Hippocampal Memory Network Research Articles

A Semi-stochastic Numerical Model of Adult Hippocampal Neurogenesis

Adult neurogenesis in dentate gyrus (DG) is a prominent contributor in the dynamics of hippocampal memory networks. This discrete model aims to estimate the temporal changes in the neural progenitor cell (NPC) populations in DG, together with the products of differentiation – immature neurons, astrocytes and oligodendrocytes. The dynamics are described in an ideal environment, where there is no limit for the total volume and all required chemical and physical cues that direct neurogenesis are continuously available. The system works independently on three levels. Each level is defined as the dynamics in a stage of neurogenesis with three types of NPCs: type I cell (radial glia), type II cell (transiently amplifying cells) and type III cell (neuroblasts). Cell fate was introduced as a semi-stochastic process (a choice) with a population limit for each cell type. Although it is based on discrete processes and has a rather simplistic approach, the simulations successfully provide a numerical template for adult neurogenesis, which can be further modified and implemented in a hippocampal trisynaptic loop network.

Associative reinstatement memory measures hippocampal function in Parkinson's Disease

In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task – Associative Reinstatement Memory (ARM) – may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD.

Hippocampal functional connectivity and episodic memory in early childhood

Episodic memory relies on a distributed network of brain regions, with the hippocampus playing a critical and irreplaceable role. Few studies have examined how changes in this network contribute to episodic memory development early in life. The present addressed this gap by examining relations between hippocampal functional connectivity and episodic memory in 4- and 6-year-old children (n=40). Results revealed similar hippocampal functional connectivity between age groups, which included lateral temporal regions, precuneus, and multiple parietal and prefrontal regions, and functional specialization along the longitudinal axis. Despite these similarities, developmental differences were also observed. Specifically, 3 (of 4) regions within the hippocampal memory network were positively associated with episodic memory in 6-year-old children, but negatively associated with episodic memory in 4-year-old children. In contrast, all 3 regions outside the hippocampal memory network were negatively associated with episodic memory in older children, but positively associated with episodic memory in younger children. These interactions are interpreted within an interactive specialization framework and suggest the hippocampus becomes functionally integrated with cortical regions that are part of the hippocampal memory network in adults and functionally segregated from regions unrelated to memory in adults, both of which are associated with age-related improvements in episodic memory ability.

Altered intrinsic hippocmapus declarative memory network and its association with impulsivity in abstinent heroin dependent subjects

Converging evidence suggests that addiction can be considered a disease of aberrant learning and memory with impulsive decision-making. In the past decades, numerous studies have demonstrated that drug addiction is involved in multiple memory systems such as classical conditioned drug memory, instrumental learning memory and the habitual learning memory. However, most of these studies have focused on the contributions of non-declarative memory, and declarative memory has largely been neglected in the research of addiction.Based on a recent finding that hippocampus, as a core functioning region of declarative memory, was proved biased the decision-making process based on past experiences by spreading associated reward values throughout memory. Our present study focused on the hippocampus. By utilizing seed-based network analysis on the resting-state functional MRI datasets with the seed hippocampus we tested how the intrinsic hippocampal memory network altered toward drug addiction, and examined how the functional connectivity strength within the altered hippocampal network correlated with behavioral index ‘impulsivity’.Our results demonstrated that HD group showed enhanced coherence between hippocampus which represents declarative memory system and non-declarative reward-guided learning memory system, and also showed attenuated intrinsic functional link between hippocampus and top-down control system, compared to the CN group. This alteration was furthered found to have behavioral significance over the behavioral index ‘impulsivity’ measured with Barratt Impulsiveness Scale (BIS). These results provide insights into the mechanism of declarative memory underlying the impulsive behavior in drug addiction.

Structural and functional imaging of the hippocampus in young people at familial risk of depression.

Major depression is associated with abnormalities in the function and structure of the hippocampus. However, it is unclear whether these abnormalities might also be present in people 'at risk' of illness. We studied 62 young people (mean age 18.8 years) at familial risk of depression (FH+) but who had never been depressed themselves. Participants underwent magnetic resonance imaging to assess hippocampal structure and neural responses to a task designed to activate hippocampal memory networks. Magnetic resonance spectroscopy was used to measure levels of a combination of glutamine and glutamate (Glx) in the right hippocampus. A total of 59 matched controls with no history of mood disorder in a first-degree relative underwent the same investigations. Hippocampal volume did not differ between FH+ participants and controls; however, relative to controls, during the memory task, FH+ participants showed increased activation in brain regions encompassing the insular cortices, putamen and pallidum as well as the dorsal anterior cingulate cortex (ACC). FH+ participants also had increased hippocampal levels of Glx. Euthymic individuals with a parental history of depression demonstrate increased activation of hippocampal-related neural networks during a memory task, particularly in brain regions involved in processing the salience of stimuli. Changes in the activity of the ACC replicate previous findings in FH+ participants using different psychological tasks; this suggests that task-related abnormalities in the ACC may be a marker of vulnerability to depression. Increased levels of Glx in the hippocampus might also represent a risk biomarker but follow-up studies will be required to test these various possibilities.

Increased functional connectivity within memory networks following memory rehabilitation in multiple sclerosis

Identifying effective behavioral treatments to improve memory in persons with learning and memory impairment is a primary goal for neurorehabilitation researchers. Memory deficits are the most common cognitive symptom in multiple sclerosis (MS), and hold negative professional and personal consequences for people who are often in the prime of their lives when diagnosed. A 10-session behavioral treatment, the modified Story Memory Technique (mSMT), was studied in a randomized, placebo-controlled clinical trial. Behavioral improvements and increased fMRI activation were shown after treatment. Here, connectivity within the neural networks underlying memory function was examined with resting-state functional connectivity (RSFC) in a subset of participants from the clinical trial. We hypothesized that the treatment would result in increased integrity of connections within two primary memory networks of the brain, the hippocampal memory network, and the default network (DN). Seeds were placed in left and right hippocampus, and the posterior cingulate cortex. Increased connectivity was found between left hippocampus and cortical regions specifically involved in memory for visual imagery, as well as among critical hubs of the DN. These results represent the first evidence for efficacy of a behavioral intervention to impact the integrity of neural networks subserving memory functions in persons with MS.

Functional convergence of developmentally and adult‐generated granule cells in dentate gyrus circuits supporting hippocampus‐dependent memory

In the hippocampus, the production of dentate granule cells (DGCs) persists into adulthood. As adult-generated neurons are thought to contribute to hippocampal memory processing, promoting adult neurogenesis therefore offers the potential for restoring mnemonic function in the aged or diseased brain. Within this regenerative context, one key issue is whether developmentally generated and adult-generated DGCs represent functionally equivalent or distinct neuronal populations. To address this, we labeled separate cohorts of developmentally generated and adult-generated DGCs and used immunohistochemical approaches to compare their integration into circuits supporting hippocampus-dependent memory in intact mice. First, in the water maze task, rates of integration of adult-generated DGCs were regulated by maturation, with maximal integration not occurring until DGCs were five or more weeks in age. Second, these rates of integration were equivalent for embryonically, postnatally, and adult-generated DGCs. Third, these findings generalized to another hippocampus-dependent task, contextual fear conditioning. Together, these experiments indicate that developmentally generated and adult-generated DGCs are integrated into hippocampal memory networks at similar rates, and suggest a functional equivalence between DGCs generated at different developmental stages.

Stratum radiatum of CA2 is an additional target of the perforant path in humans and monkeys

The perforant path (PP) connects two key components of the medial temporal memory system, the entorhinal cortex and hippocampus. Entorhinal layer II projects densely to the outer portion of the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare of CA2 and CA3 of the hippocampus. This study for the first time reports that the PP terminal zone originated from entorhinal layer II extends from the stratum lacunosum-moleculare into the stratum radiatum in CA2 but not in CA3 in both human and nonhuman primates. This result indicates that CA2 probably receives additional innervation from the PP compared with CA3 and thus may play a unique role in hippocampal memory networks.

Inhibitory and excitatory responses of single neurons in the human medial temporal lobe during recognition of faces and objects.

The medial temporal lobe (MTL) plays a critical role in transforming complex stimuli into permanent memory traces, yet little is known on how the activity of neurons in the human brain mediates this process. Recording from single neurons in the human MTL during visual encoding and retrieval of faces and objects, we found that in the hippocampus faces evoked predominantly suppression of neuronal firing below prestimulus baseline ('inhibitory responses'). These responses were also prevalent in the entorhinal cortex but were absent in the amygdala during the first second of stimulus encoding when all responses to faces were 'excitatory' (neuronal firing increased above the prestimulus baseline). Inhibitory responses were more prevalent during recognition than encoding and were also present during processing of objects, albeit less frequently than during processing of faces. Despite the prevalence in the hippocampus of cells with inhibitory responses and their relative specificity to faces, it was mainly the activity of the cells with excitatory responses that was selective for stimulus features such as gender and emotional expression of faces. These findings suggest that a large population of cells with inhibitory responses is engaged in the hippocampal memory network, but primarily cells with excitatory responses process feature-specific information.