Merging Clinical Neuropsychology and Functional Neuroimaging to Evaluate the Construct Validity and Neural Network Engagement of then-Back Task

Abstract

The n-back task is a widely used neuroimaging paradigm for studying the neural basis of working memory (WM); however, its neuropsychometric properties have received little empirical investigation. The present study merged clinical neuropsychology and functional magnetic resonance imaging (fMRI) to explore the construct validity of the letter variant of the n-back task (LNB) and to further identify the task-evoked networks involved in WM. Construct validity of the LNB task was investigated using a bootstrapping approach to correlate LNB task performance across clinically validated neuropsychological measures of WM to establish convergent validity, as well as measures of related but distinct cognitive constructs (i.e., attention and short-term memory) to establish discriminant validity. Independent component analysis (ICA) identified brain networks active during the LNB task in 34 healthy control participants, and general linear modeling determined task-relatedness of these networks. Bootstrap correlation analyses revealed moderate to high correlations among measures expected to converge with LNB (|ρ| ≥0.37) and weak correlations among measures expected to discriminate (|ρ| ≤0.29), controlling for age and education. ICA identified 35 independent networks, 17 of which demonstrated engagement significantly related to task condition, controlling for reaction time variability. Of these, the bilateral frontoparietal networks, bilateral dorsolateral prefrontal cortices, bilateral superior parietal lobules including precuneus, and frontoinsular network were preferentially recruited by the 2-back condition compared to 0-back control condition, indicating WM involvement. These results support the use of the LNB as a measure of WM and confirm its use in probing the network-level neural correlates of WM processing.

Neural activity during attentional conflict predicts reduction in tinnitus perception following rTMS

“…Furthermore, our use of bootstrapping reduces the influence of statistical outliers. The issue of whether a representative sample was obtained is partially addressed by showing that MSIT-induced neural activity among this small patient sample is strongly correlated with activity among a larger normative sample (n=43) — despite the significant age difference between samples (mean = 27 years, t-score (df) = 4.83 (53), p < 0.0001). This marked similarity validates our use of MSIT to map the neural correlates of attention among patients with tinnitus.…”

“…For example, we have established the n -back fMRI task as having strong construct validity with neuropsychological measures of working memory. (53) Including alternate paradigms like n -back task would allow us to test if these neural predictors of treatment response were specific to selective attention tasks or generalizable to other forms of executive function.…”

Increased brain activation during working memory processing after pediatric mild traumatic brain injury (mTBI)

“…The N-back paradigm has been demonstrated to be an effective and valid task for fMRI assessment of working memory [37, 38], and reliably elicits activation in bilateral frontal, parietal, cerebellar, and basal ganglia circuitry [29]. This task has been used by our research team for many years to examine alterations in working memory functioning after TBI [24, 25, 39–41].…”

Functional independence in resting-state connectivity facilitates higher-order cognition

“…The characterization of a homogenous healthy sample circumvents the methodological variance that is inherent in cross-study comparisons, thus improving the generalizability of our findings. Participants were from the Cognitive Connectome project (Gess, Fausett, Kearney-Ramos, Kilts, & James, 2014; Kearney-Ramos et al, 2014), which pairs clinical neuropsychological assessment with both task- and resting-state fMRI to evaluate the neural encoding of cognition among nine domains: motor, visuospatial, attention, language and cognitive fluency, memory, affective processing, decision making, working memory, and executive function. We hypothesized that performance among these cognitive domains would positively regress to resting-state connectivity of brain regions previously associated with each domain.…”