Identifying Unmet Needs in Major Depressive Disorder Using a Computer-Assisted Alternative to Conventional Thematic Analysis: Qualitative Interview Study With Psychiatrists.

BACKGROUND: The development of digital health tools that are clinically relevant requires a deep understanding of the unmet needs of stakeholders, such as clinicians and patients. One way to reveal unforeseen stakeholder needs is through qualitative research, including stakeholder interviews. However, conventional qualitative data analytical approaches are time-consuming and resource-intensive, rendering them untenable in many industry settings where digital tools are conceived of and developed. Thus, a more time-efficient process for identifying clinically relevant target needs for digital tool development is needed. OBJECTIVE: The objective of this study was to address the need for an accessible, simple, and time-efficient alternative to conventional thematic analysis of qualitative research data through text analysis of semistructured interview transcripts. In addition, we sought to identify important themes across expert psychiatrist advisor interview transcripts to efficiently reveal areas for the development of digital tools that target unmet clinical needs. METHODS: We conducted 10 (1-hour-long) semistructured interviews with US-based psychiatrists treating major depressive disorder. The interviews were conducted using an interview guide that comprised open-ended questions predesigned to (1) understand the clinicians' experience of the care management process and (2) understand the clinicians' perceptions of the patients' experience of the care management process. We then implemented a hybrid analytical approach that combines computer-assisted text analyses with deductive analyses as an alternative to conventional qualitative thematic analysis to identify word combination frequencies, content categories, and broad themes characterizing unmet needs in the care management process. RESULTS: Using this hybrid computer-assisted analytical approach, we were able to identify several key areas that are of interest to clinicians in the context of major depressive disorder and would be appropriate targets for digital tool development. CONCLUSIONS: A hybrid approach to qualitative research combining computer-assisted techniques with deductive techniques provides a time-efficient approach to identifying unmet needs, targets, and relevant themes to inform digital tool development. This can increase the likelihood that useful and practical tools are built and implemented to ultimately improve health outcomes for patients.

Opportunities for digital health technology: identifying unmet needs for bipolar misdiagnosis and depression care management.

Introduction: Digital health technologies (DHTs) driven by artificial intelligence applications, particularly those including predictive models derived with machine learning methods, have garnered substantial attention and financial investment in recent years. Yet, there is little evidence of widespread adoption and scant proof of gains in patient health outcomes. One factor of this paradox is the disconnect between DHT developers and digital health ecosystem stakeholders, which can result in developing technologies that are highly sophisticated but clinically irrelevant. Here, we aimed to uncover challenges faced by psychiatrists treating patients with major depressive disorder (MDD). Specifically, we focused on challenges psychiatrists raised about bipolar disorder (BD) misdiagnosis. Methods: We conducted semi-structured interviews with 10 United States-based psychiatrists. We applied text and thematic analysis to the resulting interview transcripts. Results: Three main themes emerged: (1) BD is often misdiagnosed, (2) information crucial to evaluating BD is often occluded from clinical observation, and (3) BD misdiagnosis has important treatment implications. Discussion: Using upstream stakeholder engagement methods, we were able to identify a narrow, unforeseen, and clinically relevant problem. We propose an organizing framework for development of digital tools based upon clinician-identified unmet need.

Why do mothers never stop grieving for their deceased children? Enduring alterations of brain connectivity and function.

A child's death is a profound loss for mothers and affects hundreds of thousands of women. Mothers report inconsolable and progressive grief that is distinct from depression and impacts daily emotions and functions. The brain mechanisms responsible for this relatively common and profound mental health problem are unclear, hampering its clinical recognition and care. In an initial exploration of this condition, we used resting state functional MRI (fMRI) scans to examine functional connectivity in key circuits, and task-based fMRI to examine brain network activity in grieving mothers in response to pictures of their deceased child and as well as recognizable deceased celebrities and unfamiliar individuals. We compared nine mothers who had lost an adult child and aged-matched control mothers with a living child of a similar age. Additionally, we collected diffusion imaging scans to probe structural connectivity and complemented the imaging studies with neuropsychological assessments. Increased functional activation in Ventral Attention/Salience Networks accompanied by a reduced activation in the medial prefrontal cortex in response to the deceased child's picture robustly distinguished the grieving mothers from controls. Heightened resting-state functional connectivity between the paraventricular thalamic nucleus (PVT) and the amygdala distinguished the grieving mothers from the controls and correlated with subjective grief severity. Structurally, maternal grief and its severity were associated with alterations in corticolimbic white matter tracts. Finally, grieving mothers performed worse than controls on neuropsychological tests of learning, memory, and executive function, linked with grief severity. Reduced activation in cortical regions inhibiting emotions and changes in the PVT circuitry-a region involved in long-term emotional memories and decision making under conflict-distinguish grieving mothers from controls. Notably, the magnitude of neurobiological changes correlates with the subjective severity of grief. Together, these new discoveries delineate a prevalent and under-recognized mental health syndrome and chart a path for its appreciation and care.

Distinct stress-related changes in intrinsic amygdala connectivity predict subsequent positive and negative memory performance.

Experiencing stress before an event can influence how that event is later remembered. In the current study, we examine how individual differences in one's physiological response to a stressor are related to changes to underlying brain states and memory performance. Specifically, we examined how changes in intrinsic amygdala connectivity relate to positive and negative memory performance as a function of stress response, defined as a change in cortisol. Twenty-five participants underwent a social stressor before an incidental emotional memory encoding task. Cortisol samples were obtained before and after the stressor to measure individual differences in stress response. Three resting state scans (pre-stressor, post-stressor/pre-encoding and post-encoding) were conducted to evaluate pre- to post-stressor and pre- to post-encoding changes to intrinsic amygdala connectivity. Analyses examined relations between greater cortisol changes and connectivity changes. Greater cortisol increases were associated with a greater decrease in prefrontal-amygdala connectivity following the stressor and a reversal in the relation between prefrontal-amygdala connectivity and negative vs. positive memory performance. Greater cortisol increases were also associated with a greater increase in amygdala connectivity with a number of posterior sensory regions following encoding. Consistent with prior findings in non-stressed individuals, pre- to post-encoding increases in amygdala-posterior connectivity were associated with greater negative relative to positive memory performance, although this was specific to lateral rather than medial posterior regions and to participants with the greatest cortisol changes. These findings suggest that stress response is associated with changes in intrinsic connectivity that have downstream effects on the valence of remembered emotional content.

Latent anxiety in clinical depression is associated with worse recognition of emotional stimuli.

BACKGROUND: Major Depressive Disorder, characterized by cognitive affective biases, is a considerable public health challenge. Past work has shown that higher depressive symptoms are associated with augmented memory of negative stimuli. In contrast, anxiety symptoms have been associated with overgeneralization of emotional memories. Given the high comorbidity of depression and anxiety, it is critical to understand how cognitive affective biases are differentially associated with clinical symptoms. METHOD: We used continuous measures of depression (Beck Depression Inventory [BDI-II]) and anxiety (Beck Anxiety Inventory [BAI]) to evaluate an adult sample (N = 79; 18-41 years old, 58 female). Emotional memory discrimination and recognition memory were tested using an emotional discrimination task. We applied exploratory factor analysis to questions from the BAI and BDI-II to uncover latent constructs consisting of negative affect, anhedonia, somatic anxiety, and cognitive anxiety. RESULTS: We report evidence that anxious symptoms were associated with impaired recognition of negative items after accounting for age and sex. Our exploratory factor analysis revealed that impaired negative item recognition is largely associated with somatic and cognitive anxiety factors. LIMITATIONS: Interpretations in a mixed pathology sample, especially given collinearity among factors, may be difficult. CONCLUSIONS: We provide evidence that somatic and cognitive anxiety are related to impaired recognition memory for negative stimuli. Future clinical investigations should uncover the neurobiological basis supporting the link between recognition of negative stimuli and somatic/cognitive symptoms of anxiety.

Slow oscillation-spindle coupling is negatively associated with emotional memory formation following stress.

Both stress and sleep enhance emotional memory. They also interact, with the largest effect of sleep on emotional memory being seen when stress occurs shortly before or after encoding. Slow wave sleep (SWS) is critical for long-term episodic memory, facilitated by the temporal coupling of slow oscillations and sleep spindles. Prior work in humans has shown these associations for neutral information in non-stressed participants. Whether coupling interacts with stress to facilitate emotional memory formation is unknown. Here, we addressed this question by reanalyzing an existing dataset of 64 individuals. Participants underwent a psychosocial stressor (32) or comparable control (32) prior to the encoding of 150-line drawings of neutral, positive, and negative images. All participants slept overnight with polysomnography, before being given a surprise memory test the following day. In the stress group, time spent in SWS was positively correlated with memory for images of all valences. Results were driven by those who showed a high cortisol response to the stressor, compared to low responders. The amount of slow oscillation-spindle coupling during SWS was negatively associated with neutral and emotional memory in the stress group only. The association with emotional memory was significantly stronger than for neutral memory within the stress group. These results suggest that stress around the time of initial memory formation impacts the relationship between slow wave sleep and memory.

Corrigendum: Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI.

[This corrects the article DOI: 10.3389/fnint.2021.662293.].

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI.

The paraventricular thalamic nucleus (PVT) is a small but highly connected nucleus of the dorsal midline thalamus. The PVT has garnered recent attention as a context-sensitive node within the thalamocortical arousal system that modulates state-dependent motivated behaviors. Once considered related to generalized arousal responses with non-specific impacts on behavior, accumulating evidence bolsters the contemporary view that discrete midline thalamic subnuclei belong to specialized corticolimbic and corticostriatal circuits related to attention, emotions, and cognition. However, the functional connectivity patterns of the human PVT have yet to be mapped. Here, we combined high-quality, high-resolution 7T and 3T resting state MRI data from 121 young adult participants from the Human Connectome Project (HCP) and thalamic subnuclei atlas masks to investigate resting state functional connectivity of the human PVT. The 7T results demonstrated extensive positive functional connectivity with the brainstem, midbrain, ventral and dorsal medial prefrontal cortex (mPFC), anterior and posterior cingulate, ventral striatum, hippocampus, and amygdala. These connections persist upon controlling for functional connectivity of the rest of the thalamus. Whole-brain contrasts provided further evidence that, compared to three nearby midline thalamic subnuclei, functional connectivity of the PVT is strong with the hippocampus, amygdala, ventral and dorsal mPFC, and middle temporal gyrus. These findings suggest that, even during rest, the human PVT is functionally coupled with many regions known to be structurally connected to rodent and non-human primate PVT. Further, cosine similarity analysis results suggested the PVT is integrated into the default mode network (DMN), an intrinsic connectivity network associated with episodic memory and self-referential thought. The current work provides a much-needed foundation for ongoing and future work examining the functional roles of the PVT in humans.

Support for an inhibitory model of word retrieval.

Word retrieval may involve an inhibitory process in which a target word is activated and related words are suppressed. In the current functional magnetic resonance imaging (fMRI) study, we examined the inhibition of language processing cortex by the left dorsolateral prefrontal cortex (DLPFC) during word retrieval using an anagram-solving paradigm. Participants were presented with a distractor that was read aloud followed by a to-be-solved anagram. Distractor types were defined relative to orthographic overlap with the subsequent anagram solution and included related words with one letter different (e.g., "gripe" for the anagram of "price"), related pseudo-words, and unrelated words (i.e., all five letters were different). The anagram solution reaction time was slower in both the related word and related pseudo-word distractor conditions as compared to the unrelated word distractor condition, which can be attributed to greater inhibition following related distractors. The contrast of related words and unrelated words produced one activation in the left DLPFC, a region that has been associated with memory inhibition. To identify the regions that were negatively correlated with activity in the left DLPFC for related distractors, we conducted a functional connectivity analysis between this left DLPFC region and the rest of the brain. We found negatively correlated activity between the DLPFC and language processing cortex for the related word distractor condition (and the related pseudo-word distractor condition at a relaxed threshold). These findings suggest that that the left DLPFC may inhibit related word (and pseudo-word) representations in language processing cortex.

Comparing the Impact of COVID-19-Related Social Distancing on Mood and Psychiatric Indicators in Sexual and Gender Minority (SGM) and Non-SGM Individuals.

Empirical evidence demonstrates mental health disparities between sexual and gender minority individuals (SGM) compared with cisgender heterosexual individuals. SGM individuals report elevated rates of emotional distress, symptoms related to mood and anxiety disorders, self-harm, and suicidal ideation and behavior. Social support is inversely related to psychiatric symptoms, regardless of SGM status. The COVID-19 pandemic-with its associated limited social interactions-represents an unprecedented period of acute distress with potential reductions in accessibility of social support, which might be of particular concern for SGM individuals' mental well-being. In the present study, we explored the extent to which potential changes in mental health outcomes (depressive symptoms, worry, perceived stress, positive and negative affect) throughout the duration of the pandemic were related to differences in perceptions of social support and engagement in virtual social activity, as a function of SGM status. Utilizing a large sample of US adults (N = 1,014; 18% reported SGM status), we assessed psychiatric symptoms, perceptions of social isolation, and amount of time spent socializing virtually at 3 time windows during the pandemic (between March 21 and May 21). Although SGM individuals reported greater levels of depression compared with non-SGM individuals at all 3 time points, there was no interaction between time and SGM status. Across all participants, mental health outcomes improved across time. Perceived social isolation was associated with poorer mental health outcomes. Further, time spent engaging in virtual socialization was associated with reduced depression, but only for those in self-reported quarantine. We discuss these results in terms of the nature of our sample and its impact on the generalizability of these findings to other SGM samples as well as directions for future research aimed at understanding potential health disparities in the face of the COVID-19 pandemic.

Interactive effects of stress reactivity and rapid eye movement sleep theta activity on emotional memory formation.

Sleep and stress independently enhance emotional memory consolidation. In particular, theta oscillations (4-7 Hz) during rapid eye movement (REM) sleep increase coherence in an emotional memory network (i.e., hippocampus, amygdala, and prefrontal cortex) and enhance emotional memory. However, little is known about how stress during learning might interact with subsequent REM theta activity to affect emotional memory. In the current study, we examined whether the relationship between REM theta activity and emotional memory differs as a function of pre-encoding stress exposure and reactivity. Participants underwent a psychosocial stressor (the Trier Social Stress Task; n = 32) or a comparable control task (n = 32) prior to encoding. Task-evoked cortisol reactivity was assessed by salivary cortisol rise from pre- to post-stressor, and participants in the stress condition were additionally categorized as high or low cortisol responders via a median split. During incidental encoding, participants studied 150 line drawings of negative, neutral, and positive images, followed by the complete color photo. All participants then slept overnight in the lab with polysomnographic recording. The next day, they were given a surprise recognition memory task. Results showed that memory was better for emotional relative to neutral information. Critically, these findings were observed only in the stress condition. No emotional memory benefit was observed in the control condition. In stressed participants, REM theta power significantly predicted memory for emotional information, specifically for positive items. This relationship was observed only in high cortisol responders. For low responders and controls, there was no relationship between REM theta and memory of any valence. These findings provide evidence that elevated stress at encoding, and accompanying changes in neuromodulators such as cortisol, may interact with theta activity during REM sleep to promote selective consolidation of emotional information.

Forgotten but not gone: FMRI evidence of implicit memory for negative stimuli 24 hours after the initial study episode.

Endel Tulving conducted pioneering work on the explicit and implicit memory systems and demonstrated that priming effects can be long-lasting. It is also well-established that emotion can amplify explicit and implicit memory. Prior work has utilized repetition suppression (RS) of the fMRI-BOLD signal-a reduction in the magnitude of activity over repeated presentations of stimuli-to index implicit memory. Using an explicit recognition memory paradigm, we examined emotional modulation of long-term implicit memory effects as revealed by repetition suppression (i.e., comparing second-exposure forgotten items to first-exposure correct rejections). Forty-seven participants incidentally encoded line-drawings of negative, positive, and neutral scenes followed by the full color image. Twenty-four hours later, participants underwent fMRI during a recognition memory test in which old and new line-drawings were presented. Implicit and explicit memory effects were defined by the contrasts of New-Correct Rejections > Old-Misses and Old-Hits > New-Correct Rejections, respectively. Wide-spread Negative RS was found in frontal and occipito-temporal cortex that was greater than Neutral RS in the right orbito-frontal cortex and inferior frontal gyri. Valence-specific Negative RS, compared to Positive RS, was observed in the left inferior occipital gyrus. There was no strong evidence for emotional modulation of amygdala RS, but functional connectivity analyses revealed valence-specificity: Negative and positive valence were associated with repetition suppression and repetition enhancement of amygdala-occipital connectivity, respectively. Negative implicit memory patterns in most frontal regions-but not occipital areas-overlapped with explicit memory effects. Thus, implicit memory effects for a single visual stimulus presentation are modulated by emotional valence, can be observed 24hours after initial exposure, and show some overlap with explicit memory.

Physiological arousal and visuocortical connectivity predict subsequent vividness of negative memories.

Relative to neutral memories, negative and positive memories both exhibit an increase in memory longevity, subjective memory re-experiencing and amygdala activation. These memory enhancements are often attributed to shared influences of arousal on memory. Yet, prior work suggests the intriguing possibility that arousal affects memory networks in valence-specific ways. Psychophysics work has shown that arousal-related heart rate deceleration (HRD) responses are related to enhanced amygdala-visual functional connectivity (AVFC) and visual perception of negative stimuli. However, in the memory realm, it is not known whether the effect of AVFC influences subsequent negative memory outcomes as a function of the magnitude of physiological arousal during encoding. Using psycho-autonomic interaction analyses and trial-level measures of HRD as an objective measure of arousal during encoding of emotional stimuli, our findings suggest that the magnitude of the HRD modulates the effect of AVFC on subsequent negative memory vividness. Specifically, AVFC effects in early visual regions predicted negative memory vividness, not neutral or positive vividness, but only in the presence of heightened physiological arousal. This novel approach was grounded in a replication of prior working showing enhanced HRD effects in the insula for negative stimuli. These findings demonstrate that the effect of arousal on emotional memory networks depends on valence and provide further evidence that negative valence may enhance the incorporation of visuo-sensory regions into emotional memory networks.

Post-Encoding Amygdala-Visuosensory Coupling Is Associated with Negative Memory Bias in Healthy Young Adults.

The amygdala is well documented as the critical nexus of emotionally enhanced memory, yet its role in the creation of negative memory biases, better memory for negative compared with positive stimuli, has not been clarified. Although prior work suggests valence-specific effects at the moment of "online" encoding and retrieval, with enhanced visuosensory processes supporting negative memories in particular, here we tested the novel hypothesis that the amygdala engages with distant cortical regions after encoding in a manner that predicts inter-individual differences in negative memory biases in humans. Twenty-nine young adults (males and females) were scanned while they incidentally encoded negative, neutral, and positive scenes, each preceded by a line-drawing sketch of the scene. Twenty-four hours later, participants were scanned during an Old/New recognition memory task with only the line-drawings presented as retrieval cues. We replicated and extended our prior work, showing that enhanced online visuosensory recapitulation supports negative memory. Critically, resting-state scans flanked the encoding task, allowing us to show for the first time that individual differences in "off-line" increases in amygdala resting-state functional connectivity (RSFC) immediately following encoding relate to negative and positive memory bias at test. Specifically, post-encoding increases in amygdala RSFC with visuosensory and frontal regions were associated with the degree of negative and positive memory bias, respectively. These findings provide new evidence that valence-specific negative memory biases can be linked to the way that sensory processes are integrated into amygdala-centered emotional memory networks.SIGNIFICANCE STATEMENT Decades of research has placed the amygdala at the center of the emotional memory network. Despite the clinical importance of disproportionate memory for negative compared with positive events, it is not known whether post-encoding increases in amygdala-cortical coupling, possibly reflective of early consolidation processes, bear any influence on the degree or direction of such emotional memory biases. We demonstrate that, across participants, increases in post-encoding amygdala coupling with visuosensory and frontal regions are associated with more pronounced negative and positive memory biases, respectively. These findings provide the first evidence linking post-encoding amygdala modulation to the degree of negative or positive memory bias, emphasizing the need for valence-based accounts of the amygdala's role in emotional memory.

Breathe Easy EDA: A MATLAB toolbox for psychophysiology data management, cleaning, and analysis.

Electrodermal activity (EDA) recordings are widely used in experimental psychology to measure skin conductance responses (SCRs) that reflect sympathetic nervous system arousal. However, irregular respiration patterns and deep breaths can cause EDA fluctuations that are difficult to distinguish from genuine arousal-related SCRs, presenting a methodological challenge that increases the likelihood of false positives in SCR analyses. Thus, it is crucial to identify respiration-related artifacts in EDA data. Here we developed a novel and freely distributed MATLAB toolbox, Breathe Easy EDA (BEEDA). BEEDA is a flexible toolbox that facilitates EDA visual inspection, allowing users to identify and eliminate respiration artifacts. BEEDA further includes functionality for EDA data analyses (measuring tonic and phasic EDA components) and reliability analyses for artifact identification. The toolbox is suitable for any experiment recording both EDA and respiration data, and flexibly adjusts to experiment-specific parameters (e.g., trial structure and analysis parameters).

NEVER forget: negative emotional valence enhances recapitulation.

A hallmark feature of episodic memory is that of "mental time travel," whereby an individual feels they have returned to a prior moment in time. Cognitive and behavioral neuroscience methods have revealed a neurobiological counterpart: Successful retrieval often is associated with reactivation of a prior brain state. We review the emerging literature on memory reactivation and recapitulation, and we describe evidence for the effects of emotion on these processes. Based on this review, we propose a new model: Negative Emotional Valence Enhances Recapitulation (NEVER). This model diverges from existing models of emotional memory in three key ways. First, it underscores the effects of emotion during retrieval. Second, it stresses the importance of sensory processing to emotional memory. Third, it emphasizes how emotional valence - whether an event is negative or positive - affects the way that information is remembered. The model specifically proposes that, as compared to positive events, negative events both trigger increased encoding of sensory detail and elicit a closer resemblance between the sensory encoding signature and the sensory retrieval signature. The model also proposes that negative valence enhances the reactivation and storage of sensory details over offline periods, leading to a greater divergence between the sensory recapitulation of negative and positive memories over time. Importantly, the model proposes that these valence-based differences occur even when events are equated for arousal, thus rendering an exclusively arousal-based theory of emotional memory insufficient. We conclude by discussing implications of the model and suggesting directions for future research to test the tenets of the model.

Repetition Enhancement of Amygdala and Visual Cortex Functional Connectivity Reflects Nonconscious Memory for Negative Visual Stimuli.

Most studies using a recognition memory paradigm examine the neural processes that support the ability to consciously recognize past events. However, there can also be nonconscious influences from the prior study episode that reflect repetition suppression effects-a reduction in the magnitude of activity for repeated presentations of stimuli-that are revealed by comparing neural activity associated with forgotten items to correctly rejected novel items. The present fMRI study examined the effect of emotional valence (positive vs. negative) on repetition suppression effects. Using a standard recognition memory task, 24 participants viewed line drawings of previously studied negative, positive, and neutral photos intermixed with novel line drawings. For each item, participants made an old-new recognition judgment and a sure-unsure confidence rating. Collapsed across valence, repetition suppression effects were found in ventral occipital-temporal cortex and frontal regions. Activity levels in the majority of these regions were not modulated by valence. However, repetition enhancement of the amygdala and ventral occipital-temporal cortex functional connectivity reflected nonconscious memory for negative items. In this study, valence had little effect on activation patterns but had a larger effect on functional connectivity patterns that were markers of nonconscious memory. Beyond memory and emotion, these findings are relevant to other cognitive and social neuroscientists that utilize fMRI repetition effects to investigate perception, attention, social cognition, and other forms of learning and memory.

Effect of emotional valence on retrieval-related recapitulation of encoding activity in the ventral visual stream.

While prior work has shown greater retrieval-related reactivation in the ventral visual stream for emotional stimuli compared to neutral stimuli, the effects of valence on retrieval-related recapitulation of successful encoding processes (Dm effects) have yet to be investigated. Here, seventeen participants (aged 19-35) studied line drawings of negative, positive, or neutral images followed immediately by the complete photo. After a 20-min delay, participants performed a challenging recognition memory test, distinguishing the studied line drawing outlines from novel ones. First, results replicated earlier work by demonstrating that negative and positive hits elicited greater ventral occipito-temporal cortex (VOTC) activity than neutral hits during both encoding and retrieval. Moreover, the amount of activation in portions of the VOTC correlated with the magnitude of participants' emotional memory enhancement. Second, results revealed significant retrieval-related recapitulation of Dm effects (Hits>Misses) in VOTC (anterior inferior temporal gyri) only for negative stimuli. Third, connectivity between the amygdala and fusiform gyrus during the encoding of negative stimuli increased the likelihood of fusiform activation during successful retrieval. Together, these results suggest that recapitulation in posterior VOTC reflects memory for the affective dimension of the stimuli (Emotional Hits>Neutral Hits) and the magnitude of activation in some of these regions is related to superior emotional memory. Moreover, for negative stimuli, recapitulation in more anterior portions of the VOTC is greater for remembered than forgotten items. The current study offers new evidence for effects of emotion on recapitulation of activity and functional connectivity in support of memory.

Sleep disturbances, TBI and PTSD: Implications for treatment and recovery.

Post-Traumatic Stress Disorder (PTSD), traumatic brain injury (TBI), and sleep problems significantly affect recovery and functional status in military personnel and Veterans returning from combat. Despite recent attention, sleep is understudied in the Veteran population. Few treatments and rehabilitation protocols target sleep, although poor sleep remains at clinical levels and continues to adversely impact functioning even after the resolution of PTSD or mild TBI symptoms. Recent developments in non-pharmacologic sleep treatments have proven efficacious as stand-alone interventions and have potential to improve treatment outcomes by augmenting traditional behavioral and cognitive therapies. This review discusses the extensive scope of work in the area of sleep as it relates to TBI and PTSD, including pathophysiology and neurobiology of sleep; existing and emerging treatment options; as well as methodological issues in sleep measurements for TBI and PTSD. Understanding sleep problems and their role in the development and maintenance of PTSD and TBI symptoms may lead to improvement in overall treatment outcomes while offering a non-stigmatizing entry in mental health services and make current treatments more comprehensive by helping to address a broader spectrum of difficulties.