Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility

Abstract

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement.

Dopamine D1 sensitivity in the prefrontal cortex predicts general cognitive abilities and is modulated by working memory training

“…Experiment 3: Effect of working memory training on cognitive performance and D1 sensitivity It has been reported that the imposition of a working memory training regimen with a high demand on selective attention can promote an increase in the general cognitive performance of mice Matzel et al 2011). Here we ascertained if working memory training targeted the same dopaminergic signaling mechanisms (D1R-containing neurons) that underlie innate cognitive abilities.…”

“…Since working memory training required animals to actively maintain a memory of locations in the face of interfering external stimuli, that taxation (and its use of the D1R) may have increased the sensitivity of D1R-containing neurons. It is notable in this regard that implementation of a similar working memory training regimen also resulted in improved performance on specific tests of selective attention Matzel and Kolata 2010;Matzel et al 2011).…”

“…Furthermore, it has been suggested that working memory training (with high attentional demands) can positively impact an individual's performance on tests of fluid intelligence (Jaeggi et al 2008;Tang and Posner 2009;Buschkuehl and Jaeggi 2010), and can produce functional changes in D1 dopaminergic binding in the prefrontal cortex (Olesen et al 2004;McNab et al 2009;Fischer et al 2010). Although the interpretation of "working memory training" studies is highly controversial (Chooi and Thompson 2012;Shipstead et al 2012;Redick et al 2013), we have repeatedly observed that training procedures that tax working memory capacity and selective attention reliably improve the attentional performance of mice Matzel et al 2011), and this facilitation of attention can promote performance on at least some of the tests that comprise our learning battery (see below).…”

“…Much like humans, the efficacy of an animal's working memory is correlated with, and may be a causal determinant of, general cognitive abilities (GCAs) (Kolata et al 2007;Light et al 2010;Matzel et al 2011). Here we assessed whether innate GCA (as determined by an animal's aggregate performance across a diverse set of five learning tasks) and the beneficial influence of working memory training (WMT) on GCA shared a common substrate and target.…”

Cognitive enrichment and welfare: Current approaches and future directions

“…However, in the largest human brain-training study of its kind on over 11,400 participants, Owen et al (2010) showed that, whereas a subject's performance on a trained CGT improved over a six-week period, their performance did not transfer to similar untrained CGTs. In animals, Matzel et al (2011) found that general cognitive decline in aging mice was reduced by life-long working memory exercises (navigation of 3D mazes). Most cognitive tasks provided to rats and dogs have been spatial (i.e., mazes and obstacle courses); therefore, it is difficult to determine whether cognitive performance in these cases is enhanced by "using the body" or "using the brain", or indeed both.…”