Structural and diffusion-weighted brain imaging predictors of attention-deficit/hyperactivity disorder and its symptomology in very young (4- to 7-year-old) children.

The current study aimed to identify the key neurobiology of attention-deficit/hyperactivity disorder (ADHD), as it relates to ADHD diagnostic category and symptoms of hyperactive/impulsive behaviour and inattention. To do so, we adapted a predictive modelling approach to identify the key structural and diffusion-weighted brain imaging measures and their relative standing with respect to teacher ratings of executive function (EF) (measured by the Metacognition Index of the Behavior Rating Inventory of Executive Function [BRIEF]) and negativity and emotion regulation (ER) (measured by the Emotion Regulation Checklist [ERC]), in a critical young age range (ages 4 to 7, mean age 5.52 years, 82.2% Hispanic/Latino), where initial contact with educators and clinicians typically take place. Teacher ratings of EF and ER were predictive of both ADHD diagnostic category and symptoms of hyperactive/impulsive behaviour and inattention. Among the neural measures evaluated, the current study identified the critical importance of the largely understudied diffusion-weighted imaging measures for the underlying neurobiology of ADHD and its associated symptomology. Specifically, our analyses implicated the inferior frontal gyrus as a critical predictor of ADHD diagnostic category and its associated symptomology, above and beyond teacher ratings of EF and ER. Collectively, the current set of findings have implications for theories of ADHD, the relative utility of neurobiological measures with respect to teacher ratings of EF and ER, and the developmental trajectory of its underlying neurobiology.

Is there any incremental benefit to conducting neuroimaging and neurocognitive assessments in the diagnosis of ADHD in young children? A machine learning investigation.

Given the negative trajectories of early behavior problems associated with ADHD, early diagnosis is considered critical to enable intervention and treatment. To this end, the current investigation employed machine learning to evaluate the relative predictive value of parent/teacher ratings, behavioral and neural measures of executive function (EF) in predicting ADHD in a sample consisting of 162 young children (ages 4-7, mean age 5.55, 82.6 % Hispanic/Latino). Among the target measures, teacher ratings of EF were the most predictive of ADHD. While a more extensive evaluation of neural measures, such as diffusion-weighted imaging, may provide more information as they relate to the underlying cognitive deficits associated with ADHD, the current study indicates that measures of cortical anatomy obtained in research studies, as well cognitive measures of EF often obtained in routine assessments, have little incremental value in differentiating typically developing children from those diagnosed with ADHD. It is important to note that the overlap between some of the EF questions in the BRIEF, and the ADHD symptoms could be enhancing this effect. Thus, future research evaluating the importance of such measures in predicting children's functional impairment in academic and social areas would provide additional insight into their contributing role in ADHD.

Linguistic analysis of the autobiographical memories of individuals with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is characterized by biases in memory, attention, and cognition. The present study utilized the Linguistic Inquiry and Word Count (LIWC) to examine the content of specific autobiographical memories (AMs) recalled by individuals with MDD during an autobiographical memory task. METHODS: We examined various features of the text (including use of affective, cognitive, and self-referential terms), as well as their associations with clinical and cognitive features of MDD (depression severity, autobiographical memory specificity, amygdala activity), in 45 unmedicated adults with MDD compared to 61 healthy controls. RESULTS: When recalling positive memories MDD individuals used the word "I" less, fewer positive words, more words indicating present focus (present tense verbs), and fewer words overall to describe memories compared to controls. When recalling negative memories, MDD individuals used "I" more, more words indicating present focus, and more words overall to describe memories relative to controls. Depression severity was correlated with word count, the use of "I", and words indicating present focus in negative memories and inversely correlated with word count and the use of "I" in positive memories. Autobiographical memory specificity was correlated with word count, the use of "I", and words indicating present focus for positive memories and inversely correlated with the use of "I" and words indicating present focus for negative memories. LIMITATIONS: Due to the nature of AM recall, we could not control for the number of memories which participants recalled in each mnemonic category. CONCLUSIONS: Results align with literature implicating rumination and intensive self-focus in depression and suggest that interventions targeting specific word use may be therapeutically beneficial in the treatment of MDD.

Narrative Constructions for the Organization of Self Experience: Proof of Concept via Embodied Robotics.

It has been proposed that starting from meaning that the child derives directly from shared experience with others, adult narrative enriches this meaning and its structure, providing causal links between unseen intentional states and actions. This would require a means for representing meaning from experience-a situation model-and a mechanism that allows information to be extracted from sentences and mapped onto the situation model that has been derived from experience, thus enriching that representation. We present a hypothesis and theory concerning how the language processing infrastructure for grammatical constructions can naturally be extended to narrative constructions to provide a mechanism for using language to enrich meaning derived from physical experience. Toward this aim, the grammatical construction models are augmented with additional structures for representing relations between events across sentences. Simulation results demonstrate proof of concept for how the narrative construction model supports multiple successive levels of meaning creation which allows the system to learn about the intentionality of mental states, and argument substitution which allows extensions to metaphorical language and analogical problem solving. Cross-linguistic validity of the system is demonstrated in Japanese. The narrative construction model is then integrated into the cognitive system of a humanoid robot that provides the memory systems and world-interaction required for representing meaning in a situation model. In this context proof of concept is demonstrated for how the system enriches meaning in the situation model that has been directly derived from experience. In terms of links to empirical data, the model predicts strong usage based effects: that is, that the narrative constructions used by children will be highly correlated with those that they experience. It also relies on the notion of narrative or discourse function words. Both of these are validated in the experimental literature.

Regulation of exit from mitosis in multinucleate Ashbya gossypii cells relies on a minimal network of genes.

In Saccharomyces cerevisiae, mitosis is coupled to cell division by the action of the Cdc fourteen early anaphase release (FEAR) and mitotic exit network (MEN) regulatory networks, which mediate exit from mitosis by activation of the phosphatase Cdc14. The closely related filamentous ascomycete Ashbya gossypii provides a unique cellular setting to study the evolution of these networks. Within its multinucleate hyphae, nuclei are free to divide without the spatial and temporal constraints described for budding yeast. To investigate how this highly conserved system has adapted to these circumstances, we constructed a series of mutants lacking homologues of core components of MEN and FEAR and monitored phenomena such as progression through mitosis and Cdc14 activation. MEN homologues in A. gossypii were shown to have diverged from their anticipated role in Cdc14 release and exit from mitosis. We observed defects in septation, as well as a partial metaphase arrest, in Agtem1Δ, Agcdc15Δ, Agdbf2/dbf20Δ, and Agmob1Δ. A. gossypii homologues of the FEAR network, on the other hand, have a conserved and more pronounced role in regulation of the M/G1 transition. Agcdc55Δ mutants are unable to sequester AgCdc14 throughout interphase. We propose a reduced model of the networks described in yeast, with a low degree of functional redundancy, convenient for further investigations into these networks.

Structural mutants of the spindle pole body cause distinct alteration of cytoplasmic microtubules and nuclear dynamics in multinucleated hyphae.

In the multinucleate fungus Ashbya gossypii, cytoplasmic microtubules (cMTs) emerge from the spindle pole body outer plaque (OP) in perpendicular and tangential directions. To elucidate the role of cMTs in forward/backward movements (oscillations) and bypassing of nuclei, we constructed mutants potentially affecting cMT nucleation or stability. Hyphae lacking the OP components AgSpc72, AgNud1, AgCnm67, or the microtubule-stabilizing factor AgStu2 grew like wild- type but showed substantial alterations in the number, length, and/or nucleation sites of cMTs. These mutants differently influenced nuclear oscillation and bypassing. In Agspc72Delta, only long cMTs were observed, which emanate tangentially from reduced OPs; nuclei mainly moved with the cytoplasmic stream but some performed rapid bypassing. Agnud1Delta and Agcnm67Delta lack OPs; short and long cMTs emerged from the spindle pole body bridge/half-bridge structures, explaining nuclear oscillation and bypassing in these mutants. In Agstu2Delta only very short cMTs emanated from structurally intact OPs; all nuclei moved with the cytoplasmic stream. Therefore, long tangential cMTs promote nuclear bypassing and short cMTs are important for nuclear oscillation. Our electron microscopy ultrastructural analysis also indicated that assembly of the OP occurs in a stepwise manner, starting with AgCnm67, followed by AgNud1 and lastly AgSpc72.