The medial temporal lobes distinguish between within‐item and item‐context relations during autobiographical memory retrieval

During autobiographical memory retrieval, the medial temporal lobes (MTL) relate together multiple event elements, including object (within‐item relations) and context (item‐context relations) information, to create a cohesive memory. There is consistent support for a functional specialization within the MTL according to these relational processes, much of which comes from recognition memory experiments. In this study, we compared brain activation patterns associated with retrieving within‐item relations (i.e., associating conceptual and sensory‐perceptual object features) and item‐context relations (i.e., spatial relations among objects) with respect to naturalistic autobiographical retrieval. We developed a novel paradigm that cued participants to retrieve information about past autobiographical events, non‐episodic within‐item relations, and non‐episodic item‐context relations with the perceptuomotor aspects of retrieval equated across these conditions. We used multivariate analysis techniques to extract common and distinct patterns of activity among these conditions within the MTL and across the whole brain, both in terms of spatial and temporal patterns of activity. The anterior MTL (perirhinal cortex and anterior hippocampus) was preferentially recruited for generating within‐item relations later in retrieval whereas the posterior MTL (posterior parahippocampal cortex and posterior hippocampus) was preferentially recruited for generating item‐context relations across the retrieval phase. These findings provide novel evidence for functional specialization within the MTL with respect to naturalistic memory retrieval. © 2015 Wiley Periodicals, Inc.     

Structural whole‐brain covariance of the anterior and posterior hippocampus: Associations with age and memory

The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole‐brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole‐brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole‐brain covariance of the HC in addition to regional volume, in young, middle‐aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior‐specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single‐item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole‐brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age‐related alterations.     

Meta‐analytic and functional connectivity evidence from functional magnetic resonance imaging for an anterior to posterior gradient of function along the hippocampal axis

There is considerable evidence from non‐human animal studies that the anterior and posterior regions of the hippocampus have different anatomical connections and support different behavioural functions. Although there are some recent human studies using functional magnetic resonance imaging (fMRI) that have addressed this idea directly in the memory and spatial processing domains and provided support for it, there has been no broader meta‐analysis of the fMRI literature to determine if there is consistent evidence for functional dissociations in anterior and posterior hippocampus across all of the different cognitive domains in which the hippocampus participates. The purpose of this review is to address this gap in our knowledge using three approaches. One approach involved PubMed searches to identify relevant fMRI papers reporting hippocampal activation during episodic encoding and retrieval, semantic retrieval, working memory, spatial navigation, simulation/scene construction, transitive inference, and social cognition tasks. The second was to use a large meta‐analytic database (neurosynth) to find text terms and coactivation maps associated with the anterior and posterior hippocampal regions identified in the literature search. The third approach was to contrast the resting‐state functional connectivity of the anterior and posterior hippocampal regions using a publicly available database that includes a large sample of adults. These three approaches provided converging evidence that not only are cognitive processes differently distributed along the hippocampal axis, but there also are distinct areas coactivated and functionally connected with the anterior and posterior segments. This anterior/posterior distinction involving multiple cognitive domains is consistent with the animal literature and provides strong support from fMRI for the idea of functional dissociations across the long axis of the hippocampus.     

The medial temporal lobe functional connectivity patterns associated with forming different mental representations

The medial temporal lobes (MTL), and more specifically the hippocampus, are critical for forming mental representations of past experiences—autobiographical memories—and for forming other “nonexperienced” types of mental representations, such as imagined scenarios. How the MTL coordinate with other brain areas to create these different types of representations is not well understood. To address this issue, we performed a task‐based functional connectivity analysis on a previously published dataset in which fMRI data were collected as participants created different types of mental representations under three conditions. One condition required forming and relating together details from a past event (autobiographical task), another required forming and relating together details of a spatial context (spatial task) and another condition required relating together conceptual/perceptual features of an object (conceptual task). We contrasted the connectivity patterns associated with a functionally defined region in the parahippocampal cortex (PHC) and anatomically defined anterior and posterior hippocampal segments across these tasks. Examining PHC connectivity patterns revealed that the PHC seed was distinctly connected to other MTL structures during the autobiographical task, to posterior parietal regions during the spatial task and to a distributed network of regions for the conceptual task. Examining hippocampal connectivity patterns revealed that the anterior hippocampus was preferentially connected to regions of default mode network during the autobiographical task and to areas implicated in semantic processing for the conceptual task whereas the posterior hippocampus was preferentially connected to medial‐posterior regions of the brain during the spatial task. We interpret our findings as evidence that there are MTL‐guided networks for forming distinct types of mental representations that align with functional distinctions within the hippocampus.     

Development of hippocampal functional connectivity during childhood

The hippocampus is a medial temporal lobe structure involved in memory, spatial navigation, and regulation of stress responses, making it a structure critical to daily functioning. However, little is known about the functional development of the hippocampus during childhood due to methodological challenges of acquiring neuroimaging data in young participants. This is a critical gap given evidence that hippocampally‐mediated behaviors (e.g., episodic memory) undergo rapid and important changes during childhood. To address this gap, the present investigation collected resting‐state fMRI scans in 97, 4‐ to 10‐year‐old children. Whole brain seed‐based analyses of anterior, posterior, and whole hippocampal connectivity were performed to identify regions demonstrating stable (i.e., age‐controlled) connectivity profiles as well as age‐related differences in connectivity. Results reveal that the hippocampus is a highly connected structure of the brain and that most of the major components of the adult network are evident during childhood, including both unique and overlapping connectivity between anterior and posterior regions. Despite widespread age‐controlled connectivity, the strength of hippocampal connectivity with regions of lateral temporal lobes and the anterior cingulate increased throughout the studied age range. These findings have implications for future investigations of the development of hippocampally‐mediated behaviors and methodological applications for the appropriateness of whole versus segmented hippocampal seeds in connectivity analyses. Hum Brain Mapp 38:182–201, 2017. © 2016 Wiley Periodicals, Inc.     

Individualized prediction of trait narcissism from whole‐brain resting‐state functional connectivity

Narcissism is one of the most fundamental personality traits in which individuals in general population exhibit a large heterogeneity. Despite a surge of interest in examining behavioral characteristics of narcissism in the past decades, the neurobiological substrates underlying narcissism remain poorly understood. Here, we addressed this issue by applying a machine learning approach to decode trait narcissism from whole‐brain resting‐state functional connectivity (RSFC). Resting‐state functional MRI (fMRI) data were acquired for a large sample comprising 155 healthy adults, each of whom was assessed for trait narcissism. Using a linear prediction model, we examined the relationship between whole‐brain RSFC and trait narcissism. We demonstrated that the machine‐learning model was able to decode individual trait narcissism from RSFC across multiple neural systems, including functional connectivity between and within limbic and prefrontal systems as well as their connectivity with other networks. Key nodes that contributed to the prediction model included the amygdala, prefrontal and anterior cingulate regions that have been linked to trait narcissism. These findings remained robust using different validation procedures. Our findings thus demonstrate that RSFC among multiple neural systems predicts trait narcissism at the individual level.     

The role of the hippocampus in the semantic variant of primary progressive aphasia: A resting‐state fcMRI study

The goal of the study was to determine whether the semantic variant of primary progressive aphasia (svPPA) affects the intrinsic connectivity network anchored to left and right anterior hippocampus, but spares the posterior hippocampus. A resting‐state functional connectivity MRI (rs‐fcMRI) study was conducted in a group of patients with svPPA and in controls, using a seed‐to‐voxel approach. In comparison to controls, massively reduced connectivity was found in the anterior hippocampus, mainly the left one, for svPPA patients but not in the left or right posterior hippocampus. In svPPA, the anterior hippocampus showed reduced functional connectivity with regions implicated in the semantic memory network. Significant correlation was also found between the functional connectivity strength of the left anterior hippocampus and the ventromedial cortex, and performance in semantic tasks. These findings indicate that the functional disconnection of the anterior hippocampus may be a promising in vivo biomarker of svPPA and illustrate the role of this hippocampal subregion in the semantic memory system.     

From hippocampus to whole‐brain: The role of integrative processing in episodic memory retrieval

Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole‐brain networks derived from an event‐related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole‐brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole‐brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. Hum Brain Mapp 38:2242–2259, 2017. © 2017 Wiley Periodicals, Inc.     

Recognition memory is associated with altered resting‐state functional connectivity in people at genetic risk for Alzheimer's disease

The apolipoprotein E ε4 (ApoE ε4) allele not only represents the strongest single genetic risk factor for sporadic Alzheimer's disease, but also imposes independent effects on brain function in healthy individuals where it has been shown to promote subtle memory deficits and altered intrinsic functional brain network connectivity. Based on previous work showing a potential relevance of the default mode network (DMN) functional connectivity for episodic memory function, we hypothesized that the ApoE ε4 genotype would affect memory performance via modulation of the DMN. We assessed 63 healthy individuals (50–80 years old), of which 20 carried the ε4 allele. All participants underwent resting‐state functional magnetic resonance imaging (fMRI), high‐resolution 3D anatomical MRI imaging and neuropsychological assessment. Functional connectivity analysis of resting‐state activity was performed with a predefined seed region located in the left posterior cingulate cortex (PCC), a core region of the DMN. ApoE ε4 carriers performed significantly poorer than non‐carriers in wordlist recognition and cued recall. Furthermore, ε4 carriers showed increased connectivity relative to ε4 non‐carriers between the PCC seed region and left‐hemispheric middle temporal gyrus (MTG). There was a positive correlation between recognition memory scores and resting‐state connectivity in the left MTG in ε4 carriers. These results can be interpreted as compensatory mechanisms strengthening the cross‐links between DMN core areas and cortical areas involved in memory processing.     

Resting‐state functional connectivity and motor imagery brain activation

Motor imagery (MI) relies on the mental simulation of an action without any overt motor execution (ME), and can facilitate motor learning and enhance the effect of rehabilitation in patients with neurological conditions. While functional magnetic resonance imaging (fMRI) during MI and ME reveals shared cortical representations, the role and functional relevance of the resting‐state functional connectivity (RSFC) of brain regions involved in MI is yet unknown. Here, we performed resting‐state fMRI followed by fMRI during ME and MI with the dominant hand. We used a behavioral chronometry test to measure ME and MI movement duration and compute an index of performance (IP). Then, we analyzed the voxel‐matched correlation between the individual MI parameter estimates and seed‐based RSFC maps in the MI network to measure the correspondence between RSFC and MI fMRI activation. We found that inter‐individual differences in intrinsic connectivity in the MI network predicted several clusters of activation. Taken together, present findings provide first evidence that RSFC within the MI network is predictive of the activation of MI brain regions, including those associated with behavioral performance, thus suggesting a role for RSFC in obtaining a deeper understanding of neural substrates of MI and of MI ability. Hum Brain Mapp 37:3847–3857, 2016. © 2016 Wiley Periodicals, Inc.     

Functional connectivity in category‐selective brain networks after encoding predicts subsequent memory

Activity in category selective regions of the temporal and parietal lobes during encoding has been associated with subsequent memory for face and scene stimuli. Reactivation theories of memory consolidation predict that after encoding connectivity between these category‐selective regions and the hippocampus should be modulated and predict recognition memory. However, support for this proposal has been limited in humans. Here, participants completed a resting‐state functional MRI (fMRI) scan, followed by face‐ and place‐encoding tasks, followed by another resting‐state fMRI scan during which they were asked to think about the stimuli they had previously encountered. Individual differences in face recognition memory were predicted by the degree to which connectivity between face‐responsive regions of the fusiform gyrus and perirhinal cortex increased following the face‐encoding task. In contrast, individual differences in scene recognition were predicted by connectivity between the hippocampus and a scene‐selective region of the retrosplenial cortex before and after the place‐encoding task. Our results provide novel evidence for category specificity in the neural mechanisms supporting memory consolidation.     

Brain network connectivity–behavioral relationships exhibit trait‐like properties: Evidence from hippocampal connectivity and memory

Despite a growing number of studies showing relationships between behavior and resting‐state functional MRI measures of large‐scale brain network connectivity, no study to our knowledge has sought to investigate whether intrinsic connectivity–behavioral relationships are stable over time. In this study, we investigated the stability of such brain–behavior relationships at two timepoints, approximately 1 week apart. We focused on the relationship between the strength of hippocampal connectivity to posterior cingulate cortex and episodic memory performance. Our results showed that this relationship is stable across samples of a different age and reliable over two points in time. These findings provide the first evidence that the relationship between large‐scale intrinsic network connectivity and episodic memory performance is a stable characteristic that varies between individuals. © 2015 Wiley Periodicals, Inc.     

Functional connectivity of hippocampal and prefrontal networks during episodic and spatial memory based on real‐world environments

Several recent studies have compared episodic and spatial memory in neuroimaging paradigms in order to understand better the contribution of the hippocampus to each of these tasks. In the present study, we build on previous findings showing common neural activation in default network areas during episodic and spatial memory tasks based on familiar, real‐world environments (Hirshhorn et al. (2012) Neuropsychologia 50:3094–3106). Following previous demonstrations of the presence of functionally connected sub‐networks within the default network, we performed seed‐based functional connectivity analyses to determine how, depending on the task, the hippocampus and prefrontal cortex differentially couple with one another and with distinct whole‐brain networks. We found evidence for a medial prefrontal‐parietal network and a medial temporal lobe network, which were functionally connected to the prefrontal and hippocampal seeds, respectively, regardless of the nature of the memory task. However, these two networks were functionally connected with one another during the episodic memory task, but not during spatial memory tasks. Replicating previous reports of fractionation of the default network into stable sub‐networks, this study also shows how these sub‐networks may flexibly couple and uncouple with one another based on task demands. These findings support the hypothesis that episodic memory and spatial memory share a common medial temporal lobe‐based neural substrate, with episodic memory recruiting additional prefrontal sub‐networks. © 2014 Wiley Periodicals, Inc.     

Working memory‐related changes in functional connectivity persist beyond task disengagement

We examined whether altered connectivity in functional networks during working memory performance persists following conclusion of that performance, into a subsequent resting state. We conducted functional magnetic resonance imaging (fMRI) in 50 young adults during an initial resting state, followed by an N‐back working memory task and a subsequent resting state, in order to examine changes in functional connectivity within and between the default‐mode network (DMN) and the task‐positive network (TPN) across the three states. We found that alterations in connectivity observed during the N‐back task persisted into the subsequent resting state within the TPN and between the DMN and TPN, but not within the DMN. Further, both speed of working memory performance and TPN connectivity strength during the N‐back task predicted connectivity strength in the subsequent resting state. Finally, DMN connectivity measured before and during the N‐back task predicted individual differences in self‐reported inattentiveness, but this association was not found during the post‐task resting state. Together, these findings have important implications for models of how the brain recovers following effortful cognition, as well as for experimental designs using resting and task scans. Hum Brain Mapp 35:1004–1017, 2014. © 2012 Wiley Periodicals, Inc.     

Correspondent Functional Topography of the Human Left Inferior Parietal Lobule at Rest and Under Task Revealed Using Resting‐State fMRI and Coactivation Based Parcellation

The human left inferior parietal lobule (LIPL) plays a pivotal role in many cognitive functions and is an important node in the default mode network (DMN). Although many previous studies have proposed different parcellation schemes for the LIPL, the detailed functional organization of the LIPL and the exact correspondence between the DMN and LIPL subregions remain unclear. Mounting evidence indicates that spontaneous fluctuations in the brain are strongly associated with cognitive performance at the behavioral level. However, whether a consistent functional topographic organization of the LIPL during rest and under task can be revealed remains unknown. Here, they used resting‐state functional connectivity (RSFC) and task‐related coactivation patterns separately to parcellate the LIPL and identified seven subregions. Four subregions were located in the supramarginal gyrus (SMG) and three subregions were located in the angular gyrus (AG). The subregion‐specific networks and functional characterization revealed that the four anterior subregions were found to be primarily involved in sensorimotor processing, movement imagination and inhibitory control, audition perception and speech processing, and social cognition, whereas the three posterior subregions were mainly involved in episodic memory, semantic processing, and spatial cognition. The results revealed a detailed functional organization of the LIPL and suggested that the LIPL is a functionally heterogeneous area. In addition, the present study demonstrated that the functional architecture of the LIPL during rest corresponds with that found in task processing. Hum Brain Mapp 38:1659–1675, 2017. © 2017 Wiley Periodicals, Inc.     

Delineating functional segregations of the human middle temporal gyrus with resting‐state functional connectivity and coactivation patterns

Although the middle temporal gyrus (MTG) has been parcellated into subregions with distinguished anatomical connectivity patterns, whether the structural topography of MTG can inform functional segregations of this area remains largely unknown. Accumulating evidence suggests that the brain's underlying organization and function can be directly and effectively delineated with resting‐state functional connectivity (RSFC) by identifying putative functional boundaries between cortical areas. Here, RSFC profiles were used to explore functional segregations of the MTG and defined four subregions from anterior to posterior in two independent datasets, which showed a similar pattern with MTG parcellation scheme obtained using anatomical connectivity. The functional segregations of MTG were further supported by whole brain RSFC, coactivation, and specific RFSC, and coactivation mapping. Furthermore, the fingerprint with predefined 10 networks and functional characterizations of each subregion using meta‐analysis also identified functional distinction between subregions. The specific connectivity analysis and functional characterization indicated that the bilateral most anterior subregions mainly participated in social cognition and semantic processing; the ventral middle subregions were involved in social cognition in left hemisphere and auditory processing in right hemisphere; the bilateral ventro‐posterior subregions participated in action observation, whereas the left subregion was also involved in semantic processing; both of the dorsal subregions in superior temporal sulcus were involved in language, social cognition, and auditory processing. Taken together, our findings demonstrated MTG sharing similar structural and functional topographies and provide more detailed information about the functional organization of the MTG, which may facilitate future clinical and cognitive research on this area.     

Broca’s region: linking human brain functional connectivity data and non‐human primate tracing anatomy studies

Brodmann areas 6, 44 and 45 in the ventrolateral frontal cortex of the left hemisphere of the human brain constitute the anterior language production zone. The anatomical connectivity of these areas with parietal and temporal cortical regions was recently examined in an autoradiographic tract‐tracing study in the macaque monkey. Studies suggest strong correspondence between human resting state functional connectivity (RSFC) based on functional magnetic resonance imaging data and experimentally demonstrated anatomical connections in non‐human primates. Accordingly, we hypothesized that areas 6, 44 and 45 of the human brain would exhibit patterns of RSFC consistent with patterns of anatomical connectivity observed in the macaque. In a primary analysis, we examined the RSFC associated with regions‐of‐interest placed in ventrolateral frontal areas 6, 44 and 45, on the basis of local sulcal and gyral anatomy. We validated the results of the primary hypothesis‐driven analysis with a data‐driven partitioning of ventrolateral frontal cortex into regions exhibiting distinct RSFC patterns, using a spectral clustering algorithm. The RSFC of ventrolateral frontal areas 6, 44 and 45 was consistent with patterns of anatomical connectivity shown in the macaque. We observed a striking dissociation between RSFC for the ventral part of area 6 that is involved in orofacial motor control and RSFC associated with Broca’s region (areas 44 and 45). These findings indicate rich and differential RSFC patterns for the ventrolateral frontal areas controlling language production, consistent with known anatomical connectivity in the macaque brain, and suggest conservation of connectivity during the evolution of the primate brain.     

Connectome‐based model predicts individual differences in propensity to trust

Trust constitutes a fundamental basis of human society and plays a pivotal role in almost every aspect of human relationships. Although enormous interest exists in determining the neuropsychological underpinnings of a person's propensity to trust utilizing task‐based fMRI; however, little progress has been made in predicting its variations by task‐free fMRI based on whole‐brain resting‐state functional connectivity (RSFC). Here, we combined a one‐shot trust game with a connectome‐based predictive modeling approach to predict propensity to trust from whole‐brain RSFC. We demonstrated that individual variations in the propensity to trust were primarily predicted by RSFC rooted in the functional integration of distributed key nodes—caudate, amygdala, lateral prefrontal cortex, temporal–parietal junction, and the temporal pole—which are part of domain‐general large‐scale networks essential for the motivational, affective, and cognitive aspects of trust. We showed, further, that the identified brain‐behavior associations were only evident for trust but not altruistic preferences and that propensity to trust (and its underlying neural underpinnings) were modulated according to the extent to which a person emphasizes general social preferences (i.e., horizontal collectivism) rather than general risk preferences (i.e., trait impulsiveness). In conclusion, the employed data‐driven approach enables to predict propensity to trust from RSFC and highlights its potential use as an objective neuromarker of trust impairment in mental disorders.     

Cardiorespiratory fitness predicts effective connectivity between the hippocampus and default mode network nodes in young adults

Rodent and human studies examining the relationship between aerobic exercise, brain structure, and brain function indicate that the hippocampus (HC), a brain region critical for episodic memory, demonstrates striking plasticity in response to exercise. Beyond the hippocampal memory system, human studies also indicate that aerobic exercise and cardiorespiratory fitness (CRF) are associated with individual differences in large‐scale brain networks responsible for broad cognitive domains. Examining network activity in large‐scale resting‐state brain networks may provide a link connecting the observed relationships between aerobic exercise, hippocampal plasticity, and cognitive enhancement within broad cognitive domains. Previously, CRF has been associated with increased functional connectivity of the default mode network (DMN), specifically in older adults. However, how CRF relates to the magnitude and directionality of connectivity, or effective connectivity, between the HC and other DMN nodes remains unknown. We used resting‐state fMRI and conditional Granger causality analysis (CGCA) to test the hypothesis that CRF positively predicts effective connectivity between the HC and other DMN nodes in healthy young adults. Twenty‐six participants (ages 18–35 years) underwent a treadmill test to determine CRF by estimating its primary determinant, maximal oxygen uptake (V^.O_2max), and a 10‐min resting‐state fMRI scan to examine DMN effective connectivity. We identified the DMN using group independent component analysis and examined effective connectivity between nodes using CGCA. Linear regression analyses demonstrated that CRF significantly predicts causal influence from the HC to the ventromedial prefrontal cortex, posterior cingulate cortex, and lateral temporal cortex and to the HC from the dorsomedial prefrontal cortex. The observed relationship between CRF and hippocampal effective connectivity provides a link between the rodent literature, which demonstrates a relationship between aerobic exercise and hippocampal plasticity, and the human literature, which demonstrates a relationship between aerobic exercise and CRF and the enhancement of broad cognitive domains including, but not limited to, memory.     

Resting state functional connectivity of the hippocampus associated with neurocognitive function in left temporal lobe epilepsy

The majority of patients with temporal lobe epilepsy (TLE) experience disturbances of episodic memory from structural damage or dysfunction of the hippocampus. The objective of this study was to use functional Magnetic Resonance Imaging (fMRI) to identify regions where resting state connectivity to the left hippocampus (LH) is correlated with neuropsychological measures of verbal memory retention in TLE patients. Eleven left TLE (LTLE) patients and 15 control subjects participated in resting state fMRI scans. All LTLE patients underwent neuropsychological testing. Resting state functional connectivity maps to the LH were calculated for each patient, and subsequently used in a multiple regression analysis with verbal memory retention scores as a covariate. The analysis identified brain regions whose connectivity to the LH was linearly related to memory retention scores across the group of patients. In LTLE patients, right sided (contralateral) clusters in the precuneus and inferior parietal lobule (IPL) exhibited increased connectivity to the LH with increased memory retention score; left sided (ipsilateral) regions in the precuneus and IPL showed increased connectivity to the LH with decreased retention score. Patients with high memory retention scores had greater connectivity between the LH–right parietal clusters than between the LH–left parietal clusters; in contrast, control subjects had significantly and consistently greater LH–left hemisphere than LH–right hemisphere connectivity. Our results suggest that increased connectivity in contralateral hippocampal functional pathways within the episodic verbal memory network represents a strengthening of alternative pathways in LTLE patients with strong verbal memory retention abilities. Hum Brain Mapp 35:735–744, 2014. © 2012 Wiley Periodicals, Inc.