Arousal Dysregulation Research Articles

Pupillary response during social emotion tasks in autism spectrum disorder.

Autistic individuals encounter challenges in recognizing emotional expressions of others. Pupillary response has been proposed as an indicator of arousal dysregulation or cognitive load. The pupillary response of autistic individuals during socio-affective tasks remains unclear. This study investigated pupillary response in autistic adults when viewing emotional faces/eyes and recognizing emotions during the Reading the Mind in the Eyes Test (RMET) and watching interpersonal touch scenes in the social touch task. The study included 98 participants diagnosed with autism spectrum disorder and 37 typically developing controls (TD). Pupil size was measured using the Tobii X2-30 Eye Tracker. The results showed that autistic adults had larger maximal pupil sizes, smaller minimal pupil sizes, and greater change rates of pupil size, particularly during the RMET Eyes task. Clinical correlations revealed that attention switching difficulty positively correlated with mean pupil size in TD participants, while social communication deficitspositively correlated with mean pupil size in autistic participants. In conclusion, our findings suggest atypical pupillary responses in autistic adults during socio-affective tasks, indicating heightened cognitive demand. Further investigation is necessary to understand the underlying mechanisms and their association with autistic traits.

Randomized controlled trial of individualized arousal-biofeedback for children and adolescents with disruptive behavior disorders (DBD)

Disruptive behavior disorders [including conduct disorder (CD) and oppositional defiant disorder (ODD)] are common childhood and adolescent psychiatric conditions often linked to altered arousal. The recommended first-line treatment is multi-modal therapy and includes psychosocial and behavioral interventions. Their modest effect sizes along with clinically and biologically heterogeneous phenotypes emphasize the need for innovative personalized treatment targeting impaired functions such as arousal dysregulation. A total of 37 children aged 8–14 years diagnosed with ODD/CD were randomized to 20 sessions of individualized arousal biofeedback using skin conductance levels (SCL-BF) or active treatment as usual (TAU) including psychoeducation and cognitive–behavioral elements. The primary outcome was the change in parents´ ratings of aggressive behavior measured by the Modified Overt Aggression Scale. Secondary outcome measures were subscales from the Child Behavior Checklist, the Inventory of Callous-Unemotional traits, and the Reactive-Proactive Aggression Questionnaire. The SCL-BF treatment was neither superior nor inferior to the active TAU. Both groups showed reduced aggression after treatment with small effects for the primary outcome and large effects for some secondary outcomes. Importantly, successful learning of SCL self-regulation was related to reduced aggression at post-assessment. Individualized SCL-BF was not inferior to active TAU for any treatment outcome with improvements in aggression. Further, participants were on average able to self-regulate their SCL, and those who best learned self-regulation showed the highest clinical improvement, pointing to specificity of SCL-BF regulation for improving aggression. Further studies with larger samples and improved methods, for example by developing BF for mobile use in ecologically more valid settings are warranted.

Arousal dysregulation and executive dysfunction in attention deficit hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition, that continues to have an elusive etiological background. A number of extant models and theories have historically intended to explain the many factors contributing to ADHD behaviors. One of the most accepted hypotheses has been the executive dysfunction theory associating reduction in executive control to abnormalities in structure and operational dysfunction of dopaminergic signaling networks. Nevertheless, executive functions are not always impaired in ADHD, and the literature describes other symptoms commonly reported suggesting individuals with ADHD would appear to suffer from a more general deficit. Another existing line of research, that has gained much attention recently, establishes that ADHD would have dysregulated states of brain arousal that would account for its commonly observed cognitive deficits and behavioral symptoms, described as the state regulation theory, which has now included measures of autonomic function. This article describes some important aspects that compose and challenge these two most influential theoretical constructs, executive dysfunction and state-regulation, based on their empirical evidence, implying the need to reevaluate the norms used to classify individuals and establish ADHD diagnosis. Large number of controversial results continue to exist within the study of ADHD biological and/or performance markers, possibly due to such heterogeneity and variability within the same diagnosis. The need to resolve these issues and establish newly revised diagnostic criteria for ADHD is critical, as therapeutic success depends on having accurately identified underlying neurophysiological factors in order to appropriately address them in treatment.

Astrocytic calcium waves: unveiling their roles in sleep and arousal modulation.

Neuron-astrocyte interactions are vital for the brain's connectome. Understanding astrocyte activities is crucial for comprehending the complex neural network, particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals. Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons. Astrocytes, outnumbering neurons by nearly fivefold, support and regulate neuronal and synaptic function. Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling. This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep, wakefulness, and arousal levels, exploring the involvement of noradrenaline signaling, ion channels, and glutamatergic signaling in different cortical states. These findings highlight the significant impact of astrocytes on large-scale neuronal networks, influencing brain activity and responsiveness. Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation. More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states, requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep- and arousal-related disorders.

0122 Sleep Moderates Arousal and Executive Functioning in Autistic Children

Abstract Introduction Arousal dysregulation (over- or under-arousal) and executive functioning (EF) difficulties are positively correlated and often experienced by autistic children. Arousal and task performance (e.g., EF) are connected, such that there is an optimal arousal level for an optimal performance and arousal dysregulation reduces task performance. Up to 80% of autistic children experience sleep problems, and sleep problems are positively correlated with arousal dysregulation and EF difficulties. Thus, sleep may moderate the relationship between arousal and EF in autistic children. Given that sleep is modifiable through behavioral sleep treatment, it is important to better understand these relationships in autistic children. This study examined whether subjective and objective sleep moderated the relationship between HRV and EF among autistic children. Methods Children with autism spectrum disorder (N=65), verbal IQ >70, and parent reported sleep complaints (Mage=8.95, SD=2.01, range 6-12; 74% male) completed 14 days of sleep diaries (with parental assistance) and actigraphy, Holter Monitoring (8-mins at rest), and the Connor’s Continuous Performance Test (CPT)-III (ages 8+) or Connor’s Kiddie CPT-II (ages 4-7.11). Multiple regressions (SPSS PROCESS) examined whether sleep (subjective/objective wake after sleep onset-WASO, total sleep time-TST) moderated associations between arousal (standard deviation of normal-to-normal R-R-intervals-SDNN, proportion of adjacent R-R intervals differing by >50 ms-PNN50) and EF (CPT-perseverations, omissions, commissions). Analyses controlled for age. Results Objective WASO moderated associations between SDNN and CPT-perseverations (R2=.27, p=.03). At highest WASO, higher SDNN was associated with greater perseverations, t(1,65)=5.00, p=.029. Subjective TST moderated associations between PNN50 and CPT-perseverations (R2=.32, p=.01). At highest TST, higher PNN50 was associated with greater perseverations t(1,65)=4.27, p=.04. Conclusion When autistic children sleep more and have greater sleep fragmentation, EF may suffer (i.e., greater response repetition) if arousal is not high enough. While our finding for sleep fragmentation (indicative of poor sleep) is consistent with existing literature, that for greater sleep (indicative of better sleep) is not. This suggests the relationships amongst these constructs are complex in autism, and more research using longitudinal and experimental methodology and perhaps even examining other aspects of TST (e.g., variability) are needed. Support (if any) DOD Autism Research Program (McCrae, PI; W81XWH2010399); NIAMS (R01AR055160/R01AR005160- S1; P1,McCrae).

The Benefits of Grounding Strategies in Emotion and Arousal Regulation

In this article, the author discusses the benefits of grounding strategies in modulating arousal and emotion. These essential resources are reminders of the present and are well-used in trauma therapy, temporary or persistent affect and arousal dysregulation, and crisis interventions. Grounding strategies foster emotional and physiological stabilization by focusing on the present environment and anchoring oneself in the here and now. Furthermore, they restore a sense of calmness and safety, promote a sense of control, and decrease the risk of dissociation in trauma treatment. The author analyzes from a Jungian perspective the impact of a patient’s dissociative manifestation and how to mitigate it using a compensatory grounding strategy

Individual differences in working memory capacity, attention control, fluid intelligence, and pupillary measures of arousal.

The present study examined individual differences in 3 cognitive abilities: attention control (AC), working memory capacity (WMC), and fluid intelligence (gF) as they relate the tendency to experience task-unrelated thoughts (TUTs) and the regulation of arousal. Cognitive abilities were measured with a battery of 9 laboratory tasks, TUTs were measured via thought probes inserted into 2 tasks, and arousal regulation was measured via pupillometry. Recent theorizing (Unsworth & Robison, 2017b) suggests that 1 reason why some people experience relatively frequent TUTs and relatively poor cognitive performance-especially AC and WMC-is that they exhibit dysregulated arousal. Here, we examined how arousal regulation might predict both AC and WMC, but also higher-order cognitive abilities like gF. Further, we examine direct and indirect associations with these abilities via a mediating influence of TUT. Participants who reported more TUTs also tended to exhibit poorer AC, lower WMC, and lower gF. Arousal dysregulation correlated with more TUTs and lower AC. However, there was no direct correlation between arousal regulation and WMC, nor between arousal regulation and gF. The association between arousal regulation and gF was indirect via TUT. We discuss the implications of the results in light of the arousal regulation theory of individual differences and directions for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Pupillary correlates of individual differences in long-term memory.

The present study is the first to examine individual differences in long-term memory, arousal dysregulation, and intensity of attention within the same experiment. Participants (N = 106) completed 28 lists of an immediate free-recall task while their pupil diameter was recorded via an eye-tracker during the encoding period. Two main pupillary measures were extracted: intraindividual variability in pre-list pupil diameter and evoked pupillary responses during item encoding. Variability in pre-list pupil diameter served as a measure of arousal dysregulation, and evoked pupillary responses served as a measure of intensity of attention. Based on prior work, we hypothesized that there would be a positive association between intensity of attention and recall ability, and that there would be a negative association between arousal dysregulation and recall ability. Collectively these two measures accounted for 19% of interindividual variance in recall, with 5% attributable uniquely to intensity of attention and 12% attributable uniquely to arousal regulation. The findings demonstrate that there are sources of individual differences in long-term memory that can be revealed via pupillometry, notably the amount of effort deployed during item encoding and the degree to which people exhibit dysregulated arousal. Both findings are consistent with recent theorizing regarding the role of the locus coeruleus (LC)-norepinephrine (NE) system's role in goal-directed cognition. Specifically, the LC governs both moment-to-moment arousal and NE release to cortical regions subserving cognitive processing. Among people for whom this system operates most optimally, long-term memory retention is superior.

Vocalization and physiological hyperarousal in infant-caregiver dyads where the caregiver has elevated anxiety.

Co-regulation of physiological arousal within the caregiver-child dyad precedes later self-regulation within the individual. Despite the importance of unimpaired self-regulatory development for later adjustment outcomes, little is understood about how early co-regulatory processes can become dysregulated during early life. Aspects of caregiver behavior, such as patterns of anxious speech, may be one factor influencing infant arousal dysregulation. To address this, we made day-long, naturalistic biobehavioral recordings in home settings in caregiver-infant dyads using wearable autonomic devices and miniature microphones. We examined the association between arousal, vocalization intensity, and caregiver anxiety. We found that moments of high physiological arousal in infants were more likely to be accompanied by high caregiver arousal when caregivers had high self-reported trait anxiety. Anxious caregivers were also more likely to vocalize intensely at states of high arousal and produce intense vocalizations that occurred in clusters. High-intensity vocalizations were associated with more sustained increases in autonomic arousal for both anxious caregivers and their infants. Findings indicate that caregiver vocal behavior differs in anxious parents, cooccurs with dyadic arousal dysregulation, and could contribute to physiological arousal transmission. Implications for caregiver vocalization as an intervention target are discussed.

Relationships between locus coeruleus structural integrity and nocturnal awakenings in the context of AD biomarkers: A 7T MRI study

AbstractBackgroundThe brainstem locus coeruleus (LC) may constitute the intersection of the initial pathophysiological and clinical phenotypes of Alzheimer’s disease (AD). Tau protein accumulation starts early in the LC and sleep‐wake disruption occurs in early stages of AD, potentially reflecting arousal dysregulation in wake‐promoting neurons of the LC. Here, we sought to investigate whether LC structural integrity could be related to subjective sleep‐wake measures in the context of AD biomarkers.MethodWe used an in‐house developed LC‐specific MRI sequence at 7T in 72 cognitively normal older participants (mean age = 65.2 ± 8.2y; 37 women), and we identified sub‐portions of the LC using intensity‐based cluster analyses. Participants’ reports on habitual sleep quality and nocturnal awakenings were collected. In addition, blood‐based biomarker of total tau was measured, and APOE genotype was determined.ResultTwo distinct LC segments were identified, with one covering the middle‐to‐caudal LC and displaying lower intensity compared to the middle‐to‐rostral cluster (t(70) = ‐4.40, p < .0001). Generalized linear mixed models adjusted for age, sex, depression, and APOE status showed that subjective sleep quality was not related to any LC integrity measures. However, we found that lower MRI signal intensity within the middle‐to‐caudal LC, but not in the middle‐to‐rostral LC, was associated with a higher number of self‐reported nocturnal awakenings (F1,63 = 4.89, p = 0.03). Furthermore, this association was mostly evident in individuals with elevated levels of total tau (F1,61 = 4.23, p = 0.04).ConclusionOur findings provide in vivo evidence that worse LC structural integrity is associated with more frequent nocturnal awakenings in the context of neurodegeneration, in cognitively normal older individuals. In addition, they further emphasize the role of the LC in the arousal‐ascending system as an important neurobiological correlate of sleep‐wake regulation, and hold promise for the identification of at‐risk populations for preventive interventions.

Anxious parents show higher physiological synchrony with their infants.

Interpersonal processes influence our physiological states and associated affect. Physiological arousal dysregulation, a core feature of anxiety disorders, has been identified in children of parents with elevated anxiety. However, little is understood about how parent-infant interpersonal regulatory processes differ when the dyad includes a more anxious parent. We investigated moment-to-moment fluctuations in arousal within parent-infant dyads using miniaturised microphones and autonomic monitors. We continually recorded arousal and vocalisations in infants and parents in naturalistic home settings across day-long data segments. Our results indicated that physiological synchrony across the day was stronger in dyads including more rather than less anxious mothers. Across the whole recording epoch, less anxious mothers showed responsivity that was limited to 'peak' moments in their child's arousal. In contrast, more anxious mothers showed greater reactivity to small-scale fluctuations. Less anxious mothers also showed behaviours akin to 'stress buffering' - downregulating their arousal when the overall arousal level of the dyad was high. These behaviours were absent in more anxious mothers. Our findings have implications for understanding the differential processes of physiological co-regulation in partnerships where a partner is anxious, and for the use of this understanding in informing intervention strategies for dyads needing support for elevated levels of anxiety.

Impulsivity as a multifactorial construct and its relationship to PTSD severity and threat sensitivity

Changes to the DSM-5′s conceptualization of posttraumatic stress disorder (PTSD) highlight the importance of impulsivity within the context of PTSD-related arousal dysregulation. While the relationship between PTSD and threat sensitivity is well defined, how they relate to impulsivity remains understudied. We examined the relationship between PTSD symptom severity, threat sensitivity, and impulsivity. 124 participants completed the PTSD Checklist (PCL-C) and the Barratt Impulsiveness Scale 11th ed (BIS-11). BIS-11 items were separated to define cognitive and behavioral impulsivity subdomains. A trauma-exposed subsample of 39 participants were also exposed to no, ambiguous, and high threat conditions in a threat-enhanced acoustic startle paradigm with psychophysiological response as the outcome variable. PTSD severity was significantly associated with greater overall impulsivity and behavioral impulsivity. Greater overall impulsivity and both cognitive and behavioral impulsivity subdomains were significantly associated with psychophysiological magnitudes across threat conditions in the traumatized subsample. Our results suggest PTSD severity may linked to behavioral impulsivity and both cognitive and behavioral impulsivity are associated with threat sensitivity and hyperarousal. Assessing impulsivity within the context of PTSD, particularly in terms of its cognitive and behavioral subdomains, may provide important, clinically relevant information.

Individual differences in working memory capacity and the regulation of arousal.

Previously it has been theorized that differential functioning of the locus coeruleus-norepinephrine (LC-NE) system affects people's ability to regulate arousal, which has impacts on cognitive abilities. In the present study, we investigated three potential mechanisms by which the LC-NE system can fail to regulate arousal appropriately: hypoarousal, hyperarousal, and dysregulation of arousal. Each of these three could potentially account for why arousal affects cognition. To test the contributions of these three mechanisms, the present study examined individual differences in working memory capacity (WMC) and the regulation of arousal using pupillometry. Participants completed multiple complex span and visual arrays change-detection measures of WMC. An eye-tracker recorded pupil diameter as participants completed the visual arrays tasks. We found rather mixed evidence for the three mechanisms. Arousal dysregulation correlated with lower visual arrays performance and more self-reported attentional lapses. However, arousal regulation did not correlate with complex span performance. There was also some evidence for hypoarousal as an explanatory mechanism, as arousal correlated with attentional lapses. We discuss the implications of the results for theories regarding the role of arousal regulation in cognitive performance and individual differences in cognitive abilities.

Early postnatal manganese exposure causes arousal dysregulation and lasting hypofunctioning of the prefrontal cortex catecholaminergic systems.

Studies have reported associations between environmental manganese (Mn) exposure and impaired cognition, attention, impulse control, and fine motor function in children. Our recent rodent studies established that elevated Mn exposure causes these impairments. Here, rats were exposed orally to 0, 25, or 50mg Mnkg-1 day-1 during early postnatal life (PND 1-21) or lifelong to determine whether early life Mn exposure causes heightened behavioral reactivity in the open field, lasting changes in the catecholaminergic systems in the medial prefrontal cortex (mPFC), altered dendritic spine density, and whether lifelong exposure exacerbates these effects. We also assessed astrocyte reactivity (glial fibrillary acidic protein, GFAP), and astrocyte complement C3 and S100A10 protein levels as markers of A1 proinflammatory or A2 anti-inflammatory reactive astrocytes. Postnatal Mn exposure caused heightened behavioral reactivity during the first 5-10min intervals of daily open field test sessions, consistent with impairments in arousal regulation. Mn exposure reduced the evoked release of norepinephrine (NE) and caused decreased protein levels of tyrosine hydroxylase (TH), dopamine (DA) and NE transporters, and DA D1 receptors, along with increased DA D2 receptors. Mn also caused a lasting increase in reactive astrocytes (GFAP) exhibiting increased A1 and A2 phenotypes, with a greater induction of the A1 proinflammatory phenotype. These results demonstrate that early life Mn exposure causes broad lasting hypofunctioning of the mPFC catecholaminergic systems, consistent with the impaired arousal regulation, attention, impulse control, and fine motor function reported in these animals, suggesting that mPFC catecholaminergic dysfunction may underlie similar impairments reported in Mn-exposed children.

Hyperstable arousal regulation in multiple sclerosis

BackgroundFatigue is common in multiple sclerosis (MS) patients. Exhaustion of physiological reserves and mental stress are postulated causes, the latter supported by more pronounced hypothalamic-pituitary-adrenal (HPA) axis activation in fatigued patients. Divergent dysregulation of arousal appears to play important roles in depression- (hyperstable arousal) and in cancer-related (unstable arousal) fatigue, where HPA axis is hyperactive or hypoactive, respectively. ObjectiveThis study assessed arousal regulation in multiple sclerosis patients, explored if fatigue can be physiologically described by altered arousal regulation, and if HPA axis activity corresponds to the type(s) of arousal regulation. Methods51 mildly-affected patients with relapsing-remitting MS (86% on disease-modifying treatment) and 20 healthy controls were analysed via Vigilance Algorithm Leipzig and combined dexamethasone/corticotropin releasing hormone test. ResultsHyperstable arousal pattern was significantly more frequent in patients than in controls (62.7% vs. 45.0%, p = 0.011). Patients scored higher on all fatigue, but not on sleepiness scales. All patients combined showed mild activation of the hypothalamic-pituitary-adrenal axis (p < 0.05 for post-CRH ACTH and AUC ACTH; cortisol n.s.). While fatigue was numerically more pronounced in both hyperstable and unstable arousal, HPA axis activity was highest in hyperstable and lowest in unstable arousal (p = 0.013 for post-CRH ACTH; p = 0.087 for AUC ACTH; cortisol n.s.). ConclusionFrequency of arousal patterns are altered in MS. An association with HPA axis activity was weak, possibly because the present sample was stable on immunotherapy.

Longitudinal changes of amygdala functional connectivity in adolescents prenatally exposed to cocaine

BackgroundPrenatal cocaine exposure (PCE) is associated with arousal dysregulation, but interactions between exposure and age are rarely investigated directly with longitudinal study designs. Our previous study had examined task-elicited emotional arousal and noted persistently high amygdala activations in the development of adolescents with PCE. However, while externally imposed emotional arousal could be considered a “state” effect depending on specific task stimuli, it is still unclear whether similar developmental alterations extend to intrinsic functional connectivity (FC), reflecting more of a “trait” effect. MethodsWe used a longitudinal design and analyzed resting-state functional magnetic resonance imaging data acquired twice from 25 adolescents with PCE and 16 non-exposed controls. Both groups were each scanned first at the mean age of 14.3 and then again at 16.6 years. Seeding in bilateral amygdalae and comparing the 2nd scan with the 1st, we examined the interaction effect between PCE and age on FCs in the emotional network. ResultsCompared with the younger age, we observed a generally decreased FC in the emotional network of the control group at the older age, but these FCs were generally increased at the older age in this same network of the PCE group. Additionally, this interaction effect of exposure by age in the right fusiform was positively correlated with the emotional interference imposed by external task stimuli. ConclusionsThese results provided additional data directly characterizing developmental changes in the emotional network of adolescents with PCE, complementing and extending the notion of a PCE-associated long-term teratogenic effect on arousal regulation.

Somatic Resources: Sensorimotor Psychotherapy Approach to Stabilising Arousal in Child and Family Treatment

Trauma first and foremost disrupts the normal functioning of the nervous system, leading to extremes of autonomic arousal that often does not return to baseline once traumatic events are over. Dysregulation of arousal is a common feature in relational trauma. Such dysregulation is present for the individuals and for the family unit. When carers are dysregulated their capacities to cope with the challenges of caregiving are compromised. In turn, children are left to manage not only their own dysregulation but also the fluctuations occurring in their carers. Somatic resources and the embodiment of non‐somatic relational resources are efficient for physiological arousal and emotional regulation. Sensorimotor psychotherapy offers a means to better understand arousal and dysregulation as well as employ effective strategies to stabilise children and carers in challenged families. This article will provide a sensorimotor psychotherapy framework that can help in identifying priorities for therapeutic stabilisation efforts for children with abuse and/or neglect histories and their family members. The authors will discuss the value of employing somatic resources in preference to other categories of resources, and suggest practical ways in which to convert any non‐somatic resource into a more embodied experience.

Modifiable Arousal in Attention-Deficit/Hyperactivity Disorder and Its Etiological Association With Fluctuating Reaction Times

BackgroundCognitive theories of attention-deficit/hyperactivity disorder (ADHD) propose that high within-subject fluctuations of cognitive performance in ADHD, particularly reaction time (RT) variability (RTV), may reflect arousal dysregulation. However, direct evidence of arousal dysregulation and how it may account for fluctuating RTs in ADHD is limited. We used skin conductance (SC) as a measure of peripheral arousal and aimed to investigate its phenotypic and familial association with RTV in a large sample of ADHD and control sibling pairs. MethodsAdolescents and young adults (N = 292), consisting of 73 participants with ADHD and their 75 siblings, and 72 controls and their 72 siblings, completed the baseline (slow, unrewarded) and fast-incentive conditions of a RT task, while SC was simultaneously recorded. ResultsA significant group-by-condition interaction emerged for SC level (SCL). Participants with ADHD had decreased SCL, compared with controls, in the baseline condition but not the fast-incentive condition. Baseline SCL was negatively associated with RTV, and multivariate model fitting demonstrated that the covariance of SCL with RTV, and of SCL with ADHD, was mostly explained by shared familial effects. ConclusionsADHD is associated with decreased, but modifiable, tonic peripheral arousal. A shared familial cause underlies the relationship between arousal and RTV and between arousal and ADHD. Given the malleability of SCL, if our findings are replicated, it warrants further exploration as a potential treatment target for ADHD.

Physiological Arousal and Its Dysregulation in Child Maladjustment

Arousal and its regulation are key components of emotion, temperament, and flexible responding needed for healthy adjustment. This article presents a biosocial vulnerability model suggesting that maladjustment arises when psychological mechanisms are disrupted by changes in nervous system functioning that cause the discoordination of physiological regulatory systems, potentially leading to hyper- or hypoarousal and arousal dysregulation. The model posits bidirectional relationships with adverse social context at any level, ultimately derailing affective, cognitive, and interpersonal processes, which can increase psychopathology. Applications are made to childhood aggression and autism spectrum disorder as two examples of how differences in arousal and its dysregulation can impact child adjustment.

Amygdala on the Lookout.

results present an explanatory challenge: why would the amygdala be hypoactive in paranoid individuals who exhibit heightened threat perception and elevated physiological arousal? To explain this paradoxical finding, some investigators hypothesized that reduced frontal control over the amygdala due to dysconnectivity of frontolimbic circuitry could lead to hypervigilanceand misattribution of fear to incoming signals (3). AnotherpossibilityisthatmethodologicallimitationsofBOLD fMRI have obstructed a more accurate quantification of amygdala activity. In this issue of the Journal, a new study conducted by Pinkham and colleagues (5) offers a methodological explanation for discrepant findings concerning aberrant amygdala activity in paranoid schizophrenia. The authors definitively demonstrate higher baseline amygdala activity in paranoid compared with nonparanoid patients with schizophrenia, by employing arterial spin labeling perfusion MRI. Arterial spin labeling allows for a noninvasive and quantitative measurement of regional cerebral blood flow (CBF) by using magneticallylabeledarterialbloodwaterasanendogenoustracer (asopposedtoexogenousradioactivetracersusedinpositron emission tomography) (6). There are both important methodological and conceptual advances here worthy of note. In addition to arterial spin labeling, the authors acquired BOLD fMRI data while participants rated photographs of faces for trustworthiness. By measuring resting state regional CBF and task-related BOLD activity in the same participants, the authors were able to examine group differences in baseline amygdala activity alongside differences in task-related fluctuations of amygdalaactivity.Suchcomparisonsareparticularlyrelevant to schizophrenia, as prior evidence of amygdala hypoactivation relied on BOLD contrasts blind to potential group differences in baseline activity. Indeed, Pinkham and colleagues found that acutely paranoid patients exhibited higher resting CBF in the bilateral amygdala compared with nonparanoid patients and healthy comparison subjects, who did not differ from each other. On the other hand, the BOLD fMRI task analysis revealed a general trend of amygdala hypoactivation in paranoid compared with nonparanoid participants. Thus, observed taskrelated amygdala hypoactivity likely reflects higher baseline amygdala activity that mitigates the stimulus-driven signal change detected by the BOLD contrast. Additional wholebrain group comparisons found greater CBF in the internal capsule, the corpus callosum, and portions of the inferior temporal and fusiform gyri in paranoid compared with nonparanoid patients. Overall, these results suggest that paranoia