A Pilot Study Examining Feasibility and Initial Efficacy of Remotely Delivered Cognitive Adaptation Training.

Cognitive Adaptation Training (CAT) is an evidence-based treatment that uses environmental supports including signs, text messages, checklists, smart pill containers, and the organization of belongings to bypass cognitive and motivational impairments and to cue adaptive behavior in the home or work environment. We developed and tested a remote version of CAT to make the treatment available more broadly. Because CAT is focused on working with the individual in their home environment to establish supports, CAT may not be as easy to translate into an effective virtual treatment as talk-therapies. Fifty-six members of managed care were assigned to or given their treatment preference for CAT or Remote CAT (R-CAT) for 6 months. In-person or virtual pill counts were conducted monthly and assessments of habit-formation, symptoms, functioning, and satisfaction were administered every 2 months by independent raters. Analyses using mixed models with repeated measures focused on pre-planned evaluations of within-group change. Adherence improved significantly in R-CAT, functioning improved significantly in CAT and both groups improved significantly on measures of habit-formation and symptoms across 6 months. Higher functioning individuals appeared to choose R-CAT. Satisfaction with treatment was very high in both groups. R-CAT appears to be a potentially effective treatment, particularly for medication follow-though. However, in contrast to decades of previous research, fewer than 20% of eligible Medicaid recipients agreed to participate in the study. This may have been due to recruitment during and immediately post-pandemic.

The Acceptability of Remotely Delivered Cognitive Adaptation Training.

Cognitive Adaptation Training (CAT) is a psychosocial treatment using environmental supports such as signs, checklists, technology, and the organization of belongings to bypass cognitive and motivational impairments for those with serious behavioral health problems. We conducted a survey of 204 members of managed Medicaid in Texas to examine the acceptability of, opinions about and preferences for CAT delivered in-person (CAT) or remotely (R-CAT) where supplies would be mailed and visits would occur via videoconferencing. The telephone survey presented descriptions of CAT and R-CAT in counterbalanced order eliciting general opinions about the treatments, such as (1) whether they would accept the treatments if they were offered the day of the survey at no cost, (2) which treatment was preferred, and (3) the extent to which they agreed or disagreed with a number of statements about components of the treatments. Results indicated that both R-CAT and CAT were acceptable to respondents with overall acceptance rates significantly higher for R-CAT 87% than for CAT (78%). With respect to preferences, 27% and 28% of respondents preferred CAT and R-CAT, respectively, and 41% of respondents preferred both equally. Black respondents more often preferred in-person CAT to other alternatives. Respondents agreed that they needed help, that they were comfortable with technology, and that they believed the programs would help them. The vast majority of qualitative comments about the treatments were positive. Results suggest that it will be important to assess the efficacy and effectiveness of CAT delivered remotely in randomized trials.

Acute physiological stress promotes clustering of synaptic markers and alters spine morphology in the hippocampus.

GluA2-containing AMPA receptors and their association with protein kinase M zeta (PKMζ) and post-synaptic density-95 (PSD-95) are important for learning, memory and synaptic plasticity processes. Here we investigated these synaptic markers in the context of an acute 1h platform stress, which can disrupt spatial memory retrieval for a short-term memory on the object placement task and long-term memory retrieval on a well-learned radial arm maze task. Acute stress increased serum corticosterone and elevated the expression of synaptic PKMζ while decreasing synaptic GluA2. Using co-immunoprecipitation, we found that this stressor promotes the clustering of GluA2, PKMζ and PSD-95, which is consistent with effects reported from overexpression of PKMζ in cell culture. Because PKMζ overexpression has also been shown to induce spine maturation in culture, we examined how stress impacts synaptic markers within changing spines across various hippocampal subfields. To achieve this, we employed a new technique combining Golgi staining and immmunohistochemistry to perform 3D reconstruction of tertiary dendrites, which can be analyzed for differences in spine types and the colocalization of synaptic markers within these spines. In CA1, stress increased the densities of long-thin and mushroom spines and the colocalization of GluA2/PSD-95 within these spines. Conversely, in CA3, stress decreased the densities of filopodia and stubby spines, with a concomitant reduction in the colocalization of GluA2/PSD-95 within these spines. In the outer molecular layer (OML) of the dentate gyrus (DG), stress increased both stubby and long-thin spines, together with greater GluA2/PSD-95 colocalization. These data reflect the rapid effects of stress on inducing morphological changes within specific hippocampal subfields, highlighting a potential mechanism by which stress can modulate memory consolidation and retrieval.

PKMζ differentially utilized between sexes for remote long-term spatial memory.

It is well established that male rats have an advantage in acquiring place-learning strategies, allowing them to learn spatial tasks more readily than female rats. However many of these differences have been examined solely during acquisition or in 24h memory retention. Here, we investigated whether sex differences exist in remote long-term memory, lasting 30d after training, and whether there are differences in the expression pattern of molecular markers associated with long-term memory maintenance. Specifically, we analyzed the expression of protein kinase M zeta (PKMζ) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA2. To adequately evaluate memory retention, we used a robust training protocol to attenuate sex differences in acquisition and found differential effects in memory retention 1d and 30d after training. Female cohorts tested for memory retention 1d after 60 training trials outperformed males by making significantly fewer reference memory errors at test. In contrast, male cohorts tested 30d after 60 training trials outperformed females of the same condition, making fewer reference memory errors and achieving significantly higher retention test scores. Furthermore, given 60 training trials, females tested 30d later showed significantly worse memory compared to females tested 1d later, while males tested 30d later did not differ from males tested 1d later. Together these data suggest that with robust training males do no retain spatial information as well as females do 24h post-training but maintain this spatial information for longer. Males also showed a significant increase in synaptic PKMζ expression and a positive correlation with retention test scores, while females did not. Interestingly, both sexes showed a positive correlation between retention test scores and synaptic GluA2 expression. Furthermore, the increased expression of synaptic PKMζ, associated with male memory but not with female memory, identifies another potential sex-mediated difference in memory processing.

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze.

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.