Vertebral Artery Dissection.

Vertebral artery dissections are a rare pathology that carries a high risk of stroke in a younger population. They may be caused by minor mechanisms and the index of suspicion should be high. Treatment with anticoagulation or antiplatelets should follow if no surgical management is indicated.We describe a case of a female in her 30s who fell backward off a swing and rolled over her head and complained of continued posterior neck pain. The patient was found to have a vertebral artery dissection on MRI. The patient was then anticoagulated with high-dose apixaban and low-dose aspirin.The emergency medicine provider should be aware of possible low-impact mechanisms that can cause vertebral artery dissection and should have a high index of suspicion. If surgical management is not indicated, anticoagulation should be initiated.

A Neurobehavioral Continuum of Care for Individuals with Intellectual and Developmental Disabilities with Severe Problem Behavior.

The Neurobehavioral Programs at Kennedy Krieger Institute constitute a comprehensive continuum of care designed to serve individuals with intellectual and developmental disabilities with co-occurring problem behavior. This continuum includes inpatient, intensive outpatient, outpatient, consultation, and follow-up services. The mission of these programs is to fully integrate patient care, research, training, and advocacy to achieve the best possible outcomes with patients, and to benefit the broader community of individuals with severe behavioral dysfunction. The primary treatment approach utilized across all programs is applied behavior analysis, however the inpatient unit also provides fully integrated interdisciplinary care. Factors driving the development and expansion of these programs are described, as are the processes and systems by which the mission objectives are achieved.

Rapid Conversion from Clinic to Telehealth Behavioral Services During the COVID-19 Pandemic.

Survival often depends on behavior that can adapt to rapid changes in contingencies, which should be particularly well suited to a contingency-sensitive and data-based discipline such as applied behavior analysis (ABA). The speed and scale with which contingencies shifted in early March 2020 due to the effects of COVID-19 represent a textbook case for rapid adaptation with a direct impact on the survival of many types of enterprises. We describe here the impact, changes, and outcomes achieved by a large, multifaceted ABA clinical program that has (a) ongoing data that forecasted and tracked changes, (b) staff well practiced with data-based shifts in operations (behavior), and (c) up-to-date information (data) on policy and regulations. The results showed rapid shifts in client and staff behavior on a daily basis, shifts in services from in-person services to telehealth, and increases in volumes, revenue, and margins. We detail regulations and provide actionable steps that clinical organizations can take pertinent to this shift now and in the future. The challenges of the COVID-19 pandemic underscore the importance of maintaining robust coordination and communication across our field in order to address crises that affect our field.

Identification of Emerging Self-Injurious Behavior in Young Children: A Preliminary Study.

Self-injurious behavior (SIB) is a chronic disorder that often begins in early childhood; however, few studies have examined the onset of SIB in young children. This preliminary study reports on the identification, assessment and observation of SIB in 32 children who had begun to engage in SIB within the previous 6 months. Participants were ages birth to 5 years and presented with or were at risk for intellectual and/or developmental disabilities. Assessment measures included parental interviews, developmental and language measures, standardized measures of problem behavior, and direct observations conducted in the home. Results indicated that for most children, SIB emerged prior to age 1 year, and multiple topographies of SIB and other problem behaviors developed in most children. Multiple measures were useful in identifying SIB and in characterizing the behavior by topography, frequency, and severity. Findings from the examination of child communication in relation to SIB were inconclusive. Results are discussed in relation to theories of SIB emergence, and previous observational studies of young children with SIB.

Generalized anxiety modulates frontal and limbic activation in major depression.

BACKGROUND: Anxiety is relatively common in depression and capable of modifying the severity and course of depression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited. METHODS: We used functional magnetic resonance imaging and two emotional information processing tasks to examine frontal and limbic activation in ten patients with major depression and comorbid with preceding generalized anxiety (MDD/GAD) and ten non-depressed controls. RESULTS: Consistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and middle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in MDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the effects varied with the type of emotional information presented. CONCLUSIONS: Our findings highlight frontal and limbic hypoactivation in patients with depression and comorbid anxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional context. One implication of this finding is that divergent findings reported in the imaging literature on depression could reflect modulation of activation by anxiety level in response to different types of emotional information.

Identification of epigenetically altered genes in sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a terminal disease involving the progressive degeneration of motor neurons within the motor cortex, brainstem and spinal cord. Most cases are sporadic (sALS) with unknown causes suggesting that the etiology of sALS may not be limited to the genotype of patients, but may be influenced by exposure to environmental factors. Alterations in epigenetic modifications are likely to play a role in disease onset and progression in ALS, as aberrant epigenetic patterns may be acquired throughout life. The aim of this study was to identify epigenetic marks associated with sALS. We hypothesize that epigenetic modifications may alter the expression of pathogenesis-related genes leading to the onset and progression of sALS. Using ELISA assays, we observed alterations in global methylation (5 mC) and hydroxymethylation (5 HmC) in postmortem sALS spinal cord but not in whole blood. Loci-specific differentially methylated and expressed genes in sALS spinal cord were identified by genome-wide 5mC and expression profiling using high-throughput microarrays. Concordant direction, hyper- or hypo-5mC with parallel changes in gene expression (under- or over-expression), was observed in 112 genes highly associated with biological functions related to immune and inflammation response. Furthermore, literature-based analysis identified potential associations among the epigenes. Integration of methylomics and transcriptomics data successfully revealed methylation changes in sALS spinal cord. This study represents an initial identification of epigenetic regulatory mechanisms in sALS which may improve our understanding of sALS pathogenesis for the identification of biomarkers and new therapeutic targets.

Pediatric functional magnetic resonance neuroimaging: tactics for encouraging task compliance.

BACKGROUND: Neuroimaging technology has afforded advances in our understanding of normal and pathological brain function and development in children and adolescents. However, noncompliance involving the inability to remain in the magnetic resonance imaging (MRI) scanner to complete tasks is one common and significant problem. Task noncompliance is an especially significant problem in pediatric functional magnetic resonance imaging (fMRI) research because increases in noncompliance produces a greater risk that a study sample will not be representative of the study population. METHOD: In this preliminary investigation, we describe the development and application of an approach for increasing the number of fMRI tasks children complete during neuroimaging. Twenty-eight healthy children ages 9-13 years participated. Generalization of the approach was examined in additional fMRI and event-related potential investigations with children at risk for depression, children with anxiety and children with depression (N=120). Essential features of the approach include a preference assessment for identifying multiple individualized rewards, increasing reinforcement rates during imaging by pairing tasks with chosen rewards and presenting a visual 'road map' listing tasks, rewards and current progress. RESULTS: Our results showing a higher percentage of fMRI task completion by healthy children provides proof of concept data for the recommended tactics. Additional support was provided by results showing our approach generalized to several additional fMRI and event-related potential investigations and clinical populations. DISCUSSION: We proposed that some forms of task noncompliance may emerge from less than optimal reward protocols. While our findings may not directly support the effectiveness of the multiple reward compliance protocol, increased attention to how rewards are selected and delivered may aid cooperation with completing fMRI tasks. CONCLUSION: The proposed approach contributes to the pediatric neuroimaging literature by providing a useful way to conceptualize and measure task noncompliance and by providing simple cost effective tactics for improving the effectiveness of common reward-based protocols.

Amygdala involvement in human avoidance, escape and approach behavior.

Many forms of psychopathology and substance abuse problems are characterized by chronic ritualized forms of avoidance and escape behavior that are designed to control or modify external or internal (i.e., thoughts, emotions, bodily sensations) threats. In this functional magnetic resonance imaging investigation, we examined amygdala reactivity to threatening cues when avoidance responding consistently prevented contact with an upcoming aversive event (money loss). In addition, we examined escape responding that terminated immediate escalating money loss and approach responding that produced a future money gain. Results showed cues prompting avoidance, escape and approach behavior recruited a similar fronto-striatal-parietal network. Within the amygdala, bilateral activation was observed to threatening avoidance and escape cues, even though money loss was consistently avoided, as well as to the reward cue. The magnitude of amygdala responses within subjects was relatively similar to avoidance, escape and approach cues, but considerable between-subject differences were found. The heightened amygdala response to avoidance and escape cues observed within a subset of subjects suggests threat-related responses can be maintained even when aversive events are consistently avoided, which may account for the persistence of avoidance-coping in various clinical disorders. Further assessment of the relation between amygdala reactivity and avoidance-escape behavior may prove useful in identifying individuals with or at risk for neuropsychiatric disorders.

Learning processes affecting human decision making: An assessment of reinforcer-selective Pavlovian-to-instrumental transfer following reinforcer devaluation.

In reinforcer-selective transfer, Pavlovian stimuli that are predictive of specific outcomes bias performance toward responses associated with those outcomes. Although this phenomenon has been extensively examined in rodents, recent assessments have extended to humans. Using a stock market paradigm adults were trained to associate particular symbols and responses with particular currencies. During the first test, individuals showed a preference for responding on actions associated with the same outcome as that predicted by the presented stimulus (i.e., a reinforcer-selective transfer effect). In the second test of the experiment, one of the currencies was devalued. We found it notable that this served to reduce responses to those stimuli associated with the devalued currency. This finding is in contrast to that typically observed in rodent studies, and suggests that participants in this task represented the sensory features that differentiate the reinforcers and their value during reinforcer-selective transfer. These results are discussed in terms of implications for understanding associative learning processes in humans and the ability of reward-paired cues to direct adaptive and maladaptive behavior.

Nothing to fear? Neural systems supporting avoidance behavior in healthy youths.

Active avoidance involving controlling and modifying threatening situations characterizes many forms of clinical pathology, particularly childhood anxiety. Presently our understanding of the neural systems supporting human avoidance is largely based on nonhuman research. Establishing the generality of nonhuman findings to healthy children is a needed first step towards advancing developmental affective neuroscience research on avoidance in childhood anxiety. Accordingly, this investigation examined brain activation patterns to threatening cues that prompted avoidance in healthy youths. During functional magnetic resonance imaging, fifteen youths (ages 9-13) completed a task that alternately required approach or avoidance behaviors. On each trial either a threatening 'Snake' cue or a 'Reward' cue advanced towards a bank containing earned points. Directional buttons enabled subjects to move cues away from (Avoidance) or towards the bank (Approach). Avoidance cues elicited activation in regions hypothesized to support avoidance in nonhumans (amygdala, insula, striatum and thalamus). Results also highlighted that avoidance response rates were positively correlated with amygdala activation and negatively correlated with insula and anterior cingulate activation. Moreover, increased amygdala activity was associated with decreased insula and anterior cingulate activity. Our results suggest that nonhuman neurophysiological research findings on avoidance may generalize to neural systems associated with avoidance in childhood. Perhaps most importantly, the amygdala/insula activation observed suggests that threat-related responses can be maintained even when aversive events are consistently avoided, which may account for the persistence of avoidance-coping in childhood anxiety. The present approach may offer developmental affective neuroscience a conceptual and methodological framework for investigating avoidance in childhood anxiety.

Neural correlates of derived relational responding on tests of stimulus equivalence.

BACKGROUND: An essential component of cognition and language involves the formation of new conditional relations between stimuli based upon prior experiences. Results of investigations on transitive inference (TI) highlight a prominent role for the medial temporal lobe in maintaining associative relations among sequentially arranged stimuli (A > B > C > D > E). In this investigation, medial temporal lobe activity was assessed while subjects completed "Stimulus Equivalence" (SE) tests that required deriving conditional relations among stimuli within a class (A identical with B identical with C). METHODS: Stimuli consisted of six consonant-vowel-consonant triads divided into two classes (A1, B1, C1; A2, B2, C2). A simultaneous matching-to-sample task and differential reinforcement were employed during pretraining to establish the conditional relations A1:B1 and B1:C1 in class 1 and A2:B2 and B2:C2 in class 2. During functional neuroimaging, recombined stimulus pairs were presented and subjects judged (yes/no) whether stimuli were related. SE tests involved presenting three different types of within-class pairs: Symmetrical (B1 A1; C1 B1; B2 A2; C2 B2), and Transitive (A1 C1; A2 C2) and Equivalence (C1 A1; C2 A2) relations separated by a nodal stimulus. Cross-class 'Foils' consisting of unrelated stimuli (e.g., A1 C2) were also presented. RESULTS: Relative to cross-class Foils, Transitive and Equivalence relations requiring inferential judgments elicited bilateral activation in the anterior hippocampus while Symmetrical relations elicited activation in the parahippocampus. Relative to each derived relation, Foils generally elicited bilateral activation in the parahippocampus, as well as in frontal and parietal lobe regions. CONCLUSION: Activation observed in the hippocampus to nodal-dependent derived conditional relations (Transitive and Equivalence relations) highlights its involvement in maintaining relational structure and flexible memory expression among stimuli within a class (A identical with B identical with C).

Occipitoparietal contributions to recognition memory: stimulus encoding prompted by verbal instructions and operant contingencies.

BACKGROUND: Many human neuroimaging investigations on recognition memory employ verbal instructions to direct subject's attention to a stimulus attribute. But do the same or a similar neurophysiological process occur during nonverbal experiences, such as those involving contingency-shaped responses? Establishing the spatially distributed neural network underlying recognition memory for instructed stimuli and operant, contingency-shaped (i.e., discriminative) stimuli would extend the generality of contemporary domain-general views of recognition memory and clarify the involvement of declarative memory processes in human operant behavior. METHODS: Fifteen healthy adults received equivalent amounts of exposure to three different stimulus sets prior to neuroimaging. Encoding of one stimulus set was prompted using instructions that emphasized memorizing stimuli (Instructed). In contrast, encoding of two additional stimulus sets was prompted using a GO/NO-GO operant task, in which contingencies shaped appropriate GO and NO-GO responding. During BOLD functional MRI, subjects completed two recognition tasks. One required passive viewing of stimuli. The second task required recognizing whether a presented stimulus was a GO/NO-GO stimulus, an Instructed stimulus, or novel (NEW) stimulus. Retrieval success related to recognition memory was isolated by contrasting activation from each stimulus set to a novel stimulus (i.e., an OLD > NEW contrast). To explore differences potentially related to source memory, separate contrasts were performed between stimulus sets. RESULTS: No regions reached supralevel thresholds during the passive viewing task. However, a relatively similar set of regions was activated during active recognition regardless of the methods and included dorsolateral and ventrolateral prefrontal cortex, right inferior and posterior parietal regions and the occipitoparietal region, precuneus, lingual, fusiform gyri and cerebellum. Results also showed the magnitude of the functional response in the occipitoparietal region was inversely correlated with reaction times (RTs), such that the largest functional response and slowest RTs occurred to Instructed stimuli and the smallest functional response and fastest RTs occurred to GO stimuli, with effects to NO-GO stimuli intermediate. The inverse relation was also present bilaterally in the parahippocampus and hippocampus. Comparisons between stimulus sets also revealed regional differences potentially related to source memory. CONCLUSION: Recognition of stimuli previously associated with instructions and operant contingencies (i.e., discriminative stimuli) generally recruited similar inferior frontal and occipitoparietal regions and right posterior parietal cortex, with the right occipitoparietal region showing the largest effect. These findings suggest domain-general views of recognition memory may be applicable to understanding the neural correlates of control exerted by discriminative stimuli and suggest declarative memory processes are involved in human operant behavior.

New knowledge derived from learned knowledge: functional-anatomic correlates of stimulus equivalence.

Forming new knowledge based on knowledge established through prior learning is a central feature of higher cognition that is captured in research on stimulus equivalence (SE). Numerous SE investigations show that reinforcing behavior under control of distinct sets of arbitrary conditional relations gives rise to stimulus control by new, derived relations. This investigation examined whether frontal-subcortical and frontal-parietal networks known to support reinforced conditional relations also support derived conditional relations. Twelve adult subjects completed matching-to-sample (MTS) training with correct/wrong feedback to establish four trained conditional relations within two distinct, three-member stimulus classes: (1) A1-->B1, B1-->C1 and (2) A2-->B2, B2-->C2. Afterwards, functional neuroimaging was performed when MTS trials were presented involving matching two identical circles (a sensorimotor control condition), trained relations (A-->B, B-->C), and derived relations: symmetry (B-->A, C-->B), transitivity (A-->C), and equivalence (C-->A). Conditional responding to trained and derived relations was similarly correlated with bilateral activation in the targeted networks. Comparing trained to derived relations, however, highlighted greater activation in several prefrontal regions, the caudate, thalamus, and putamen, which may represent the effects of extended training or feedback present during imaging. Each derived relation also evidenced a unique activation pattern. Collectively, the findings extend the role of frontal-subcortical and frontal-parietal networks to derived conditional relations and suggest that regional involvement varies with the type of derived conditional relation.

Integrating functional neuroimaging and human operant research: brain activation correlated with presentation of discriminative stimuli.

Results of numerous human imaging studies and nonhuman neurophysiological studies on "reward" highlight a role for frontal, striatal, and thalamic regions in operant learning. By integrating operant and functional neuroimaging methodologies, the present investigation examined brain activation to two types of discriminative stimuli correlated with different contingencies. Prior to neuroimaging, 10 adult human subjects completed operant discrimination training in which money was delivered following button pressing (press-money contingency) in the presence of one set of discriminative stimuli, and termination of trials followed not responding (no response-next trial contingency) in the presence of a second set of discriminative stimuli. After operant training, subjects were instructed to memorize a third set of control stimuli unassociated with contingencies. Several hours after training, functional magnetic resonance imaging was performed while subjects viewed discriminative and control stimuli that were presented individually for 1,500 ms per trial, with stimulus presentations occurring, on average, every 6 s. Activation was found in frontal and striatal brain regions to both sets of discriminative stimuli relative to control stimuli. In addition, exploratory analyses highlighted activation differences between discriminative stimuli. The results demonstrate the utility of coupling operant and imaging technologies for investigating the neural substrates of operant learning in humans.

Operant-contingency-based preparation of children for functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) is used to study brain function during behavioral tasks. The participation of pediatric subjects is problematic because reliable task performance and control of head movement are simultaneously required. Differential reinforcement decreased head motion and improved vigilance task performance in 4 children (2 with behavioral disorders) undergoing simulated fMRI scans. Results show that behavior analysis techniques can improve child cooperation during fMRI procedures.