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Large-scale topology and the default mode network in the mouse connectome
Significance Noninvasive brain imaging holds great promise for expanding our capabilities of treating human neurologic and psychiatric disorders. However, key limitations exist in human-only studies, and the ability to use animal models would greatly advance our understanding of human brain function. Mice offer sophisticated genetic and molecular methodology, but correlating these data to functional brain imaging in the mouse brain has remained a major hurdle. This study is the first, to our knowledge, to use whole-brain functional imaging to show large-scale functional architecture with structural correlates in the mouse. Perhaps more important is the finding of conservation in brain topology and default network among rodents and primates, thereby clearing the way for a bridge measurement between human and mouse models.
Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)—a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans.
Journal Article
في الغياب : أعمال طارق الغصين الفوتوغرافية
يتناول كتاب (في الغياب : أعمال طارق الغصين الفوتوغرافية) والذي قام بتأليفه (طارق الغصين) في حوالي (146) صفحة من القطع المتوسط موضوع (التصوير الفوتوغرافي) مستعرضا المحتويات التالية : اللوحات : 1- سلسلة Self portrait series حوار مع الفنان مع جاسر املي، 2 سلسلة A + B series بلا عنوان لا مكان للقريب بقلم سوزان كوتر، 3- سلسلة C series بلا عنوان الزمان والمكان بقلم أنتوتيا كارفر ... إلخ.
BOOK
A systematic review of effort discounting research in humans: Current knowledge, recommendations, and future directions
Effort is a ubiquitous feature in the decision-making literature. Increasing numbers of studies examine the effect of effort requirements on behavior using a discounting framework, assessing the process by which the subjective value of an outcome decreases as the effort required to obtain it increases. Therefore, a review of methodological approaches, findings, and issues is timely. Accordingly, in this systematic review, we identified research studies examining effort discounting to explore how choice architecture factors used in delay discounting and other experimental manipulations affected effort discounting, and the mathematical descriptors used to summarize the relationship between subjective value and effort requirements. Our analysis suggests an area ripe for future research and identifies important knowledge gaps. These gaps are attributable to the use of divergent definitions of effort, as well as highly heterogeneous methodologies, which limit our ability to generate strong conclusions about the intersection between effort and delay discounting processes.
Journal Article
Opposing effects of impulsivity and mindset on sources of science self-efficacy and STEM interest in adolescents
Impulsivity has been linked to academic performance in the context of Attention Deficit Hyperactivity Disorder, though its influence on a wider spectrum of students remains largely unexplored, particularly in the context of STEM learning (i.e. science, technology, engineering, and math). STEM learning was hypothesized to be more challenging for impulsive students, since it requires the practice and repetition of tasks as well as concerted attention to task performance. Impulsivity was assessed in a cross-sectional sample of 2,476 students in grades 6-12. Results show impulsivity affects a larger population of students, not limited to students with learning disabilities. Impulsivity was associated with lower sources of self-efficacy for science (SSSE), interest in most STEM domains (particularly math), and self-reported STEM skills. The large negative effect size observed for impulsivity was opposed by higher mindset, which describes a student's belief in the importance of effort when learning is difficult. Mindset had a large positive effect size associated with greater SSSE, STEM interest, and STEM skills. When modeled together, results offer that mindset interventions may benefit impulsive students who struggle with STEM. Together, these data suggest important interconnected roles for impulsivity and mindset that can influence secondary students' STEM trajectories.
Journal Article
Effects of short-term nicotine deprivation on decision-making: Delay, uncertainty and effort discounting
Experimental evidence suggests that when opioid-dependent drug users are deprived of heroin, they become more likely to behave impulsively on a computer task. The current study examined whether nicotine deprivation has similar effects in cigarette smokers, causing an increase in impulsive decision-making. Simultaneously, the impact of deprivation on several other related decision-making tasks was assessed. Eleven smokers (≥ 15 cigarettes/day) participated in two experimental sessions. For one session, they smoked as usual until the session began. For the other, participants did not smoke for 24 hr. Abstinence was verified using levels of breath carbon monoxide and urinary cotinine. During each session, they completed computer tasks that assessed impulsivity by measuring the tendency to choose small, immediate rewards (cigarettes or money) over US$10 available following a delay, as well as tasks in which smokers chose between small, certain, easily obtained rewards and US$10 whose availability was uncertain or required high levels of effort to obtain. Deprivation increased preference for immediate cigarettes over delayed money, but did not alter preference for immediate money over delayed money. These findings indicate that short-term nicotine abstinence does increase impulsive decision-making, but only when the impulsive choice is drug-related. Increases were not related to a general increase in the value of immediate rewards per se or a general increase in aversion to delayed rewards. Decision-making in the other tasks followed a similar pattern: Deprivation increased preference for the cigarette alternative but did not alter the decision-making processes for nondrug rewards.
Journal Article
Effectiveness of an Immersive Telemedicine Platform for Delivering Diabetes Medical Group Visits for African American, Black and Hispanic, or Latina Women With Uncontrolled Diabetes: The Women in Control 2.0 Noninferiority Randomized Clinical Trial
Medically underserved people with type 2 diabetes mellitus face limited access to group-based diabetes care, placing them at risk for poor disease control and complications. Immersive technology and telemedicine solutions could bridge this gap.
The purpose of this study was to compare the effectiveness of diabetes medical group visits (DMGVs) delivered in an immersive telemedicine platform versus an in-person (IP) setting and establish the noninferiority of the technology-enabled approach for changes in hemoglobin A
(HbA
) and physical activity (measured in metabolic equivalent of task [MET]) at 6 months.
This study is a noninferiority randomized controlled trial conducted from February 2017 to December 2019 at an urban safety net health system and community health center. We enrolled adult women (aged ≥18 years) who self-reported African American or Black race or Hispanic or Latina ethnicity and had type 2 diabetes mellitus and HbA
≥8%. Participants attended 8 weekly DMGVs, which included diabetes self-management education, peer support, and clinician counseling using a culturally adapted curriculum in English or Spanish. In-person participants convened in clinical settings, while virtual world (VW) participants met remotely via an avatar-driven, 3D VW linked to video teleconferencing. Follow-up occurred 6 months post enrollment. Primary outcomes were mean changes in HbA
and physical activity at 6 months, with noninferiority margins of 0.7% and 12 MET-hours, respectively. Secondary outcomes included changes in diabetes distress and depressive symptoms.
Of 309 female participants (mean age 55, SD 10.6 years; n=195, 63% African American or Black; n=105, 34% Hispanic or Latina; n=151 IP; and n=158 in VW), 207 (67%) met per-protocol criteria. In the intention-to-treat analysis, we confirmed noninferiority for primary outcomes. We found similar improvements in mean HbA
by group at 6 months (IP: -0.8%, SD 1.9%; VW: -0.5%, SD 1.8%; mean difference 0.3, 97.5% CI -∞ to 0.3; P<.001). However, there were no detectable improvements in physical activity (IP: -6.5, SD 43.6; VW: -9.6, SD 44.8 MET-hours; mean difference -3.1, 97.5% CI -6.9 to ∞; P=.02). The proportion of participants with significant diabetes distress and depressive symptoms at 6 months decreased in both groups.
In this noninferiority randomized controlled trial, immersive telemedicine was a noninferior platform for delivering diabetes care, eliciting comparable glycemic control improvement, and enhancing patient engagement, compared to IP DMGVs.
ClinicalTrials.gov NCT02726425; https://clinicaltrials.gov/ct2/show/NCT02726425.
Journal Article
Cortical activation during delay discounting in abstinent methamphetamine dependent individuals
Background
Methamphetamine (MA)-dependent individuals prefer smaller immediate over larger delayed rewards in delay discounting (DD) tasks. Human and animal data implicate ventral (amygdala, ventral striatum, ventrolateral prefrontal cortex insula) and dorsal (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex and posterior parietal cortex) systems in DD decisions. The ventral system is hypothesized to respond to the salience and immediacy of rewards while the dorsal system is implicated in the process of comparison and choice.
Methods
We used functional Magnetic Resonance Imaging to probe the neural correlates of DD in 19 recently abstinent MA-dependent patients and 17 age- and gender-matched controls.
Results
Hard DD choices were associated with greatest activation in bilateral middle cingulate, posterior parietal cortex (PPC), and the right rostral insula. Control subjects showed more activation than MA patients bilaterally in the precuneus and in the right caudate nucleus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Magnitude of discounting was correlated with activity in the amygdala, DLPFC, posterior cingulate cortex and PPC.
Conclusions
Our findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions. Patients addicted to MA, who strongly prefer smaller immediate over larger delayed rewards, activate the dorsal cognitive control system in order to overcome their preference. Activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting, suggesting that heavily discounting MA-dependent individuals may be more responsive to the negative salience of delayed rewards than controls.
Journal Article
Environmental enrichment promotes adaptive responding during tests of behavioral regulation in male heterogeneous stock rats
Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n = 200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n = 64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (ii) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant.
Journal Article
Reward maximization assessed using a sequential patch depletion task in a large sample of heterogeneous stock rats
Choice behavior requires animals to evaluate both short- and long-term advantages and disadvantages of all potential alternatives. Impulsive choice is traditionally measured in laboratory tasks by utilizing delay discounting (DD), a paradigm that offers a choice between a smaller immediate reward, or a larger more delayed reward. This study tested a large sample of Heterogeneous Stock (HS) male (n = 896) and female (n = 898) rats, part of a larger genetic study, to investigate whether measures of reward maximization overlapped with traditional models of delay discounting via the patch depletion model using a Sequential Patch Depletion procedure. In this task, rats were offered a concurrent choice between two water “patches” and could elect to “stay” in the current patch or “leave” for an alternative patch. Staying in the current patch resulted in decreasing subsequent reward magnitudes, whereas the choice to leave a patch was followed by a delay and a resetting to the maximum reward magnitude. Based on the delay in a given session, different visit durations were necessary to obtain the maximum number of rewards. Visit duration may be analogous to an indifference point in traditional DD tasks. Males and females did not significantly differ on traditional measures of DD (e.g. delay gradient; AUC). When examining measures of patch utilization, females made fewer patch changes at all delays and spent more time in the patch before leaving for the alternative patch compared to males. Consistent with this, there was some evidence that females deviated from reward maximization more than males. However, when controlling for body weight, females had a higher normalized rate of reinforcement than males. Measures of reward maximization were only weakly associated with traditional DD measures and may represent distinctive underlying processes. Taken together, females performance differed from males with regard to reward maximization that were not observed utilizing traditional measures of DD, suggesting that the patch depletion model was more sensitive to modest sex differences when compared to traditional DD measures in a large sample of HS rats.
Journal Article