recovery across a range of areas of mental health. Experimental psychopathology research indicates that a computerized cognitive training paradigm involving generation of positive mental imagery can increase state positive affect, and more recent clinical studies have suggested that this training could be used as an adjunct treatment module to target symptoms related to positive affect deficits, specifically anhedonia. The current study investigates the feasibility of adding a positive mental imagery computerized training module to treatment for patients in inpatient mental health settings, with a focus on increasing positive affect and reducing anhedonia. The positive mental imagery training (PMIT) is added to treatment as usual (TAU) in the inpatient setting, and compared to TAU alone, or TAU plus an alternative cognitive training module not hypothesized to increase positive affect, cognitive control training (CCT). METHODS: The study is a feasibility randomized controlled trial with three parallel arms. Up to 90 patients admitted to inpatient mental health treatment clinics in Germany will be randomized to PMIT + TAU, CCT + TAU, or TAU on a 1:1:1 ratio. PMIT or CCT consist of an introductory session followed by up to 8 full training sessions over 2 weeks. All three arms (including TAU) include regular completion of mood measures over the 2-week period. Outcome measures are completed pre and post this 2-week training/monitoring period, and at 2-week follow-up. Data will be presented in the form of both raw means and standardized effect sizes, with 95% confidence intervals, for both intention-to-treat and per-protocol samples. DISCUSSION: The study will inform feasibility of conducting a fully powered randomized controlled trial investigating the addition of the positive mental imagery training as a treatment adjunct to inpatient treatments for mental health, including potential refinement of study procedures, inclusion/exclusion criteria, and preliminary indications of the likely range of effect sizes. TRIAL REGISTRATION: clinicaltrials.gov, NCT02958228 (date registered: 4 November 2016).

From grid cells to place cells with realistic field sizes.

While grid cells in the medial entorhinal cortex (MEC) of rodents have multiple, regularly arranged firing fields, place cells in the cornu ammonis (CA) regions of the hippocampus mostly have single spatial firing fields. Since there are extensive projections from MEC to the CA regions, many models have suggested that a feedforward network can transform grid cell firing into robust place cell firing. However, these models generate place fields that are consistently too small compared to those recorded in experiments. Here, we argue that it is implausible that grid cell activity alone can be transformed into place cells with robust place fields of realistic size in a feedforward network. We propose two solutions to this problem. Firstly, weakly spatially modulated cells, which are abundant throughout EC, provide input to downstream place cells along with grid cells. This simple model reproduces many place cell characteristics as well as results from lesion studies. Secondly, the recurrent connections between place cells in the CA3 network generate robust and realistic place fields. Both mechanisms could work in parallel in the hippocampal formation and this redundancy might account for the robustness of place cell responses to a range of disruptions of the hippocampal circuitry.

Wealth, justice and freedom: Objective and subjective measures predicting poor mental health in a study across eight countries.

BACKGROUND: Macro-level factors (MF) such as wealth, justice and freedom measured with objective country-level indicators (objective MF), for instance the Gross Domestic Product (GDP), have been investigated in relation to health and well-being, but rarely in connection with depression, anxiety and stress subsumed as poor mental health. Also, a combination of different objective MF and of how individuals perceive those MF (subjective MF) has not been taken into consideration. In the present study, we combined subjective and objective measures of wealth, justice and freedom and examined their relationship with poor mental health. METHOD: Population-based interviews were conducted in France, Germany, Poland, Russia, Spain, Sweden, U.K. and U.S.A. (n ≈ 1000 per country). GDP, GINI coefficient, Justice Index and Freedom Index were used as objective MF, whereas subjective MF were perceived wealth, justice and freedom measured at the individual level. Poor mental health was assessed as a combination of symptoms of depression, anxiety and stress. RESULTS: In a random-intercept-model, GINI coefficient and Freedom Index were significant positive country-level, and perceived wealth, justice, and freedom significant negative individual-level predictors of symptoms of poor mental health. CONCLUSION: Multiple subjective and objective MF should be combined to assess the macrosystem's relationship with poor mental health more precisely. The relationship between MF and poor mental health indicates that the macrosystem should be taken into account as relevant context for mental health problems, too.

Memory storage fidelity in the hippocampal circuit: the role of subregions and input statistics.

In the last decades a standard model regarding the function of the hippocampus in memory formation has been established and tested computationally. It has been argued that the CA3 region works as an auto-associative memory and that its recurrent fibers are the actual storing place of the memories. Furthermore, to work properly CA3 requires memory patterns that are mutually uncorrelated. It has been suggested that the dentate gyrus orthogonalizes the patterns before storage, a process known as pattern separation. In this study we review the model when random input patterns are presented for storage and investigate whether it is capable of storing patterns of more realistic entorhinal grid cell input. Surprisingly, we find that an auto-associative CA3 net is redundant for random inputs up to moderate noise levels and is only beneficial at high noise levels. When grid cell input is presented, auto-association is even harmful for memory performance at all levels. Furthermore, we find that Hebbian learning in the dentate gyrus does not support its function as a pattern separator. These findings challenge the standard framework and support an alternative view where the simpler EC-CA1-EC network is sufficient for memory storage.