The intersection between the oculomotor and hippocampal memory systems: empirical developments and clinical implications

Decades of cognitive neuroscience research has shown that where we look is intimately connected to what we remember. In this article, we review findings from human and nonhuman animals, using behavioral, neuropsychological, neuroimaging, and computational modeling methods, to show that the oculomotor and hippocampal memory systems interact in a reciprocal manner, on a moment- to- moment basis, mediated by a vast structural and functional network. Visual exploration serves to efficiently gather information from the environment for the purpose of creating new memories, updating existing memories, and reconstructing the rich, vivid details from memory. Conversely, memory increases the efficiency of visual exploration. We call for models of oculomotor control to consider the influence of the hippocampal memory system on the cognitive control of eye movements, and for models of hippocampal and broader medial temporal lobe function to consider the influence of the oculomotor system on the development and expression of memory. We describe eye movement- based applications for the detection of neurodegeneration and delivery of therapeutic interventions for mental health disorders for which the hippocampus is implicated and memory dysfunctions are at the forefront.Decades of cognitive neuroscience research has shown that where we look is intimately connected to what we remember. In this article, we review findings from human and nonhuman animals, using behavioral, neuropsychological, neuroimaging, and computational modeling methods, to show that the oculomotor and hippocampal memory systems interact in a reciprocal manner, on a moment- to- moment basis, mediated by a vast structural and functional network.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154644/1/nyas14256_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154644/2/nyas14256.pd

Examining the Roles of Thalamocortical and Frontoparietal Circuitry for Working Memory in the Rat

Working memory (WM) is the cognitive capacity for short-term maintenance and manipulation of stimuli and goals for the purpose of guiding behaviour. Research in primates has indicated that WM relies on a large network including the prefrontal cortex, various posterior cortical areas, and subcortical nuclei. However, the circuit mapping of WM in rodents is incomplete as it pertains to the specific involvement of thalamocortical and frontoparietal circuitry across WM tasks. In this dissertation, I present the findings of three sets of experiments using two different rodent WM tasks: The odour span task (OST), an incrementing delayed non-matching-to-sample task using odours, and; the Trial-Unique Non-matching-to-Location (TUNL) task, a touchscreen-based visuospatial delayed non-matching-to-sample task. 1) I found evidence that the OST relies on a thalamocortical circuit connecting the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (mdThal). Moreover, the mPFC and mdThal played dissociable roles in the foraging element of the OST, with mdThal inactivation causing a dramatic reduction in exploratory motor activity. 2) I examined the role of the PPC in the OST and found that it is not necessary for OST performance. 3) I found that the PPC is critical for TUNL, confirming that the rodent PPC plays an essential role in visuospatial WM. Additionally, I found that TUNL is independent of NMDA signalling in the PPC and instead depends only on AMPA/Kainate receptors in contrast to previous research showing an important role for NMDA receptors in WM. Overall, the results indicate that thalamocortical and frontoparietal pathways are differentially involved across WM tasks, with frontoparietal circuitry being more sensory modality-specific than thalamocortical circuitry

Search-Related Suppression of Hippocampus and Default Network Activity during Associative Memory Retrieval

Episodic memory retrieval involves the coordinated interaction of several cognitive processing stages such as mental search, access to a memory store, associative re-encoding, and post-retrieval monitoring. The neural response during memory retrieval is an integration of signals from multiple regions that may subserve supportive cognitive control, attention, sensory association, encoding, or working memory functions. It is particularly challenging to dissociate contributions of these distinct components to brain responses in regions such as the hippocampus, which lies at the interface between overlapping memory encoding and retrieval, and “default” networks. In the present study, event-related functional magnetic resonance imaging (fMRI) and measures of memory performance were used to differentiate brain responses to memory search from subcomponents of episodic memory retrieval associated with successful recall. During the attempted retrieval of both poorly and strongly remembered word pair associates, the hemodynamic response was negatively deflected below baseline in anterior hippocampus and regions of the default network. Activations in anterior hippocampus were functionally distinct from those in posterior hippocampus and negatively correlated with response times. Thus, relative to the pre-stimulus period, the hippocampus shows reduced activity during intensive engagement in episodic memory search. Such deactivation was most salient during trials that engaged only pre-retrieval search processes in the absence of successful recollection or post-retrieval processing. Implications for interpretation of hippocampal fMRI responses during retrieval are discussed. A model is presented to interpret such activations as representing modulation of encoding-related activity, rather than retrieval-related activity. Engagement in intensive mental search may reduce neural and attentional resources that are otherwise tonically devoted to encoding an individual’s stream of experience into episodic memory

Functional Connectivity in Tactile Object Discrimination—A Principal Component Analysis of an Event Related fMRI-Study

BACKGROUND: Tactile object discrimination is an essential human skill that relies on functional connectivity between the neural substrates of motor, somatosensory and supramodal areas. From a theoretical point of view, such distributed networks elude categorical analysis because subtraction methods are univariate. Thus, the aim of this study was to identify the neural networks involved in somatosensory object discrimination using a voxel-based principal component analysis (PCA) of event-related functional magnetic resonance images. METHODOLOGY/PRINCIPAL FINDINGS: Seven healthy, right-handed subjects aged between 22 and 44 years were required to discriminate with their dominant hand the length differences between otherwise identical parallelepipeds in a two-alternative forced-choice paradigm. Of the 34 principal components retained for analysis according to the 'bootstrapped' Kaiser-Guttman criterion, t-tests applied to the subject-condition expression coefficients showed significant mean differences between the object presentation and inter-stimulus phases in PC 1, 3, 26 and 32. Specifically, PC 1 reflected object exploration or manipulation, PC 3 somatosensory and short-term memory processes. PC 26 evinced the perception that certain parallelepipeds could not be distinguished, while PC 32 emerged in those choices when they could be. Among the cerebral regions evident in the PCs are the left posterior parietal lobe and premotor cortex in PC 1, the left superior parietal lobule (SPL) and the right cuneus in PC 3, the medial frontal and orbitofrontal cortex bilaterally in PC 26, and the right intraparietal sulcus, anterior SPL and dorsolateral prefrontal cortex in PC 32. CONCLUSIONS/SIGNIFICANCE: The analysis provides evidence for the concerted action of large-scale cortico-subcortical networks mediating tactile object discrimination. Parallel to activity in nodes processing object-related impulses we found activity in key cerebral regions responsible for subjective assessment and validation

Contributions of episodic retrieval and mentalizing to autobiographical thought: Evidence from functional neuroimaging, resting-state connectivity, and fMRI meta-analyses

A growing number of studies suggest the brain's "default network" becomes engaged when individuals recall their personal past or simulate their future. Recent reports of heterogeneity within the network raise the possibility that these autobiographical processes comprised of multiple component processes, each supported by distinct functional-anatomic subsystems. We previously hypothesized that a medial temporal subsystem contributes to autobiographical memory and future thought by enabling individuals to retrieve prior information and bind this information into a mental scene. Conversely, a dorsal medial subsystem was proposed to support social-reflective aspects of autobiographical thought, allowing individuals to reflect on the mental states of one's self and others (i.e. "mentalizing"). To test these hypotheses, we first examined activity in the default network subsystems as participants performed two commonly employed tasks of episodic retrieval and mentalizing. In a subset of participants, relationships among task-evoked regions were examined at rest, in the absence of an overt task. Finally, large-scale fMRI meta-analyses were conducted to identify brain regions that most strongly predicted the presence of episodic retrieval and mentalizing, and these results were compared to meta-analyses of autobiographical tasks. Across studies, laboratory-based episodic retrieval tasks were preferentially linked to the medial temporal subsystem, while mentalizing tasks were preferentially linked to the dorsal medial subsystem. In turn, autobiographical tasks engaged aspects of both subsystems. These results suggest the default network is a heterogeneous brain system whose subsystems support distinct component processes of autobiographical thought

Quantification of neural substrates of vergence system via fMRI

Vergence eye movement is one of the oculomotor systems which allow depth perception via disconjugate movement of the eyes. Neuroimaging methods such as functional magnetic resonance imaging (fMRI) measure neural activity changes activity in the brain while subjects perform experimental tasks. A rich body of primate investigations on vergence is already established in the neurophysiology literature; on the other hand, there are a limited number of fMRI studies on neural mechanisms behind the vergence system. The results demonstrated that vergence system shares neural sources and also shows differentiation within the boundaries of frontal eye fields (FEF) and midbrain of the brainstem in comparison to saccadic, rapid conjugate eye movements, system with application of simple tracking experiment. Functional activity within the FEF was located anterior to the saccadic functional activity (z \u3e 2.3; p \u3c 0.03). Functional activity within the midbrain was observed as a result of application of vergence task, but not for the saccade data set. The novel memory-guided vergence experiment also showed a relationship between posterior parahippocampal area and memory where two other experiments were implemented for comparison of memory load in this region. Significant percent change in the functional activity was observed for the posterior parahippocampal area. Furthermore, an increase in the interconnectivity was observed for vergence tasks via utilization of Granger-Causality Analysis. When prediction was involved the increase in the number of causal interactions was statistically significant (p\u3c 0.05). The comparison of the number of influences between prediction-evoked vergence task and simple tracking vergence task was also statistically significant for these two experimental paradigms, p \u3c 0.0001. Another result observed in this dissertation was the application of hierarchical independent component analysis from to the fronto-parietal and cerebellar components within saccade and vergence tasks. Interestingly, cerebellar component showed delayed latency in the group level signal in comparison to fronto-parietal group level signals, which was evaluated to determine why segregation existed between the components acquired from the implementation of independent component analysis. Lastly, region of interet (ROI) based analysis in comparison to global (whole) brain analysis indicated more sensitive results on frontal, parietal, brainstem and occipital areas at both individual and group levels. Overall, the purpose of this dissertation was to investigate neural control of vergence movements by 1-spatial mapping of vergence induced functional activity, 2- applying different signal processing methods to quantify neural correlates of the vergence system at causal functional connectivity, underlying sources and region of interests (ROI) based levels. It was concluded that quantification of vergence movements via fMRI can build a synergy with behavioral investigations and may also shed light on neural differentiation between healthy individuals and patients with neural dysfunctions and injuries by serving as a biomarker