Understanding Career Goals Set by Autistic Youth.

IMPORTANCE: Recent years have seen a shift to strengths-based approaches promoting self-determination and career-related interests among autistic youth. Research is needed to understand the career-related goals set by autistic youth on the basis of their interests. OBJECTIVE: To descriptively explore the career design goals set by autistic youth engaged in the self-determined career design model (SDCDM) intervention. DESIGN: Content analysis was used to analyze the types of goals set by youth during intervention. Two researchers separately reviewed the goal set by each autistic youth (one goal per youth) and determined categories for each goal. SETTING: Preferred community location (usually the youth's home) in an urban Midwestern city. PARTICIPANTS: Twenty-one autistic youth. INTERVENTION: SDCDM. OUTCOMES AND MEASURES: Participants set goals as part of the SDCDM, which were recorded using Goal Attainment Scaling (GAS). Researchers used GAS to support each participant in setting a measurable and objective goal and describing criteria for meeting the goal. RESULTS: Categories included enhancing self-management, obtaining employment, exploring career opportunities, enhancing learning, and enhancing self-advocacy. CONCLUSIONS AND RELEVANCE: The findings from this study indicate that autistic youth set goals related to obtaining employment and enhancing generalizable 21st-century skills, such as self-advocacy and self-management. What This Article Adds: The SDCDM is a tool occupational therapy practitioners can use to support youth in setting and working toward career goals.

Isotopic-Perturbation NMR Study of Hydrogen-Bond Symmetry in Solution: Temperature Dependence and Comparison of OHO and ODO Hydrogen Bonds.

Is a hydrogen bond symmetric, with the hydrogen centered between two donor atoms, or is it asymmetric, with the hydrogen closer to one but jumping to the other? The NMR method of isotopic perturbation has been used to distinguish these. Previous evidence from isotope shifts implies that a wide variety of dicarboxylate monanions are asymmetric, present as a rapidly equilibrating mixture of tautomers. However, calculations of hydrogen trajectories across an anharmonic potential-energy surface could reproduce the observed isotope shifts in a phthalate monoanion. Therefore, it was concluded that those isotope shifts are instead consistent with isotope-induced desymmetrization on a symmetric potential-energy surface. To distinguish between these two interpretations, the 18O-induced isotope effects on the 13C NMR chemical shifts of cyclohexene-1,2-dicarboxylate monoanion in chloroform-d and on the 19F NMR chemical shifts of difluoromaleate monoanion in D2O have been investigated. In both cases the isotope effects are larger at lower temperature and also with deuterium in the hydrogen bond. It is concluded that these behaviors are consistent with the perturbation of an equilibrium between asymmetric tautomers and inconsistent with isotope-induced desymmetrization on a symmetric potential-energy surface.

The Activators of Cyclin-Dependent Kinase 5 p35 and p39 Are Essential for Oligodendrocyte Maturation, Process Formation, and Myelination.

The regulation of oligodendrocyte development and myelin formation in the CNS is poorly defined. Multiple signals influence the rate and extent of CNS myelination, including the noncanonical cyclin-dependent kinase 5 (Cdk5) whose functions are regulated by its activators p35 and p39. Here we show that selective loss of either p35 or p39 perturbed specific aspects of oligodendrocyte development, whereas loss of both p35 and p39 completely inhibited the development of mature oligodendrocytes and myelination. In the absence of p35, oligodendrocyte differentiation was delayed, process outgrowth was truncated in vitro, and the patterning and extent of myelination were perturbed in the CNS of p35(-/-) mice. In the absence of p39, oligodendrocyte maturation was transiently affected both in vitro and in vivo. However, loss of both p35 and p39 in oligodendrocyte lineage cells completely inhibited oligodendrocyte progenitor cell differentiation and myelination both in vitro and after transplantation into shiverer slice cultures. Loss of p35 and p39 had a more profound effect on oligodendrocyte development than simply the loss of Cdk5 and could not be rescued by Cdk5 overexpression. These data suggest p35 and p39 have specific and overlapping roles in oligodendrocyte development, some of which may be independent of Cdk5 activation.

Cyclin-dependent kinase 5 mediates adult OPC maturation and myelin repair through modulation of Akt and GsK-3ß signaling.

Failure of remyelination in diseases, such as multiple sclerosis (MS), leads to permanent axonal damage and irreversible functional loss. The mechanisms controlling remyelination are currently poorly understood. Recent studies implicate the cyclin-dependent kinase 5 (Cdk5) in regulating oligodendrocyte (OL) development and myelination in CNS. In this study, we show that Cdk5 is also an important regulator of remyelination. Pharmacological inhibition of Cdk5 inhibits repair of lysolecithin lesions. This inhibition is a consequence of Cdk5 disruption in neural cells because remyelination in slice cultures is blocked by Cdk5 inhibitors, whereas specific deletion of Cdk5 in OLs inhibits myelin repair. In CNP-Cre;Cdk5(fl/fl) conditional knock-out mouse (Cdk5 cKO), myelin repair was delayed significantly in response to focal demyelinating lesions compared with wild-type animals. The lack of myelin repair was reflected in decreased expression of MBP and proteolipid protein and a reduction in the total number of myelinated axons in the lesion. The number of CC1(+) cells in the lesion sites was significantly reduced in Cdk5 cKO compared with wild-type animals although the total number of oligodendrocyte lineage cells (Olig2(+) cells) was increased, suggesting that Cdk5 loss perturbs the transition of early OL lineage cell into mature OL and subsequent remyelination. The failure of remyelination in Cdk5 cKO animals was associated with a reduction in signaling through the Akt pathway and an enhancement of Gsk-3ß signaling pathways. Together, these data suggest that Cdk5 is critical in regulating the transition of adult oligodendrocyte precursor cells to mature OLs that is essential for myelin repair in adult CNS.

Can a secondary isotope effect be larger than a primary?

Primary and secondary (18)O equilibrium isotope effects on the acidities of a variety of Brønsted and Lewis acids centered on carbon, boron, nitrogen, and phosphorus were computed by density-functional theory. For many of these acids, the secondary isotope effect was found to be larger than the primary isotope effect. This is a counterintuitive result, because the H atom that is lost is closer to the (18)O atom that is responsible for the primary isotope effect. The relative magnitudes of the isotope effects can be associated with the vibrational frequency and zero-point energy of the X═O vibrations, which are greater than those of the X-O vibrations. However, the difference between these contributions is small, and the major responsibility for the larger secondary isotope effect comes from the moment-of-inertia factor, which depends on the position of the (18)O atom relative to the principal axes of rotation.

Variable-temperature study of hydrogen-bond symmetry in cyclohexene-1,2-dicarboxylate monoanion in chloroform-d.

The symmetry of the hydrogen bond in hydrogen cyclohexene-1,2-dicarboxylate monoanion was determined in chloroform using the NMR method of isotopic perturbation. As the temperature decreases, the (18)O-induced (13)C chemical-shift separations increase not only at carboxyl carbons but also at ipso (alkene) carbons. The magnitude of the ipso increase is consistent with an (18)O isotope effect on carboxylic acid acidity. Therefore it is concluded that this monoanion is a mixture of tautomers in rapid equilibrium, rather than a single symmetric structure in which a chemical-shift separation arises from coupling between a desymmetrizing vibration and anharmonic isotope-dependent vibrations, which is expected to show the opposite temperature dependence.

The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards.

Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making, was critical for the former but not for the latter form of conditioned reinforcement.

Instructional Content and Self-Determination in Individualized Education Program Annual Goals for Students With Extensive Support Needs.

Under the Individuals With Disabilities Education Act, individualized education program (IEP) annual goals are required to enable students with disabilities to be involved in and make progress in the general education curriculum and to address other educational needs. This study reports findings from a content analysis of the annual goals in 88 IEPs for K-12 students with extensive support needs. Results reflect a lack of comprehensive academic content goals to promote involvement and progress in the general education curriculum, and limited opportunities for students to develop skills associated with self-determination. Findings also show a focus within goals on student compliance rather than the development of meaningful skills and knowledge. Implications for research and practice are provided.

Barriers and facilitators to use of buprenorphine in state-licensed specialty substance use treatment programs: A survey of program leadership.

INTRODUCTION: Medications for opioid use disorder (MOUD), including buprenorphine, reduce overdose risk and improve outcomes for individuals with opioid use disorder (OUD). However, historically, most non-opioid treatment program (non-OTP) specialty substance use treatment programs have not offered buprenorphine. Understanding barriers to offering buprenorphine in specialty substance use treatment settings is critical for expanding access to buprenorphine. This study aims to examine program-level attitudinal, financial, and regulatory factors that influence clients' access to buprenorphine in state-licensed non-OTP specialty substance use treatment programs. METHODS: We surveyed leadership from state-licensed non-OTP specialty substance use treatment programs in New Jersey about organizational characteristics, including medications provided on- and off-site and percentage of OUD clients receiving any type of MOUD, and perceived attitudinal, financial, and regulatory barriers and facilitators to buprenorphine. The study estimated prevalence of barriers and compared high MOUD reach (n = 36, 35 %) and low MOUD reach (n = 66, 65 %) programs. RESULTS: Most responding organizations offered at least one type of MOUD either on- or off-site (n = 80, 78 %). However, 71 % of organizations stated that fewer than a quarter of their clients with OUD use any type of MOUD. Endorsement of attitudinal, financial, and institutional barriers to buprenorphine were similar among high and low MOUD reach programs. The most frequently endorsed government actions suggested to increase use of buprenorphine were facilitating access to long-acting buprenorphine (n = 95, 96 %), education and stigma reduction for clients and families (n = 95, 95 %), and financial assistance to clients to pay for medications (n = 90, 90 %). CONCLUSIONS: Although non-OTP specialty substance use programs often offer clients access to MOUD, including buprenorphine, most OUD clients do not actually receive MOUD. Buprenorphine uptake in these settings may require increased financial support for programs and clients, more robust education and training for providers, and efforts to reduce the stigma associated with medication among clients and their families.

Ventral striatum and orbitofrontal cortex are both required for model-based, but not model-free, reinforcement learning.

In many cases, learning is thought to be driven by differences between the value of rewards we expect and rewards we actually receive. Yet learning can also occur when the identity of the reward we receive is not as expected, even if its value remains unchanged. Learning from changes in reward identity implies access to an internal model of the environment, from which information about the identity of the expected reward can be derived. As a result, such learning is not easily accounted for by model-free reinforcement learning theories such as temporal difference reinforcement learning (TDRL), which predicate learning on changes in reward value, but not identity. Here, we used unblocking procedures to assess learning driven by value- versus identity-based prediction errors. Rats were trained to associate distinct visual cues with different food quantities and identities. These cues were subsequently presented in compound with novel auditory cues and the reward quantity or identity was selectively changed. Unblocking was assessed by presenting the auditory cues alone in a probe test. Consistent with neural implementations of TDRL models, we found that the ventral striatum was necessary for learning in response to changes in reward value. However, this area, along with orbitofrontal cortex, was also required for learning driven by changes in reward identity. This observation requires that existing models of TDRL in the ventral striatum be modified to include information about the specific features of expected outcomes derived from model-based representations, and that the role of orbitofrontal cortex in these models be clearly delineated.

Curricular Philosophies Reflected in Individualized Education Program Goals for Students With Complex Support Needs.

Individualized education program (IEP) goals are meant to be personalized to address the unique needs of students with disabilities, while also reflecting the student's grade-aligned general education curriculum. IEP goals describe what, how, and where students with disabilities are taught, and reflect the curriculum used to provide instruction. In this study, we analyzed how IEP goals align with the different curricular philosophies for students with severe disabilities. Using a sample of 88 IEPs for students with complex support needs (i.e., severe disabilities) in Grades K-12, we found most goals (57%) reflect curricular philosophies of the 1970s-1990s (i.e., developmental, functional, and social inclusion) eras, with only 26% of IEP goals representative of modern curricular philosophies (i.e., grade-aligned academic content). We also found secondary-aged students were less likely to have grade-aligned academic goals compared to elementary-aged students. We offer implications for ensuring individualization and goals reflecting skills needed for the 21st century.

Goal Attainment Scaling: A Framework for Research and Practice in the Intellectual and Developmental Disabilities Field.

Goal setting and attainment is often a targeted outcome in the intellectual and developmental disabilities field; however, standardizing the measurement of attainment of individualized goals is challenging. The purpose of this article is to introduce a four-domain framework that provides a series of questions to research and evaluation teams in planning for the use of goal attainment scaling (GAS) as an outcome measure at the individual or aggregate level. We intend to stimulate discussion and ongoing work to further systematize how GAS is used in (a) intervention research to establish evidence-based practices and (b) practice to assess the extent to which interventions and supports lead to intended outcomes. The goal is to promote a clear planning process to inform data collection on individualized goal attainment outcomes that are rooted in goals and outcomes valued by people with intellectual and developmental disabilities.

Employment Trends in Rhode Island From 2011 to 2017 for Adults With Intellectual Disability and Developmental Disabilities.

This study reports on state-level data in Rhode Island on employment and non-work activities of adults with intellectual and developmental disabilities receiving services between 2011 and 2017. The goal was to examine the complex patterns of change over time in individual-level employment outcomes and the potential short-term impacts of a consent decree entered into by the state of Rhode Island to address integrated employment outcomes. Findings suggest that policy initiatives such as the consent decree can lead to reductions in reliance on facility-based work, but also highlight the importance of planning for the transition to competitive, integrated employment and not simply a shift toward non-work activities. Further, the data support the notion that the best predictor of integrated employment over time is previous experiences in integrated employment (not facility-based or other work or non-work activities), suggesting the role of ongoing supported employment and transition services that create and support the maintenance of integrated employment.

Examining the Impact of the SDLMI and Whose Future Is It? Over a Two-Year Period With Students With Intellectual Disability.

The purpose of this study was to examine self-determination outcome data in the year following a one-year cluster randomized controlled trial (C-RCT) comparing the impacts of a Self-Determined Learning Model of Instruction (SDLMI) only condition to a SDLMI + Whose Future Is It? (SDLMI + WF) condition. Using multilevel B-spline model analysis with Bayesian estimation, we examined ongoing patterns of growth after the trial ended and all students were exposed to SDLMI + WF. The findings suggest that the inclusion of an additional year of outcome data provided additional insight into the impact of more intensive intervention conditions over time. Specifically, after the initial year of implementation, the SDLMI + WF condition predicted greater annual gains than the SDLMI only condition, unlike findings in the first year which reflected the opposite pattern. This evidence suggests a nonlinear growth pattern over multiple years of intervention with more intensive interventions. Implications for future research and practice are discussed.

The Self-Determined Learning Model of Instruction and Students With Extensive Support Needs in Inclusive Settings.

There is a strong link between the development of skills associated with self-determination (i.e., choice-making, decision-making, problem solving, goal setting and attainment, planning, self-management, self-advocacy, self-awareness, and self-knowledge) and positive school (e.g., academic achievement) and postschool (e.g., employment, community access) outcomes. In this article, we advocate for an examination of research related to the impact, usability, and cultural sustainability of an evidence-based intervention intended to enable students to enhance skills associated with self-determination, the Self-Determined Learning Model of Instruction (SDLMI), when used to support students with extensive support needs, including students with intellectual and developmental disability (IDD). Theoretical foundations of the construct of self-determination and its applicability for all people and extant research on implementation of the SDLMI and students with extensive support needs are presented. Implications for researchers are addressed, including the impact, usability, and cultural sustainability of the SDLMI for students with extensive support needs, and the potential of the SDLMI to support all students in inclusive settings when implemented as a universal support.

Orbitofrontal inactivation impairs reversal of Pavlovian learning by interfering with 'disinhibition' of responding for previously unrewarded cues.

Orbitofrontal cortex (OFC) is critical for reversal learning. Reversal deficits are typically demonstrated in complex settings that combine Pavlovian and instrumental learning. Yet recent work has implicated the OFC specifically in behaviors guided by cues and the features of the specific outcomes they predict. To test whether the OFC is important for reversing such Pavlovian associations in the absence of confounding instrumental requirements, we trained rats on a simple Pavlovian task in which two auditory cues were presented, one paired with a food pellet reward and the other presented without reward. After learning, we reversed the cue-outcome associations. For half the rats, OFC was inactivated prior to each reversal session. Inactivation of OFC impaired the ability of the rats to reverse conditioned responding. This deficit reflected the inability of inactivated rats to develop normal responding for the previously unrewarded cue; inactivation of OFC had no impact on the ability of the rats to inhibit responding to the previously rewarded cue. These data show that OFC is critical to reversal of Pavlovian responding, and that the role of OFC in this behavior cannot be explained as a simple deficit in response inhibition. Furthermore, the contrast between the normal inhibition of responding, reported here, and impaired inhibition of responding during Pavlovian over-expectation, reported previously, suggests the novel hypothesis that OFC may be particularly critical for learning (or behavior) when it requires the subject to generate predictions about outcomes by bringing together or integrating disparate pieces of associative information.

Oligodendrocyte-specific loss of Cdk5 disrupts the architecture of nodes of Ranvier as well as learning and memory.

Myelination of the central nervous system is important for normal motor and sensory neuronal function and recent studies also link it to efficient learning and memory. Cyclin-dependent kinase 5 (Cdk5) is required for normal oligodendrocyte development, myelination and myelin repair. Here we show that conditional deletion of Cdk5 by targeting with CNP (CNP;Cdk5 CKO) results in hypomyelination and disruption of the structural integrity of Nodes of Ranvier. In addition, CNP;Cdk5 CKO mice exhibited a severe impairment of learning and memory compared to controls that may reflect perturbed neuron-glial interactions. Co-culture of cortical neurons with CNP;Cdk5 CKO oligodendrocyte lineage cells resulted in a significant reduction in the density of neuronal dendritic spines. In short term fear-conditioning studies, CNP;Cdk5 CKO mice had decreased hippocampal levels of immediate early genes such as Arc and Fos, and lower levels of p-CREB and p-cofilin suggested these pathways are affected by the levels of myelination. The novel roles of Cdk5 in oligodendrocyte lineage cells may provide insights for helping understand the cognitive changes sometimes seen in demyelinating diseases such as multiple sclerosis.

Should I stay or should I go? Transformation of time-discounted rewards in orbitofrontal cortex and associated brain circuits.

Animals prefer a small, immediate reward over a larger delayed reward (time discounting). Lesions of the orbitofrontal cortex (OFC) can either increase or decrease the breakpoint at which animals abandon the large delayed reward for the more immediate reward as the delay becomes longer. Here we argue that the varied effects of OFC lesions on delayed discounting reflect two different patterns of activity in OFC; one that bridges the gap between a response and an outcome and another that discounts delayed reward. These signals appear to reflect the spatial location of the reward and/or the action taken to obtain it, and are encoded independently from representations of absolute value. We suggest a dual role for output from OFC in both discounting delayed reward, while at the same time supporting new learning for them.

Neural correlates of inflexible behavior in the orbitofrontal-amygdalar circuit after cocaine exposure.

Addiction is characterized by compulsive or inflexible behavior, observed both in the context of drug-seeking and in contexts unrelated to drugs. One possible contributor to these inflexible behaviors may be drug-induced dysfunction within circuits that support behavioral flexibility, including the basolateral amygdala (ABL) and the orbitofrontal cortex (OFC). Here we describe data demonstrating that chronic cocaine exposure causes long-lasting changes in encoding properties in the ABL and the OFC during learning and reversal in an odor-guided task. In particular, these data suggest that inflexible encoding in ABL neurons may be the proximal cause of cocaine-induced behavioral inflexibility, and that a loss of outcome-expectant encoding in OFC neurons could be a more distal contributor to this impairment. A similar mechanism of drug-induced orbitofrontal-amygdalar dysfunction may cause inflexible behavior when animals and addicts are exposed to drug-associated cues and contexts.

Cerebral Microdialysis.

A variety of neuromonitoring techniques are available to aid in the care of neurocritically ill patients. However, traditional monitors lack the ability to measure brain biochemistry and may provide inadequate warning of potentially reversible deleterious conditions. Cerebral microdialysis (CMD) is a safe, novel method of monitoring regional brain biochemistry. Analysis of CMD analytes as part of a multimodal approach may help inform clinical decision making, guide medical treatments, and aid in prognostication of patient outcome. Its use is most frequently documented in traumatic brain injury and subarachnoid hemorrhage. Incorporating CMD into clinical practice is a multidisciplinary effort.