Medial Temporal Memory System Research Articles

Subjective Cognitive Decline Is Associated With Altered Default Mode Network Connectivity in Individuals With a Family History of Alzheimer’s Disease

BackgroundBoth subjective cognitive decline (SCD) and a family history of Alzheimer’s disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. MethodsWe studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD+). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. ResultsSixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values > .05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD+ compared with SCD− (all false discovery rate–adjusted p values < .05). When compared with SCD−, SCD+ subjects showed increased pDMN–MTMS connectivity (false discovery rate–adjusted p < .05). Higher connectivity between the MTMS and the rest of the brain was associated with better baseline immediate memory, attention, and global cognition, whereas higher MTMS and pDMN–MTMS connectivity were associated with lower immediate memory over time (all false discovery rate–adjusted p values < .05). ConclusionsSCD in cognitively normal individuals is associated with diminished immediate memory practice effects and a brain connectivity pattern that mirrors early AD-related connectivity failure.

Discrimination of a medial functional module within the temporal lobe using an effective connectivity model: A CCEP study

The temporal lobe is classically divided in two functional systems: the ventral visual pathway and the medial temporal memory system. However, their functional separation has been challenged by studies suggesting that the medial temporal lobe could be best understood as an extension of the hierarchically organized ventral visual pathway. Our purpose was to investigate (i) whether cerebral regions within the temporal lobe could be grouped into distinct functional assemblies, and (ii) which regions were central within these functional assemblies. We studied low intensity and low frequency electrical stimulations (0.5 mA, 1 Hz, 4 ms) performed during sixteen pre-surgical intracerebral EEG investigations in patients with medically intractable temporal or temporo-occipital lobe epilepsies. Eleven regions of interest were delineated per anatomical landmarks such as gyri and sulci. Effective connectivity based on electrophysiological feature (amplitude) of cortico-cortical evoked potentials (CCEPs) was evaluated and subjected to graph metrics. The amplitudes discriminated one medial module where the hippocampus could act as a signal amplifier. Mean amplitudes of CCEPs in regions of the temporal lobe showed a generalized Pareto distribution of probability suggesting neural synchronies to be self-organized critically. Our description of effective interactions within the temporal lobe provides a regional electrophysiological model of effective connectivity which is discussed in the context of the current hypothesis of pattern completion.

The medial temporal memory system in Down syndrome: Translating animal models of hippocampal compromise.

Recent studies have highlighted the dentate gyrus as a region of increased vulnerability in mouse models of Down syndrome (DS). It is unclear to what extent these findings are reflected in the memory profile of people with the condition. We developed a series of novel tasks to probe distinct medial temporal functions in children and young adults with DS, including object, spatial, and temporal order memory. Relative to mental age-matched controls (n = 45), individuals with DS (n = 28) were unimpaired on subtests involving short-term object or configural recall that was divorced from spatial or temporal contexts. By contrast, the DS group had difficulty recalling spatial locations when contextual information was salient and recalling the order in which objects were serially presented. Results are consistent with dysfunction of spatial and temporal contextual pattern separation abilities in individuals with DS, mediated by the hippocampus, including the dentate gyrus. Amidst increasing calls to bridge human and animal work, the memory profile demonstrated here in humans with DS is strikingly similar to that of the Ts65Dn mouse model of DS. The study highlights the trisynaptic circuit as a potentially fruitful intervention target to mitigate cognitive impairments associated with DS.

Comparative anatomy of the prosubiculum, subiculum, presubiculum, postsubiculum, and parasubiculum in human, monkey, and rodent

The subicular complex, including the prosubiculum (ProS), subiculum (Sub), presubiculum, postsubiculum (PoS), and parasubiculum (PaS), plays important roles in the medial temporal memory system and is heavily involved in many neurological diseases such as Alzheimer's disease and epilepsy. In the literature, the ProS (in primate) and PoS (in rodent) are inconstantly identified, making data comparison difficult across species. This review is an attempt to discuss equivalencies and extent of the five subicular components in human, monkey, and rodent based on available information on their cytoarchitecture, chemoarchitecture, molecular signature, and neural connectivity. All five subicular cortices exist in human, monkey, and rodent. In human and monkey, the ProS and Sub extend into the uncal region anteriorly, and the PoS and PaS reach the cingulate isthmus posteriorly. In rodent, most of the typical subicular cortices are located in the dorsal and caudal portions of the hippocampal formation, and the modified version of the ventral ProS and Sub corresponds to the modified description of the uncal ProS and Sub in monkey and human. An interesting triangular region in rodent located at the juncture of the PoS, PaS, retrosplenial cortex, and visual cortex appears to be the equivalent of the monkey area prostriata. Major connections of the five subicular cortices are also summarized based on unified criteria discussed in this review, with distinct connections revealed between the ProS and the Sub.

Volumetric correlates of cognitive functioning in nondemented patients with Parkinson's disease

A challenge in Parkinson's disease (PD) is to identify biomarkers of early cognitive change because functioning in some domains may be more prognostic of dementia. Few studies have investigated whether structural magnetic resonance imaging (MRI) correlates in a regionally specific manner with functioning in different cognitive domains. The aim of this study was to identify neuroanatomical correlates of executive functioning, memory, and visual cognition in PD without dementia. 3T MRI was conducted in 51 PD patients and 39 control participants. Brain volumes were measured in structures comprising the frontostriatal cognitive-control system, the medial temporal memory system, the ventral object-based system, and the dorsal spatial-based system. Measures of executive functioning (Stroop Test; Letter Fluency), memory (California Verbal Learning Test), visuospatial cognition (Judgment of Line Orientation), and visuoconstruction (Pentagon Copy) were correlated with volumes comprising each system. Poorer executive functioning largely correlated with decreased frontostriatal volumes. Poorer memory correlated with decreased volumes in all medial temporal regions, but also with frontostriatal volumes. Poorer visuospatial cognition correlated with decreased volumes in the object-based system, whereas poorer visuoconstruction correlated with decreased frontal and object-based system volumes. These relationships were nonsignificant in the control group. This is the first study to demonstrate that subtle changes in multiple cognitive domains in PD without dementia correlate with regional volumes in specific systems implicated in the development of cognitive impairment. The findings suggest that structural MRI holds promise as a marker of early changes in different brain systems, some of which may predict future cognitive deterioration.

The Cognitive Mechanism and Neural Bases of Statistical Learning*

In this review,we mainly discuss the origin and the development of statistical learning research,as well as constraints and brain neural bases of statistical learning.Researches of statistical learning originated from the studies on speech segmentation in human infants since 1990's.From then on,lots of studies have explored statistical learning on both non-linguistic continuous sound streams and visual shape sequences.Evidence from these researches suggest that statistical learning is involved in discovering and extracting regularities,and it is domain-general.However,statistical learning in different domains is constrained by domain-related factors.For example,statistical learning in language(s) is constrained by language-specific factors;while non-linguistic statistical learning is constrained by stimulus characteristics and presentation modality.In recent years,several studies have examined the temporal course of statistical learning by employing event-related potentials(ERPs) technique and investigated its neural substrates by using functional magnetic resonance imaging(fMRI) technique.ERPs studies consistently found that a negative ERP component at around 400 ms was related with the extraction of regularities,and findings of fMRI studies suggested that statistical learning mainly involved left superior temporal gyrus,right striatum and right medial temporal memory system.

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.

Anatomical Pathways for Auditory Memory in Primates

Episodic memory or the ability to store context-rich information about everyday events depends on the hippocampal formation (entorhinal cortex, subiculum, presubiculum, parasubiculum, hippocampus proper, and dentate gyrus). A substantial amount of behavioral-lesion and anatomical studies have contributed to our understanding of the organization of how visual stimuli are retained in episodic memory. However, whether auditory memory is organized similarly is still unclear. One hypothesis is that, like the “visual ventral stream” for which the connections of the inferior temporal gyrus with the perirhinal cortex are necessary for visual recognition in monkeys, direct connections between the auditory association areas of the superior temporal gyrus and the hippocampal formation and with the parahippocampal region (temporal pole, perhirinal, and posterior parahippocampal cortices) might also underlie recognition memory for sounds. Alternatively, the anatomical organization of memory could be different in audition. This alternative “indirect stream” hypothesis posits that, unlike the visual association cortex, the majority of auditory information makes one or more synapses in intermediate, polymodal areas, where they may integrate information from other sensory modalities, before reaching the medial temporal memory system. This review considers anatomical studies that can support either one or both hypotheses – focusing on anatomical studies on the primate brain, primarily in macaque monkeys, that have reported not only direct auditory association connections with medial temporal areas, but, importantly, also possible indirect pathways for auditory information to reach the medial temporal lobe memory system.

Imaging systems level consolidation of novel associate memories: A longitudinal neuroimaging study

Previously, a standard theory of systems level memory consolidation was developed to describe how memory recall becomes independent of the medial temporal memory system. More recently, an extended consolidation theory was proposed that predicts seven changes in regional neural activity and inter-regional functional connectivity. Using longitudinal event-related functional magnetic resonance imaging of an associate memory task, we simultaneously tested all predictions and additionally tested for consolidation-related changes in recall of associate memories at a sub-trial temporal resolution, analyzing cue, delay and target periods of each trial separately. Results consistent with the theoretical predictions were observed though two inconsistent results were also obtained. In particular, while medial temporal recall related delay period activity decreased with consolidation as predicted, visual cue activity increased for consolidated memories. Though the extended theory of memory consolidation is largely supported by our study, these results suggest that the extended theory needs further refinement and the medial temporal memory system has multiple, temporally distinct roles in associate memory recall. Neuroimaging analysis at a sub-trial temporal resolution, as used here, may further clarify the role of the hippocampal complex in memory consolidation.

Functional magnetic resonance imaging of verbal learning in children with heavy prenatal alcohol exposure

We examined functional MRI activation patterns corresponding to verbal paired associate learning in a group of 11 children with heavy prenatal alcohol exposure compared with 16 typically developing children. Among the typically developing children, prominent activation was observed in the left medial temporal lobe, left dorsal frontal lobe and bilateral posterior temporal cortices during learning and recall. Analyses revealed significantly less activation in left medial and posterior temporal regions and significantly more activation in right dorsal frontal cortex in the alcohol-exposed children relative to controls, even when group differences in memory test performance were statistically controlled. These results may indicate an increased reliance on frontal memory systems in the children with heavy prenatal alcohol exposure, perhaps compensating for dysfunctional medial temporal memory systems. Our findings are consistent with neuropsychological and structural imaging studies, and provide the first evidence for brain activation abnormalities, independent of group performance differences, during verbal learning and recall in children with heavy prenatal alcohol exposure.

Memory deficits for implicit contextual information in amnesic subjects with hippocampal damage.

The role of the hippocampus and adjacent medial temporal lobe structures in memory systems has long been debated. Here we show in humans that these neural structures are important for encoding implicit contextual information from the environment. We used a contextual cuing task in which repeated visual context facilitates visual search for embedded target objects. An important feature of our task is that memory traces for contextual information were not accessible to conscious awareness, and hence could be classified as implicit. Amnesic patients with medial temporal system damage showed normal implicit perceptual/skill learning but were impaired on implicit contextual learning. Our results demonstrate that the human medial temporal memory system is important for learning contextual information, which requires the binding of multiple cues.