Fiona McNab

Prefrontal cortex and basal ganglia control access to working memory

Our capacity to store information in working memory might be determined by the degree to which only relevant information is remembered. The question remains as to how this selection of relevant items to be remembered is accomplished. Here we show that activity in the prefrontal cortex and basal ganglia preceded the filtering of irrelevant information and that activity, particularly in the globus pallidus, predicted the extent to which only relevant information is stored. The preceding frontal and basal ganglia activity were also associated with inter-individual differences in working memory capacity. These findings reveal a mechanism by which frontal and basal ganglia activity exerts attentional control over access to working memory storage in the parietal cortex in humans, and makes an important contribution to inter-individual differences in working memory capacity.

Mechanism for top-down control of working memory capacity

Working memory capacity, the maximum number of items that we can transiently store in working memory, is a good predictor of our general cognitive abilities. Neural activity in both dorsolateral prefrontal cortex and posterior parietal cortex has been associated with memory retention during visuospatial working memory tasks. The parietal cortex is thought to store the memories. However, the role of the dorsolateral prefrontal cortex, a top-down control area, during pure information retention is debated, and the mechanisms regulating capacity are unknown. Here, we propose that a major role of the dorsolateral prefrontal cortex in working memory is to boost parietal memory capacity. Furthermore, we formulate the boosting mechanism computationally in a biophysical cortical microcircuit model and derive a simple, explicit mathematical formula relating memory capacity to prefrontal and parietal model parameters. For physiologically realistic parameter values, lateral inhibition in the parietal cortex limits mnemonic capacity to a maximum of 2–7 items. However, at high loads inhibition can be counteracted by excitatory prefrontal input, thus boosting parietal capacity. Predictions from the model were confirmed in an fMRI study. Our results show that although memories are stored in the parietal cortex, interindividual differences in memory capacity are partly determined by the strength of prefrontal top-down control. The model provides a mechanistic framework for understanding top-down control of working memory and specifies two different contributions of prefrontal and parietal cortex to working memory capacity.

Common and unique components of inhibition and working memory : An fMRI, within-subjects investigation

Behavioural findings indicate that the core executive functions of inhibition and working memory are closely linked, and neuroimaging studies indicate overlap between their neural correlates. There has not, however, been a comprehensive study, including several inhibition tasks and several working memory tasks, performed by the same subjects. In the present study, 11 healthy adult subjects completed separate blocks of 3 inhibition tasks (a stop task, a go/no-go task and a flanker task), and 2 working memory tasks (one spatial and one verbal). Activation common to all 5 tasks was identified in the right inferior frontal gyrus, and, at a lower threshold, also the right middle frontal gyrus and right parietal regions (BA 40 and BA 7). Left inferior frontal regions of interest (ROIs) showed a significant conjunction between all tasks except the flanker task. The present study could not pinpoint the specific function of each common region, but the parietal region identified here has previously been consistently related to working memory storage and the right inferior frontal gyrus has been associated with inhibition in both lesion and imaging studies. These results support the notion that inhibitory and working memory tasks involve common neural components, which may provide a neural basis for the interrelationship between the two systems.

The SNAP25 Gene Is Linked to Working Memory Capacity and Maturation of the Posterior Cingulate Cortex During Childhood

BACKGROUND Working memory (WM) is the ability to retain task relevant information. This ability is important for a wide range of cognitive tasks, and WM deficits are a central cognitive impairment in neurodevelopment disorders such as attention-deficit/hyperactivity disorder (ADHD). Although WM capacity is known to be highly heritable, most genes involved remain unidentified. METHODS Single nucleotide polymorphisms in genes previously associated with cognitive functions or ADHD were selected for genotyping. Associations of these with WM tasks were investigated in a community sample of 330 children and young adults. One single nucleotide polymorphisms was also investigated in an independent sample of 88 4-year-old children. Furthermore, association between brain structure and activity, as measured by magnetic resonance imaging techniques, and single nucleotide polymorphisms alleles were estimated in 88 participants. RESULTS Genotype at rs363039, located in the gene coding for synaptosomal-associated protein, 25 kDa (SNAP25) was associated to WM capacity in both samples. Associations in the community sample were also found with measures of other cognitive functions. In addition, this polymorphism affected the gray matter and brain activity in the posterior cingulate cortex, an area included in the so-called default mode network previously correlated to regulation of attention and hypothesized to be implicated in ADHD. CONCLUSIONS A novel gene-brain-behavior network was identified in which a genotype located in SNAP25 affects WM and has age-dependent effects on both brain structure and brain activity. Identifying such networks could be a key to better understanding cognitive development as well as some of its disorders.

Crowdsourcing for cognitive science--the utility of smartphones.

By 2015, there will be an estimated two billion smartphone users worldwide. This technology presents exciting opportunities for cognitive science as a medium for rapid, large-scale experimentation and data collection. At present, cost and logistics limit most study populations to small samples, restricting the experimental questions that can be addressed. In this study we investigated whether the mass collection of experimental data using smartphone technology is valid, given the variability of data collection outside of a laboratory setting. We presented four classic experimental paradigms as short games, available as a free app and over the first month 20,800 users submitted data. We found that the large sample size vastly outweighed the noise inherent in collecting data outside a controlled laboratory setting, and show that for all four games canonical results were reproduced. For the first time, we provide experimental validation for the use of smartphones for data collection in cognitive science, which can lead to the collection of richer data sets and a significant cost reduction as well as provide an opportunity for efficient phenotypic screening of large populations.

Age-related changes in working memory and the ability to ignore distraction

Significance We reveal a novel and highly significant change in how items are held in mind in healthy aging. Using smartphones, data were collected from 29,631 participants, between the ages of 18–69 y. We compare the ability to exclude distractors when items are entered into working memory (WM) (encoding distraction, ED) and when items are held in mind (delay distraction, DD). In older adults, WM in the absence of distraction was more similar to ED exclusion than DD exclusion. A greater reliance on focused attention during encoding may reflect compensation for the more pronounced deterioration we observed in DD exclusion in older age. This can inform other areas of cognition and strategies to ameliorate or manage debilitating age-related cognitive decline. A weakened ability to effectively resist distraction is a potential basis for reduced working memory capacity (WMC) associated with healthy aging. Exploiting data from 29,631 users of a smartphone game, we show that, as age increases, working memory (WM) performance is compromised more by distractors presented during WM maintenance than distractors presented during encoding. However, with increasing age, the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction. A significantly greater contribution of distractor filtering at encoding represents a potential compensation for reduced WMC in older age.

Does maintenance of colour categories rely on language? Evidence to the contrary from a case of semantic dementia

Recent neuropsychological evidence, supporting a strong version of Whorfian principles of linguistic relativity, has reinvigorated debate about the role of language in colour categorisation. This paper questions the methodology used in this research and uses a novel approach to examine the unique contribution of language to categorisation behaviour. Results of three investigations are reported. The first required development of objective measures of category coherence and consistency to clarify questions about healthy control performance on the freesorting colour categorisation task used in previous studies. Between-participant consistency was found to be only moderate and the number of colour categories generated was found to vary markedly between individuals. The second study involved longitudinal neuropsychological examination of a patient whose colour categorisation strategy was monitored in the context of a progressive decline in language due to semantic dementia. Performance on measures of category coherence and consistency was found to be relatively stable over time despite a profound decline in the patients colour language. In a final investigation we demonstrated that, for both the patient and controls, between- and within-participant consistency were higher than expected by (a) random sorting and (b) sorting perceptually similar chips together. These findings indicate that the maintenance of colour categorisation need not depend on language.

Individual differences in explicit and implicit visuomotor learning and working memory capacity.

The theoretical basis for the association between high working memory capacity (WMC) and enhanced visuomotor adaptation is unknown. Visuomotor adaptation involves interplay between explicit and implicit systems. We examined whether the positive association between adaptation and WMC is specific to the explicit component of adaptation. Experiment 1 replicated the positive correlation between WMC and adaptation, but revealed this was specific to the explicit component of adaptation, and apparently driven by a sub-group of participants who did not show any explicit adaptation in the correct direction. A negative correlation was observed between WMC and implicit learning. Experiments 2 and 3 showed that when the task restricted the development of an explicit strategy, high WMC was no longer associated with enhanced adaptation. This work reveals that the benefit of high WMC is specifically linked to an individual’s capacity to use an explicit strategy. It also reveals an important contribution of individual differences in determining how adaptation is performed.

Semantic and phonological task-set priming and stimulus processing investigated using magnetoencephalography (MEG)

In this study the neural substrates of semantic and phonological task priming and task performance were investigated using single word task-primes. Magnetoencephalography (MEG) data were analysed using Synthetic Aperture Magnetometry (SAM) to determine the spatiotemporal and spectral characteristics of cortical responses. Comparisons were made between the task-prime conditions for evidence of differential effects as a function of the nature of the task being primed, and between the task-prime and the task performance responses for evidence of parallels in activation associated with preparation for and completion of a specific task. Differential priming effects were found. Left middle temporal and inferior frontal voxels showed a statistically significant power decrease associated with the semantic task-prime, and a power increase associated with the phonological task-prime, within beta and gamma frequency bands respectively. Similarities between the task-related differential effects associated with task-prime presentation and those associated with target stimulus presentation were also found. For example, within the semantic task condition, left superior frontal and middle temporal regions showed a significant power decrease within both task-prime and target epochs; within the phonological task condition there were significant parietal and cerebellar power decreases within both types of epoch. In addition there was evidence within the priming epochs of dissociable patterns of activity which could be interpreted as indices of de-activation of task-irrelevant networks. Following a phonological task-prime, significant power increases were observed in those inferior frontal and middle temporal regions in which significant power decreases were associated with semantic task priming and performance.

Working Memory Remediation and the D1 Receptor

Dopamine receptors from the D2 family are localized in high concentrations in the basal ganglia (panel A), while D1 family receptors, also present in the basal ganglia, are prominent in the prefrontal cortex (panel B). The D1 receptors in the prefrontal cortex have been associated with working memory performance in humans as well as animals and are affected by the release of cortical dopamine during working memory tasks. Working memory is the ability to retain information for short periods of time and underlies many cognitive functions. Moreover, cognitive training on working memory tasks improves working memory in humans, although the molecular mechanisms are not known. The availability of dopamine in the prefrontal cortex affects the movement of D1 dopamine receptors to and from the plasma membrane. However, alterations in dopamine receptors accompanying cognition training have not been identified. The images illustrate the results of 13 healthy male volunteers who participated in working memory training for 35 minutes daily for a period of 5 weeks, with task difficulty dynamically adjusted to performance levels. Before and after the working memory training, the following imaging measures were collected for each volunteer: 1) D1 receptor binding potential (BP) using (11C)SCH23390; 2) D2 receptor BP using (11C)-raclopride; and 3) a functional magnetic resonance imaging blood-oxygen-level-dependent experiment with a working memory task to identify the brain regions active in mediating working memory. Five cortical regions were activated in mediating working memory (the three right-sided regions shown in panel C). Working memory training did not affect D2 dopamine BP in the basal ganglia. However, the D1 dopamine receptor in the prefrontal cortex showed a relationship to working memory training. In general, within the measured range, the increases in working memory after training a BP=binding potential; WM=working memory; R=right; L=left. A 4.5