Limbic Activity Research Articles

Brain signatures of threat-safety discrimination in adolescent chronic pain.

Approximately 1.7 million youth suffer from debilitating chronic pain in the US alone, conferring risk of continued pain in adulthood. Aberrations in threat-safety (T-S) discrimination are proposed to contribute to pain chronicity in adults and youth by interacting with pain-related distress. Yet, few studies have examined the neural circuitry underlying T-S discrimination in patients with chronic pain or how T-S discrimination relates to pain-related distress. In this study, 91 adolescents (10-24 years; 78 females) including 30 chronic pain patients with high pain-related distress, 29 chronic pain patients with low pain-related distress, and 32 healthy peers without chronic pain completed a developmentally appropriate T-S learning paradigm. We measured self-reported fear, psychophysiology (skin conductance response), and functional magnetic resonance imaging responses (N = 72 after functional magnetic resonance imaging exclusions). After controlling for age and anxiety symptoms, patients with high pain-related distress showed altered self-reported fear and frontolimbic activity in response to learned threat and safety cues compared with both patients with low pain-related distress and healthy controls. Specifically, adolescent patients with high pain-related distress reported elevated fear and showed elevated limbic (hippocampus and amygdala) activation in response to a learned threat cue (CS+). In addition, they showed decreased frontal (vmPFC) activation and aberrant frontolimbic connectivity in response to a learned safety cue (CS-). Patients with low pain-related distress and healthy controls appeared strikingly similar across brain and behavior. These findings indicate that altered T-S discrimination, mediated by frontolimbic activation and connectivity, may be one mechanism maintaining pain chronicity in adolescents with high levels of pain-related distress.

Visual event-related potentials in external emotional conditions in bipolar disorders I and II

Mutual influences of cognitive and emotional functions occur in bipolar disorder, but specific alterations in relation to external emotional stimuli in bipolar I (BD I) and II (BD II) subtypes remain unknown. This study aimed to explore the effects of external emotional stimuli on cerebral attentional function in BD I and BD II. We tested visual oddball event-related potentials (ERPs) during various external emotional stimuli (Disgust, Fear, Erotica, Happiness, Neutral and Sadness) in 31 patients with BD I, 19 BD II and 47 healthy volunteers. Participants' concurrent affective states were also evaluated. The ERP N2 latencies during Fear and Happiness were prolonged, P3 amplitudes during Disgust and Erotica were decreased in BD I; P3 amplitudes during Disgust, Erotica, Happiness and Neutral conditions were decreased in BD II. Increased frontal and parietal and decreased temporal and occipital activations were found in BD I, while increased occipital and parietal and decreased frontal and limbic activations in BD II in relation to different external emotions. ERP components were not correlated with concurrent affective states in patients. Automatic attention during Happiness and Fear, and voluntary attention during Disgust and Erotica conditions were impaired in BD I; and voluntary attention during Disgust, Happiness, Erotica and Neutral conditions was impaired in BD II. Our study illustrates different patterns of visual attentional deficits associated with different external emotional stimuli in BD I and BD II.

Calretinin+-neurons-mediated GABAergic inhibition in mouse prefrontal cortex

The prefrontal cortex (PFC) is a center for executive and cognitive functions. Although many studies have been carried out to elucidate the role of different subtypes of GABAergic neurons in other brain areas, their functional relevance in PFC is still not fully understood. Calretinin+-GABAergic neurons are heterogeneous in their morphology and intrinsic properties. Previous studies showed an involvement of CR+-GABAergic neurons in the disinhibition of the other GABAergic neurons in neocortex and hippocampus. Furthermore, the loss of CR+- and PV+-interneurons in human brain has been linked to the vulnerability of the interneurons and to the overall increase in the network excitability associated with mental diseases. In the present study, the intensity of CR+-neuropil was higher in layer II/III, whereas the intensity of PV+-neuropil was higher in deeper layers within the PFC. In addition, pronounced CR expression was detected in layer II and III of prelimbic and infralimbic cortex whereas they were less abundant in anterior cingulate cortex and motor cortex 2. Our results showed that bipolar CR+- neurons in layer V not only feedback inhibited multipolar CR+- and other interneurons in layer II/III, but the majority of bipolar CR+-neurons in layer II/III also provide long-range forward-inhibition to pyramidal neurons in deeper layers of PFC. Thus, given the importance of the neuronal network of PFC in central control of emotion and cognition and in the pathology of mental diseases, CR+-GABAergic neuron-mediated feed-forward and -backward modulation within PFC would differentially modulate the downstream limbic activity and subsequently shape the cognitive and emotional behavior.

Social anxiety, posterior insula activation, and autonomic response during self-initiated action in a Cyberball game

BackgroundAn earlier study characterized the neural correlates of self-initiated actions in a Cyberball game in healthy individuals. It remains unclear how social anxiety may influence these neural processes. MethodsWe examined regional activations to self-initiated actions in 25 adults with low and 25 with high social anxiety (LA and HA, respectively). Skin conductance was recorded concurrently with fMRI. We followed published routines in the analyses of imaging and skin conductance data. ResultsWe hypothesized that HA as compared to LA individuals would demonstrate increased cortical limbic activations during self-initiated actions (tossing or T > receiving or R trials, to control for motor activities) in social exclusion (EX) vs. fair game (FG) scenario. At a corrected threshold, HA as compared with LA group showed increases in bilateral posterior insula activation during T vs. R trials in EX as compared to FG. Further, HA as compared to LA showed higher skin conductance response to tossing trials during EX as compared to FG. LimitationsWith a limited sample size, we did not examine potential sex effects. Further, we cannot rule out the effects of depression on the findings. ConclusionsTogether, the results suggest that individuals with more severe social anxiety engaged the somatosensory insula to a greater extent and exhibited higher physiological arousal when initiating ball toss during social exclusion in the Cyberball game. Posterior insula response to self-initiated action may represent a biomarker of social anxiety. It remains to be investigated whether interventions to decrease physiological arousal may alleviate social anxiety.

The Organization of the Primate Insular Cortex.

Long perceived as a primitive and poorly differentiated brain structure, the primate insular cortex recently emerged as a highly evolved, organized and richly connected cortical hub interfacing bodily states with sensorimotor, environmental, and limbic activities. This insular interface likely substantiates emotional embodiment and has the potential to have a key role in the interoceptive shaping of cognitive processes, including perceptual awareness. In this review, we present a novel working model of the insular cortex, based on an accumulation of neuroanatomical and functional evidence obtained essentially in the macaque monkey. This model proposes that interoceptive afferents that represent the ongoing physiological status of all the organs of the body are first being received in the granular dorsal fundus of the insula or “primary interoceptive cortex,” then processed through a series of dysgranular poly-modal “insular stripes,” and finally integrated in anterior agranular areas that serve as an additional sensory platform for visceral functions and as an output stage for efferent autonomic regulation. One of the agranular areas hosts the specialized von Economo and Fork neurons, which could provide a decisive evolutionary advantage for the role of the anterior insula in the autonomic and emotional binding inherent to subjective awareness.

Emotion-based brain mechanisms and predictors for SSRI and CBT treatment of anxiety and depression: a randomized trial.

Mechanisms and predictors for the successful treatment of anxiety and depression have been elusive, limiting the effectiveness of existing treatments and curtailing the development of new interventions. In this study, we evaluated the utility of three widely used neural probes of emotion (experience, regulation, and perception) in their ability to predict symptom improvement and correlate with symptom change following two first-line treatments-selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT). Fifty-five treatment-seeking adults with anxiety and/or depression were randomized to 12 weeks of SSRI or CBT treatment (ClinicalTrials.gov identifier: NCT01903447). Functional magnetic resonance imaging (fMRI) was used to examine frontolimbic brain function during emotion experience, regulation, and perception, as probed by the Emotion Regulation Task (ERT; emotion experience and regulation) and emotional face assessment task (EFAT; emotion perception). Brain function was then related to anxiety and depression symptom change. Results showed that both SSRI and CBT treatments similarly attenuated insula and amygdala activity during emotion perception, and greater treatment-related decrease in insula and amygdala activity was correlated with greater reduction in anxiety symptoms. Both treatments also reduced amygdala activity during emotion experience but brain change did not correlate with symptom change. Lastly, greater pre-treatment insula and amygdala activity during emotion perception predicted greater anxiety and depression symptom improvement. Thus, limbic activity during emotion perception is reduced by both SSRI and CBT treatments, and predicts anxiety and depression symptom improvement. Critically, neural reactivity during emotion perception may be a non-treatment-specific mechanism for symptom improvement.

S40. Tinnitus Severity in Posttraumatic Stress Disorder (PTSD) is Directly Correlated With Hyperarousal and Inversely Correlated With Rapid Eye Movement (REM) Sleep Percentage and Duration

Tinnitus has been studied primarily in war veterans and refugees with PTSD, often exposed to head injury. A 50% tinnitus prevalence is reported in PTSD (versus a 10%-15% general population prevalence). Tinnitus is associated with both cochlear and central nervous pathologies including limbic activation. Overnight polysomnography of non-psychiatric tinnitus patients has revealed lower %REM (6.4%±4.9%) in tinnitus patients versus controls (21.5%±3.6%)(Attanasio G, 2013). To my knowledge, there are no polysomnographic studies of PTSD patients with tinnitus.

Central nervous system signatures of affect in asthma: associations with emotion-induced bronchoconstriction, airway inflammation, and asthma control.

The effects of asthma on affect have been noted for some time, but little is known about associated brain processes. We therefore examined whether emotion-induced bronchoconstriction, airway inflammation, and asthma control are related to specific patterns of brain activity during processing negative affective stimuli. Fifteen adults with asthma viewed alternating blocks of distressing film clips (negative condition), affectively neutral film clips (neutral condition), and a crosshair image (baseline condition) while undergoing blood oxygenation level-dependent (BOLD) functional MRI (fMRI). Block-design fMRI analysis evaluated the BOLD response to "negative-baseline" and "neutral-baseline" contrasts. Airway response to these film clips was also assessed with impulse oscillometry in a separate session. Measures of airway inflammation [fractional exhaled nitric oxide (FENO)] and asthma control [Asthma Control Questionnaire (ACQ)] were additionally obtained. A whole brain voxel-based regression analysis of contrast maps was performed against respiratory resistance increase during negative and neutral films, FENO, and ACQ. Peak airway obstruction to negative affective stimulation was associated with stronger activation of the anterior and middle cingulate gyrus, including the dorsal anterior cingulate cortex (dACC). Stronger airway inflammation and lower asthma control were associated with reduced activation to negative stimuli in the superior frontal gyrus, middle cingulate gyrus, and supplementary motor area. Activation of the dACC in negative-affect-induced airway obstruction could be part of an integrated defensive response to critical environmental change. In addition, reduced frontal and limbic activation during processing of negative affect may reflect consequences of pathophysiological processes for CNS functioning. NEW & NOTEWORTHY This functional magnetic resonance imaging study shows, for the first time, that the degree of airway constriction due to negative affective stimuli in asthma is associated with stronger response to these stimuli in the dorsal anterior and middle cingulate cortex. Asthma patients with stronger airway inflammation and reduced asthma control also show reduced activation in a number of cortical and subcortical areas relevant for affective processing and breathing control.

Dreaming during REM sleep: autobiographically meaningful or a simple reflection of a Hebbian-based memory consolidation process?

REM sleep is a state of desynchronized electrophysiological activity of the brain. It is usually accompanied by mental activity characterized by a succession of complex visual experiences commonly referred to as dreaming. Although REM sleep and dreaming are not implicitly conjoined, when they co-occur, they have a very distinct phenomenology, as, typically, the dream plot is bizarre and incohesive which is mirrored in heightened brain activation coupled with strongly attenuated coherence levels. At the same time, owing to increased limbic system activity, REM sleep dreams are highly emotional. Moreover, concrete emotions are often unrelated to dream events. Nevertheless, REM sleep dreams are often subjectively perceived as story-like and autobiographically meaningful. Indeed, elements of salient life events, attachment figures, and personally relevant emotions, especially trauma, seem to have a higher probability of re-appearing in dreams, albeit the dream plot itself remains highly distorted. This has prompted several theories on the interpretability of dreams, some authors leaning towards dreams reflecting waking mentation, others suggesting complete dissociation between waking and dreaming, both sides not fully accounting for empirical findings. In this review, we provide an overview of recent findings on the factors mediating REM sleep neurophysiology and dream content. As a first step towards integration of conflicting research results, we introduce a testable model (Trace-Spur-model) based on Hebbian theory of neural networks, proposing that dream bizarreness is a function of state-related modulations in synaptic strength allowing for hyper-associative mental activity, possibly enabling either a restructuring and integrative consolidation or extinction of learning experiences acquired in waking. In this model, dreams are viewed as phenomenological expressions of this neurophysiologic activity where dream recall allows a fragmentary witnessing of such processes, similar to peeking into an enduring and complex networking system. However, the content of the recollected dream is probably strongly deterred by autobiographical memory bias, favoring those images we can form some sort of association with.

Neural Correlates of Affective Disturbances: A Comparative Meta-analysis of Negative Affect Processing in Borderline Personality Disorder, Major Depressive Disorder, and Posttraumatic Stress Disorder

BackgroundBorderline personality disorder (BPD), major depressive disorder (MDD), and posttraumatic stress disorder (PTSD) are prominent examples of mental disorders with affective disturbances. Notably, all three disorders share a generally heightened negative affect, which is presumably the result of shared neural abnormalities in affective processing. In this meta-analysis, we aimed to identify transdiagnostic and disorder-specific abnormalities during the processing of negative compared with neutral stimuli. MethodsWe synthesized neuroimaging findings of affect processing in BPD, MDD, and PTSD and calculated combined coordinate- and image-based meta-analyses. The analysis comprised 70 distinct study samples with a total of 31 unthresholded statistical parametric maps. Twenty-four studies had a focus on BPD (431 individuals with BPD, 436 healthy control subjects [HCs]), 32 studies on MDD (789 individuals with current MDD, 870 HCs), and 14 studies on PTSD (247 individuals with PTSD, 245 HCs). ResultsFindings showed limbic hyperactivations in BPD and PTSD compared with limbic activation of HCs. In contrast, patients with MDD showed blunted amygdala activation in comparison with that of HCs. Additionally, the calculation of overlapping brain abnormalities in BPD, MDD, and PTSD highlighted transdiagnostic hyperactivation of the right median cingulate gyri and hypoactivation of the right middle frontal gyrus and the right middle occipital gyrus. Finally, disorder-specific comparisons also illustrate unique abnormalities for each mental disorder. ConclusionsThe present results support shared and disorder-specific neural abnormalities in patients with affective disturbances.

Volitional limbic neuromodulation exerts a beneficial clinical effect on Fibromyalgia

Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplificating effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation.We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation would improve chronic pain in patients suffering from Fibromyalgia, by reducing sleep disorder improving emotion regulation. We further expected that improved clinical status would correspond with successful training as indicated by improved down modulation of the Amygdala-EFP signal.Thirty-Four Fibromyalgia patients (31F; age 35.6 ± 11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions or sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion.REM latency and objective sleep quality index were robustly improved following the treatment course only in the real-neurofeedback group (time × group p < 0.05) and to a greater extent among good modulators (time × sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the neurofeedback training. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the real-neurofeedback group (time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures.Our findings suggest that Amyg-EFP-neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation treatment in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the substantial link between somatic and affective dysregulation that can be successfully targeted using neurofeedback.

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions.

BACKGROUND. Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive.METHODS. We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometric analyses) in healthy men, in a randomized double-blinded 2-way placebo-controlled study.RESULTS. Kisspeptin’s modulation of the default mode network (DMN) correlated with increased limbic activity in response to sexual stimuli (globus pallidus r = 0.500, P = 0.005; cingulate r = 0.475, P = 0.009). Furthermore, kisspeptin’s DMN modulation was greater in men with less reward drive (r = –0.489, P = 0.008) and predicted reduced sexual aversion (r = –0.499, P = 0.006), providing key functional significance. Kisspeptin also enhanced key mood connections including between the amygdala-cingulate, hippocampus-cingulate, and hippocampus–globus pallidus (all P < 0.05). Consistent with this, kisspeptin’s enhancement of hippocampus–globus pallidus connectivity predicted increased responses to negative stimuli in limbic structures (including the thalamus and cingulate [all P < 0.01]).CONCLUSION. Taken together, our data demonstrate a previously unknown role for kisspeptin in the modulation of functional brain connectivity and networks, integrating these with reproductive hormones and behaviors. Our findings that kisspeptin modulates resting brain connectivity to enhance sexual and emotional processing and decrease sexual aversion, provide foundation for kisspeptin-based therapies for associated disorders of body and mind.FUNDING. NIHR, MRC, and Wellcome Trust.

Neurophysiological Correlates of Collective Trauma Recall in 2009 L'Aquila Earthquake Survivors.

In the present study, we aimed to explore neural correlates of survivors of the 2009 L'Aquila, Italy earthquake in response to being shown pictures featuring their own city before and after an earthquake as well as those of an unfamiliar city. Moreover, we explored the associations among psychological variables and brain responses to the pictures of L'Aquila after the earthquake. Our final sample (N = 30 adults) comprised 15 survivors (M age = 31.40 years, SD = 9.42) and 15 controls (M age = 30.53 years, SD = 10.01). Participants' electroencephalographic (EEG) data were recorded during a visual task that included earthquake-related stimuli. Participants were assessed for posttraumatic and dissociation symptoms and event-related potential components, and low-resolution electromagnetic tomography (sLORETA) were analyzed. Compared to the control group, source localization in survivors indicated a lower intensity of the amygdala, hippocampal, parahippocampal, and temporopolar areas in response to visual stimuli concerning the earthquake, p < .001 to p < .0001. Results indicated a reduced limbic activation in response to visual stimuli that evoked the recall of earthquake in survivors. This finding suggests that survivors likely adopted a distancing strategy toward stimuli that may have elicited an emotional activation related to collective trauma.

The effect of nicotine patches on craving in the brain: A functional MRI study on heavy smokers.

Background:Smoking is a common phenomenon and kills over 6 million people every year. Many smokers try to quit smoking by using nicotine replacement therapy (NRT). Most of the time, relapse occurs in less than six months after finishing the program of NRT. We performed a single blinded study in which our aim was to figure out what the effect of the nicotine patch is on craving in the brain of smokers deprived from smoking.Methods:Five heavy smokers (Fagerström Test for Nicotine Dependence ≥4) underwent a functional magnetic resonance imaging (fMRI) in 4 random conditions: smoking (S); smoking deprivation (SD); SD combined with a NP (SD + NP); SD combined with a placebo patch (SD + PP). Visual stimulation provoked craving in block design by randomly displaying images of smoking related scenes. After image preprocessing, a fixed-effect analysis was performed to compare average group activations. The Questionnaire for Smoking Urges (QSU) was obtained before and after each scan.Results:The fMRI results showed higher activation in areas involved in craving in S compared with SD + NP, SD + PP, and SD. In the SD + NP, limbic circuit and attention area were higher activated compared with SD and SD + PP. The SD + PP and SD showed higher activation in the frontal cortex and limbic system compared with S and SD + NP. Nonsmokers showed higher limbic activation compared with SD.The QSU increased significantly after the fMRI experiment in S (P = .036).The SD had higher QSU scores compared with the S before (P = .002), and also after (P = .022) the fMRI experiment. The NP showed lower scores than the SD before the experiment (P = .046).Conclusion:The fMRI experiment revealed lower activity in areas associated with attention when subjects were nicotine deprived (SD + PP and SD). Areas involved with craving showed less activity when nicotine is present (S and SD + NP). The QSU showed a significant difference between SD and when nicotine is present (S and SD + NP).

Is REM sleep a paradoxical state showing muscle atonia and a cortical activity similar to waking?

Michel Jouvet renamed REM sleep paradoxical sleep (PS) after his discovery that it displays an EEG similar to waking but with a complete muscle paralysis. To determine whether the cortical activation is similar during PS and waking, we recently identified at cellular level the populations of cortical neurons activated and displaying plasticity during waking and PS hypersomnia by means of functional neuroanatomy [3] . Our mapping clearly shows for the first time that only a small number of limbic structures are activated during PS in contrast to waking. These structures are the cortical amygdaloid nucleus, the anterior cingulate, retrosplenial and medial entorhinal cortices, the claustrum and the dentate gyrus (DG) [3] . Further, combining retrograde tracing, neurotoxic lesion and FOS immunostaining, we showed that neurons of the claustrum and from the lateral part of the supramammillary nucleus (SuML) are responsible for the activation of the cortical structures and the DG during PS [3] . We further recently showed using stimulation of the SuML/DG pathway using optogenetic induces an increase in theta power and frequency indicating that this pathway plays a role in theta. These surprising results pointed out for the first time that the claustrum and the SuML activate a subset of limbic cortical neurons specifically during PS in contrast to waking during which the aminergic, cholinergic and the hypocretin systems activate the cortex. We propose that the limbic cortical activation revealed in our study might play a key role in the previously reported beneficial effect of PS on learning and memory. Indeed, many studies clearly indicate that PS is instrumental for memory consolidation [1] . Further, it has recently been shown that PS deprivation in rats impairs consolidation of contextual fear conditioning [2] .

Psychotherapy of Depression as Neurobiological Process - Evidence from Neuroimaging

Research on neurobiological effects of psychotherapy in depression facilitates the improvement of treatment strategies. The cortico-limbic dysregulation model serves as a framework for numerous studies on neurobiological changes in depression. In this model, depression is described as hypoactivation of dorsal cortical brain regions in conjunction with hyperactivation of ventral paralimbic regions. This assumption has been supported by various studies of structural and functional brain abnormalities in depression. However, also regions not included in the original cortico-limbic dysregulation model, such as the dorsomedial prefrontal cortex, seem to play an important role in depression. Functional connectivity studies of depression have revealed an enhanced connectivity within the so-called default mode network which is involved in self-referential thinking. Studies also point to a normalization of limbic and cortical brain activity, especially in the anterior cingulate cortex, during psychotherapy. Some neurobiological markers like the activity of the anterior cingulate cortex, striatum and insula as well as hippocampal volume have been proposed to predict treatment response on a group-level. The activity of the anterior insula appears to be a candidate bio-marker for differential indication for psychotherapy or pharmacotherapy. The cortico-limbic dysregulation model and following research have inspired new forms of treatment for depression like deep brain stimulation of the subgenual anterior cingulate cortex, repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex, neurofeedback and attention training.

Attentional engagement increases inferior frontal gyrus activity and mutes limbic activity in pediatric bipolar disorder: Meta-analyses of fMRI studies

ObjectivesAttention deficit has been shown to exist in adult and pediatric bipolar disorder across the life span. Given that emotion dysregulation is central to bipolar disorder, this study hypothesizes that emotional circuitry regions are altered along with anomalies in the attentional systems during cognitive deployment in bipolar disorder. MethodsAn activation likelihood estimation meta-analysis of attentional activities using GingerALE software was completed for adult and pediatric bipolar disorder populations in all published studies till December 2017. The meta-analysis of all fMRI studies included a total of ten pediatric studies (comprised of pediatric bipolar disorder (PBD) and typically developing (TD) groups) and nine adult patient studies (comprised of adult bipolar disorder (ABD) and healthy control (HC) groups). ResultsWhile engaged in attentional tasks, increased activation was seen in inferior frontal gyrus with decreased activation in limbic regions in subjects with PBD, relative to TD. Differential patterns of underactivity were also noted in the dorsal attentional system i.e., frontostriatal circuit (dorsolateral prefrontal cortex, anterior cingulate cortex, right lentiform nucleus and right globus pallidus) in PBD patients relative to the TD. However, we did not see any significant differences between the adult groups i.e., ABD vs. HC. ConclusionsIn PBD, deploying attentional system potentially improves the fronto-limbic affective circuitry function, despite impaired dorsal attentional system i.e., fronto-striatal circuitry. In contrast, these neural correlates underlying attentional engagement appeared to be not significant in adult BD. LimitationsWe examined the PBD vs. TD and the ABD vs. HC separately instead of four-way contrast (dual meta-analytic study). Also, attentional tasks were not unidimensional and tend to capture selective and sustained attention along with response inhibition, thereby recruiting multiple brain circuits.

Oxytocin reduces a chemosensory-induced stress bias in social perception

Social transmission of fear is not restricted to visual or auditory cues, but extends to the phylogenetically more ancient olfactory domain. Anxious individuals exhibit heightened sensitivity towards chemosensory stress signals in sweat; however,it is still unknown whether endogenous neuromodulators such as the peptide hormone oxytocin (OXT) influence the chemosensory communication of stress. Here, we investigated whether OXT selectively diminishes behavioral and neural responses to social chemosensory stress cues utilizing a randomized, double-blind, placebo (PLC)-controlled, within-subject functional MRI study design. Axillary sweat was obtained from 30 healthy male donors undergoing the Trier Social Stress Test (stress) and bicycle ergometer training (sport). Subsequently, 58 healthy participants (30 females) completed a forced-choice emotional face recognition task with stimuli of varying intensities (neutral to fearful) while they were exposed to both sweat stimuli and a non-social control odor following intranasal OXT or PLC administration, respectively. OXT diminished stress-induced recognition accuracy and response time biases towards fear. On the neural level, OXT reduced stress-evoked responses in the amygdala in both sexes, the anterior cingulate cortex (ACC) in females, and the hippocampus in males. Furthermore, OXT reinstated the functional connectivity between the ACC and the fusiform face area that was disrupted by stress odors under PLC. Our findings reveal a new role for OXT signaling in the modulation of chemosensory communication of stress in humans. Mechanistically, this effect appears to be rooted in a downregulation of stress-induced limbic activations and concomitant strengthening of top-down control descending from the ACC to the fusiform face area.

Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal.

Synthetic androgens (i. e., anabolic-androgenic steroids) are the primary component to the majority of problematic appearance and performance enhancing drug (APED) use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc.) via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

Evaluaton of regional cerebral blood flow alterations by limbic activation in patients with schizophrenia

The aim of study is to evaluate the functions of limbic system in schizophrenia by performing procaine administration and using single photon emission computed tomography (SPECT). 22 patients and 19 controls were included in the study. Patients were evaluated with Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A), Calgary Depression Rating Scale for Schizophrenia (CDSS) and the controls were evaluated with BPRS, HAM-D and HAM-A. The regional cerebral blood flow (rCBF) values were measured by SPECT. The rCBF following placebo and the alteration ratios of the rCBF following procaine of patients compared to controls. The rCBF following placebo in bilateral frontal, bilateral superior temporal, bilateral parahippocampus, thalamus, insula and alteration ratios of rCBF following procaine in bilateral anterior cingulate cortex (ACC) and left thalamus of patients were lower. Poor limbic activation to procaine was observed in the ACC and left thalamus of patients with schizophrenia. These findings support that the ACC and thalamus are crucial role in pathophysiology of schizophrenia.