Transforming a head direction signal into a goal-oriented steering command.

To navigate, we must continuously estimate the direction we are headed in, and we must correct deviations from our goal1. Direction estimation is accomplished by ring attractor networks in the head direction system2,3. However, we do not fully understand how the sense of direction is used to guide action. Drosophila connectome analyses4,5 reveal three cell populations (PFL3R, PFL3L and PFL2) that connect the head direction system to the locomotor system. Here we use imaging, electrophysiology and chemogenetic stimulation during navigation to show how these populations function. Each population receives a shifted copy of the head direction vector, such that their three reference frames are shifted approximately 120° relative to each other. Each cell type then compares its own head direction vector with a common goal vector; specifically, it evaluates the congruence of these vectors via a nonlinear transformation. The output of all three cell populations is then combined to generate locomotor commands. PFL3R cells are recruited when the fly is oriented to the left of its goal, and their activity drives rightward turning; the reverse is true for PFL3L. Meanwhile, PFL2 cells increase steering speed, and are recruited when the fly is oriented far from its goal. PFL2 cells adaptively increase the strength of steering as directional error increases, effectively managing the tradeoff between speed and accuracy. Together, our results show how a map of space in the brain can be combined with an internal goal to generate action commands, via a transformation from world-centric coordinates to body-centric coordinates.

Promoting gender-informed mentorship in neuropsychology: Reflections and suggestions from early career women.

INTRODUCTION: While women now represent a majority of neuropsychology trainees, men remain prominent in senior positions. As such, female mentees are often paired with senior male mentors, a practice referred to as "cross-gender mentorship." Although cross-gender mentoring dynamics have inherent potential for missteps due to implicit power differentials, when approached through a gender-informed lens, they can be optimized and lead to personal and professional growth for women neuropsychologists. The present article provides a framework for promoting gender-informed mentorship by cataloging first-hand accounts of early career women and discussing resultant lessons and concrete suggestions for mentorship. METHOD: The authors provide first-hand accounts of experiences related to cross-gender mentorship across a variety of settings and professional contexts. From these accounts, the following steps offer a framework to encourage effective mentorship: 1) Set appropriate expectations and boundaries, 2) Address challenging clinical interactions through a gender-informed lens, 3) Foster personal and professional development, 4) Understand the intersection between gender and multicultural traits, 5) Advocate for advancement of women in the field, and 6) Maintain knowledge of women's issues. CONCLUSIONS: Providing effective mentorship for women in neuropsychology is crucial to promote ascension of women to leadership positions and close long-established disparities in the field. The authors hope that our shared experiences can serve as useful tools for both women trainees and their mentors as they embark on mentoring relationships. Practically, we envision that mentoring dyads may discuss this article at the outset of their relationship to understand potential challenges and collaboratively establish a groundwork for optimal mentoring.

Elevation of insulin-like growth factor binding protein-2 level in Pallister-Killian syndrome: implications for the postnatal growth retardation phenotype.

Pallister-Killian syndrome (PKS) is a multi-system developmental disorder caused by tetrasomy 12p that exhibits tissue-limited mosaicism. Probands with PKS often demonstrate a unique growth profile consisting of macrosomia at birth with deceleration of growth postnatally. We have previously demonstrated that cultured skin fibroblasts from PKS probands have significantly elevated expression of insulin-like growth factor binding protein-2 (IGFBP2). To further evaluate the role of IGFBP2 in PKS, the amount of IGFBP2 secreted from cultured skin fibroblast cell lines and serum IGFBP2 levels were measured in probands with PKS. Approximately 60% of PKS fibroblast cell lines secreted higher levels of IGFBP2 compared to control fibroblasts, although the remaining 40% of PKS samples produced comparable level of IGFBP2 to that of control fibroblasts. Serum IGFBP2 levels were also measured in PKS probands and were elevated in 40% of PKS probands. PKS probands with elevated IGFBP2 manifested with severe postnatal growth retardation. IGFBPs are the family of related proteins that bind IGFs with high affinity and are typically thought to attenuate IGF action. We suggest that elevated IGFBP2 levels might play a role in the growth retardation phenotype of PKS.

Construct validity of the Memory for Intentions Screening Test (MIST) in healthy older adults.

The Memory for Intentions Screening Test (MIST) is a clinical measure of prospective memory. There is emerging support for the sensitivity and ecological relevance of the MIST in clinical populations. In the present study, the construct validity of the MIST was evaluated in 40 younger (18-30 years), 24 young-old (60-69 years), and 37 old-old (70+ years) healthy adults. Consistent with expectations derived from the prospective memory and aging literature, older adults demonstrated lower scores on the MIST's primary scale scores (particularly on the time-based scale), but slightly better performance on the seminaturalistic 24-hour trial. Among the healthy older adults, the MIST showed evidence of both convergent (e.g., verbal fluency) and divergent (e.g., visuoperception) correlations with standard clinical tests, although the magnitude of those correlations were comparable across the time- and event-based scales. Together, these results support the discriminant and convergent validity of the MIST as a measure of prospective memory in healthy older adults.

Semantic cueing improves category verbal fluency in persons living with HIV infection.

HIV-associated neurocognitive disorders (HAND) remain highly prevalent in the era of combination antiretroviral therapies, but there are no validated psychological interventions aimed at improving cognitive outcomes. This study sought to determine the potential benefit of semantic cueing on category fluency deficits, which are prevalent in HIV and affect daily functioning. A group of 86 HIV-infected individuals and 87 demographically-matched seronegative participants were administered a standard (i.e., uncued) and a cued category fluency task. Results revealed significant improvements in cued versus uncued performance in HIV, particularly for persons with lower levels of education. The cueing benefit observed may inform rehabilitation efforts aimed at ameliorating HAND.

Self-generation enhances verbal recall in individuals infected with HIV.

Despite the prevalence of HIV-associated episodic memory impairment and its adverse functional impact, there are no empirically validated cognitive rehabilitation strategies for HIV-infected persons. The present study examined the self-generation approach, which is theorized to enhance new learning by elaborating and deepening encoding. Participants included 54 HIV-infected and 46 seronegative individuals, who learned paired word associates in both self-generated and didactic encoding experimental conditions. Results revealed main effects of HIV serostatus and encoding condition, but no interaction. Planned comparisons showed that both groups recalled significantly more words learned in the self-generation condition, and that HIV+ individuals recalled fewer words overall compared to their seronegative counterparts at delayed recall. Importantly, HIV+ participants with clinical memory impairment evidenced similar benefits of self-generation compared to unimpaired HIV+ subjects. Self-generation strategies may improve verbal recall in individuals with HIV infection and may, therefore, be an appropriate and potentially effective cognitive rehabilitation tool in this population.

Prospective memory in substance abusers at treatment entry: associations with education, neuropsychological functioning, and everyday memory lapses.

Individuals with substance use disorders (SUDs) commonly report lapses in prospective memory (PM) in their daily lives; however, our understanding of the profile and predictors of laboratory-based PM deficits in SUDs and their associations with everyday PM failures is still very preliminary. The current study examined these important questions using well-validated measures of self-report and laboratory-based PM in a mixed cohort of 53 SUD individuals at treatment entry and 44 healthy adults. Consistent with prior research, the SUD group endorsed significantly more self-cued and environmentally based PM failures in their daily lives. Moreover, the SUD group demonstrated significantly lower time-based PM performance, driven largely by cue detection errors. The effect of SUDs on PM was particularly strong among participants with fewer years of education. Within the SUD cohort, time-based PM was correlated with clinical measures assessing executive functions, retrospective memory, and psychomotor speed. Importantly, time-based PM was uniquely associated with elevated PM failures in daily lives of the SUD participants, independent of current affective distress and other neurocognitive deficits. Findings suggest that individuals with SUD are vulnerable to deficits in PM, which may in turn increase their risk for poorer everyday functioning outcomes (e.g., treatment non-compliance).