The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

The developmental trajectory of 1H-MRS brain metabolites from childhood to adulthood.

Human brain development is ongoing throughout childhood, with for example, myelination of nerve fibers and refinement of synaptic connections continuing until early adulthood. 1H-Magnetic Resonance Spectroscopy (1H-MRS) can be used to quantify the concentrations of endogenous metabolites (e.g. glutamate and γ -aminobutyric acid (GABA)) in the human brain in vivo and so can provide valuable, tractable insight into the biochemical processes that support postnatal neurodevelopment. This can feasibly provide new insight into and aid the management of neurodevelopmental disorders by providing chemical markers of atypical development. This study aims to characterize the normative developmental trajectory of various brain metabolites, as measured by 1H-MRS from a midline posterior parietal voxel. We find significant non-linear trajectories for GABA+ (GABA plus macromolecules), Glx (glutamate + glutamine), total choline (tCho) and total creatine (tCr) concentrations. Glx and GABA+ concentrations steeply decrease across childhood, with more stable trajectories across early adulthood. tCr and tCho concentrations increase from childhood to early adulthood. Total N-acetyl aspartate (tNAA) and Myo-Inositol (mI) concentrations are relatively stable across development. Trajectories likely reflect fundamental neurodevelopmental processes (including local circuit refinement) which occur from childhood to early adulthood and can be associated with cognitive development; we find GABA+ concentrations significantly positively correlate with recognition memory scores.

Interhemispheric functional brain connectivity predicts new language learning success in adults.

Investigating interhemispheric interactions between homologous cortical regions during language processing is of interest. Despite prevalent left hemisphere lateralization of language, the right hemisphere also plays an important role and interhemispheric connectivity is influenced by language experience and is implicated in second language (L2) acquisition. Regions involved in language processing have differential connectivity to other cortical regions and to each other, and play specific roles in language. We examined the interhemispheric interactions of subregions of the inferior frontal gyrus (areas 44 and 45), the adjacent area 9/46v in the middle frontal gyrus, the superior temporal gyrus (STG), and the posterior inferior parietal lobule (pIPL) in relation to distinct and specific aspects of L2 learning success. The results indicated that the connectivity between left and right areas 44 and 9/46v predicted improvement in sentence repetition, connectivity between left and right area 45 and mid-STG predicted improvement in auditory comprehension, and connectivity between left and right pIPL predicted improvement in reading speed. We show interhemispheric interactions in the specific context of facilitating performance in adult L2 acquisition that follow an anterior to posterior gradient in the brain, and are consistent with the respective roles of these regions in language processing.

Development of the neural correlates of recollection.

Recollection of past events has been associated with the core recollection network comprising the posterior medial temporal lobe and parietal regions, as well as the medial prefrontal cortex (mPFC). The development of the brain basis for recollection is understudied. In a sample of adults (n = 22; 18-25 years) and children (n = 23; 9-13 years), the present study aimed to address this knowledge gap using a cued recall paradigm, known to elicit recollection experience. Successful recall was associated with activations in regions of the core recollection network and frontoparietal network. Adults exhibited greater successful recall activations compared with children in the precuneus and right angular gyrus. In contrast, similar levels of successful recall activations were observed in both age groups in the mPFC. Group differences were also seen in the hippocampus and lateral frontal regions. These findings suggest that the engagement of the mPFC in episodic retrieval may be relatively early maturing, whereas the contribution to episodic retrieval of more posterior regions such as the precuneus and angular gyrus undergoes more protracted maturation.

Frontoparietal Anatomical Connectivity Predicts Second Language Learning Success.

There is considerable individual variability in second language (L2) learning abilities in adulthood. The inferior parietal lobule, important in L2 learning success, is anatomically connected to language areas in the frontal lobe via the superior longitudinal fasciculus (SLF). The second and third branches of the SLF (SLF II and III) have not been examined separately in the context of language, yet they are known to have dissociable frontoparietal connections. Studying these pathways and their functional contributions to L2 learning is thus of great interest. Using diffusion MRI tractography, we investigated individuals undergoing language training to explore brain structural predictors of L2 learning success. We dissected SLF II and III using gold-standard anatomical definitions and related prelearning white matter integrity to language improvements corresponding with hypothesized tract functions. SLF II properties predicted improvement in lexical retrieval, while SLF III properties predicted improvement in articulation rate. Finer grained separation of these pathways enables better understanding of their distinct roles in language, which is essential for studying how anatomical connectivity relates to L2 learning abilities.

Development of self-referential effect on memory recollection.

Information learned in relation to oneself is typically better remembered, termed the self-reference effect (SRE). This study aimed to elucidate the developmental trajectory of the SRE in recollection and source memory from mid-childhood to young adulthood. In 2018-2019 in Baltimore, Maryland, 136 seven- to thirty-year-olds (77 female; approximately 80% White, 15% Asian American, 5% Black) viewed objects on one of two backgrounds and answered a self-referential or semantic question for each. A recognition test probed memory for objects and source details (inherent: question type; peripheral: background image). SRE increased with age for detailed recollection (r = .189), but not familiarity, and extended to inherent source memory. This suggests that self-referencing promotes richer memory in children and develops into young adulthood.

Brain functional organization and structure in patients with arteriovenous malformations.

PURPOSE: Developmental in nature, brain arteriovenous malformations (AVM) have the potential to affect whole brain organization. Here we investigated the impact of AVM on functional and structural brain organization using resting-state functional MRI (rsfMRI) and cortical thickness measures. METHODS: We investigated brain functional organization and structure using rsfMRI in conjunction with cortical thickness analyses in 23 patients with cerebral arteriovenous malformations (AVMs) and 20 healthy control subjects. RESULTS: Healthy controls showed the expected anti-correlation between activity in the default mode network (DMN) and frontal areas that are part of the attentional control network. By contrast, patients demonstrated a disruption of this anti-correlation. Disruptions to this anti-correlation were even observed in a subgroup of patients with lesions remote from the main nodes of the DMN and were unrelated to differences in perfusion. Functional connectivity differences were accompanied by reduced cortical thickness in frontal attentional areas in patients compared to the controls. CONCLUSIONS: These results contribute to the discussion that AVMs affect whole brain networks and not simply the area surrounding the lesion.

Lewis-Base-Catalyzed [1 + 2 + 2] Annulation Reaction of Morita-Baylis-Hillman Carbonates with Unsaturated Pyrazolones: Construction of All-Stereogenic Carbon Cyclopentane-Fused Dispiropyrazolones.

The first Lewis-base-catalyzed unexpected [1 + 2 + 2] annulation reaction between Morita-Baylis-Hillman carbonates and unsaturated pyrazolones was developed. The multicyclic cyclopentane-fused dispiropyrazolone constructions containing five contiguous stereogenic centers, including two spiro quaternary centers, were prepared with excellent yields (81-98%) and moderate to good diastereoselectivities (1:1 to 13:1). Further transformation and gram-scale operations were also achieved efficiently.

Impaired Frontal-Limbic White Matter Maturation in Children at Risk for Major Depression.

Depression is among the most common neuropsychiatric disorders. It remains unclear whether brain abnormalities associated with depression reflect the pathological state of the disease or neurobiological traits predisposing individuals to depression. Parental history of depression is a risk factor that more than triples the risk of depression. We compared white matter (WM) microstructure cross-sectionally in 40 children ages 8-14 with versus without parental history of depression (At-Risk vs. Control). There were significant differences in age-related changes of fractional anisotropy (FA) between the groups, localized in the anterior fronto-limbic WM pathways, including the anterior cingulum and the genu of the corpus callosum. Control children exhibited typical increasing FA with age, whereas At-Risk children exhibited atypical decreasing FA with age in these fronto-limbic regions. Furthermore, dorsal cingulate FA significantly correlated with depressive symptoms for At-Risk children. The results suggest maturational WM microstructure differences in mood-regulatory neurocircuitry that may contribute to neurodevelopmental risk for depression. The study provides new insights into neurodevelopmental susceptibility to depression and related disabilities that may promote early preventive intervention approaches.

Effects of Early and Late Bilingualism on Resting-State Functional Connectivity.

Of current interest is how variations in early language experience shape patterns of functional connectivity in the human brain. In the present study, we compared simultaneous (two languages from birth) and sequential (second language learned after age 5 years) bilinguals using a seed-based resting-state MRI approach. We focused on the inferior frontal gyrus (IFG) as our ROI, as recent studies have demonstrated both neurofunctional and neurostructural changes related to age of second language acquisition in bilinguals in this cortical area. Stronger functional connectivity was observed for simultaneous bilinguals between the left and right IFG, as well as between the inferior frontal gyrus and brain areas involved in language control, including the dorsolateral prefrontal cortex, inferior parietal lobule, and cerebellum. Functional connectivity between the left IFG and the right IFG and right inferior parietal lobule was also significantly correlated with age of acquisition for sequential bilinguals; the earlier the second language was acquired, the stronger was the functional connectivity. In addition, greater functional connectivity between homologous regions of the inferior frontal gyrus was associated with reduced neural activation in the left IFG during speech production. The increased connectivity at rest and reduced neural activation during task performance suggests enhanced neural efficiency in this important brain area involved in both speech production and domain-general cognitive processing. Together, our findings highlight how the brain's intrinsic functional patterns are influenced by the developmental timeline in which second language acquisition occurs. SIGNIFICANCE STATEMENT: Of current interest is how early life experience leaves its footprint on brain structure and function. In this regard, bilingualism provides an optimal way to determine the effects of the timing of language learning because a second language can be learned from birth or later in life. We used resting-state fMRI to look at simultaneous and sequential bilinguals who differed only in age of acquisition, and found stronger connectivity between language and cognitive control regions in bilinguals who learned their two languages simultaneously, a pattern that was associated with more efficient brain activation during speech. Our findings highlight how functional connections in the brain differ depending upon when learning takes place.

Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human capacity to learn a second language can be predicted by an individual's intrinsic functional connectivity within the language network.

Simultaneous learning of two languages from birth positively impacts intrinsic functional connectivity and cognitive control.

This study explores the effect of individual differences in the age of acquisition of a second language using resting-state functional magnetic resonance imaging (rs-fMRI) to examine functional connectivity and its relation with cognitive control within bilinguals. We compared simultaneous bilinguals, who learned two languages from birth, to sequential bilinguals, who learned a second language following mastery of their first language. Results show an effect of language experience on the strength of anticorrelation between the default mode network and the task-positive attention network and on cognitive control, with simultaneous bilinguals demonstrating stronger anticorrelations between the two networks, as well as superior cognitive control compared to sequential bilinguals. These findings demonstrate that the timing of language learning may have an impact on cognitive control, with the simultaneous learning of two languages being associated with more optimal brain connectivity for cognitive control compared to sequential language learning.

Lower gray matter density and functional connectivity in the anterior insula in smokers compared with never smokers.

Although nicotine addiction is characterized by both structural and functional abnormalities in brain networks involved in salience and cognitive control, few studies have integrated these data to understand how these abnormalities may support addiction. This study aimed to (1) evaluate gray matter density and functional connectivity of the anterior insula in cigarette smokers and never smokers and (2) characterize how differences in these measures were related to smoking behavior. We compared structural magnetic resonance imaging (MRI) (gray matter density via voxel-based morphometry) and seed-based functional connectivity MRI data in 16 minimally deprived smokers and 16 matched never smokers. Compared with controls, smokers had lower gray matter density in left anterior insula extending into inferior frontal and temporal cortex. Gray matter density in this region was inversely correlated with cigarettes smoked per day. Smokers exhibited negative functional connectivity (anti-correlation) between the anterior insula and regions involved in cognitive control (left lPFC) and semantic processing/emotion regulation (lateral temporal cortex), whereas controls exhibited positive connectivity between these regions. There were differences in the anterior insula, a central region in the brain's salience network, when comparing both volumetric and functional connectivity data between cigarette smokers and never smokers. Volumetric data, but not the functional connectivity data, were also associated with an aspect of smoking behavior (daily cigarettes smoked).

Selective development of anticorrelated networks in the intrinsic functional organization of the human brain.

We examined the normal development of intrinsic functional connectivity of the default network (brain regions typically deactivated for attention-demanding tasks) as measured by resting-state fMRI in children, adolescents, and young adults ages 8-24 years. We investigated both positive and negative correlations and employed analysis methods that allowed for valid interpretation of negative correlations and that also minimized the influence of motion artifacts that are often confounds in developmental neuroimaging. As age increased, there were robust developmental increases in negative correlations, including those between medial pFC (MPFC) and dorsolateral pFC (DLPFC) and between lateral parietal cortices and brain regions associated with the dorsal attention network. Between multiple regions, these correlations reversed from being positive in children to negative in adults. Age-related changes in positive correlations within the default network were below statistical threshold after controlling for motion. Given evidence in adults that greater negative correlation between MPFC and DLPFC is associated with superior cognitive performance, the development of an intrinsic anticorrelation between MPFC and DLPFC may be a marker of the large growth of working memory and executive functions that occurs from childhood to young adulthood.

Development of deactivation of the default-mode network during episodic memory formation.

Task-induced deactivation of the default-mode network (DMN) has been associated in adults with successful episodic memory formation, possibly as a mechanism to focus allocation of mental resources for successful encoding of external stimuli. We investigated developmental changes of deactivation of the DMN (posterior cingulate, medial prefrontal, and bilateral lateral parietal cortices) during episodic memory formation in children, adolescents, and young adults (ages 8-24), who studied scenes during functional magnetic resonance imaging (fMRI). Recognition memory improved with age. We defined DMN regions of interest from a different sample of participants with the same age range, using resting-state fMRI. In adults, there was greater deactivation of the DMN for scenes that were later remembered than scenes that were later forgotten. In children, deactivation of the default-network did not differ reliably between scenes that were later remembered or forgotten. Adolescents exhibited a pattern of activation intermediate to that of children and adults. The hippocampal region, often considered part of the DMN, showed a functional dissociation with the rest of the DMN by exhibiting increased activation for later remembered than later forgotten scene that was similar across age groups. These findings suggest that development of memory ability from childhood through adulthood may involve increased deactivation of the neocortical DMN during learning.

Predicting depression risk in early adolescence via multimodal brain imaging.

Depression is an incapacitating psychiatric disorder with increased risk through adolescence. Among other factors, children with family history of depression have significantly higher risk of developing depression. Early identification of pre-adolescent children who are at risk of depression is crucial for early intervention and prevention. In this study, we used a large longitudinal sample from the Adolescent Brain Cognitive Development (ABCD) Study (2658 participants after imaging quality control, between 9-10 years at baseline), we applied advanced machine learning methods to predict depression risk at the two-year follow-up from the baseline assessment, using a set of comprehensive multimodal neuroimaging features derived from structural MRI, diffusion tensor imaging, and task and rest functional MRI. Prediction performance underwent a rigorous cross-validation method of leave-one-site-out. Our results demonstrate that all brain features had prediction scores significantly better than expected by chance, with brain features from rest-fMRI showing the best classification performance in the high-risk group of participants with parental history of depression (N = 625). Specifically, rest-fMRI features, which came from functional connectomes, showed significantly better classification performance than other brain features. This finding highlights the key role of the interacting elements of the connectome in capturing more individual variability in psychopathology compared to measures of single brain regions. Our study contributes to the effort of identifying biological risks of depression in early adolescence in population-based samples.

From vision to memory: How scene-sensitive regions support episodic memory formation during child development.

Previous brain imaging studies have identified three brain regions that selectively respond to visual scenes, the parahippocampal place area (PPA), the occipital place area (OPA), and the retrosplenial cortex (RSC). There is growing evidence that these visual scene-sensitive regions process different types of scene information and may have different developmental timelines in supporting scene perception. How these scene-sensitive regions support memory functions during child development is largely unknown. We investigated PPA, OPA and RSC activations associated with episodic memory formation in childhood (5-7 years of age) and young adulthood, using a subsequent scene memory paradigm and a functional localizer for scenes. PPA, OPA, and RSC subsequent memory activation and functional connectivity differed between children and adults. Subsequent memory effects were found in activations of all three scene regions in adults. In children, however, robust subsequent memory effects were only found in the PPA. Functional connectivity during successful encoding was significant among the three regions in adults, but not in children. PPA subsequently memory activations and PPA-RSC subsequent memory functional connectivity correlated with accuracy in adults, but not children. These age-related differences add new evidence linking protracted development of the scene-sensitive regions to the protracted development of episodic memory.

Family Environment Modulates Linkage of Transdiagnostic Psychiatric Phenotypes and Dissociable Brain Features in the Developing Brain.

BACKGROUND: Family environment has long been known for shaping brain function and psychiatric phenotypes, especially during childhood and adolescence. Accumulating neuroimaging evidence suggests that across different psychiatric disorders, common phenotypes may share common neural bases, indicating latent brain-behavior relationships beyond diagnostic categories. However, the influence of family environment on the brain-behavior relationship from a transdiagnostic perspective remains unknown. METHODS: We included a community-based sample of 699 participants (ages 5-22 years) and applied partial least squares regression analysis to determine latent brain-behavior relationships from whole-brain functional connectivity and comprehensive phenotypic measures. Comparisons were made between diagnostic and nondiagnostic groups to help interpret the latent brain-behavior relationships. A moderation model was introduced to examine the potential moderating role of family factors in the estimated brain-behavior associations. RESULTS: Four significant latent brain-behavior pairs were identified that reflected the relationship of dissociable brain network and general behavioral problems, cognitive and language skills, externalizing problems, and social dysfunction, respectively. The group comparisons exhibited interpretable variations across different diagnostic groups. A warm family environment was found to moderate the brain-behavior relationship of core symptoms in internalizing disorders. However, in neurodevelopmental disorders, family factors were not found to moderate the brain-behavior relationship of core symptoms, but they were found to affect the brain-behavior relationship in other domains. CONCLUSIONS: Our findings leveraged a transdiagnostic analysis to investigate the moderating effects of family factors on brain-behavior associations, emphasizing the different roles that family factors play during this developmental period across distinct diagnostic groups.

High-effect gene-coding variants impact cognition, mental well-being, and neighborhood safety substrates in brain morphology.

Our genetic makeup, together with environmental and social influences, shape our brain's development. Yet, the imaging genetics field has struggled to integrate all these modalities to investigate the interplay between genetic blueprint, environment, human health, daily living skills and outcomes. Hence, we interrogated the Adolescent Brain Cognitive Development (ABCD) cohort to outline the effects of rare high-effect genetic variants on brain architecture and corresponding implications on cognitive, behavioral, psychosocial, and socioeconomic traits. Specifically, we designed a holistic pattern-learning algorithm that quantitatively dissects the impacts of copy number variations (CNVs) on brain structure and 962 behavioral variables spanning 20 categories in 7,657 adolescents. Our results reveal associations between genetic alterations, higher-order brain networks, and specific parameters of the family well-being (increased parental and child stress, anxiety and depression) or neighborhood dynamics (decreased safety); effects extending beyond the impairment of cognitive ability or language capacity, dominantly reported in the CNV literature. Our investigation thus spotlights a far-reaching interplay between genetic variation and subjective life quality in adolescents and their families.

The development of brain systems associated with successful memory retrieval of scenes.

Neuroanatomical and psychological evidence suggests prolonged maturation of declarative memory systems in the human brain from childhood into young adulthood. Here, we examine functional brain development during successful memory retrieval of scenes in children, adolescents, and young adults ages 8-21 via functional magnetic resonance imaging. Recognition memory improved with age, specifically for accurate identification of studied scenes (hits). Successful retrieval (correct old-new decisions for studied vs unstudied scenes) was associated with activations in frontal, parietal, and medial temporal lobe (MTL) regions. Activations associated with successful retrieval increased with age in left parietal cortex (BA7), bilateral prefrontal, and bilateral caudate regions. In contrast, activations associated with successful retrieval did not change with age in the MTL. Psychophysiological interaction analysis revealed that there were, however, age-relate changes in differential connectivity for successful retrieval between MTL and prefrontal regions. These results suggest that neocortical regions related to attentional or strategic control show the greatest developmental changes for memory retrieval of scenes. Furthermore, these results suggest that functional interactions between MTL and prefrontal regions during memory retrieval also develop into young adulthood. The developmental increase of memory-related activations in frontal and parietal regions for retrieval of scenes and the absence of such an increase in MTL regions parallels what has been observed for memory encoding of scenes.