Developmental Cognitive Neuroscience in the Era of Networks and Big Data: Strengths, Weaknesses, Opportunities, and Threats

Developmental cognitive neuroscience is being pulled in new directions by network science and big data. Brain imaging [e.g., functional magnetic resonance imaging (fMRI), functional connectivity MRI], analytical advances (e.g., graph theory, machine learning), and access to large computing resources have empowered us to collect and process neurobehavioral data faster and in larger populations than ever before. The translational potential from these advances is unparalleled, as a better understanding of complex human brain functions is best grounded in the onset of these functions during human development. However, the maturation of developmental cognitive neuroscience has seen the emergence of new challenges and pitfalls, which have significantly slowed progress and need to be overcome to maintain momentum. In this review, we examine the state of developmental cognitive neuroscience in the era of networks and big data. In addition, we provide a discussion of the strengths, weaknesses, opportunities, and threats (SWOT) of the field to advance developmental cognitive neuroscience's scientific and translational potential. Expected final online publication date for the Annual Review of Developmental Psychology, Volume 3 is December 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Human Fronto-Striatal Connectivity is Organized into Discrete Functional Subnetworks

The striatum is interconnected with the cerebral cortex via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate cortico-striatal connections can be precisely mapped using invasive tract-tracing. However, noninvasive human research has not mapped these connections with anatomical precision, limited by the practice of averaging neuroimaging data across individuals. Here we utilized highly-sampled resting-state functional connectivity MRI for individually-specific precision functional mapping of cortico-striatal connections. We identified ten discrete, individual-specific subnetworks linking cortex—predominately frontal cortex—to striatum. These subnetworks included previously unknown striatal connections to the human language network. The discrete subnetworks formed a stepped rostral-caudal gradient progressing from nucleus accumbens to posterior putamen; this organization was strongest for projections from medial frontal cortex. The stepped gradient organization fit patterns of fronto-striatal connections better than a smooth, continuous gradient. Thus, precision subnetworks identify detailed, individual-specific stepped gradients of cortico-striatal connectivity that include human-specific language networks.

The Detailed Organization of the Human Cerebellum Estimated by Intrinsic Functional Connectivity Within the Individual

Distinct regions of the cerebellum connect to separate regions of the cerebral cortex forming a complex topography. While cerebellar organization has been examined in group-averaged data, study of individuals provides an opportunity to discover features that emerge at a higher spatial resolution. Here functional connectivity MRI was used to examine the cerebellum of two intensively-sampled individuals (each scanned 31 times). Connectivity to somatomotor cortex showed the expected crossed laterality and topography of the body maps. A surprising discovery was connectivity to the primary visual cortex along the vermis with evidence for representation of the central field. Within the hemispheres, each individual displayed a hierarchical progression from the inverted anterior lobe somatomotor map through to higher-order association zones. The hierarchy ended at Crus I/II and then progressed in reverse order through to the upright somatomotor map in the posterior lobe. Evidence for a third set of networks was found in the most posterior extent of the cerebellum. Detailed analysis of the higher-order association networks revealed robust representations of two distinct networks linked to the default network, multiple networks linked to cognitive control, as well as a separate representation of a language network. While idiosyncratic spatial details emerged between subjects, each network could be detected in both individuals, and seed regions placed within the cerebellum recapitulated the full extent of the spatially-specific cerebral networks. The observation of multiple networks in juxtaposed regions at the Crus I/II apex confirms the importance of this zone to higher-order cognitive function and reveals new organizational details.

Prevalent and sex-biased breathing patterns modify functional connectivity MRI in young adults

Resting state functional connectivity magnetic resonance imaging (fMRI) is a tool for investigating human brain organization. Here we identify, visually and algorithmically, two prevalent influences on fMRI signals during 440 h of resting state scans in 440 healthy young adults, both caused by deviations from normal breathing which we term deep breaths and bursts. The two respiratory patterns have distinct influences on fMRI signals and signal covariance, distinct timescales, distinct cardiovascular correlates, and distinct tendencies to manifest by sex. Deep breaths are not sex-biased. Bursts, which are serial taperings of respiratory depth typically spanning minutes at a time, are more common in males. Bursts share features of chemoreflex-driven clinical breathing patterns that also occur primarily in males, with notable neurological, psychiatric, medical, and lifespan associations. These results identify common breathing patterns in healthy young adults with distinct influences on functional connectivity and an ability to differentially influence resting state fMRI studies.

O2.2. EVALUATION OF THE RELATIONSHIP BETWEEN GLUTAMATE AND BRAIN CONNECTIVITY IN ANTIPSYCHOTIC-NAïVE FIRST EPISODE PATIENTS – A COMBINED MAGNETIC RESONANCE SPECTROSCOPY AND RESTING STATE FUNCTIONAL CONNECTIVITY MRI STUDY

Background Schizophrenia is thought to be a disorder of brain dysconnectivity. An imbalance between cortical excitation/inhibition is also implicated, but the link between these abnormalities remains unclear. The present study used resting state functional connectivity MRI (rs-fcMRI) and magnetic resonance spectroscopy (MRS) to investigate how measurements of glutamate + glutamine (Glx) in the anterior cingulate cortex (ACC) relate to rs-fcMRI in medication-naïve first episode psychosis (FEP) subjects compared to healthy controls (HC). Based on our previous findings, we hypothesized that in HC would show correlations between Glx and rs-fMRI in the salience and default mode network, but these relationships would be altered in FEP. Methods Data from 53 HC (age = 24.70 ±6.23, 34M/19F) and 60 FEP (age = 24.08 ±6.29, 38M/22F) were analyzed. To obtain MRS data, a voxel was placed in the ACC (PRESS, TR/TE = 2000/80ms). Metabolite concentrations were quantified with respect to internal water using the AMARES algorithm in jMRUI. rs-fMRI data were processed using a standard preprocessing pipeline in the CONN toolbox. BOLD signal from a priori brain regions of interest from posterior cingulate cortex (default mode network, DMN), anterior cingulate cortex (salience network, SN), and right posterior parietal cortex (central executive network, CEN) were extracted and correlated with the rest of the brain to measure functional connectivity (FC). Group analyses were performed on Glx, FC, and Glx-FC interactions while controlling for age, gender, and motion when applicable. FC and Glx-FC analyses were performed using small volume correction [(p < 0.01, threshold-free cluster enhancement corrected (TFCE)]. Results No significant between-group differences were found in Glx concentration in the ACC [F(1, 108) = 0.34, p = 0.56], but reduced FC was found on each network in FEP compared to HC (pTFCE corrected). Group Glx-FC interactions were found in the form of positive correlations between Glx and FC in DMN and SN in the HC group, but not in FEP; and negative correlations in CEN in HC, but not in FEP. Discussion While we did not find significant group differences in ACC Glx measurements, ACC Glx modulated FC differentially in FEP and HC. Positive correlations between Glx and FC were found in the SN and DMN, suggesting long range modulation of the two networks in HC, but not in FEP. Additionally, negative correlations between Glx and FC were found in CEN in HC, but not in FEP. Overall, these results suggest that even in the absence of group differences in Glx concentration, the long-range modulation of these 3 networks by ACC Glx is altered in FEP.

Functional and resting-state characterizations of a periventricular heterotopic nodule associated with epileptogenic activity

The object of this study was to extensively characterize a region of periventricular nodular heterotopia (PVNH) in an epilepsy patient to reveal its possible neurocognitive functional role(s). The authors used 3-T MRI approaches to exhaustively characterize a single, right hemisphere heterotopion in a high-functioning adult male with medically responsive epilepsy, which had manifested during late adolescence. The heterotopion proved to be spectroscopically consistent with a cortical-like composition and was interconnected with nearby ipsilateral cortical fundi, as revealed by fiber tractography (diffusion-weighted imaging) and resting-state functional connectivity MRI (rsfMRI). Moreover, the region of PVNH demonstrated two novel characterizations for a heterotopion. First, functional MRI (fMRI), as distinct from rsfMRI, showed that the heterotopion was significantly modulated while the patient watched animated video scenes of biological motion (i.e., cartoons). Second, rsfMRI, which demonstrated correlated brain activity during a task-negative state, uniquely showed directionality within an interconnected network, receiving positive path effects from patent cortical and cerebellar foci while outputting only negative path effects to specific brain foci.These findings are addressed in the context of the impact on noninvasive presurgical brain mapping strategies for adult and pediatric patient workups, as well as the impact of this study on an understanding of the functional cortical architecture underlying cognition from a neurodiversity and evolutionary perspective.