The medial (MHb) and lateral (LHb) habenulae are a small group of nuclei that regulate the activity of monoaminergic neurons. Disruptions to these nuclei lead to deficits in a range of cognitive and motor functions from sleep to decision making. Interestingly, the habenular nuclei are present in all vertebrates, suggesting that they provide a common neural mechanism to influence these diverse functions. To unravel conserved habenula circuitry and approach an understanding of their basic function, we investigated the organization of these nuclei in the lamprey, one of the phylogenetically oldest vertebrates. Based on connectivity and molecular expression, we show that the MHb and LHb circuitry is conserved in the lamprey. As in mammals, separate populations of neurons in the LHb homolog project directly or indirectly to dopamine and serotonin neurons through a nucleus homologous to the GABAergic rostromedial mesopontine tegmental nucleus and directly to histamine neurons. The pallidal and hypothalamic inputs to the LHb homolog are also conserved. In contrast to other species, the habenula projecting pallidal nucleus is topographically distinct from the dorsal pallidum, the homolog of the globus pallidus interna. The efferents of the MHb homolog selectively target the interpeduncular nucleus. The MHb afferents arise from sensory (medial olfactory bulb, parapineal, and pretectum) and not limbic areas, as they do in mammals; consequently, the "context" in which this circuitry is recruited may have changed during evolution. Our results indicate that the habenular nuclei provide a common vertebrate circuitry to adapt behavior in response to rewards, stress, and other motivating factors.basal ganglia | neuromodulator T he habenular complex, a small group of nuclei in the epithalamus, links the limbic forebrain to mid-and hind-brain regions involved in adapting the internal cerebral state (1-4). Lesion and genetic inactivation studies have implicated the habenula in a range of functions from control of the circadian rhythm to adapting the behavioral response to fear and reward, as well as to higher cognitive functions, such as attention and value-based decision making (5-8). The habenula is present in all classes of vertebrates, including those that seemingly lack highlevel cognitive functions (9). This suggests that it regulates processes crucial to survival through a basic neural mechanism common to all vertebrates. To unravel the neural basis for the habenula's basic and complex functions, it will be important to elucidate the basic circuitry and determine how this has evolved to regulate higher cognitive functions.In mammals, the habenula is subdivided into two nuclei: the medial habenula (MHb) and lateral habenula (LHb) (10). The LHb receives value-related signals from the basal ganglia [globus pallidus interna/entopeduncular nucleus (GPi/EP)] as well as inputs from the diagonal band of Broca and the lateral hypothalamus (1, 11). The LHb projects to the GABAergic rostromedial mesopontine tegmental nucleus (RMTg), a...

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There is a dearth of long‐term follow‐up studies of adults diagnosed with ADHD. Here, the aim was to evaluate long‐term outcomes in a group of ADHD patients diagnosed in adulthood and receiving routine psychiatric health care. Adults diagnosed with any type of ADHD ( n = 52) and healthy controls ( n = 73) were assessed at baseline and at a 5‐year follow‐up, using Global Assessment of Functioning (GAF), Clinical Global Impression (CGI), Brown ADD Scale (BADDS) and Adult ADHD Self‐Report Scale (ASRS). A multivariate regression method was used to identify factors predicting 5‐year outcomes, including baseline ratings, medication intensity, comorbidity, intelligence quotient (IQ), age, and sex. After 5 years, ADHD patients reported fewer and/or less severe symptoms compared to baseline, but remained at clinically significant symptom levels and with functional deficits. Baseline self‐reports of ADHD symptoms predicted their own 5‐year outcome and low baseline functioning level predicted improved global functioning at follow‐up. Factors previously reported to predict short‐term outcomes (i.e., medication, comorbidity, IQ, age, and sex) did not anticipate long‐term outcomes in present study.

Motivated by the fast adoption of WebAssembly, we propose the first functional pipeline to support the superoptimization of Web-Assembly bytecode. Our pipeline works over LLVM and Souper. We evaluate our superoptimization pipeline with 12 programs from the Rosetta code project. Our pipeline improves the code section size of 8 out of 12 programs. We discuss the challenges faced in superoptimization of WebAssembly with two case studies.