Beatriz Luna

An Integrative Model of the Maturation of Cognitive Control

Brains systems undergo unique and specific dynamic changes at the cellular, circuit, and systems level that underlie the transition to adult-level cognitive control. We integrate literature from these different levels of analyses to propose a novel model of the brain basis of the development of cognitive control. The ability to consistently exert cognitive control improves into adulthood as the flexible integration of component processes, including inhibitory control, performance monitoring, and working memory, increases. Unique maturational changes in brain structure, supported by interactions between dopaminergic and GABAergic systems, contribute to enhanced network synchronization and an improved signal-to-noise ratio. In turn, these factors facilitate the specialization and strengthening of connectivity in networks supporting the transition to adult levels of cognitive control. This model provides a novel understanding of the adolescent period as an adaptive period of heightened experience-seeking necessary for the specialization of brain systems supporting cognitive control.

The Contribution of Network Organization and Integration to the Development of Cognitive Control.

Abstract Cognitive control, which continues to mature throughout adolescence, is supported by the ability for well-defined organized brain networks to flexibly integrate information. However, the development of intrinsic brain network organization and its relationship to observed improvements in cognitive control are not well understood. In the present study, we used resting state functional magnetic resonance imaging (RS-fMRI), graph theory, the antisaccade task, and rigorous head motion control to characterize and relate developmental changes in network organization, connectivity strength, and integration to inhibitory control development. Subjects were 192 10–26-y-olds who were imaged during 5 min of rest. In contrast to initial studies, our results indicate that network organization is stable throughout adolescence. However, cross-network integration, predominantly of the cingulo-opercular/salience network, increased with age. Importantly, this increased integration of the cingulo-opercular/salience network significantly moderated the robust effect of age on the latency to initiate a correct inhibitory control response. These results provide compelling evidence that the transition to adult-level inhibitory control is dependent upon the refinement and strengthening of integration between specialized networks. Our findings support a novel, two-stage model of neural development, in which networks stabilize prior to adolescence and subsequently increase their integration to support the cross-domain incorporation of information processing critical for mature cognitive control.

Functional Near-Infrared Spectroscopy Evidence for Development of Prefrontal Engagement in Working Memory in Early Through Middle Childhood

The neural underpinnings of working memory are hypothesized to develop incrementally across preschool and early school age, coinciding with the rapid maturation of executive function occurring during this period. This study investigates the development of prefrontal cortex function between the ages of 3 and 7. Children (n = 68) participated in a novel spatial working memory task while their middle and lateral prefrontal cortex (LPFC) was monitored using functional near infrared spectroscopy (fNIRS). We found increased activation of the LPFC when comparing working memory to rest. Greater LPFC increase was noted for longer compared with shorter delay periods. Increase in LPFC activation, accuracy, and response speed were positively correlated with child age, suggesting that developmental changes in prefrontal function might underlie effective development of executive function in this age range.

Development of White Matter Microstructure and Intrinsic Functional Connectivity Between the Amygdala and Ventromedial Prefrontal Cortex: Associations With Anxiety and Depression

BACKGROUND Connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) is compromised in multiple psychiatric disorders, many of which emerge during adolescence. To identify to what extent the deviations in amygdala-vmPFC maturation contribute to the onset of psychiatric disorders, it is essential to characterize amygdala-vmPFC connectivity changes during typical development. METHODS Using an accelerated cohort longitudinal design (1-3 time points, 10-25 years old, n = 246), we characterized developmental changes of the amygdala-vmPFC subregion functional and structural connectivity using resting-state functional magnetic resonance imaging and diffusion-weighted imaging. RESULTS Functional connectivity between the centromedial amygdala and rostral anterior cingulate cortex (rACC), anterior vmPFC, and subgenual cingulate significantly decreased from late childhood to early adulthood in male and female subjects. Age-associated decreases were also observed between the basolateral amygdala and the rACC. Importantly, these findings were replicated in a separate cohort (10-22 years old, n = 327). Similarly, structural connectivity, as measured by quantitative anisotropy, significantly decreased with age in the same regions. Functional connectivity between the centromedial amygdala and the rACC was associated with structural connectivity in these same regions during early adulthood (22-25 years old). Finally, a novel time-varying coefficient analysis showed that increased centromedial amygdala-rACC functional connectivity was associated with greater anxiety and depression symptoms during early adulthood, while increased structural connectivity in centromedial amygdala-anterior vmPFC white matter was associated with greater anxiety/depression during late childhood. CONCLUSIONS Specific developmental periods of functional and structural connectivity between the amygdala and the prefrontal systems may contribute to the emergence of anxiety and depressive symptoms and may play a critical role in the emergence of psychiatric disorders in adolescence.

Cortical Neurodynamics of Inhibitory Control

The ability to inhibit prepotent responses is critical for successful goal-directed behaviors. To investigate the neural basis of inhibitory control, we conducted a magnetoencephalography study where human participants performed the antisaccade task. Results indicated that neural oscillations in the prefrontal cortex (PFC) showed significant task modulations in preparation to suppress saccades. Before successfully inhibiting a saccade, beta-band power (18–38 Hz) in the lateral PFC and alpha-band power (10–18 Hz) in the frontal eye field (FEF) increased. Trial-by-trial prestimulus FEF alpha-band power predicted successful saccadic inhibition. Further, inhibitory control enhanced cross-frequency amplitude coupling between PFC beta-band (18–38 Hz) activity and FEF alpha-band activity, and the coupling appeared to be initiated by the PFC. Our results suggest a generalized mechanism for top-down inhibitory control: prefrontal beta-band activity initiates alpha-band activity for functional inhibition of the effector and/or sensory system.

Frontal preparatory neural oscillations associated with cognitive control: A developmental study comparing young adults and adolescents.

Functional magnetic resonance imaging (fMRI) studies suggest that age-related changes in the frontal cortex may underlie developmental improvements in cognitive control. In the present study we used magnetoencephalography (MEG) to identify frontal oscillatory neurodynamics that support age-related improvements in cognitive control during adolescence. We characterized the differences in neural oscillations in adolescents and adults during the preparation to suppress a prepotent saccade (antisaccade trials-AS) compared to preparing to generate a more automatic saccade (prosaccade trials-PS). We found that for adults, AS were associated with increased beta-band (16-38Hz) power in the dorsal lateral prefrontal cortex (DLPFC), enhanced alpha- to low beta-band (10-18Hz) power in the frontal eye field (FEF) that predicted performance, and increased cross-frequency alpha-beta (10-26Hz) amplitude coupling between the DLPFC and the FEF. Developmental comparisons between adults and adolescents revealed similar engagement of DLPFC beta-band power but weaker FEF alpha-band power, and lower cross-frequency coupling between the DLPFC and the FEF in adolescents. These results suggest that lateral prefrontal neural activity associated with cognitive control is adult-like by adolescence; the development of cognitive control from adolescence to adulthood is instead associated with increases in frontal connectivity and strengthening of inhibition signaling for suppressing task-incompatible processes.

Protracted development of executive and mnemonic brain systems underlying working memory in adolescence: A longitudinal fMRI study

&NA; Working memory (WM), the ability to hold information on‐line to guide planned behavior, improves through adolescence in parallel with continued maturation of critical brain systems supporting cognitive control. Initial developmental neuroimaging studies with one or two timepoints have provided important though varied results limiting our understanding of which and how neural systems change during this transition into mature WM. In this study, we leverage functional magnetic resonance imaging (fMRI) longitudinal data spanning up to 9 years in 129 normally developing individuals to identify which systems demonstrate growth changes that accompany improvements in WM performance. We used a memory guided saccade task that allowed us to probe encoding, pure maintenance, and retrieval neural processes of WM. Consistent with prior research, we found that WM performance continued to improve into the early 20s. fMRI region of interest (ROI) analyses revealed developmental (1) increases in sensorimotor‐related (encoding/retrieval) activity in visual cortex from childhood through early adulthood that were associated with WM accuracy and (2) decreases in sustained (maintenance) activity in executive regions from childhood through mid‐adolescence that were associated with response latency in childhood and early adolescence. Together these results provide compelling evidence that underlying the maturation of WM is a transition from reliance on executive systems to specialized regions related to the domain of mnemonic requirements of the task leading to optimal performance. Graphical abstract Figure. No caption available. HighlightsProtracted development of working memory and underlying neural processes into 20s.Increases in encoding/retrieval activity in visual cortex.Decreases in maintenance activity in prefrontal/subcortical regions.Association of precision error and encoding activity reflecting mnemonic processing.Association of latency and maintenance activity reflecting executive processing.

Functional connectivity differences in autism during face and car recognition: underconnectivity and atypical age-related changes.

Face recognition abilities improve between adolescence and adulthood over typical development (TD), but plateau in autism, leading to increasing face recognition deficits in autism later in life. Developmental differences between autism and TD may reflect changes between neural systems involved in the development of face encoding and recognition. Here, we focused on whole-brain connectivity with the fusiform face area (FFA), a well-established face-preferential brain region. Older children, adolescents, and adults with and without autism completed the Cambridge Face Memory Test, and a matched car memory test, during fMRI scanning. We then examined task-based functional connectivity between the FFA and the rest of the brain, comparing autism and TD groups during encoding and recognition of face and car stimuli. The autism group exhibited underconnectivity, relative to the TD group, between the FFA and frontal and primary visual cortices, independent of age. Underconnectivity with the medial and rostral lateral prefrontal cortex was face-specific during encoding and recognition, respectively. Conversely, underconnectivity with the L orbitofrontal cortex was evident for both face and car encoding. Atypical age-related changes in connectivity emerged between the FFA and the R temporoparietal junction, and R dorsal striatum for face stimuli only. Similar differences in age-related changes in autism emerged for FFA connectivity with the amygdala across both face and car recognition. Thus, underconnectivity and atypical development of functional connectivity may lead to a less optimal face-processing network in the context of increasing general and social cognitive deficits in autism.

Adolescent cannabis use and brain systems supporting adult working memory encoding, maintenance, and retrieval

ABSTRACT Given prior reports of adverse effects of cannabis use on working memory, an executive function with a protracted developmental course during adolescence, we examined associations between developmental patterns of cannabis use and adult working memory (WM) processes. Seventy‐five adults with longitudinal assessments of cannabis use (60 with reported use, 15 with no reported use) and prenatal drug exposure assessment completed a spatial WM task during fMRI at age 28. All subjects passed a multi‐drug urine screen on the day of testing and denied recreational drug use in the past week. A fast event‐related design with partial trials was used to separate the BOLD response associated with encoding, maintenance, and retrieval periods of the WM task. Behavioral results showed that subjects who began using cannabis earlier in adolescence had longer reaction times (RT) than those with later initiation. Cannabis age of onset was further associated with reduced posterior parietal cortex (PPC) encoding BOLD activation, which significantly mediated age of onset WM RT associations. However, cannabis age of onset brain‐behavior associations did not differ between groups with a single reported use and those with repeated use, suggesting age of onset effects may reflect substance use risk characteristics rather than a developmentally‐timed cannabis exposure effect. Within repeated cannabis users, greater levels of total cannabis use were associated with performance‐related increases in dorsolateral prefrontal cortex (DLPFC) activation during maintenance. This pattern of significant results remained unchanged with inclusion of demographic and prenatal measures as covariates. Surprisingly, however, at the group level, cannabis users generally performed better than participants who reported never using cannabis (faster RT, higher accuracy). We extend previous investigations by identifying that WM associations with cannabis age of onset may be primary to PPC stimulus encoding activity, while the amount of cannabis use is associated with DLPFC maintenance processes. Poorer performance of participants who reported never using cannabis and the consistency of cannabis age of onset associations across single and repeated users limit interpretation of direct developmental effects of cannabis on WM in adulthood. HighlightsCannabis age of onset is negatively associated with WM reaction time (RT).Age of onset RT effects are mediated by parietal activity supporting WM encoding.Greater cannabis use is associated with increased maintenance activation in PFC.Adults who never used cannabis preform worse on WM task than users.

The expression of established cognitive brain states stabilizes with working memory development

We present results from a longitudinal study conducted over 10 years in a sample of 126 8–33 year olds demonstrating that adolescent development of working memory is supported by decreased variability in the amplitude of expression of whole brain states of task-related activity. fMRI analyses reveal that putative gain signals affecting maintenance and retrieval aspects of working memory processing stabilize during adolescence, while those affecting sensorimotor processes do not. We show that trial-to-trial variability in the reaction time and accuracy of eye-movements during a memory guided saccade task are related to fluctuations in the amplitude of expression of task-related brain states, or brain state variability, and also provide evidence that individual developmental trajectories of reaction time variability are related to individual trajectories of brain state variability. These observations demonstrate that the stabilization of widespread gain signals affecting already available cognitive processes underlies the maturation of cognition during adolescence.