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Floatation-REST (Reduced Environmental Stimulation Therapy) minimizes stimulation of the nervous system by immersing subjects in an environment without sound or light while they effortlessly float in thermoneutral water supersaturated with Epsom salt. Here we investigated the relationship between altered states of consciousness (ASC) and its association with the affective changes induced by Floatation-REST. Using a within-subject crossover design, 50 healthy subjects were randomized to 60 min of Floatation-REST or 60 min of Bed-REST (an active control condition that entailed lying supine on a warm waterbed in a dark and quiet room). Following Floatation-REST, subjects felt significantly more relaxed, less anxious, and less tired than after Bed-REST. Floatation-REST also induced significantly more pronounced ASC characterized by the dissolution of body boundaries and the distortion of subjective time. The loss of body boundaries mediated the loss of anxiety, revealing a novel mechanism by which Floatation-REST exerts its anxiolytic effect. [ABSTRACT FROM AUTHOR]

Floatation-REST (Reduced Environmental Stimulation Therapy) reduces sensory input to the nervous system through the act of floating supine in a pool of water saturated with Epsom salt. The float experience is calibrated so that sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational and proprioceptive channels are minimized, as is most movement and speech. This open-label study aimed to examine whether Floatation-REST would attenuate symptoms of anxiety, stress, and depression in a clinical sample. Fifty participants were recruited across a spectrum of anxiety and stress-related disorders (posttraumatic stress, generalized anxiety, panic, agoraphobia, and social anxiety), most (n = 46) with comorbid unipolar depression. Measures of self-reported affect were collected immediately before and after a 1-hour float session, with the primary outcome measure being the pre- to post-float change score on the Spielberger State Anxiety Inventory. Irrespective of diagnosis, Floatation-REST substantially reduced state anxiety (estimated Cohen’s d > 2). Moreover, participants reported significant reductions in stress, muscle tension, pain, depression and negative affect, accompanied by a significant improvement in mood characterized by increases in serenity, relaxation, happiness and overall well-being (p < .0001 for all variables). In reference to a group of 30 non-anxious participants, the effects were found to be more robust in the anxious sample and approaching non-anxious levels during the post-float period. Further analysis revealed that the most severely anxious participants reported the largest effects. Overall, the procedure was well-tolerated, with no major safety concerns stemming from this single session. The findings from this initial study need to be replicated in larger controlled trials, but suggest that Floatation-REST may be a promising technique for transiently reducing the suffering in those with anxiety and depression. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

See Manohar and Akam (doi10.1093/brain/awx119) ForA Scientific Commentary On This Article.: [ABSTRACT FROM AUTHOR]

We previously demonstrated that carbon dioxide inhalation could induce panic anxiety in a group of rare lesion patients with focal bilateral amygdala damage. To further elucidate the amygdala-independent mechanisms leading to aversive emotional experiences, we retested two of these patients (B.G. and A.M.) to examine whether triggering palpitations and dyspnea via stimulation of nonchemosensory interoceptive channels would be sufficient to elicit panic anxiety. Participants rated their affective and sensory experiences following bolus infusions of either isoproterenol, a rapidly acting peripheral β-adrenergic agonist akin to adrenaline, or saline. Infusions were administered during two separate conditions: a panic induction and an assessment of cardiorespiratory interoception. Isoproterenol infusions induced anxiety in both patients, and full-blown panic in one (patient B.G.). Although both patients demonstrated signs of diminished awareness for cardiac sensation, patient A.M., who did not panic, reported a complete lack of awareness for dyspnea, suggestive of impaired respiratory interoception. These findings indicate that the amygdala may play a role in dynamically detecting changes in cardiorespiratory sensation. The induction of panic anxiety provides further evidence that the amygdala is not required for the conscious experience of fear induced via interoceptive sensory channels. [ABSTRACT FROM AUTHOR]

Although the amygdala plays an important part in the pathogenesis of anxiety and generation of exteroceptive fear, recent discoveries have challenged the directionality of this brain-behavior relationship with respect to interoceptive fear. Here we highlight several paradoxical findings including: (1) amygdala lesion patients who experience excessive fear and panic following inhalation of carbon dioxide (CO 2), (2) clinically anxious patients who have significantly smaller (rather than larger) amygdalae and a pronounced hypersensitivity toward CO 2 , and (3) epilepsy patients who exhibit apnea immediately following stimulation of their amygdala yet have no awareness that their breathing has stopped. The above findings elucidate an entirely novel role for the amygdala in the induction of apnea and inhibition of CO 2 -induced fear. Such a role is plausible given the strong inhibitory connections linking the central nucleus of the amygdala with respiratory and chemoreceptive centers in the brainstem. Based on this anatomical arrangement, we propose a model of Apnea-induced Anxiety (AiA) which predicts that recurring episodes of apnea are being unconsciously elicited by amygdala activation, resulting in transient spikes in CO 2 that provoke fear and anxiety, and lead to characteristic patterns of escape and avoidance behavior in patients spanning the spectrum of anxiety. If this new conception of AiA proves to be true, and activation of the amygdala can repeatedly trigger states of apnea outside of one's awareness, then it remains possible that the chronicity of anxiety disorders is being interoceptively driven by a chemoreceptive system struggling to maintain homeostasis in the midst of these breathless states. • The causal role of the amygdala with regard to fear and anxiety remains controversial. • Research is reviewed across lesion studies, intracranial stimulation, and volumetric MRI. • The amygdala inhibits fear evoked by elevations in CO 2. • Stimulation of the amygdala triggers a state of apnea outside of one's awareness. • We propose a model of apnea-induced anxiety that can be tested in future studies. [ABSTRACT FROM AUTHOR]

The lesion method provides unique insight into how the human brain generates emotion and feeling. Recent work has explored a number of interesting topics including the dissociation of emotional experience from memory in patients with amnesia, the reliability of specific emotional deficits following focal brain damage (including fear and the amygdala), and the investigation of compensatory neural mechanisms in lesion patients. Several detailed case studies have challenged the necessary role of the insular cortex in both awareness and feeling by showing that even in rare instances of complete bilateral insula destruction, the patient remains fully sentient and capable of expressing and feeling emotion. These findings highlight the distributed nature of emotion processing in the human brain and emphasize the importance of utilizing the lesion method for elucidating brain–behavior relationships. [ABSTRACT FROM AUTHOR]

It has been proposed that self-awareness (SA), a multifaceted phenomenon central to human consciousness, depends critically on specific brain regions, namely the insular cortex, the anterior cingulate cortex (ACC), and the medial prefrontal cortex (mPFC). Such a proposal predicts that damage to these regions should disrupt or even abolish SA. We tested this prediction in a rare neurological patient with extensive bilateral brain damage encompassing the insula, ACC, mPFC, and the medial temporal lobes. In spite of severe amnesia, which partially affected his "autobiographical self", the patient's SA remained fundamentally intact. His Core SA, including basic self-recognition and sense of self-agency, was preserved. His Extended SA and Introspective SA were also largely intact, as he has a stable self-concept and intact higher-order metacognitive abilities. The results suggest that the insular cortex, ACC and mPFC are not required for most aspects of SA. Our findings are compatible with the hypothesis that SA is likely to emerge from more distributed interactions among brain networks including those in the brainstem, thalamus, and posteromedial cortices. [ABSTRACT FROM AUTHOR]

Summary: Although clinical observations suggest that humans with amygdala damage have abnormal fear reactions and a reduced experience of fear [], these impressions have not been systematically investigated. To address this gap, we conducted a new study in a rare human patient, SM, who has focal bilateral amygdala lesions []. To provoke fear in SM, we exposed her to live snakes and spiders, took her on a tour of a haunted house, and showed her emotionally evocative films. On no occasion did SM exhibit fear, and she never endorsed feeling more than minimal levels of fear. Likewise, across a large battery of self-report questionnaires, 3 months of real-life experience sampling, and a life history replete with traumatic events, SM repeatedly demonstrated an absence of overt fear manifestations and an overall impoverished experience of fear. Despite her lack of fear, SM is able to exhibit other basic emotions and experience the respective feelings. The findings support the conclusion that the human amygdala plays a pivotal role in triggering a state of fear and that the absence of such a state precludes the experience of fear itself. [ABSTRACT FROM AUTHOR]

Can the experience of an emotion persist once the memory for what induced the emotion has been forgotten? We capitalized on a rare opportunity to study this question directly using a select group of patients with severe amnesia following circumscribed bilateral damage to the hippocampus. The amnesic patients underwent a sadness induction procedure (using affectively-laden film clips) to ascertain whether their experience of sadness would persist beyond their memory for the madness-inducing films. The experiment showed that the patients continued to experience elevated levels of sadness well beyond the point in time at which they had lost factual memory for the film clips. A second experiment using a happiness induction procedure yielded similar results, suggesting that both positive and negative emotional experiences can persist independent of explicit memory for the inducing event. These findings provide direct evidence that a feeling of emotion can endure beyond the conscious recollection for the events that initially triggered the emotion. [ABSTRACT FROM AUTHOR]

Neuroticism is a core personality trait that profoundly affects how individuals interpret and interact with their environment. Understanding neuroticism at a neurobiological level will be an important step toward identifying novel vulnerability factors for psychiatric illnesses such as depression and anxiety. Along these lines, recent work has identified neural activation patterns within the right anterior insula that correlates with an individual's degree of neuroticism. The present study aims to further characterize the circumstances under which neuroticism modulates insular activity. Sixteen healthy participants underwent functional magnetic resonance imaging while playing a card game with varying degrees of outcome uncertainty. Activation within the bilateral anterior insula was found during all decisions, irrespective of uncertainty. However, a significant positive correlation between neuroticism and anterior insula activity was found only during 'certain decisions' (i.e. situations where the most probable outcome was clearly evident). Moreover, an increase in the right anterior insula activity during certain decisions was related to a behavioral mirroring effect such that the response latency for certain decisions approached the response latency for uncertain decisions. These findings suggest that increasing levels of neuroticism modulate neural activation in such a way that the brain interprets certainty as uncertain. [ABSTRACT FROM AUTHOR]

Abstract: Decision-making is a complex process that comprises the assessment of a situation, the selection of an action, and the evaluation of an outcome. Distinct neural systems may contribute differentially during various stages within a decision-making situation. This study investigated whether neural activation during assessment or action selection is critically dependent on previous outcomes or actions. Twelve healthy, right-handed subjects (6 females) played a Rock Paper Scissors (RPS) computer game during functional magnetic resonance imaging. Bilateral insula and medial prefrontal cortex (including the anterior cingulate) were specifically engaged during the assessment and action selection stages of decision-making, whereas bilateral superior frontal gyrus and right inferior parietal lobule activated more during the outcome. Two regions of activation within the bilateral superior temporal gyrus activated only when the previous outcome was a win. Moreover, right insula and superior temporal gyrus were active more when the subject switched responses relative to staying with the same choice made on the previous trial. These findings support the hypothesis that distinct neural systems underlie different stages of the decision-making process. Furthermore, the superior temporal gyrus may play an important role in integrating previous actions and successful outcomes into one''s decision-making strategy. [Copyright &y& Elsevier]

Background: Individuals with high trait anxiety (HTA) can be studied to examine the effect of elevated levels of anxiety on the processing of stimuli and the selection of actions. The anterior cingulate cortex has been implicated in the detection and processing of errors. This investigation examined the hypothesis that HTA subjects are more sensitive to errors than nonanxious comparison subjects during a simple decision-making task and show increased activation in the anterior cingulate, particularly at low error rates.Methods: Thirteen HTA subjects were compared with 13 normal trait anxiety (NTA: 40th–60th percentile) subjects during functional magnetic resonance imaging while performing a two-choice prediction task at three different error rates.Results: Both HTA and NTA subjects performed similarly during a simple two-choice prediction task; however, during the low-error-rate condition, activation in the anterior cingulate and medial prefrontal cortex was significantly higher in HTA subjects and was correlated with trait but not state anxiety.Conclusions: These results support the idea that HTA subjects devote more processing resources to decision making than do NTA subjects during times in which there is little chance of incorrect responding (i.e., the low-error-rate condition). The extent to which this altered activation within the anterior cingulate contributes to anxiety-proneness remains to be determined. [Copyright &y& Elsevier]

In recent years, cognitive neuroscientists have began to explore the process of how sensory information gains access to awareness. To further probe this process, event-related functional magnetic resonance imaging (fMRI) was used while testing subjects with a paradigm known as the “attentional blink.” In this paradigm, visually presented information sporadically fails to reach awareness. It was found that the magnitude and time course of activation within the anterior cingulate (BA 32), medial prefrontal cortex (BA 9), and frontopolar cortex (BA 10) predicted whether or not information was consciously perceived during the critical period for the attentional blink. These results are discussed in light of a neural framework for conscious processing. [Copyright &y& Elsevier]

The process of accurately predicting which actions are associated with advantageous versus disadvantageous outcomes is an important function of daily life. An integral part of this process is being able to detect when the association between an action and an outcome changes. This investigation examined the hypothesis that the inferior prefrontal cortex is critical for the detection of trends and that a trend process derived from the temporal difference model accomplishes this detection. Nineteen normal right-handed volunteers completed 120 4-s trials of a Rock Paper Scissors (RPS) task during functional magnetic resonance imaging. Subjects acquired the selection of advantageous actions during the RPS task. Activations in the medial frontal gyrus (BA 10), left ventrolateral frontal gyrus (BA 11/47), and left pallidum were significantly higher during trials in which subjects acquired the advantageous action. The time course of individually derived trend detection functions was found to be time-locked to the hemodynamic changes in the inferior frontal gyrus. These findings are consistent with the hypothesis that the inferior prefrontal cortex computes a trend from previously experienced action–outcome sequences based on a value function derived from the temporal difference model. [Copyright &y& Elsevier]

Decades of research have highlighted the amygdala's influential role in fear. We found that inhalation of 35% CO2 evoked not only fear, but also panic attacks, in three rare patients with bilateral amygdala damage. These results indicate that the amygdala is not required for fear and panic, and make an important distinction between fear triggered by external threats from the environment versus fear triggered internally by CO2. [ABSTRACT FROM AUTHOR]

Background: Reduced Environmental Stimulation Therapy via floatation (floatation-REST) is a behavioral intervention designed to attenuate exteroceptive sensory input to the nervous system. Prior studies in anxious and depressed individuals demonstrated that single sessions of floatation-REST are safe, well-tolerated, and associated with an acute anxiolytic and antidepressant effect that persists for over 48 hours. However, the feasibility of using floatation-REST as a repeated intervention in anxious and depressed populations has not been well-investigated. Methods: In this single-blind safety and feasibility trial, 75 individuals with anxiety and depression were randomized to complete six sessions of floatation-REST in different formats: pool-REST (weekly 1-hour float sessions), pool-REST preferred (float sessions with flexibility of duration and frequency), or an active comparator (chair-REST; weekly 1-hour sessions in a Zero Gravity chair). Feasibility (primary outcome) was assessed via an 80% rate of adherence to the assigned intervention; tolerability via study dropout and duration/frequency of REST utilization; and safety via incidence of adverse events and ratings about the effects of REST. Results: Of 1,715 individuals initially screened, 75 participants were ultimately randomized. Six-session adherence was 85% for pool-REST (mean, M = 5.1 sessions; standard deviation, SD = 1.8), 89% for pool-REST preferred (M = 5.3 sessions; SD = 1.6), and 74% for chair-REST (M = 4.4 sessions; SD = 2.5). Dropout rates at the end of the intervention did not differ significantly between the treatment conditions. Mean session durations were 53.0 minutes (SD = 12.3) for pool-REST, 75.4 minutes (SD = 29.4) for pool-REST preferred, and 58.4 minutes (SD = 4.3) for chair-REST. There were no serious adverse events associated with any intervention. Positive experiences were endorsed more commonly than negative ones and were also rated at higher levels of intensity. Conclusions: Six sessions of floatation-REST appear feasible, well-tolerated, and safe in anxious and depressed individuals. Floatation-REST induces positively-valenced experiences with few negative effects. Larger randomized controlled trials evaluating markers of clinical efficacy are warranted. Clinical Trial Registration Identifier: NCT03899090. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 44-year-old woman who developed treatment resistant major depressive disorder despite a history of stable and focal bilateral amygdala lesions. Topics include how she underwent extensive diagnostic screening, which confirmed preserved neuropsychological functioning such as memory, attention, and cognitive flexibility; and how there was no effect of any of the multimodal treatment attempts on her, such as behavioral ,and bilateral electroconvulsive therapy.

A.V. is a young herpes simplex encephalitis (HSE) survivor who suffered extensive bilateral damage to the medial temporal lobe (MTL) leading to a severe and pervasive form of anterograde amnesia. Structural Magnetic Resonance Imaging (MRI) revealed lesions that encompass the hippocampus and amygdala in both hemispheres and that extend more laterally in the right temporal lobe. At the same time, detailed neuropsychological testing showed that the disparity between A.V.'s preserved intellectual functioning (Full Scale IQ: 115) and severe memory deficit (Delayed Memory Index: 42) is one of the largest on record. Despite this deficit, A.V. has regained a higher level of functioning and autonomy compared to previously documented amnesic cases with major bilateral MTL lesions. As a millennial, one advantage which A.V. has over prior amnesic cases is fluency with digital technology - particularly the smartphone. The analysis of his phone and specific app usage showed a pattern that is consistent with the strategy to offload cognitive tasks that would normally be supported by the MTL. A.V.'s behavior is significant in terms of rehabilitation and may have broader implications at the societal level and for public health given the ubiquity of smartphone technology and its potential to become integrated with neural mnemonic functions. [ABSTRACT FROM AUTHOR]

Never before have individuals had to adapt to social environments defined by such magnitudes of ethnic diversity and cultural differentiation. However, neurobiological evidence informing about strategies to reduce xenophobic sentiment and foster altruistic cooperation with outsiders is scarce. In a series of experiments settled in the context of the current refugee crisis, we tested the propensity of 183 Caucasian participants to make donations to people in need, half of whom were refugees (outgroup) and half of whom were natives (ingroup). Participants scoring low on xenophobic attitudes exhibited an altruistic preference for the outgroup, which further increased after nasal delivery of the neuropeptide oxytocin. In contrast, participants with higher levels of xenophobia generally failed to exhibit enhanced altruism toward the outgroup. This tendency was only countered by pairing oxytocin with peer-derived altruistic norms, resulting in a 74% increase in refugee-directed donations. Collectively, these findings reveal the underlying sociobiological conditions associated with outgroup-directed altruism by showing that charitable social cues co-occurring with enhanced activity of the oxytocin system reduce the effects of xenophobia by facilitating prosocial behavior toward refugees. [ABSTRACT FROM AUTHOR]

Background: Exposure-based therapy is an effective first-line treatment for anxiety-, obsessive–compulsive, and trauma- and stressor-related disorders; however, many patients do not improve, resulting in prolonged suffering and poorly used resources. Basic research on fear extinction may inform the development of a biomarker for the selection of exposure-based therapy. Growing evidence links orexin system activity to deficits in fear extinction and we have demonstrated that reactivity to an inhaled carbon dioxide (CO2) challenge—a safe, affordable, and easy-to-implement procedure—can serve as a proxy for orexin system activity and predicts fear extinction deficits in rodents. Building upon this basic research, the goal for the proposed study is to validate CO2 reactivity as a biomarker of exposure-based therapy non-response. Methods: We will assess CO2 reactivity in 600 adults meeting criteria for one or more fear- or anxiety-related disorders prior to providing open exposure-based therapy. By incorporating CO2 reactivity into a multivariate model predicting treatment non-response that also includes reactivity to hyperventilation as well as a number of related predictor variables, we will establish the mechanistic specificity and the additive predictive utility of the potential CO2 reactivity biomarker. By developing models independently within two study sites (University of Texas at Austin and Boston University) and predicting the other site's data, we will validate that the results are likely to generalize to future clinical samples. Discussion: Representing a necessary stage in translating basic research, this investigation addresses an important public health issue by testing an accessible clinical assessment strategy that may lead to a more effective treatment selection (personalized medicine) for patients with anxiety- and fear-related disorders, and enhanced understanding of the mechanisms governing exposure-based therapy. Trial registration: ClinicalTrials.gov Identifier: NCT05467683 (20/07/2022). [ABSTRACT FROM AUTHOR]

The amygdala and the hippocampus are associated with emotional processing and declarative memory, respectively. Studies have shown that patients with bilateral hippocampal damage caused by anoxia/ischemia, and patients with probable Alzheimer's disease (AD), can experience emotions for prolonged periods of time, even when they cannot remember what caused the emotion in the first place (Feinstein et al. (2010) Proc Natl Acad Sci USA 107:7674-7679; Guzmán-Vélez et al. (2014) Cogn Behav Neurol 27:117-129). This study aimed to investigate, for the first time, the roles of the amygdala and hippocampus in the dissociation between feelings of emotion and declarative memory for emotion-inducing events in patients with AD. Individuals with probable AD ( N = 12) and age-matched healthy comparisons participants (HCP; N = 12) completed a high-resolution (0.44 × 0.44 × 0.80 mm) T2-weighted structural MR scan of the medial temporal lobe. Each of these individuals also completed two separate emotion induction procedures (sadness and happiness) using film clips. We collected real-time emotion ratings at baseline and multiple times postinduction, and administered a test of declarative memory shortly after each induction. Consistent with previous research, hippocampal volume was significantly smaller in patients with AD compared with HCP, and was positively correlated with memory for the film clips. Sustained feelings of emotion and amygdala volume did not significantly differ between patients with AD and HCP. Follow-up analyses showed a significant negative correlation between amygdala volume and sustained sadness, and a significant positive correlation between amygdala volume and sustained happiness. Our findings suggest that the amygdala is important for regulating and sustaining an emotion independent of hippocampal function and declarative memory for the emotion-inducing event. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective: Increased amygdala reactivity during processing of certain types of emotional stimuli (e.g., fear, anger) has been observed in patients with anxiety disorders such as social phobia and posttraumatic stress disorder (PTSD). It is uncertain whether this heightened amygdala reactivity is specific to treatment-seeking patients with anxiety disorders or is a general feature of individuals with increased anxiety-related temperamental traits. Method: Thirty-two physically healthy subjects 18-21 years old were recruited from a large pool of college students. Of these, 16 were chosen on the basis of scoring in the upper-15th percentile on a measure of trait anxiety (anxiety-prone group), and 16 were chosen on the basis of scoring in the normative range (40th-60th percentile). Subjects participated in functional magnetic resonance imaging (fMRI) during an emotion face assessment task that has been shown to reliably engage amygdala and associated limbic structures. Results: Anxiety-prone subjects had significantly greater bilateral amygdala and insula activation to emotional faces than did the anxiety-normative comparison subjects. Higher scores on several measures assessing anxiety proneness (eg, neuroticism, trait anxiety, and anxiety sensitivity) were associated with greater activation of the amygdala (predominantly left-sided) and the anterior insula (bilateral). Conclusions: Increased amygdala and insula reactivity to certain types of emotional processing is seen in young adults with increased anxiety-related temperamental traits. Therefore, this brain emotion-processing profile may be a functional endophenotype for proneness to (certain kinds of) anxiety disorders. [ABSTRACT FROM AUTHOR]

Several studies have examined the role of different neurotransmitter systems in modulating risk-taking behavior. This investigation was aimed to determine whether the benzodiazepine lorazepam dose-dependently alters risk-taking behavior and underlying neural substrates. Fifteen healthy, nonsmoking, individuals (six women, nine men), aged 18–39 years (mean 27.6 ± 1.4 years) with 12–18 years of education (mean 15.6 ± 0.3 years) underwent functional magnetic resonance imaging while performing a risk-taking decision-making task. Our results show that lorazepam did not affect risky behavior at 0.25 and 1 mg, but dose-dependently attenuated activation in (a) the amygdala and medial prefrontal cortex during the response selection phase, and in (b) the bilateral insular cortex and amygdala during the outcome (i.e., rewarded or punished) phase. Furthermore, a lorazepam-induced increase in insular cortex activation was associated with less risky responses. Taken together, our findings support the idea that GABAergic modulation in limbic and paralimbic structures is important during both the response selection and outcome phase of risk-taking decision-making. [ABSTRACT FROM AUTHOR]

Abstract: Background: Young adults who use stimulants (e.g., cocaine, amphetamines) are at particular risk of transitioning to dependence. Previously, we demonstrated increased risk-taking in young adults who had used stimulants (Leland, D.S., Paulus, M.P., 2005. Increased risk-taking decision-making but not altered response to punishment in stimulant-using young adults. Drug. Alcohol Depend. 78, 83-90). Since outcome uncertainty is a critical element of risk, we investigated whether such individuals have different neural responses to uncertainty than their stimulant-naive peers. Method: Eleven young adults (age 18–25) who had used stimulants were compared with 11 age- and education-matched stimulant-naive controls using functional magnetic resonance imaging and a card prediction task with relatively certain/uncertain outcome conditions. Results: The caudate, an area involved in processing salient events, was among those regions more active in users than controls in response to uncertainty. Personality measures revealed that users were more impulsive than controls, and that neural response to uncertainty in a number of areas, including the thalamus/caudate, was positively correlated with impulsivity. Conclusions: These results are consistent with the idea that young adults who have used stimulants find uncertainty particularly salient, due in part to preexisting differences in impulsivity, and may be subject to more “action pressure” when making decisions under uncertainty. This neural and personality profile may constitute a marker for increased risk of stimulant use. [Copyright &y& Elsevier]

Abstract: Semantic organization, an aspect of semantic processing, requires a pre-existing network of semantic knowledge that relies on a widely distributed neural network. The inferior prefrontal cortex (IPFC) has been identified as a vital structure for processing competing semantic information when making a decision about the meaning of a stimulus. However, the precise role of the IPFC in maintaining or creating a consistent semantic organizational structure is unclear. In this study, a semantic triadic decision-making task (Tallent, K.A., Weinberger, D.R., and Goldberg, T.E. 2001. Associating semantic space abnormalities with formal thought disorder in schizophrenia: use of triadic comparisons. J. Clin. Exp. Neuropsychol. 285–296) was used during functional magnetic resonance imaging to test the hypothesis that the degree of activation in the IPFC correlates with the consistency of semantic organization in healthy subjects. In this sample, subjects who had greater activation in the IPFC also demonstrated smaller stress coefficients in a two-dimensional “semantic space”, indicating a greater organization of words along semantic dimensions. This finding is consistent with the role of the IPFC in establishing self-generated semantic relationships between stimuli. [Copyright &y& Elsevier]

Little is known about the role of declarative memory in the ongoing perception of one's personality. Seven individuals who developed a rare and severe type of anterograde amnesia following damage to their medial temporal lobes were identified from our neurological patient registry. We examined the stability of their personality ratings on the Big Five Inventory over five retest periods and assessed the accuracy of their ratings via analyses of self–caregiver agreement. The patients portrayed a stable sense of self over the course of 1 year. However, their self-ratings differed from those provided by the caregivers. Intriguingly, these discrepancies diminished when caregivers retrospectively rated the patients' personalities prior to their brain injury, suggesting that patients' perceptions of themselves were stuck in the past. We interpret our findings to indicate that the ability to form new declarative memories is not required for maintaining a stable sense of self but may be important for updating one's sense of self over time. [ABSTRACT FROM AUTHOR]

Floatation‐Reduced Environmental Stimulation Therapy (REST) is a procedure that reduces stimulation of the human nervous system by minimizing sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational, and proprioceptive channels, in addition to minimizing musculoskeletal movement and speech. Initial research has found that Floatation‐REST can elicit short‐term reductions in anxiety, depression, and pain, yet little is known about the brain networks impacted by the intervention. This study represents the first functional neuroimaging investigation of Floatation‐REST, and we utilized a data‐driven exploratory analysis to determine whether the intervention leads to altered patterns of resting‐state functional connectivity (rsFC). Healthy participants underwent functional magnetic resonance imaging (fMRI) before and after 90 min of Floatation‐REST or a control condition that entailed resting supine in a zero‐gravity chair for an equivalent amount of time. Multivariate Distance Matrix Regression (MDMR), a statistically‐stringent whole‐brain searchlight approach, guided subsequent seed‐based connectivity analyses of the resting‐state fMRI data. MDMR identified peak clusters of rsFC change between the pre‐ and post‐float fMRI, revealing significant decreases in rsFC both within and between posterior hubs of the default‐mode network (DMN) and a large swath of cortical tissue encompassing the primary and secondary somatomotor cortices extending into the posterior insula. The control condition, an active form of REST, showed a similar pattern of reduced rsFC. Thus, reduced stimulation of the nervous system appears to be reflected by reduced rsFC within the brain networks most responsible for creating and mapping our sense of self. [ABSTRACT FROM AUTHOR]

A network of cortical brain regions, including the insula and anterior cingulate cortex (ACC), has been proposed as the critical and sole substrate for interoceptive awareness. Combining lesion and pharmacological approaches in humans, we found that the insula and ACC were not critical for awareness of heartbeat sensations. Instead, this awareness was mediated by both somatosensory afferents from the skin and a network that included the insula and ACC. Together, these pathways enable the core human experience of the cardiovascular state of the body. [ABSTRACT FROM AUTHOR]

Background: Electroencephalography (EEG) studies suggest that major depressive disorder (MDD) is associated with lower left than right frontal brain activity (asymmetry), a pattern appearing stronger in women than men, and when elicited during emotionally-relevant paradigms versus an uncontrolled resting state. However, it is unclear whether this asymmetry pattern generalizes to the common presentation of MDD with co-occurring anxiety. Moreover, asymmetry may differ for anxiety subtypes, wherein anxious apprehension (AnxApp: worry characteristic of generalized anxiety disorder) appears left-lateralized, but anxious arousal (AnxAro: panic characteristic of social anxiety, posttraumatic stress, and panic disorders) may be right-lateralized.Methods: This analysis attempted to replicate frontal EEG asymmetry patterns using functional magnetic resonance imaging (fMRI). Participants completed clinical interviews and a monetary incentive delay (MID) task during fMRI recording. We compared five groups of right-handed women from the Tulsa 1000 study, MDD (n=40), MDD-AnxApp (n=26), MDD-AnxAro (n=34), MDD-Both (with AnxApp and AnxAro; n=26), and healthy controls (CTL; n=24), as a function of MID anticipation condition (no win/loss, win, loss) and hemisphere on frontal blood oxygen-level-dependent (BOLD) signal.Results: CTL exhibited higher bilateral superior, middle, and inferior middle frontal gyrus BOLD signal than the four MDD groups for high arousal (win and loss) conditions. However, frontal attenuations were unrelated to current depression/anxiety symptoms, suggestive of a trait as opposed to a state marker.Limitations: This was a cross-sectional analysis restricted to women.Conclusions: Reduced prefrontal cortex recruitment during processing of both positively and negatively valenced stimuli is consistent with the emotion context insensitivity theory of MDD. [ABSTRACT FROM AUTHOR]

Several studies have recently suggested that an abnormal processing of respiratory interoceptive and nociceptive (painful) stimuli may contribute to eating disorder (ED) pathophysiology. Mood and anxiety disorders (MA) are also characterized by abnormal respiratory symptoms, and show substantial comorbidity with ED. However, no studies have examined both respiratory and pain processing simultaneously within ED and MA. The present study systematically evaluated responses to perturbations of respiratory and nociceptive signals across the levels of physiology, behavior, and symptom report in a transdiagnostic ED sample (n = 51) that was individually matched to MA individuals (n = 51) and healthy comparisons (HC; n = 51). Participants underwent an inspiratory breath-holding challenge as a probe of respiratory interoception and a cold pressor challenge as a probe of pain processing. We expected both clinical groups to report greater stress and fear in response to respiratory and nociceptive perturbation than HCs, in the absence of differential physiological and behavioral responses. During breath-holding, both the ED and MA groups reported significantly more stress, feelings of suffocation, and suffocation fear than HC, with the ED group reporting the most severe symptoms. Moreover, anxiety sensitivity was related to suffocation fear only in the ED group. The heightened affective responses in the current study occurred in the absence of group differences in behavioral (breath hold duration, cold pressor duration) and physiological (end-tidal carbon dioxide, end-tidal oxygen, heart rate, skin conductance) responses. Against our expectations, there were no group differences in the response to cold pain stimulation. A matched-subgroup analysis focusing on individuals with anorexia nervosa (n = 30) produced similar results. These findings underscore the presence of abnormal respiratory interoception in MA and suggest that hyperreactivity to respiratory signals may be a potentially overlooked clinical feature of ED. [ABSTRACT FROM AUTHOR]

Abstract: Cardiorespiratory fluctuations such as changes in heart rate or respiration volume influence the temporal dynamics of cerebral blood flow (CBF) measurements during arterial spin labeling (ASL) fMRI. This “physiological noise” can confound estimates of resting state network activity, and it may lower the signal‐to‐noise ratio of ASL during task‐related experiments. In this study we examined several methods for minimizing the contributions of both synchronized and non‐synchronized physiological noise in ASL measures of CBF, by combining the RETROICOR approach with different linear deconvolution models. We evaluated the amount of variance in CBF that could be explained by each method during physiological rest, in both resting state and task performance conditions. To further demonstrate the feasibility of this approach, we induced low‐frequency cardiorespiratory deviations via peripheral adrenergic stimulation with isoproterenol, and determined how these fluctuations influenced CBF, before and after applying noise correction. By suppressing physiological noise, we observed substantial improvements in the signal‐to‐noise ratio at the individual and group activation levels. Our results suggest that variations in cardiac and respiratory parameters can account for a large proportion of the variance in resting and task‐based CBF, and indicate that regressing out these non‐neuronal signal variations improves the intrinsically low signal‐to‐noise ratio of ASL. This approach may help to better identify and control physiologically driven activations in ASL resting state and task‐based analyses. [ABSTRACT FROM AUTHOR]

Background: The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social competence and individual amygdala size correlates with that of social networks. While rare patients with focal bilateral amygdala lesion typically show impaired recognition of fearful faces, this deficit is variable, and an intriguing possibility is that other brain regions can compensate to support fear and social signal processing. Methods: To investigate the brain''s functional compensation of selective bilateral amygdala damage, we performed a series of behavioral, psychophysiological, and functional magnetic resonance imaging experiments in two adult female monozygotic twins (patient 1 and patient 2) with equivalent, extensive bilateral amygdala pathology as a sequela of lipoid proteinosis due to Urbach-Wiethe disease. Results: Patient 1, but not patient 2, showed preserved recognition of fearful faces, intact modulation of acoustic startle responses by fear-eliciting scenes, and a normal-sized social network. Functional magnetic resonance imaging revealed that patient 1 showed potentiated responses to fearful faces in her left premotor cortex face area and bilaterally in the inferior parietal lobule. Conclusions: The premotor cortex face area and inferior parietal lobule are both implicated in the cortical mirror-neuron system, which mediates learning of observed actions and may thereby promote both imitation and empathy. Taken together, our findings suggest that despite the pre-eminent role of the amygdala in processing social information, the cortical mirror-neuron system may sometimes adaptively compensate for its pathology. [Copyright &y& Elsevier]

Abstract: Affective appraisal often involves processing complex and ambiguous stimuli, such as the mood of a group people. However, affective neuroimaging research often uses individual faces as stimuli when exploring the neural circuitry involved in social appraisal. Results from studies using single face paradigms may not generalize to settings where multiple faces are simultaneously processed. The goal of the current study was to use a novel task that presents groups of affective faces to probe the medial prefrontal cortex (PFC), a region that is critically involved in appraisal of ambiguous affective stimuli, in healthy volunteers. In the current study, 27 subjects performed the Wall of Faces (WOF) task in which multiple matrices of faces were briefly presented during functional MRI. Subjects were asked to decide whether there were more angry or happy faces (emotional decision) or whether there were more male or female faces (gender decision). In each condition, the array contained either an equal (ambiguous trials) or an unequal (unambiguous trials) distribution of one affect or gender. Ambiguous trials relative to unambiguous trials activated regions implicated in conflict monitoring and cognitive control, including the dorsal anterior cingulate cortex (ACC), dorsolateral PFC, and posterior parietal cortex. When comparing ambiguous affective decisions with ambiguous gender decisions, the ventromedial PFC (including the ventral ACC) was significantly more active. This supports the dissociation of the ACC into dorsal cognitive and ventral affective divisions, and suggests that the ventromedial PFC may play a critical role in appraising affective tone in a complex display of multiple human faces. [Copyright &y& Elsevier]

Decision making and risk taking are interrelated processes that are important for daily functioning. The somatic marker hypothesis has provided a conceptual basis for processes involved in risk-taking decision making and has been used to link discrete neural substrates to risk-related behaviors. This investigation examined the hypothesis that the degree of risk-taking is related to the degree of activation in the insular cortex. Seventeen healthy, right-handed subjects performed a risk-taking decision-making task during functional magnetic resonance imaging (fMRI) using a fast event-related design. This investigation yielded three main findings. First, right insula (BA 13) activation was significantly stronger when subjects selected a “risky” response versus selecting a “safe” response. Second, the degree of insula activation was related to the probability of selecting a “safe” response following a punished response. Third, the degree of insula activation was related to the subjects'' degree of harm avoidance and neuroticism as measured by the TCI and NEO personality questionnaires, respectively. These results are consistent with the hypothesis that insula activation serves as a critical neural substrate to instantiate aversive somatic markers that guide risk-taking decision-making behavior. [Copyright &y& Elsevier]