21 Clinical Trials for Various Conditions
This project represents a unique collaborative opportunity to pursue the essential proof-of-principle demonstration that non-invasive interference of sensory cortical memory consolidation shortly after an emotional experience can attenuate the cued fear response and potentially reduce the risk of developing post-traumatic stress disorder (PTSD). If successful, the study results would anchor a potential advance in the treatment of patients after a traumatic event and seed future animal and clinical studies of emotional sensory cortical memory consolidation to reduce the prevalence and negative sequelae of PTSD.
The goal of the proposed project is to identify the impact vagal activity during sleep for memory formation. Nearly 100 years of research contends that sleep plays a critical role in memory consolidation (i.e. the transformation of recent experiences into stable, long-term memories), yet much of this literature has focused on the central nervous system and technologies like electroencephalography (EEG) to unpack neural correlates involved in memory processing. Sleep is also a unique period of autonomic variation and an expansive literature has indicated the critical importance of the autonomic nervous system for memory formation. This project would be amongst the first to examine the autonomic nervous system during sleep as a critical, causal pathway linking sleep to memory processing. The investigators will assess the impact of non-invasive, transcutaneous vagal nerve stimulation on sleep and post-sleep memory performance. Autonomic physiology, including electrocardiography and impedance cardiography, will be gathered at baseline, before the memory task and continuously during sleep to examine vagal tone (i.e. heart rate variability) and sympathetic activation (i.e. pre-ejection period) in response to both active and sham stimulation conditions. Polysomnography will also be gathered during the nap to examine sleep architecture. The proposed research will address a critical gap in the literature by: 1) examining the causal role of the ANS for memory functioning in humans, 2) extending the current understanding of sleep's impact on memory processing, and 3) set the groundwork for novel, sleep-based interventions with the goal of improving cognitive health.
The purpose of this research study is to understand the neural mechanisms underlying long-term memory formation in older adults. Both sleep and memory decrease with age. The investigators are interested in discovering whether these two biological changes are related. This study is specifically focused on understanding what are the critical components of sleep that facilitate memory formation and are they impaired in older adults. The investigators will be using the hypnotic zolpidem, a sleep drug that has been shown to increase a specific aspect of sleep that have been shown to correlate with memory improvement in young adults. The Food and Drug Administration (FDA) have approved zolpidem for use in certain sleep disorders, specifically in the treatment of sleeplessness (i.e., insomnia). In the current study, the investigators will examine whether zolpidem (5mg), compared with placebo, increases memory-related sleep events in older adults and test the impact of these drug-related sleep changes on post-sleep memory recall. This is a research study because the investigators are using pharmacological interventions to investigate our hypotheses about memory consolidation. The investigators are not studying the efficacy of zolpidem to treat conditions for which the FDA has already approved it.
This study tests a memory-based account of atypical speech perception in adults with language-based learning disability (also known as developmental language impairment \[LI\]). One perspective regarding the its etiology considers impoverished speech sound representations to be central to the linguistic symptoms observed in LI. This project examines a potential abnormality in the process of building speech sound representations in LI. Previous work by the PI has found that sleep is important for learning speech sounds. Furthermore, different measures of speech perception (identification and discrimination), reveal distinct patterns of learning that are consistent with that of declarative and procedural memory consolidation. A division of labor by declarative and procedural memory systems in the building of speech representations may imply that problems with phonology may stem from selective weaknesses in declarative or procedural memory in predictive ways. The first project Aim is to identify the memory substrates of novel phonetic category formation. In Experiment 1, the investigators will obtain behavioral measures of declarative, procedural, and speech sound learning before and after post-training sleep in 40 typical adults and 20 adults with LI. Among typical adults, a double dissociation is predicted in which speech identification will be predicted by individual differences in declarative memory, and speech discrimination will be predicted by individual differences in procedural memory. Moreover, adults with LI are predicted to demonstrate consolidation deficits across memory types. The second project Aim is to identify the neural substrates of phonetic category formation. In Experiment 2, the investigators will obtain functional magnetic resonance (fMRI) recordings of 20 TD and 20 LI adults performing post-training identification and discrimination tasks on a trained speech contrast before and after sleep. In typical adults, a Time by Speech-task interaction is predicted. Speech identification will recruit episodic (hippocampal) information on Day 1 relative to classic regions for phonological processing on Day 2. Speech discrimination will result in a change in magnitude of activation from Days 1 and 2 in the left inferior frontal gyrus (IFG), reflecting an overnight decrease in effort. LI (n=20) is predicted to demonstrate reduced overnight change in neural activation relative to TD in both tasks.
This study will attempt to use a type of non-invasive brain stimulation technology during sleep to improve measures of sleep quality and memory in young healthy students and older adults. The type of brain stimulation is called transcranial direct current stimulation (tDCS), which uses small currents of electricity to increase or decrease the activity of specific areas of the brain.
The overarching goal of the research proposed here is to test the hypothesis (i) that the pathophysiological mechanisms of OSA lead to deterioration in sleep-dependent memory consolidation across memory systems, with the genetic marker APOε4 as a modulator, and (ii) that CPAP can reverse some or all of these measured memory deficits. In addition, we are exploring which aspects of OSA (e.g., changes in sleep architecture, measures of hypoxemia, or the EEG power spectrum) most likely impact sleep-dependent memory processing.To this end, we are using specific cognitive tasks for which sleep-dependent memory consolidation processes have previously been demonstrated by our group and others. In addition, we are carrying out quantitative EEG power spectral analyses, to delineate abnormal functioning of brain regions with more precision.
The purpose of the study is to learn how differences in learning under mildly-stressful circumstances may be changed by taking oxytocin. Oxytocin is a hormone made naturally in the body. The investigators will also examine the impact of any anxiety, depression, and stress related symptoms on learning processes.
Background: * The brain needs sleep to function normally, but the purpose of sleep is not understood. Brain activity decreases during sleep, so it may be that sleep is important to maintain, repair, or reorganize brain cells. In animals, the formation of brain proteins increases during sleep, and the same thing may happen in humans. * There is also evidence that learning and memory are helped by sleep, and that the synthesis of proteins in the brain are involved. Objectives: * To examine the formation of proteins in the brain while people are awake, deprived of sleep, and during sleep. * To look at the formation of proteins in the brain while awake or asleep and following learning a task. Eligibility: * Healthy volunteers between 18 and 28 years of age. * Volunteers must not have psychiatric, neurologic, or sleep disorders or certain types of vision problems, and must be able to undergo imaging studies. Design: * Study Part I (protein formation in waking, sleep deprivation, and sleep): * Participants will wear an actigraph (a unit to record motor activity) for 2 weeks prior to admission. * Participants will have physical and psychological examinations, along with a blood sample. * After admission participants will have three positron emission tomography (PET) scans to study protein formation and one magnetic resonance imaging (MRI) scan over the course of two days. * Participants may be asked to stay awake for as long as 20 hours and will be monitored throughout. * Participants will be able to sleep overnight after they complete the required scans and monitoring, and will be discharged the following morning. * Study Part II (protein formation in waking and sleep combined with a learning task): * Participants will wear an actigraph (a unit to record motor activity) for 2 weeks prior to admission. * Participants will have physical and psychological examinations, along with a blood sample. * After admission participants may be asked to stay awake for as long as 20 hours and will be monitored throughout. * The next morning, participants will be trained to perform a computerized visual discrimination task, and will be tested 8 hours later (after sleep or after remaining awake) on the visual discrimination task. * Some participants may have PET and MRI scans as part of the study. * Participants will be able to sleep overnight after they complete the required tests and scans, and will be discharged the following morning. * Participants will receive financial compensation for their participation in these studies.
This study will examine whether various drugs affecting sleep cycles can improve different kinds of memory.
In any given cognitive domain, representations of individual elements are not independent but are organized by means of structured relations. Representations of this underlying structure are powerful, allowing generalization and inference in novel environments. In the semantic domain, structure captures associations between different semantic features or concepts (e.g., green, wings, can fly) and is known to influence the development and deterioration of semantic knowledge. The investigators recently found that humans more easily learn novel categories that contain clusters of reliably co-occurring features, revealing an influence of structure on novel category formation. However, a critical unknown is whether learned representations of structure are closely tied to category-specific elements, or whether such representations become abstract to some extent, transformed away from the experienced features. Further, if abstract structural representations do emerge, prior work provides intriguing hints that these representations may require offline consolidation during awake rest or sleep. The investigators have developed a paradigm in which carefully designed graph structures govern the pattern of feature co-occurrences within individual categories. Here the investigators implement a "structure transfer" extension of this paradigm in order to determine whether learning one structured category facilitates learning of a second identically structured category defined by a new set of features. This facilitation would provide evidence that structure representations are abstract to some degree. Aim 1 will use these methods to evaluate whether abstract structural representations emerge immediately during learning. Aim 2 will determine whether these representations persist, or emerge, over a delay, and whether sleep-based consolidation in particular is needed. The role of replay of recent experience during sleep will be evaluated using electroencephalography (EEG) paired with closed-loop targeted memory reactivation (TMR), a technique that enables causal influence over the consolidation of recently learned information in humans. This work will inform and constrain theories of semantic learning as well as theories of structure learning and representation more broadly.
This study evaluates whether a scent applied during exposure therapy and during subsequent sleep will increase the durability of treatment effects for individuals with fear of spiders, contamination, and enclosed spaces.
Memory influences emotional well being. Research has shown that having a negative emotional bias contributes to both emotion dysregulation and depression. Conversely, reactivating positive memories has been shown to reduce stress and symptoms of depression. In young adults, sleep is widely implicated in emotional processing, including consolidation of emotional memories. Evidence suggests that aging is associated with changes in emotion, including a positive memory bias and enhanced emotional well-being. These changes have been termed the "age-related positivity effect." However, the influence of sleep on these measures has not been investigated in healthy older individuals. The objective of this research is to understand the role of sleep in emotional memory consolidation and emotional well-being across adulthood. We hypothesize that sleep contributes to the age-related positivity effect in memory and affect. Our alternative hypothesis is that age-related decreases in sleep are responsible for reduced emotional memory processing over healthy aging.
There are two specific aims for this study. Aim 1 is to test whether low-level laser therapy (LLLT) can enhance the efficacy of fear extinction training in the modification of pathological fear. Aim 2 is to investigate the efficacy of low-level laser therapy (LLLT) as a stand-alone intervention for anxiety/phobias.
Investigators will examine whether post-exposure naps can be used to strengthen therapeutic extinction memories formed during exposure therapy for extreme social anxiety. Thirty-two individuals with high levels of social anxiety, evidenced by scores of 60 or greater on the Liebowitz Social Anxiety Scale, by self-report during a clinical interview and by demonstrated enhanced psychophysiological reactivity when imagining a socially stressful scenario, will be enrolled as one of four participants in one of eight successive offerings of a validated 5-session exposure-based group treatment for extreme social anxiety. The third and fourth sessions conclude with each participant delivering a speech on a topic individually chosen to elicit significant social anxiety. Following these sessions, participants will go to the sleep laboratory where two will be given a 2-hour sleep opportunity with polysomnographic (PSG) monitoring and two will be similarly instrumented but undergo 2 hours of monitored quiet wakefulness. Before and after treatment, participants will be individually assessed for social anxiety symptoms using standardized self-report instruments and a Trier Social Stress Test (TSST) modified for continuous psychophysiological monitoring. Ambulatory monitoring of home sleep will also be obtained using actigraphy and sleep diaries. The investigators hypothesize that, post treatment, those individuals who napped will show greater questionnaire-based clinical improvement as well as lesser psychophysiological reactivity during the modified TSST compared to those who remained quietly awake. The investigators further hypothesize that characteristics of sleep quality and architecture during naps, specifically durations of total sleep, REM and slow-wave sleep, as well as REM continuity, will predict greater clinical improvement and lesser psychophysiological reactivity to the TSST in those who napped following their third and fourth therapy sessions. Positive results will provide the first proof-of-principle for sleep augmentation of exposure therapy for clinically significant extreme social anxiety.
Background: The poor prognosis and public health burden of PTSD necessitates the development of more effective and broader treatment approaches. In the etiopathogenesis of PTSD, trauma memories become ingrained into key brain areas through conditioned learning and are triggered by various situations of daily life. The brain glutamate system plays a key role in the process of trauma learning and trauma memories via long-term potentiation. Ketamine administration modulates the glutamate system and has been used in the treatment of depression and PTSD. Previous studies demonstrate that a single low dose of ketamine rapidly improves symptoms of refractory PTSD and treatment resistant depression. Unfortunately the observed response is short-lived (4-7 days, maximum up to 2 weeks) and multiple doses often produce unacceptable side effects. TIMBER (Trauma Interventions using Mindfulness Based Extinction and Reconsolidation for trauma memory) psychotherapy, is a manualized and translational mindfulness based cognitive behavioral therapy specifically designed to target trauma memories and their expressions in PTSD patients. The placebo controlled pilot study examined the efficacy of a protocol combining a single infusion of low dose ketamine (0.5mg/kg) and TIMBER psychotherapy in subjects suffering from chronic PTSD. The objective of this pilot study was to optimize and individualize treatment of chronic PTSD using a rapid, effective, trauma specific, user friendly and inexpensive approach that uses cutting edge psychopharmacological combined with novel psychotherapeutic approaches. Methodology: The randomized, double blind, placebo-controlled pilot study used a crossover design. Ten subjects with refractory PTSD were assigned to one of two arms: one arm (n=5) received combined ketamine infusion and TIMBER therapy (TIMBER-K arm) and the second (n=5) received combined placebo (normal saline) infusion and TIMBER therapy (TIMBER-P arm). All 10 subjects received a short version of TIMBER therapy after 10 minutes of onset of the infusion in which reactivation of trauma memories was initiated in a controlled manner using standardized scales and scripted narrative of the index trauma. This was followed by a standardized mindfulness based cognitive therapy module to quickly de-escalate the arousal symptoms followed by induction of detached observation and reappraisal of the trauma experience. After completion of the 40-min infusion, all subjects were trained on the full version of TIMBER therapy using methods of mindfulness based graded exposure therapy and a twice-daily schedule of home practice was initiated. The investigators are currently in a process of recruiting fifty more subjects to examine the effects in a larger sample.
Forgetting is often perceived as the inability to retain information, but in fact at least some memory deterioration is due to active suppression processes, that are behaviorally adaptive. These active processes are thought to involve new, inhibitory learning, suggesting that sleep may serve to enhance them as it does other forms of learning. If this were the case, sleep may be harnessed to weaken non-adaptive memories in a manner that may be beneficial for healthy and clinical populations suffering from memory-related symptoms of disorders such as post-traumatic stress disorder (PTSD). To test this idea, this suggested nap study will incorporate specific memories in a suppression context during sleep monitored by encephalography (EEG). First, participants will take part in an item-based directed forgetting task, in which they will be exposed to different words, immediately followed by instructions to either remember the preceding word or not. The instructions will be conveyed using two distinct odors. In fact, the purpose of this first part would be to cement the associations of these odors with the instructions. Next, in an unrelated task, participants will learn the spatial locations of images on a screen. These images will be presented along with congruent sounds (e.g., cat - meow). During a subsequent nap, some of these sounds will be unobtrusively presented along with one of the two previously learned odors or along with a novel odor. In a final spatial-location test, memory for the images whose sounds were presented along with the "forget" odor during sleep is expected to be worse than for the images that were not cued. Memory for the locations of the images whose sounds were presented with one of the two other odors during sleep are expected to improve, possibly more so for the sounds presented with the "remember" odor relative to those presented with the novel odor. If successful, these results would be a first step towards interventions that may serve to selectively weaken memory during sleep.
Memory benefits from sleep and these benefits are putatively achieved through reactivation of the neural memory trace during sleep. Studies examining the effects of reactivation commonly focus on single, isolated items - but real-life memories never exist in a vacuum. Individual memories are bound to the context (e.g., the location, time and state of mind in which they are encoded) and this context is later reinstated to recall the details related to the memory. The question of how context participated in the process of sleep reactivation has never been directly examined. This experiment will monitor brain activity during memory encoding, sleep and finally retrieval to investigate the role context plays in sleep-related memory consolidation. Monitoring will be done using functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) recordings. Participants will go through a series of training trials, in which they will have to learn to associate several small images of items or animals with a larger image of scenes - and also learn the spatial location of these smaller images on the screen. The order of the presented images and the scenes in which they are embedded will remain constant throughout training, creating a solid, consistent temporal context in which item memories will be embedded. After training, participants will receive a 90 minute nap opportunity, during which the sounds associated with specific images will be unobtrusively presented. I expect memory for the spatial location of the cued images to improve. Importantly, I hypothesize that this effect will carry over to other items associated with the same scene (i.e., embedded in the same context) and that the temporal order in which the images were learned will govern this effect. I will use the EEG and fMRI data to estimate, on the basis of neuronal pattern activity, the level of contextual reinstatement and will build on these data, in combination with the behavioral results, to model the level of contextual involvement during sleep. These results could pave the way towards a unified theory of sleep's role in memory consolidation, which would encompass computational models of context and memory as well.
The context in which memories are encoded is a major factor influencing how memories are organized. Individual memories are bound to the context (e.g., the location, time and state of mind in which they are encoded) and this context is later reinstated to recall the details related to the memory. Although the role of context has been explored with regard to memory encoding and retrieval, its role during sleep-related memory consolidation has not been explored. Memories are thought to be reactivated during sleep, subsequently benefitting from the process. This study will use encephalography (EEG) in humans to consider several competing hypotheses regarding context's role in sleep reactivation, thereby enhancing the current understanding of how reactivation of memory over sleep relates to models of context and memory. Participants will learn to associate pictures of scenes to different sounds and to smaller images of items and animals, and then learn the spatial locations of these smaller images on a grid. Crucially, for half of these scenes, the sounds themselves will then also be linked directly to some of images during training. The associated sounds will then be unobtrusively presented during sleep, in a manner that has been shown to improve associated memories. The subsequent memory benefits will reveal whether (1) all images associated with the cued scene will benefit from cuing, demonstrating a context-reactivation effect; (2) only the images directly associated with presented sound will benefit from the cuing, demonstrating a item-reactivation effect; or (3) some composite of these two models. Regardless of which hypothesis is correct, the results will expand our current understanding regarding the role context plays in sleep consolidation.
The purpose of this research study is to investigate whether minimizing interference improves memory in multiple sclerosis.
Acting adaptively requires quickly picking up on structure in the environment and storing the acquired knowledge for effective future use. Dominant theories of the hippocampus have focused on its ability to encode individual snapshots of experience, but the investigators and others have found evidence that it is also crucial for finding structure across experiences. The mechanisms of this essential form of learning have not been established. The investigators have developed a neural network model of the hippocampus instantiating the theory that one of its subfields can quickly encode structure using distributed representations, a powerful form of representation in which populations of neurons become responsive to multiple related features of the environment. The first aim of this project is to test predictions of this model using high resolution functional magnetic resonance imaging (fMRI) in paradigms requiring integration of information across experiences. The results will clarify fundamental mechanisms of how humans learn novel structure, adjudicating between existing models of this process, and informing further model development. There are also competing theories as to the eventual fate of new hippocampal representations. One view posits that during sleep, the hippocampus replays recent information to build longer-term distributed representations in neocortex. Another view claims that memories are directly and independently formed and consolidated within the hippocampus and neocortex. The second aim of this project is to test between these theories. The investigators will assess changes in hippocampal and cortical representations over time by re-scanning participants and tracking changes in memory at a one-week delay. Any observed changes in the brain and behavior across time, however, may be due to generic effects of time or to active processing during sleep. The third aim is thus to assess the specific causal contributions of sleep to the consolidation of structured information. The investigators will use real-time sleep electroencephalography to play sound cues to bias memory reactivation. The investigators expect that this work will clarify the anatomical substrates and, critically, the nature of the representations that support encoding and consolidation of novel structure in the environment.
To date, the effects of pain on motor learning have not been thoroughly investigated, particularly in older adults. Broadly, the purpose of this research is to investigate the impact of acute pain on locomotor learning and its retention in older adults. The investigators hypothesize that acute pain impairs retention of locomotor learning in young and older adults and that in older adults, these deficits are worsened and are related to the degree of normal age-related cognitive decline.