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Conclusions: These results indicate that neural reinstatement and retrieved context may help resolve memory competition between opposing sources of emotional information.

Understanding how the human brain separately encodes and retrieves memories of fear and safety has broad implications for the study of healthy emotional memory and the neuropathophysiology of affective disorders.

Quantifying mental context reactivation could be used as an innovative measure to evaluate successful treatment in disorders marked by excessive fear and anxiety.

Background: Posttraumatic stress disorder PTSD has been associated with difficulties modulating emotion. Deficits in emotion modulation are associated with increased activation in brain regions associated with emotion processing insula, amygdala , decreased activation in emotion modulation regions regions in prefrontal cortex , and differences in connectivity within and between these emotion processing and modulation regions.

The purpose of this study was to examine neural mechanisms underlying emotion processing and modulation as predictors of PTSD treatment response.

Symptom assessment and fMRI scanning occurred before and after treatment. An additional 27 combat control CC participants were studied at pre-treatment as a baseline comparison.

There were no main effects of, or interactions with, treatment group. Differences in neural function during emotion processing and modulation were not associated with treatment drop out.

Conclusions: This study is one of the first to examine task-based activation and connectivity in a PTSD treatment trial, with evidence to suggest that the function of regions involved in emotion processing and modulation are important predictors of treatment response.

Background: Fear and avoidance are two key characteristics of anxiety disorders. Differential threat conditioning is often used to examine how individuals learn fear.

In differential threat conditioning studies, an aversive stimulus i. As a result of learning, threat responses e.

Additionally, work is needed to understand the relationship between threat learning and avoidance behavior.

Methods: Thirty adults 16 females, In the approach avoidance task, generalization stimuli, i. Individuals distinguished between two background colors via button press.

Each button pressed either enlarged the image size to mimic approach behavior or decreased the image size to mimic avoidance behavior.

Imaging data for both paradigms were modeled at the individual level. To capture variability in threat learning, bilateral amygdala activation was extracted from the threat conditioning paradigm using an anatomical mask.

These preliminary data suggest that the amygdala activation during threat learning may be an important factor in subsequent approach and avoidance behavior, which offers clinical implications for exposure-based treatments.

Background: There is a higher prevalence of depression in women than in men and there are strong sexual dimorphism in symptom manifestation and in response to antidepressant treatment.

Previously, we have shown that combination treatment to simultaneously target stress-induced peripheral inflammation and synaptic maladaptation can promote resilience in the chronic social defeat stress CSDS model for depression in male mice.

In this study, we tested its efficacy in a newly developed female mouse model of CSDS. A battery of behavioral testings including the social avoidance test, elevated plus maze test were used to evaluate the efficacy of lead compounds on depression-like phenotypes.

RNA-seq was conducted in the brain regions that are pathophysiologically associated with depression including the nucleus accumbens NAc and the prefrontal cortex PFC to assess for transcriptome changes in response to stress and treatment.

Results: We found that the combination treatment significantly attenuated depression-like behavior in female mice.

Similar to male mice, CSDS also induced peripheral inflammation in female mice as reflected by increased IL-6 production following the defeat.

In the NAc of male mice, we found genes that were significantly upregulated and genes were significantly downregulated by stress. Interestingly, we found that only 2.

We are currently conducting gene ontology of these regulated transcripts to identify top networks that are dysregulated by stress in both male and female mice.

Similar analysis is carried out in the PFC. Conclusions: Our study demonstrated that the combination therapy is also effective in attenuating depression-like phenotype in female mice.

Transcriptome profiling of NAc showed different gene regulation in response to stress in male and female and in response to treatment.

Our results point to distinction in the biological process following stress and provide novel insights into transcriptional mechanisms underlying stress-related depression between male and females.

Background: Complicated grief CG is hypothesized to include both attachment and traumatic distress symptoms, and a preliminary diagnosis has been placed in the trauma and stressor related DSM-5 category APA, Preliminary data suggest posttraumatic stress symptoms PTSS may be present across patients with CG, and not vary by whether the loss is violent or accidental in nature such as required for PTSD diagnoses Simon et al.

Much less is known about how PTSS changes with CG targeted treatment, whether this change is impacted by the nature of the death, or whether it may be necessary to target PTSS separately from grief to improve functional outcomes.

DTS total score of 40 was proposed by the developers of the scale as a cut-off for a diagnosis of PTSD, and has been frequently used as a threshold in previous studies Davidson et al.

Our primary analysis examined the adjusted mean difference from baseline in the DTS total and subscale scores i. In follow-up analyses, we investigated whether cause of death violent vs.

Results: In the full sample, the mean DTS total score at baseline was There was a general decreasing trend of mean DTS total scores over the week period with a mean adjusted reduction of There was no significant difference in change in DTS total score at week 12 by treatment group.

PLA, there was 8. Conclusions: Adults with primary CG assigned to CGT with or without medication demonstrated a significantly larger reduction in PTSS compared to pill placebo, whereas citalopram alone did not.

These data parallel findings from the primary study findings for grief Shear et al. For those who lost someone to violent death, while these data found initial support for greater PTSS reduction for combination therapy with CGT and citalopram compared to placebo, we did not find evidence for a significant benefit of combined therapy over CGT alone for CG due to violent loss.

More research is needed to fully understand the role of traumatic distress and its optimal treatment in CG. Background: Anxiety disorders are common and debilitating conditions that can be treated with cognitive behavioral therapy CBT.

Increased understanding of the neurobiological correlates of CBT may inform treatment improvements and personalization.

We sought to extend earlier work by examining the relationship between symptom changes assessed over the course of CBT treatment sessions and pre- to post-treatment neural change during an emotion regulation task.

Methods: A sample of 30 participants with panic disorder or generalized anxiety disorder completed a reappraisal-based emotion regulation task while undergoing fMRI.

During the task, participants viewed negative images and were cued to either reduce emotions using cognitive reappraisal or to maintain emotions.

This task was completed before and after completing CBT as part of a larger clinical trial ClinicalTrials. Change in neural activation was operationalized as percent signal change extracted from the ROI identified in the 3dLME analysis, i.

Results: Reduced activation in a region spanning the parahippocampal gyrus and fusiform gyrus was observed from pre- to post-treatment during periods of reducing versus maintaining emotion.

Conclusions: Results suggest that, from pre- to post-CBT, participants demonstrated downregulation of neural responses during effortful cognitive emotion regulation.

Effects were not observed in frontoparietal systems as would be hypothesized based on prior literature, suggesting that treatment-related change could occur outside of top-down control and limbic regions that are central to most models of neural functioning in anxiety disorders.

Continued work is needed to better understand how CBT affects cognitive control and memory processes that are hypothesized to support reappraisal as a strategy for emotion regulation.

In animal models circadian rhythm disruptions, such as light cycle manipulations, can cause depression and anxiety-like behaviors. However, it is unclear whether light cycle manipulations induce anxiety and depression-like behaviors through a mechanism that is dependent on the suprachiasmatic nucleus SCN , the master pacemaker in the brain.

Thus, here our goal was to directly determine if chronically dampening or shifting the neural firing rhythms of the SCN increases anxiety and depression-like behaviors by using optogenetics.

Mice were then individually housed in PiezoSleep Signal Solutions boxes to measure homecage activity rhythms, a behavioral output of the SCN.

Here we stimulated the SCN at a time late in the active phase CT21 of the mice that would be expected to advance rhythms.

Control mice received sham stimulations. Results: Unpredictable stimulation of the SCN during the dark phase dampened the amplitude of homecage activity rhythms.

Stimulating the SCN late in the active phase CT21 shortened the period of and dampened homecage activity rhythms. In mice that received optogenetic stimulation of the SCN at unpredictable times during the dark phase or late in the active phase, correlations were observed between the amplitude of homecage activity rhythms and anxiety-like behavior; indicating that dampened rhythms were correlated with increased anxiety-like behavior in stimulated mice.

We did not observe correlations between homecage activity amplitude and anxiety-like behavior in sham stimulated mice. In addition, we did not observe consistent correlations between homecage activity amplitude and depression-like behavior in the forced swim test.

Conclusions: Overall, our findings suggest that SCN neural activity rhythms directly regulate anxiety-like behavior.

Specifically, our findings thus far indicate that dampening SCN neural activity rhythms increases anxiety-like behavior. Follow-up studies will focus on whether enhancing SCN neural activity rhythms has anxiolytic effects.

Exposure therapy is hypothesized to work via the mechanisms of fear extinction learning, and considerable efforts have been made to identify ways of boosting extinction learning towards the goal of improving exposure therapy efficacy.

The role of dopaminergic signaling during the post-fear extinction consolidation window has not been investigated in PTSD, despite a growing body of data implicating dopamine as a critical mechanism underlying fear extinction learning, consolidation, and subsequent recall.

Participants completed a resting-state scan before the task and again 45 min following drug ingestion to characterize effects of L-DOPA on extinction memory neural reactivation patterns during consolidation.

Results: Both active drug groups demonstrated increased reactivation of extinction encodings in the amygdala during the post-task resting-state scan compared to placebo.

For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the mg group.

For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo.

Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network.

Conclusions: Across both SCR, neural network, and voxelwise indices of fear recall, the most robust association with L-DOPA was decreased fear responding following reinstatement.

With respect to potential acute mechanisms by which L-DOPA boosts consolidation of extinction learning, the data demonstrated increased neural reactivation of amygdala patterns engaged in response to stimulus offsets i.

The specificity of reactivations to the extinction, rather than acquisition, offset patterns is important, as it rules out an alternative explanation of these data: that L-DOPA impairs consolidation of acquisition memories rather than boosting consolidation of extinction memories.

These results from a multi-site trial suggest the potential for targeting dopaminergic signaling during the post-extinction consolidation window as a means of boosting clinical outcomes for exposure therapy in PTSD.

Future research is needed to corroborate these findings and pinpoint the specific role of dopaminergic consolidation processes on reducing fear reinstatement rather than improving fear extinction recall.

Background: Anger and aggression are common and debilitating symptoms of post-traumatic stress disorder PTSD. Although fMRI studies have identified regions underlying anger experience and expression, how these circuits interact with trauma remains unclear.

Here we performed the first study examining neural correlates of anger in patients with PTSD. Methods: Resting-state fMRI was recorded from trauma-exposed veterans age Global functional connectivity values were calculated for cortical and subcortical regions and entered into a generalized linear model comparing healthy controls, high-anger PTSD patients, and low-anger PTSD patients, while controlling for age, gender, education, IQ, PTSD severity, depression severity, and site of fMRI acquisition.

Regions with significant global connectivity differences after FDR correction were subsequently analyzed for group differences in pairwise functional connectivity.

In both regions, PTSD patients with low anger scores showed stronger global connectivity than high-anger patients, who resembled controls.

Subsequent analysis of pairwise connectivity revealed a significant association between anger levels and fronto-striatal connectivity.

Conclusions: Patients with PTSD present with varying levels of anger and aggression, and these differences are strongly associated with global connectivity and excitability in prefrontal cortex, along with changes in fronto-striatal connectivity.

These results may help pave the way for circuit-based treatments for anger in PTSD. Background: Avoidance of anxiety-provoking situations plays a central role in the maintenance of anxiety- and fear-based disorders, such as obsessive-compulsive and posttraumatic stress disorders.

The success of exposure-based psychotherapies for these disorders relies on no longer avoiding anxiety-provoking situations.

While initial fear acquisition and avoidance generalizes easily across contexts, subsequently learning to not avoid is context-bound and may not readily generalize.

The influence of context on learning is mediated by hippocampal-prefrontal connections and represents a novel target for future treatment development.

To this end, transcranial direct current stimulation tDCS targeting the prefrontal cortex may disrupt contextual encoding to subsequently facilitate generalization of avoidance-based associative learning to novel contexts.

However, prefrontal inhibition due to tDCS should also impair avoidance-based associative learning. Here we tested whether cathodal tDCS applied during a contextually-bound reversal learning task 1 acutely impaired avoidance-based associative learning, and 2 facilitated generalization of avoidance-based associative learning to a novel context indicative of reduced contextual encoding.

Methods: Fifty-seven participants 34FM; mean Selecting images A and C resulted mostly in losing points, whereas B and D resulted mostly in no points lost.

After participants successfully learned this pattern, participants started the second reversal phase.

Regardless of context, all contingencies reversed, i. Participants were asked to select the image they preferred most.

In order to test generalization of previous learning and effects of tDCS on generalization of reversal learning, no accuracy feedback was provided during this test phase.

Examination of preferences during the third phase, i. There was also no significant main effect of active vs. Moreover, this finding was prominent during context-dependent reversal, where context provided additional information indicating changing associations.

Indeed, across both groups, context-independent reversal, where no additional contextual information was provided, was more difficult than context-dependent reversal, consistent with the importance of context in associative learning.

These data support the notion that contextual information from hippocampus to prefrontal cortex can be disrupted with tDCS targeting prefrontal regions.

Moreover, the pattern of responses during the test phase in the novel i. Yet, tDCS had no effect on the generalization of learned avoidance associations regardless of the presence of contextual information.

Ultimately, these findings may provide insight into how tDCS can be combined with exposure-based psychotherapies in which contextual information and avoidance play a critical role.

Background: Social anxiety disorder SAD is one of the most common psychiatric illnesses in the world, with lifetime prevalence rates ranging from 3.

Despite ongoing clinical efforts response rates to conventional pharmacotherapies remain low, constituting a need for the investigation of new neurobiological mechanisms.

Preclinical evidence suggests that deficient signalling of the major endocannabinoid neurotransmitter, anandamide, through upregulated activity of its enzyme, fatty acid amide hydrolase FAAH , may be associated with the pathophysiology of anxiety-spectrum disorders.

Preliminary findings revealed that compared to healthy controls, individuals with SAD had a trend for Background: While selective serotonin reuptake inhibitors represent the first-line pharmacotherapy for pediatric anxiety disorders, including generalized anxiety disorder GAD , the SSRI, escitalopram, has not been systematically evaluated in adolescents with GAD.

Additionally, in pediatric anxiety disorders, there are limited data to aid clinicians in determining which patients will respond to which SSRI.

With these considerations in mind, we examined the efficacy and tolerability of escitalopram in adolescents with GAD as well as pharmacogenomic predictors of the magnitude and trajectory of escitalopram-related improvement e.

Additionally, we sought to examine the impact of CYP2C19 phenotype on escitalopram pharmacokinetics. For categorical outcomes e.

For continuous outcomes, logarithmic mixed effect models were employed to determine predicted mean outcome values at weeks 0, 1, 2, 4, 6 and 8 or early termination to examine group differences.

Mixed-effects models included indicator variables for week and treatment as fixed effects.

Each model was created with limited covariates e. The trajectory of improvement in anxiety escitalopram vs.

Vital signs, QTc and adverse events were similar in the escitalopram-treated adolescents compared to those receiving placebo. Conclusions: Consistent with most studies of SSRIs in pediatric anxiety disorders, escitalopram was superior to placebo in reducing anxiety symptoms.

In fact, the NNT 2. Pharmacogenomic variables—including pharmacodynamic and pharmacokinetic genes—influenced the trajectory and magnitude of improvement.

Finally, variation in CYP2C19 metabolism accounts for pharmacokinetic variation of escitalopram in adolescents, raising the possibility that—like in adults—CYP2C19 phenotype should be considered when dosing escitalopram.

Background: Re-experiencing symptoms are core to posttraumatic stress disorder PTSD and are often dominated by the recollection of sensory-perceptual elements of the trauma Brewin et al This phenomenology points to involvement of the thalamus, a key hub for relaying and modulating sensory information across brain networks.

In PTSD, functional activation and connectivity of the thalamus has been implicated in flashbacks and processing of trauma-related cues e.

However, less research has examined trauma re-experiencing in relation to thalamus anatomy. Moreover, despite substantial evidence that thalamic nuclei are anatomically and functionally heterogeneous, it is unknown whether re-experiencing and other symptoms of PTSD are differentially related to particular nuclei.

In this study, we examined re-experiencing symptoms in relation to volumes of thalamic nuclei implicated in sensory information processing.

We hypothesized that re-experiencing, controlling for other PTSD symptoms, would be significantly associated with volumes of the pulvinar nuclei that are involved in visual salience, of the ventroposterolateral thalamic VPL nuclei that mediate somatosensory functions, and of the lateral and medial geniculate nuclei LGN, MGN that relay primary visual and auditory information.

We also predicted that re-experiencing symptoms would not be significantly associated with the aggregate volume of remaining, predominantly non-sensory, thalamic nuclei.

Freesurfer was used to estimate volumes of thalamic nuclei and intracranial volume ICV; Iglesias et al CAPS scores were derived for current re-experiencing, anxious arousal, dysphoric arousal, emotional numbing, and active avoidance symptoms Pietrzak et al The independent variables in all four analyses were the five CAPS symptom dimensions entered as simultaneous predictors, with age and sex as covariates.

Conclusions: Re-experiencing and anxious arousal symptoms were associated with volumes of thalamic nuclei that have a central role in processing primary sensory information, as well as modulating and integrating sensory information within large-scale cortical and subcortical networks.

In a cross-sectional study, we cannot differentiate whether these correlations suggest that individual differences in thalamus volumes confer vulnerability to developing re-experiencing and hyperarousal symptoms, or whether PTSD symptoms may induce changes in the morphology of thalamic nuclei.

Overall, these results encourage further examination of specific thalamic nuclei whose functional differentiation may be mechanistically relevant to trauma intrusions in PTSD.

In mice, the output region of the ventral hippocampus, the ventral CA1 vCA1 , has direct connections to both fear and reward circuits and mediates expression of innate and learned fear as well as reward-seeking behavior.

Parvalbumin PV -expressing interneurons help regulate outputs from the vCA1, and altered functioning of this cell population has been implicated in stress models and psychiatric disease states.

In these studies, we determine the behavioral and local network activity effects of PV cell inhibition using optogenetics and immediate early gene quantification.

We also examine in vivo PV cell activity during anxiety-like and reward-seeking behaviors using calcium imaging with miniature microscopes.

Mice then freely explored various environments that included innately anxiogenic zones, fear-conditioned contexts, or palatable rewards in familiar or novel environments.

During behavioral tests, inhibitory opsins on PV cells were stimulated by timed light delivery in optogenetic experiments. For calcium imaging experiments, calcium signals from PV cells was imaged using miniaturized microscopes.

At the end of optogenetic experiments, mice explored either an open field or sucrose gustometer while light was delivered to active or control opsins.

Animals were perfused 90 minutes later and brain tissue was collected. Results: Optogenetic inhibition of vCA1 PV cells increased avoidance of innately anxiogenic environments, such as the center of an open field.

PV inhibition decreased expression of learned fear after contextual fear conditioning, as measured by decreased time spent freezing in the fearful context one day after conditioning.

When mice had access to variable sucrose concentrations, delivered in a random order and with a cue signaling the end of the intertrial interval, PV cell inhibition increased reward-seeking, as measured by decreased latency to lick the spout delivering sucrose reward.

Comparisons of PV cell inhibition effects on latency versus consumption behavior i. Conclusions: Our findings demonstrate that acute manipulation of PV interneuron activity in the vCA1 is sufficient to alter anxiety-related behavior.

Inhibiting PV interneurons would be presumed to disinhibit local excitatory pyramidal cells. Consistent with this prediction, the behavioral effects of PV inhibition in innate and learned anxiogenic conditions were in the opposite direction from the effects of optogenetically inhibiting vCA1 pyramidal cells.

Here, we show disparate effects of PV cell inhibition on innate versus learned fear expression. These studies suggest how PV cell dysfunction in the vCA1 might affect anxiety-related and reward-seeking behavior.

Background: Post-traumatic stress disorder PTSD is characterized primarily by a dysregulated fear response and memory, with some anxiety and panic episodes, depression and avoidance coping symptoms.

Current treatments are effective for some individuals but are limited for most patients. Thus, it is imperative to develop new therapeutics for the treatment of PTSD-like symptoms by understanding the pathological changes of this disaster.

However, whether PDE2 inhibition could rescue PTSD-like symptoms such as anxiety, depression and fear memory disorder are still unknown.

They were treated with Bay 0. The behavioral tests such as open field, forced swimming test, elevated plus maze, and contextual fear paradigm were conducted to determine the effects of the selective PDE2 inhibitor Bay on SPS-induced depression- and anxiety-like behavior and fear memory deficits.

All test results that yielded a P-value less than 0. Results: The results suggested that Bay increased the time spent in the center zone time, the open arm entries and time spent onto the open arms in the open field and elevated plus maze tests, which were reduced in mice subjected to SPS.

Bay also reversed SPS-induced increase in the immobility time in forced swimming test and the percentage of freezing time in the contextual fear paradigm.

Background: Internalizing disorders such as anxiety and depression are common psychiatric disorders, frequently begin in youth, and exhibit marked heterogeneity in treatment response and clinical course.

Given that symptom-based classification approaches do not align with underlying neurobiology, an alternative approach is to identify neurobiologically-informed subtypes based on brain imaging data.

Methods: We used a recently developed semi-supervised machine learning method HYDRA to delineate patterns of neurobiological heterogeneity within youth with internalizing symptoms using structural data collected at 3T from a sample of 1, youth.

Data were analyzed using generalized additive models with penalized splines to capture both linear and nonlinear developmental effects.

Age, sex, and data quality were included as covariates. Subtype 1, defined by smaller brain volumes and reduced cortical thickness, was marked by impaired cognitive performance and higher levels of psychopathology than both Subtype 2 and typically developing youth.

Using resting-state fMRI and diffusion images not considered during clustering, we found that Subtype 1 also showed reduced amplitudes of low-frequency fluctuations in fronto-limbic regions at rest and reduced fractional anisotropy in several white matter tracts.

In contrast, Subtype 2 showed intact cognitive performance, greater volume, cortical thickness, and amplitudes during rest compared to Subtype 1 and typically developing youth, despite still showing clinically significant levels of psychopathology.

Conclusions: We identified two subtypes of internalizing youth differentiated by abnormalities in brain structure, function, and white matter integrity, with one subtype showing poorer functioning across multiple domains.

Identification of biologically-grounded internalizing subtypes may assist in targeting early interventions and assessing longitudinal prognosis.

Background: Neuroticism is a heritable trait characterized by a proclivity towards anxiety, depressed mood, and stress-sensitivity.

It is correlated with severity and prognosis of a variety of psychopathological conditions, including mood, anxiety, and psychosis.

Despite its clinical significance, the neurobiological underpinnings of neuroticism are poorly understood. Whether these potential neural phenotypes are meaningfully linked to newly identified genetic contributors to this trait remains untested.

Additionally, participants were genotyped and, using data derived from a meta-analysis of GWAS studies examining neuroticism in , individuals Nagel et al, , a series of neuroticism polygenic association scores were derived using a range of p-value thresholds, and the first principal component of these scores PAS was carried forward for voxel-wise analyses within the striatum.

There were no striatal findings with [11C]NNC Conclusions: Individuals with greater polygenic risk for neuroticism may have lower presynaptic dopamine synthesis and dopamine receptor availability in regions important for mood, anxiety, and reinforcement learning, consistent with the literature on neuroticism itself, but also increased presynaptic dopamine synthesis in limbic temporal lobes.

These results lend support for associations between putative molecular foundations of neuroticism and dopamine systems in the healthy human brain and merit further study in patient populations.

While treatments like cognitive-behavioral therapy are effective at reducing overall anxiety, they are largely ineffective in reducing worry severity in older adults.

In this study we investigate the neural basis of both induction and reappraisal of worry using an in-scanner personalized worry task.

We identified several regions that were associated with worry severity and conducted an open-label treatment using intermittent theta-burst stimulation iTBS [a form of transcranial magnetic stimulation TMS ] of an identified target in 5 participants.

Based on the clinical interview with each participant, we built a participant-specific list of worry induction and worry reappraisal sentences.

These sentences one per block were presented to participants during functional magnetic resonance imaging fMRI with fixation in between blocks.

Worry induction blocks were followed either by neutral blocks control condition, included random factual sentences — e. Following each block, participants rated their worry severity After motion correction, spatial normalization to a standard anatomical space, and smoothing we conducted mass-univariate general linear modeling to model worry induction, reappraisal, and neutral blocks.

Using statistical non-parametric mapping SnPM12 , we performed a paired t-test to identify regions that were significantly more parametrically modulated during worry induction compared to worry reappraisal.

We also conducted paired t-tests to identify regions that were activated more during worry induction and reappraisal compared to neutral.

We identified several regions that had activation that increased parametrically with in-scanner worry severity.

We targeted the right supramarginal gyrus see results. Neuronavigation software was used to target the right supramarginal gyrus identified in our study.

The same regions had greater activation associated with lower in-scanner worry severity rating following worry reappraisal. Conclusions: The dACC and the temporoparietal junction showed greater activation during worry induction when participants reported higher levels of worry at the end of worry-induction blocks.

This result may indicate an increased level of affective mentalizing SMG coupled with a more sustained effort toward implicit-controlled regulation dACC in participants who exhibit higher level of worry following induction.

In contrast, the activation in these regions was greater during reappraisal if the participants reported lower levels of worry at the end of worry-reappraisal blocks.

This result may be interpreted as a marker of successful reappraisal and points toward to role of both dACC and SMG in cognitively regulating worry severity.

These results indicate potential targets for future interventions designed to alleviate severe worry in older adults e.

TMS of the TPJ seems to show potential for reducing worry-modulated activation and while not significant due to small sample sizes , there is potential for its development as a treatment for severe worry.

Background: The ability to flexibly respond to changes in the environment is critical for adaptive behavior. Reversal learning is a form of associative learning that tests the ability of an organism to change responses when contingencies are altered.

For example, conditions that were once rewarding may become threatening and vice versa. Successful reversal learning is thought to be mediated by cortico-striatal and medial temporal lobe MTL systems.

Interestingly, a previous study in patients with confirmed MTL atrophy reported specific deficits in reversal of contextual associations, but intact reversal of cue associations, independent of the outcome valence.

Reversal learning of contextual versus cue associations may rely on different components on this system; however, this has not been investigated.

Methods: 34 adults mean age Pairs of cues objects and contexts background color were presented with one of two outcomes money or bomb , and then the outcome association of either the cue or context was reversed, requiring participants to form new associations between the context or cue and outcome.

Neural activation during contextual versus cue reversal learning was compared in MTL subregions e.

Conclusions: These findings support previous evidence that the MTL is critical for the reversal of associations that involve contextual but not cue information.

Furthermore, our results implicate cortico-striatal regions in the reversal of cue-based associations. Background: Mitochondria are responsive to both acute and chronic exposure to psychosocial stress.

A few recent studies suggest that circulating cell-free mitochondrial DNA ccf-mtDNA may rise with psychopathology and acute psychosocial stress.

No prior work has examined ccf-mtDNA in relation to adversity or trauma exposure. This study assessed ccf-mtDNA at baseline and in the context of an acute stressor in a sample of healthy young adults, with or without a history of parental loss and maltreatment.

Conclusions: These preliminary findings add to the evidence that cell-free DNA may be involved in the response to acute psychosocial stressors.

Because elevations in ccf-mtDNA are known to be elevated in physiologic stress, such as exercise or illness, elevations in response to a psychosocial stressor may indicate the role of mitochondrial signaling in broader systemic responses to psychosocial stress.

Higher ratio of ccf-mtDNA to ccf-nDNA was also linked to current trauma and stressor-related disorders, suggesting the possibility of mitochondrial changes may be associated with underlying psychological functioning.

Human studies using actigraphy-based tracking in real time have revealed the central role of disturbances in motor activity in mood disorders, particularly Bipolar Disorder BD that is characterized by dysregulation of patterns of motor activity.

Likewise, the atypical subtype of depression, characterized by overeating and oversleeping is associated with disrupted patterns of both activity and sleep based on objectively tracked assessments.

At present, there are well-established methods for measuring motor activity in different species, such as non-human primates and rodents.

However, the widespread variability of tools limits comparisons across these studies as well as applying the findings to human research.

This presentation will examine the use of actigraphy in humans and monkeys as a first step in developing cross species approaches to examine patterns of motor activity.

Second, we present data on the definitions, measures and correlates of motor activity in rodents based on infrared motion detectors.

The monkey data are derived from a sample of adult female rhesus monkeys from a study of predictors of degeneration of nigrostriatal dopaminergic neurons.

Results: First, we asked how similar were daily activity patterns in monkeys and humans? Moreover, the 4 highest loading components of monkeys explained Conversely, the 4 highest loading components from human explain Second, we asked if there were detectable differences in activity patterns in humans with Bipolar disorder?

In addition, the general activity of single-housed adult male mice was monitored using both infrared motion detectors mounted to the top of the cages and wheels.

Patterns of motor activity in response to light were examined to identify whether there were particular light conditions that led to depression like behaviors.

Conclusions: These findings demonstrate the value of studying a core component of behavior across humans and animals. The use of motor activity as a core behavioral measure of depression can in part minimize the limitation of current behavioral models of depression in basic science.

Harmonization of measures that distinguish motor activity from exercise in humans, and motor activity from motivation in animals will be critical to provide valid comparisons both within basic science and between basic and human studies.

Background: The human prefrontal cortex PFC is a region of the cerebral cortex expanded in primates and associated with higher-order cognitive function including abstract thinking, moral reasoning, and language.

Comparative analyses of the PFC have identified human-specific changes in cell number, morphology, and types as well as microcircuitry and long-range connections, which are thought to underlie human advanced cognitive capabilities and possibly, susceptibility to disease.

These changes in circuitry are likely mediated by divergent changes in spatiotemporal patterns of gene expression and cis-regulatory element activity, most evident during early fetal and mid-fetal stages.

Linking these genomic changes with human-specific changes in cortical anatomy will be integral to modeling and understanding development of human and primate-specific cortical circuitry, as well as how dysfunction in this circuitry lead to neuropsychiatric disease.

However, this process has been arduous due to difficulty accessing high-quality human and primate expression data. To remedy this problem, our laboratory along with multiple other laboratories have created a spatiotemporal atlas of gene expression in humans and macaques spanning from embryonic ages to adulthood, as part of the PsychEncode initiative, called BrainSpan.

Using this database, we are able to identify candidate genes differentially expressed in the human and primate PFC during important periods of development, which can be then be studied in animal models to identify their role in development and dysfunction of the cerebral cortex.

Methods: We used the BrainSpan database to identify genes and signaling pathways enriched in the frontal lobe during mid-fetal development, a crucial developmental period for the formation of neuronal circuits with an enrichment of expression of genes implicated in schizophrenia and ASD.

Expression of select candidate genes was further profiled in various species including mouse, macaque, and human using In Situ Hybridization and RNA-sequencing.

In addition, we utilized comparative genetics combined with both in vitro and in vivo assays to identify non-coding elements that underlie these species-specific shifts in expression.

Finally, we studied the function of select candidate genes and regulatory elements in mouse using CRISPR-Cas9 technology and in utero electroporation combined with a diverse set of assays including diffusion tensor imaging DTI and RNA-sequencing to study the functional significance of this network.

Results: We identified an enrichment of genes involved in synaptogenesis and axon development in the frontal lobe during human mid-fetal development PCW Pathway analysis identified that many of these enriched genes are regulated by the same upstream signaling pathway, whose function in later cortical development has not been explored.

Reduction in activity of this signaling pathway in the early postnatal mouse medial frontal cortex leads to selective loss of reciprocal thalamocortical connectivity both through DTI Furthermore, expansion of this signaling pathway in mouse frontal cortex, to replicate the lateral expansion of activity of this signaling pathway seen in humans, leads to an increase in the thickness of layer IV in motor regions.

In addition, we identified an enhancer regulated by this pathway with a hominini-specific human, great apes deletion. Targeted replacement with the human enhancer in mouse leads to increased excitatory synapses of both upper Conclusions: Using the BrainSpan database, we were able to identify genes enriched in the human PFC which are co-regulated by a signaling pathway previously linked to schizophrenia.

Using mouse models, we identified that this signaling pathway is required for mediodorsal thalamus innervation and density of excitatory synapses in the PFC.

Connections between the mediodorsal thalamus and PFC are implicated in working memory, behavioral flexibility and goal-directed behaviors and are disrupted in schizophrenia.

Together, we have identified a possible mechanistic link between a previously described dysregulation in a specific signaling pathway, cognitive dysfunction, and schizophrenia.

Background: Behavioral activation system BAS and behavioral inhibition system BIS traits play a central role in determining individual variations in behavioral disposition and vulnerability.

With voxel-based morphometry VBM Li et al. In addition to whole-brain analyses, we also conducted ROI analyses to replicate the findings of Li et al.

We only considered subjects for which raw images were available. Structural magnetic resonance imaging MRI was acquired using optimized protocol for 3T machines including Siemens Prisma, GE and Philips with voxel size 1 mm isotropic.

This modified version shortens the Reward Responsiveness subscale but includes the BAS Fun known to be a reliable predictor of substance involvement in older samples.

Voxel-based morphometry or VBM is used to identify differences in the local composition of brain tissue and its association with behavioral and cognitive measures, while discounting large scale differences in gross anatomy and position.

CAT12 provides several components optimized for morphometry, including an internal interpolation, affine preprocessing affine registration of bias-corrected images , partial volume segmentation, denoising, DARTEL normalization, local adaptive segmentation, skull-stripping, an adaptive maximum a posteriori AMAP segmentation, and a final clean-up.

We used the ABCD raw images as opposed to the preprocessed data supposedly optimized to be used with Freesurfer in order to avoid any interference with the CAT12 preprocessing pipeline.

In regions of interest analyses, we focused on the left parahippocampal gyrus, ventromedial prefrontal cortex, and right parietal cortex, regions that were identified from Li et al.

Girls showed higher BIS score than boys 7. In contrast, girls demonstrated lower BAS score than boys Further, replicating Li et al.

Background: The striatum is associated with goal-directed behaviors and has been mapped extensively in primate models. One complex limbic-cognitive task for both human and nonhuman primates is living in social groups.

We assessed the literature to determine striatal sites implicated in these functions in humans, and used Macaques to place retrograde tracer injections in each region.

Our goal was to assess the range and combinatorial profile of cortical inputs across striatal zones associated with social activity.

Methods: Regions of interest were chosen from a meta-analysis of fMRI studies that assessed a variety of social behavior in the human Baez-Mendoza and Schultz, Following a 2-week survival period, animals were sacrificed, and the brains were prepared for visualization of tracer using immunocytochemical and histologic techniques.

In the current study we mapped retrogradely labeled cells in the prefrontal cortex, insula, and amygdala. A subset of these injection sites additionally resulted in high concentrations of labeled cells in the agranular, dysgranular, and in some cases posterior granular insula.

The latter sites also had many retrogradely labeled cells in the amygdala. In addition to these inputs, striatal regions in the caudal ventral striatum receive strong inputs from the insula, area 32, and the amygdala, regions implicated in many affiliative behavioral paradigms.

Together, these data suggest networks to the caudal ventral striatum that code for behavioral responses involving social stimuli.

However, the molecular mechanism underlying this process and the pathophysiological consequences that occur when it is disrupted during prenatal development remain unclear.

In this study, we investigated a potential protein-protein interaction between D1R and SynGAP, and its role in GABAergic interneuron migration and physiological consequences in the behaviors of adulthood.

Immunofluorescent staining was used to analyze the distribution of GABAergic interneurons at various developmental stages. Locomotor, pre-pulse inhibition, visual discrimination and social behaviors were assessed to determine whether the prenatal impairment of GABAergic interneuron migration caused behavioral deficits in adulthood.

Interestingly, disrupting this complex during embryonic development resulted in pronounced GABAergic interneuron tangential migration deficits, possibly due to altered actin and microtubule dynamics.

More importantly, administration of TAT-D1Rpep to pregnant mice led to abnormalities in locomotor activity, pre-pulse inhibition, sociability and visual discrimination in the offspring.

Conclusions: Our study discovered a novel protein-protein interaction between D1R and SynGAP, and this interaction plays a critical role in the prenatal GABAergic interneuron migration and development of important behaviors in adulthood.

Background: Methylphenidate has been used to treat patients with attention-deficit hyperactivity disorder ADHD since the s with significant effects on clinical symptoms and functional improvement.

The data on the neural substrates for brain activity changes after treatment with methylphenidate is limited. These brain regions might play a role as biological markers for the treatment effectiveness of methylphenidate.

One challenge in FXS treatment development is a lack of rigorous, synchronized outcome readouts across animal and human study. We have developed across the mouse fmr1 KO and human FXS lab EEG evaluations that 1 present stimuli in a similar manner; 2 have EEG data processed using the same analysis methods across mouse and human study; and 3 show baseline results indicating a similar aberrant patterns of brain activity across mouse and human study.

Racemic baclofen has been extensively evaluated in the mouse model of FXS and racemic baclofen is readily available for immediate use in human FXS study.

Following surgical implantation at days and then two days to recover the mice underwent pre-dose 5 minutes of resting EEG followed by trains of the up chirp auditory entrainment paradigm.

For chronic daily dosing, the mice received the same baclofen dose daily for 2 weeks and then EEG paradigms were repeated after repeated dosing.

In humans, thirteen 15 to year olds years with full mutation received 30mg of oral racemic baclofen or matching placebo with a two week washout period between dosing days.

Prior to drug dosing the patients completed resting state and auditory chirp EEG paradigms consistent with the EEG work in the mice.

Four hours post-dose the humans repeated all EEG measures. In addition, the humans completed pre- and post-dose clinical measures including the Woodcock Johnson auditory attention subscale, the Repeatable Battery of Neuropsychiatric Status RBANS , the KiTap computer-based continuous performance testing, and eye tracking.

The reductions in gamma band power were consistent across left and right frontal, medial, and temporal brain regions.

Aber auch die Steaks sind sehr lecker. Ein besonderes Highlight ist auch der Nachtisch für zwei, aber Vorsicht, denn danach ist man mehr als satt : Besonders Also, ins Ritmo könnte ich täglich gehen Klasse Tapas in historischer Kulisse.

Die Steaks sind klasse! Der Service hat bei der ein oder anderen Kraft hinsichtlich Freundlichkeit noch Luft nach oben.

Wir waren mit Freunden dort. Das Personal war freundlichen und aufmerksam. Bestellt haben wir verschiedene Sorten von Tapas.

Diese wurden zeitnah serviert und waren durchweg sehr lecker. Wir kommen garantiert wieder. Hier komme ich sehr gerne hin.

Im Sommer mit gemütlichem Aussenbereich, hier ist dann allerdings eine Reservierung sinnvoll. Hier arbeitet der Chef noch mit Alles im Ganzen sehr zu empfehlen, probiert es selber aus.

Das Essen dauerte ewig und war eher mässig. Der Kellner hat ein Bier über eine Freundin geschüttet, so dass die Kleidung im Hotel gewechselt werden musste.

Entschuldigung Fehlanzeige. Auch kein Angebot zur Kompensation. Auf unsere Beschwerde wude die Bedienung patzig. Nie wieder! Das Esssen war echt schlecht.

Wir haben Steak bestellt. Es wurde nichtmal annähern so geliefert , wie es bestellt wurde. Dass ich Brot, das ich nachbestelle bezahlen muss finde ich nicht angemessen.

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Speaker: Renate Künast and Fritz Kuhn. Members: Tauss. List of members of the 16th Bundestag.

Members of the 17th Bundestag Speaker: Volker Kauder. Speaker: Frank-Walter Steinmeier. Speaker: Birgit Homburger and Rainer Brüderle.

Speaker: Gregor Gysi. Speaker: Renate Künast and Jürgen Trittin. List of members of the 17th Bundestag. Members of the 18th Bundestag Members: Steinbach.

List of members of the 18th Bundestag. Current members of the Bundestag Speaker: Ralph Brinkhaus.

Speaker: Rolf Mützenich. Speaker: Alexander Gauland , Alice Weidel. Speaker: Christian Lindner. List of members of the 19th Bundestag.

Members of the german Bundestag from North Rhine-Westphalia. Matthias W. Namespaces Article Talk.

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Flüge Ferienwohnungen Restaurants Aktivitäten. Ritmo Tapas Bar, Höxter. Alle Restaurants in Höxter ansehen.

Ritmo Tapas Bar Beansprucht. Alle Fotos Zertifikat für Exzellenz Gewinner - Alle Details anzeigen mahlzeiten, funktionen, beschreibung.

Standort und Kontakt Weserstr. Ist dieses Restaurant für Kinder geeignet? Ja Nein Unsicher. Ist dieser Ort hauptsächlich für Bars und Kneipen bekannt?

Ist dieses Restaurant für Geschäftsessen geeignet? Können an diesem Ort Zutaten erworben werden, um das Essen selbst zuzubereiten? Handelt es sich bei diesem Ort um eine Weinbar?

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