bioRxiv Science⌕ Search

Biology subjects

Garin, C. M.

Publications and source records attributed to Garin, C. M..

8 recordsLinked to original sources

Trajectories of Response Inhibition Development in Adolescence

Adolescence is a pivotal developmental period during which cognitive control and the ability to suppress maladaptive impulses undergo profound refinement. Despite extensive behavioral and imaging studies in humans, the neural circuit mechanisms that drive the maturation of inhibitory control remain poorly understood. To address this gap, we performed a longitudinal multimodal study in macaque monkeys spanning the transition from puberty to adulthood, combining behavioral measurements, prefrontal neurophysiology, and structural neuroimaging within the same individuals. Behavioral performance in multiple variants of the antisaccade task improved dramatically across adolescence. In parallel, prefrontal cortical neurons exhibited robust developmental increases in task-related firing, particularly around the generation of goal-directed saccades, indicating maturation of neural representations supporting inhibitory control. Strikingly, trajectories of behavioral improvement and neural activity maturation were tightly predicted by the development of long-range white matter pathways linking frontal cortex with distributed brain networks. These findings identify white matter development as a key systems-level mechanism underlying the emergence of mature inhibitory control and prefrontal neural dynamics and establish a primate framework for understanding developmental vulnerabilities associated with neuropsychiatric disorders that emerge in adolescence and early adulthood.

neuroscience↗

Brain Charts for the Rhesus Macaque Lifespan

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

neuroscience↗

Brain structure and activity predicting cognitive maturation in adolescence

Cognitive abilities of primates, including humans, continue to improve through adolescence 1,2. While a range of changes in brain structure and connectivity have been documented 3,4, how they affect neuronal activity that ultimately determines performance of cognitive functions remains unknown. Here, we conducted a multilevel longitudinal study of monkey adolescent neurocognitive development. The developmental trajectory of neural activity in the prefrontal cortex accounted remarkably well for working memory improvements. While complex aspects of activity changed progressively during adolescence, such as the rotation of stimulus representation in multidimensional neuronal space, which has been implicated in cognitive flexibility, even simpler attributes, such as the baseline firing rate in the period preceding a stimulus appearance had predictive power over behavior. Unexpectedly, decreases in brain volume and thickness, which are widely thought to underlie cognitive changes in humans 5 did not predict well the trajectory of neural activity or cognitive performance changes. Whole brain cortical volume in particular, exhibited an increase and reached a local maximum in late adolescence, at a time of rapid behavioral improvement. Maturation of long-distance white matter tracts linking the frontal lobe with areas of the association cortex and subcortical regions best predicted changes in neuronal activity and behavior. Our results provide evidence that optimization of neural activity depending on widely distributed circuitry effects cognitive development in adolescence.

neuroscience↗

Alteration of mean amplitude of low frequency fluctuations measured by fMRI at 11.7 T in the aging brain of mouse lemur primate

Non-human primates are a critical species for the identification of key biological mechanisms in normal and pathological aging. One of these primates, the mouse lemur, has been widely studied as a model of cerebral aging or Alzheimers disease. The amplitude of low-frequency fluctuations of blood oxygenation level-dependent (BOLD) can be measured with functional MRI. Within specific frequency bands (e.g. the 0.01-0.1 Hz), these amplitudes were proposed to indirectly reflect neuronal activity as well as glucose metabolism. Here, we first created whole brain maps of the mean amplitude of low frequency fluctuations (mALFF) in middle-aged mouse lemurs. Then, we extracted mALFF in old lemurs to identify age-related changes. A high level of mALFF was detected in the temporal cortex (Brodmann area 20), somatosensory areas (Brodmann area 5), insula (Brodmann area 13-6) and the parietal cortex (Brodmann area 7) of healthy middle-aged mouse lemurs. Aging was associated with alteration of mALFF in somatosensory areas (area 5) and the parietal cortex (area 7). Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/521367v2_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@15c9556org.highwire.dtl.DTLVardef@1505c78org.highwire.dtl.DTLVardef@e6f3fcorg.highwire.dtl.DTLVardef@9c6053_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe characterized mean amplitude of fluctuation at low frequencies (mALFF) in mouse lemurs. C_LIO_LImALFF was the highest in regions involved in visuo-somatosensory-motor function (Brodmann areas 5, 7, 20) and in more integrative functions (area 13-16). C_LIO_LImALFF was affected by aging in regions involved in visuo-somatosensory-motor function (parietal areas 5 and 7). C_LIO_LImALFF is a useful marker to investigate age-related cerebral dysfunction in animals. C_LI Significance StatementO_LIThe amplitude of low-frequency fluctuations (ALFF) is expected to reflect neuronal activity. It has been proposed as an MRI-based method to evaluate brain function. C_LIO_LIALFF has been used to investigate different cerebral pathologies in animal models but the regional differences of ALFF signal and the impact of cerebral aging on ALFF has never been characterized. C_LIO_LIHere, we highlight for the first time regional difference of ALFF. High signal was detected in regions involved in visuo-somatosensory-motor function as well as in more integrative functions. ALFF was reduced in regions involved in visuo-somatosensory-motor function during aging. ALFF is thus a useful marker to investigate age-related cerebral dysfunction. C_LI

neuroscience↗

Whole brain mapping of glutamate in adult and old primates at 11.7T

Glutamate is the amino acid with the highest cerebral concentration. It plays a central role in brain metabolism. It is also the principal excitatory neurotransmitter in the brain and is involved in multiple cognitive functions. Alterations of the glutamatergic system may contribute to the pathophysiology of many neurological disorders. For example, changes of glutamate availability are reported in rodents and humans during Alzheimers and Huntingtons diseases, epilepsy as well as during aging. Most studies evaluating cerebral glutamate have used invasive or spectroscopy approaches focusing on specific brain areas. Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) is a recently developed imaging technique that can map glutamate distribution in the entire brain with higher sensitivity and at higher resolution than previous techniques. It thus has strong potential clinical applications to assess glutamate changes in the brain. High field is a key condition to perform gluCEST images with a meaningful signal to noise ratio. Thus, even if some studies started to evaluate gluCEST in humans, most studies focused on rodent models that can be imaged at high magnetic field. In particular, systematic characterization of gluCEST contrast distribution throughout the whole brain has never been performed in humans or non-human primates. Here, we characterized for the first time the distribution of the glutamate index in the whole brain and in large-scale networks of mouse lemur primates at 11.7 Tesla. Because of its small size, this primate can be imaged in high magnetic field systems. It is widely studied as a model of cerebral aging or Alzheimers disease. We observed high gluCEST contrast in cerebral regions such as the nucleus accumbens, septum, basal forebrain, cortical areas 24 and 25. Age-related alterations of this biomarker were detected in the nucleus accumbens, septum, basal forebrain, globus pallidus, hypophysis, cortical areas 24, 21, 6 and in olfactory bulbs. An age-related gluCEST contrast decrease was also detected in specific neuronal networks, such as fronto-temporal and evaluative limbic networks. These results outline regional differences of gluCEST contrast and strengthen its potential to provide new biomarkers of cerebral function in primates. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=85 SRC="FIGDIR/small/459778v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@d672a5org.highwire.dtl.DTLVardef@100e883org.highwire.dtl.DTLVardef@a0f827org.highwire.dtl.DTLVardef@3cad0_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

An Automated Open-Source Workflow for Standards-Compliant Integration of Small Animal Magnetic Resonance Imaging Data

Large-scale research integration is contingent on seamless access to data in standardized formats. Standards enable researchers to understand external experiment structures, pool results, and apply homogeneous preprocessing and analysis workflows. Particularly, they facilitate these features without the need for numerous potentially confounding compatibility add-ons. In small animal magnetic resonance imaging, an overwhelming proportion of data is acquired via the ParaVision software of the Bruker Corporation. The original data structure is predominantly transparent, but fundamentally incompatible with modern pipelines. Additionally, it sources metadata from free-field operator input, which diverges strongly between laboratories and researchers. In this article we present an open-source workflow which automatically converts and reposits data from the ParaVision structure into the widely supported and openly documented Brain Imaging Data Structure (BIDS). Complementing this workflow we also present operator guidelines for appropriate ParaVision data input, and a programmatic walk-through detailing how preexisting scans with uninterpretable metadata records can easily be made compliant after the acquisition.

neuroscience↗

Resting state cerebral networks in mouse lemur primates: from multilevel validation to comparison with humans

Measures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Animal models are critical to further address experimentally the function of brain networks and their roles in pathologies. Here we describe for the first time brain network organization in the mouse lemur (Microcebus murinus), a small primate attracting increased attention as a model for neuroscience. Resting-state functional MR images were recorded at 11.7 Tesla. Forty-eight functional regions were identified and used to identify networks using graph theory, dictionary learning and seed-based analyses. Comparison of results issued from these three complementary methods allowed the description of the most robust networks from mouse lemurs. Large scale networks were then identified from resting-state functional MR images of humans using the same method as for lemurs. Strong homologies were outlined between cerebral networks in mouse lemurs and humans.

neuroscience↗

Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories world-wide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a murine default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

neuroscience↗