Biology subjects

Kohut, S.

Publications and source records attributed to Kohut, S..

3 recordsLinked to original sources

bioRxiv2023

Age-related development in prefrontal-subcortical resting-state functional connectivity in nonhuman primates

IntroductionUnderstanding age-related changes in functional connectivity (FC) with regards to the maturation trajectories of cortical-subcortical circuits is critical for identifying biomarkers for disease vulnerability. The present study investigated resting-state FC in adolescent and adult nonhuman primates to characterize developmentally-sensitive functional brain circuits. MethodsResting-state fMRI data were acquired in adolescent (33.3{+/-}1.59 months; n=22) and adult (117.29{+/-}2.86 months; n=15) squirrel monkeys and FC was compared in seven prefrontal and ten subcortical regions-of-interest (ROIs). The effect of subject age on FC between each pair of ROIs was evaluated to identify nodes with the most age-sensitive connections (hubs) which were then used in seed-to-whole-brain FC analyses. A subset of adolescents (n=7) was also assessed over 3 longitudinal scans to track changes in hub connectivity throughout adolescence. ResultsA significant effect of age on ROI-ROI FC was found for adolescent (p<0.001), but not adult, subjects (p=0.8). Evaluation of parameter estimates ({beta}) for each ROI-ROI pair found three within-prefrontal (dorsolateral (dlPFC), dorsomedial (dmPFC), and medial orbitofrontal cortices), two within-subcortical (R amygdala and L hippocampus), and three between prefrontal-subcortical (dlPFC, dmPFC, L caudate) hubs with the highest number of age-related connections. Large-scale organizational differences were also observed between the adolescent and adult groups. Longitudinal scans found within-subject changes in FC consistent with group effect. ConclusionsThe relationship between changes in FC and age during adolescence indicates dynamic maturation of several prefrontal-subcortical circuits in nonhuman primates. These findings provide specificity in our understanding of the development of functional brain circuits during and into late adolescence. SignificanceAdolescence marks a period of rapid development in the brain, but also increased vulnerability to mental health disorders. Age-related prefrontal-subcortical resting-state functional connectivity was evaluated in awake adolescent and adult squirrel monkeys. Identification of functional connectivity differences highlight a network of hubs with a high number of connections evolving from early to late adolescence, indicating selectivity in maturation during different stages of aging. Compared to adults, adolescents also show several large-scale organizational differences in circuits originating from important seed regions-of-interest. Longitudinal analysis reveals functional connectivity trajectories emerging from early adolescence and maturing into adult-like patterns during late adolescence. These findings identify functional connections that change dramatically during adolescence suggesting specific circuits that could be at heightened sensitivity to disease vulnerability.

neuroscience↗

bioRxiv2023

Oxycodone self-administration and reinstatement in male and female squirrel monkeys: Effects of alternative reinforcer availability

The use of non-drug alternative reinforcers has long been utilized as a component of therapeutic interventions for the management of substance use disorder; however, the conditions under which alternative reinforcers are most effective are not well characterized. This study evaluated the impact of varying the magnitude of an alternative reinforcer on oxycodone self-administration and reinstatement in male and female squirrel monkeys. Subjects (n=4/sex) were trained under concurrent second-order schedules of reinforcement for intravenous oxycodone (0.001-0.1mg/kg/inj) on one lever, and sweetened condensed milk (5, 10, 20, 30% in water) on another. Oxycodone-primed reinstatement was evaluated by administering 0.32mg/kg oxycodone prior to sessions in which saline was available on the drug-paired lever. During oxycodone self-administration sessions, milk availability decreased oxycodone self-administration and preference in a concentration-dependent manner; low milk concentrations were more effective at decreasing oxycodones reinforcing potency in males. During reinstatement tests, milk significantly attenuated oxycodone-primed responding in both males and females; low milk concentrations were more effective at decreasing the priming effects of oxycodone in females. That alternative reinforcers differentially impacted self-administration and reinstatement in a sex-dependent manner suggests that treatment strategies that utilize alternative reinforcers may be more effective in males or females depending on when they are implemented.

pharmacology and toxicology↗

bioRxiv2023

Resting state networks of awake adolescent and adult squirrel monkeys using ultra-high field (9.4T) functional magnetic resonance imaging

Resting state networks (RSNs) are increasingly forwarded as candidate biomarkers for neuropsychiatric disorders. Such biomarkers may provide objective measures for evaluating novel therapeutic interventions in nonhuman primates often used in translational neuroimaging research. This study aimed to characterize the RSNs of awake squirrel monkeys and compare the characteristics of those networks in adolescent and adult subjects. Twenty-seven squirrel monkeys (n=12 adolescents [6 male/6 female] [~]2.5 years and n=15 adults [7 male/8 female] [~]9.5 years) were gradually acclimated to awake scanning procedures; whole-brain fMRI images were acquired with a 9.4 Tesla scanner. Group level independent component (IC) analysis (30 ICs) with dual regression was used to detect and compare RSNs. Twenty ICs corresponding to physiologically meaningful networks representing a range of neural functions, including motor, sensory, reward (e.g., basal ganglia), and cognitive processes were identified in both adolescent and adult monkeys. Significant age-related differences between the adult and adolescent subjects (adult > adolescent) were found in two networks of interest: (1) the right upper occipital region with an OFC IC and (2) the left temporal cortex, bilateral visual areas, and cerebellum with the cingulate IC. These results demonstrate that squirrel monkey RSNs are stable and consistent with RSNs previously identified in humans, rodents, and other nonhuman primate species. These data also identify several networks in adolescence that are conserved and others that may change into adulthood. Significance StatementFunctional magnetic resonance imaging procedures have revealed important information about how the brain is modified by experimental manipulations, disease states, and aging throughout the lifespan. Preclinical neuroimaging, especially in nonhuman primates, has become a frequently used means to answer targeted questions related to brain resting-state functional connectivity. The present study characterized resting state networks (RSNs) in adult and adolescent squirrel monkeys; twenty RSNs corresponding to networks representing a range of neural functions were identified. The RSNs identified here can be utilized in future studies examining the effects of experimental manipulations on brain connectivity in squirrel monkeys. These data also may be useful for comparative analysis with other primate species to provide an evolutionary perspective for understanding brain function and organization.

neuroscience↗