Maintenance of Procedural Motor Memory across Brief Rest Periods Requires the Hippocampus.

Research on the role of the hippocampus in memory acquisition has generally focused on active learning. But to understand memory, it is at least as important to understand processes that happen offline, during both wake and sleep. In a study of patients with amnesia, we previously demonstrated that although a functional hippocampus is not necessary for the acquisition of procedural motor memory during training session, it is required for its offline consolidation during sleep. Here, we investigated whether an intact hippocampus is also required for the offline consolidation of procedural motor memory while awake. Patients with amnesia due to hippocampal damage (n = 4, all male) and demographically matched controls (n = 10, 8 males) trained on the finger tapping motor sequence task. Learning was measured as gains in typing speed and was divided into online (during task execution) and offline (during interleaved 30 s breaks) components. Amnesic patients and controls showed comparable total learning, but differed in the pattern of performance improvement. Unlike younger adults, who gain speed across breaks, both groups gained speed only while typing. Only controls retained these gains over the breaks; amnesic patients slowed down and compensated for these losses during subsequent typing. In summary, unlike their peers, whose motor performance remained stable across brief breaks in typing, amnesic patients showed evidence of impaired access to motor procedural memory. We conclude that in addition to being necessary for the offline consolidation of motor memories during sleep, the hippocampus maintains access to motor memory across brief offline periods during wake.

The Hippocampus Contributes to Temporal Discounting When Delays and Rewards Are Experienced in the Moment.

Temporal discounting (TD) represents the mental devaluation of rewards that are available after a delay. Whether the hippocampus is critical for TD remains unclear, with marked discrepancies between animal and human studies: although animals with discrete hippocampal lesions display impaired TD, human participants with similar lesions show intact performance on classic intertemporal choice tasks. A candidate explanation for this discrepancy is that delays and rewards are experienced in the moment in animal studies but tend to be hypothetical in human studies. We tested this hypothesis by examining the performance of amnesic participants with hippocampal lesions (one female, six males) on a novel experiential intertemporal choice task that used interesting photographs occluded by thick lines as rewards (Patt et al., 2021). Using a logistic function to model indifference points data, we compared performance to that on a classic intertemporal choice task with hypothetical outcomes. Participants with hippocampal lesions displayed impaired patterns of choices in the experiential task but not in the hypothetical task. Specifically, hippocampal lesions were associated with decreased amplitude of the delay-reward trade-off, with persistent choice of the delayed option despite delay increase. These results help explain previous discrepancies across animal and human studies, indicating that the hippocampus plays a critical role in temporal discounting when the outcomes of decisions are experienced in the moment, but not necessarily when they are hypothetical.SIGNIFICANCE STATEMENT Impaired temporal discounting (TD) has been related to maladaptive behaviors, including substance dependence and nonadherence to medical treatment. There is consensus that TD recruits the brain valuation network but whether the hippocampal memory system is additionally recruited remains unclear. This study examined TD in hippocampal amnesia, providing a unique opportunity to explore the role of the hippocampus in cognition. Whereas most human studies have used hypothetical outcomes, this study used a novel experiential task with real-time delays and rewards. Results demonstrated hippocampal involvement in the experiential task, but not in a classic hypothetical task administered for comparison. These findings elucidate previous discrepancies between animal and human TD studies. This reconciliation is critical as animals serve as models of human neurocognition.

Leveraging Prior Knowledge to Support Short-term Memory: Exploring the Role of the Ventromedial Prefrontal Cortex.

It is well established that the ventromedial prefrontal cortex (vmPFC) plays a critical role in memory consolidation and the retrieval of remote long-term memories. Recent evidence suggests that the vmPFC also supports rapid neocortical learning and consolidation over shorter timescales, particularly when novel events align with stored knowledge. One mechanism by which the vmPFC has been proposed to support this learning is by integrating congruent information into existing neocortical knowledge during memory encoding. An important outstanding question is whether the vmPFC also plays a critical role in linking congruent information with existing knowledge before storage in long-term memory. The current study investigated this question by testing whether lesions to the vmPFC disrupt the ability to leverage stored knowledge in support of short-term memory. Specifically, we investigated the visuospatial bootstrapping effect, the phenomenon whereby immediate verbal recall of visually presented stimuli is better when stimuli appear in a familiar visuospatial array that is congruent with prior knowledge compared with an unfamiliar visuospatial array. We found that the overall magnitude of the bootstrapping effect did not differ between patients with vmPFC lesions and controls. However, a reliable bootstrapping effect was not present in the patient group alone. Post hoc analysis of individual patient performance revealed that the bootstrapping effect did not differ from controls in nine patients but was reduced in two patients. Although mixed, these results suggest that vmPFC lesions do not uniformly disrupt the ability to leverage stored knowledge in support of short-term memory.

Imagining emotional future events in PTSD: clinical and neurocognitive correlates.

Emotional future thinking serves important functions related to goal pursuit and emotion regulation but has been scantly studied in posttraumatic stress disorder (PTSD). The current study sought to characterize emotional future thinking in PTSD and to identify clinical and neurocognitive profiles associated with potential alterations in the level of detail in narratives of imagined future events. Fifty-eight, trauma-exposed, war-zone veterans, who were classified into current PTSD, past PTSD, and no-PTSD groups, were asked to vividly imagine future events in response to positive and negative cue words occurring in the near and distant future. These narratives were scored for internal (i.e., pertaining to the main event) and external (i.e., tangential to the main event) details. Participants also performed neurocognitive tasks of generative ability, working memory, and relational verbal memory. Linear mixed modeling revealed that the current and past PTSD groups generated fewer internal details than the no-PTSD group across positive and negative cue words and across temporal proximity. Partial least squares analysis revealed that symptom severity for all PTSD clusters was inversely associated with production of internal details, albeit with the association relatively weaker for intrusion symptoms. Among the neurocognitive tasks, only relational verbal memory was associated with production of internal details. These findings suggest, as predicted, that functional avoidance may underlie reduced detail generation but also point to potential additional mechanisms to be further investigated. That future event simulation remains overgeneral even when PTSD symptoms abate highlights the importance of addressing alterations in future thinking in this population.

Hippocampal Contribution to Probabilistic Feedback Learning: Modeling Observation- and Reinforcement-based Processes.

Simple probabilistic reinforcement learning is recognized as a striatum-based learning system, but in recent years, has also been associated with hippocampal involvement. This study examined whether such involvement may be attributed to observation-based learning (OL) processes, running in parallel to striatum-based reinforcement learning. A computational model of OL, mirroring classic models of reinforcement-based learning (RL), was constructed and applied to the neuroimaging data set of Palombo, Hayes, Reid, and Verfaellie [2019. Hippocampal contributions to value-based learning: Converging evidence from fMRI and amnesia. Cognitive, Affective & Behavioral Neuroscience, 19(3), 523-536]. Results suggested that OL processes may indeed take place concomitantly to reinforcement learning and involve activation of the hippocampus and central orbitofrontal cortex. However, rather than independent mechanisms running in parallel, the brain correlates of the OL and RL prediction errors indicated collaboration between systems, with direct implication of the hippocampus in computations of the discrepancy between the expected and actual reinforcing values of actions. These findings are consistent with previous accounts of a role for the hippocampus in encoding the strength of observed stimulus-outcome associations, with updating of such associations through striatal reinforcement-based computations. In addition, enhanced negative RL prediction error signaling was found in the anterior insula with greater use of OL over RL processes. This result may suggest an additional mode of collaboration between the OL and RL systems, implicating the error monitoring network.

Episodic processes in moral decisions: Evidence from medial temporal lobe amnesia.

Theoretical accounts of moral decision making imply distinct ways in which episodic memory processes may contribute to judgments about moral dilemmas that entail high conflict between a harmful action and a greater good resulting from such action. Yet, studies examining the status of moral judgment in amnesic patients with medial temporal lobe (MTL) lesions have yielded inconsistent results. To examine whether and how episodic processes contribute to high conflict moral decisions, amnesic patients with MTL damage and control participants were asked to judge the moral acceptability of a harmful action across two conditions that differed in the framing of the moral question. We predicted that personal (but not abstract) framing would engage episodic processes involved in mental simulation, yielding a selective impairment in MTL patients in the personal framing condition. This prediction was not confirmed as neither patients nor controls were influenced by the framing of the moral question. With the exception of a patient whose lesion extended into the amygdala bilaterally, patients were less willing than controls to endorse the utilitarian option, rejecting the harmful action despite its beneficial outcome. They also rated actions as emotionally more intense than did controls. These findings suggest that episodic processes involved in mental simulation are necessary to prospectively evaluate action-outcome contingencies.

Probabilistic value learning in medial temporal lobe amnesia.

A prevailing view in cognitive neuroscience suggests that different forms of learning are mediated by dissociable memory systems, with a mesolimbic (i.e., midbrain and basal ganglia) system supporting incremental trial-and-error reinforcement learning and a hippocampal-based system supporting episodic memory. Yet, growing evidence suggests that the hippocampus may also be important for trial-and-error learning, particularly value or reward-based learning. In the present report, we use a lesion-based neuropsychological approach to clarify hippocampal contributions to such learning. Six amnesic patients with medial temporal lobe damage and a group of healthy controls were administered a simple value-based learning task involving probabilistic trial-and-error acquisition of stimulus-response-outcome (reward or none) contingencies modeled after Li et al. (Proceedings of the National Academy of Sciences , 2011, 108 (1), 55-60). As predicted, patients were significantly impaired on the task, demonstrating reduced learning of the contingencies. Our results provide further supportive evidence that the hippocampus' role in cognition extends beyond episodic memory tasks and call for further refinement of theoretical models of hippocampal functioning.

Autobiographical recall of a stressful negative event in veterans with PTSD.

Posttraumatic stress disorder (PTSD) is characterised by alterations in autobiographical memory for traumatic and non-traumatic events. Studies that focus on event construction - the ability to search for and identify a specific event - have documented overgeneral memory in PTSD. However, the quality of autobiographical memory also depends on the ability to elaborate on an event once constructed by providing additional details. In a prior study, individuals with PTSD generated as many episodic (event-specific) details as trauma-exposed controls when demands on event construction were minimized, albeit the PTSD group generated more non-episodic details. The current study sought to further characterize PTSD-related alterations in event elaboration by asking participants to describe a stressful negative event specified by the experimenter, thus minimizing event construction demands. Narratives were scored for episodic and non-episodic details and relations with measures of executive function and self-reported avoidance were examined. Compared to controls, the PTSD group generated narratives with equivalent episodic detail but greater non-episodic detail, including semantic information and repeated or extended events. Non-episodic detail generation was associated with greater avoidance but not executive functions. Elaborated non-trauma memories may be perceived as overgeneral in PTSD due to greater generation of non-episodic details, rather than diminished episodic detail.

The Human Medial Temporal Lobe Is Necessary for Remembering Durations within a Sequence of Events but Not Durations of Individual Events.

Recent interest in the role of the hippocampus in temporal aspects of cognition has been fueled, in part, by the observation of "time" cells in the rodent hippocampus-that is, cells that have differential firing patterns depending on how long ago an event occurred. Such cells are thought to provide an internal representation of elapsed time. Yet, the hippocampus is not needed for processing temporal duration information per se, at least on the order of seconds, as evidenced by intact duration judgments in rodents and humans with hippocampal damage. Rather, it has been proposed that the hippocampus may be essential for coding higher order aspects of temporal mnemonic processing, such as those needed to temporally organize a sequence of events that form an episode. To examine whether (1) the hippocampus uses duration information in the service of establishing temporal relations among events and (2) its role in memory for duration is unique to sequences, we tested amnesic patients with medial-temporal lobe damage (including the hippocampus). We hypothesized that medial-temporal lobe damage should impair the ability to remember sequential duration information but leave intact judgments about duration devoid of a sequential demand. We found that amnesics were impaired in making judgments about durations within a sequence but not in judging single durations. This impairment was not due to higher cognitive load associated with duration judgments about sequences. In convergence with rodent and human fMRI work, these findings shed light on how time coding in the hippocampus may contribute to temporal cognition.

Medial Temporal Lobe Amnesia Is Associated with a Deficit in Recovering Temporal Context.

Medial-temporal lobe (MTL) lesions are associated with severe impairments in episodic memory. In the framework of the temporal context model, the hypothesized mechanism for episodic memory is the reinstatement of a prior experienced context (i.e., "jump back in time"), which relies upon the MTL [Howard, M. W., Fotedar, M. S., Datey, A. V., & Hasselmo, M. E. The temporal context model in spatial navigation and relational learning: Toward a common explanation of medial temporal lobe function across domains. Psychological Review, 112, 75-116, 2005]. This hypothesis has proven difficult to test in amnesia because of the floor-level performance by patients in recall tasks. To circumvent this issue, in this study, we used a "looped-list" format, in which a set of verbal stimuli was presented multiple times in a consistent order. This allowed for comparison of statistical properties such as probability of first recall and lag-conditional response probability (lag-CRP) between amnesic patients and healthy controls. Results revealed that the lag-CRP, but not the probability of first recall, is altered in amnesia, suggesting a selective disruption of temporal contiguity. To further characterize the results, we fit a scale-invariant version of the temporal context model [Howard, M. W., Shankar, K. H., Aue, W. R., & Criss, A. H. A distributed representation of internal time. Psychological Review, 122, 24-53, 2015] to the probability of first recall and lag-CRP curves. The modeling results suggested that the deficit in temporal contiguity in amnesia is best described as a failure to recover temporal context. These results provide the first direct evidence for an impairment in a jump-back-in-time mechanism in patients with MTL amnesia.

The hippocampus is necessary for the consolidation of a task that does not require the hippocampus for initial learning.

During sleep, the hippocampus plays an active role in consolidating memories that depend on it for initial encoding. There are hints in the literature that the hippocampus may have a broader influence, contributing to the consolidation of memories that may not initially require the area. We tested this possibility by evaluating learning and consolidation of the motor sequence task (MST) in hippocampal amnesics and demographically matched control participants. While the groups showed similar initial learning, only controls exhibited evidence of overnight consolidation. These results demonstrate that the hippocampus can be required for normal consolidation of a task without being required for its acquisition, suggesting that the area plays a broader role in coordinating memory consolidation than has previously been assumed.

Hippocampal contributions to value-based learning: Converging evidence from fMRI and amnesia.

Recent evidence suggests that the human hippocampus-known primarily for its involvement in episodic memory-plays a role in a host of motivationally relevant behaviors, including some forms of value-based decision-making. However, less is known about the role of the hippocampus in value-based learning. Such learning is typically associated with a striatal system, yet a small number of studies, both in human and nonhuman species, suggest hippocampal engagement. It is not clear, however, whether this engagement is necessary for such learning. In the present study, we used both functional MRI (fMRI) and lesion-based neuropsychological methods to clarify hippocampal contributions to value-based learning. In Experiment 1, healthy participants were scanned while learning value-based contingencies (whether players in a "game" win money) in the context of a probabilistic learning task. Here, we observed recruitment of the hippocampus, in addition to the expected ventral striatal (nucleus accumbens) activation that typically accompanies such learning. In Experiment 2, we administered this task to amnesic patients with medial temporal lobe damage and to healthy controls. Amnesic patients, including those with damage circumscribed to the hippocampus, failed to acquire value-based contingencies, thus confirming that hippocampal engagement is necessary for task performance. Control experiments established that this impairment was not due to perceptual demands or memory load. Future research is needed to clarify the mechanisms by which the hippocampus contributes to value-based learning, but these findings point to a broader role for the hippocampus in goal-directed behaviors than previously appreciated.

Functional Brain Alterations Associated With Cognitive Control in Blast-Related Mild Traumatic Brain Injury.

OBJECTIVES: Research on the cognitive sequelae of mild traumatic brain injury (mTBI) suggests that, despite generally rapid recovery, difficulties may persist in the domain of cognitive control. The goal of this study was to examine whether individuals with chronic blast-related mTBI show behavioral or neural alterations associated with cognitive control. METHODS: We collected event-related functional magnetic resonance imaging (fMRI) data during a flanker task in 17 individuals with blast-related mTBI and 16 individuals with blast-exposure without TBI (control). RESULTS: Groups did not significantly differ in behavioral measures of cognitive control. Relative to the control group, the mTBI group showed greater deactivation of regions associated with the default mode network during the processing of errors. Additionally, error processing in the mTBI group was associated with enhanced negative coupling between the default mode network and the dorsal anterior cingulate cortex as well as the dorsolateral prefrontal cortex, regions of the salience and central executive networks that are associated with cognitive control. CONCLUSIONS: These results suggest that deactivation of default mode network regions and associated enhancements of connectivity with cognitive control regions may act as a compensatory mechanism for successful cognitive control task performance in mTBI. (JINS, 2018, 24, 662-672).

Mild traumatic brain injury is associated with reduced cortical thickness in those at risk for Alzheimer's disease.

Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance in individuals at genetic risk for Alzheimer's disease, with the caveat that the order of causal effects cannot be inferred from cross-sectional studies. These results underscore the importance of documenting head injuries even within the mild range as they may interact with genetic risk to produce negative long-term health consequences such as neurodegenerative disease.

Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults.

Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO2), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy.

COMT Val158Met polymorphism moderates the association between PTSD symptom severity and hippocampal volume.

BACKGROUND: Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume. METHODS: Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume. RESULTS: We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume. LIMITATIONS: The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both. CONCLUSION: Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.

Neuropsychological Investigations of Human Amnesia: Insights Into the Role of the Medial Temporal Lobes in Cognition.

The past 30 years of research on human amnesia has yielded important changes in our understanding of the role of the medial temporal lobes (MTL) in memory. On the one hand, this body of evidence has highlighted that not all types of memory are impaired in patients with MTL lesions. On the other hand, this research has made apparent that the role of the MTL extends beyond the domain of long-term memory, to include working memory, perception, and future thinking. In this article, we review the discoveries and controversies that have characterized this literature and that set the stage for a new conceptualization of the role of the MTL in cognition. This shift toward a more nuanced understanding of MTL function has direct relevance for a range of clinical disorders in which the MTL is implicated, potentially shaping not only theoretical understanding but also clinical practice. (JINS, 2017, 23, 732-740).

White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.

Traumatic Brain Injury as a Disorder of Brain Connectivity.

OBJECTIVES: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. METHODS: We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. RESULTS: The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. CONCLUSIONS: TBI has a negative impact on distributed brain networks that lead to behavioral disturbance.