Inferring brain-wide interactions using data-constrained recurrent neural network models

Behavior arises from the coordinated activity of numerous anatomically and functionally distinct brain regions. Modern experimental tools allow unprecedented access to large neural populations spanning many interacting regions brain-wide. Yet, understanding such large-scale datasets necessitates both scalable computational models to extract meaningful features of inter-region communication and principled theories to interpret those features. Here, we introduce Current-Based Decomposition (CURBD), an approach for inferring brain-wide interactions using data-constrained recurrent neural network models that directly reproduce experimentally-obtained neural data. CURBD leverages the functional interactions inferred by such models to reveal directional currents between multiple brain regions. We first show that CURBD accurately isolates inter-region currents in simulated networks with known dynamics. We then apply CURBD to multi-region neural recordings obtained from mice during running, macaques during Pavlovian conditioning, and humans during memory retrieval to demonstrate the widespread applicability of CURBD to untangle brain-wide interactions underlying behavior from a variety of neural datasets

Emotion, social behaviour and decision-making in the medial and orbital frontal cortices

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Foraging with the frontal cortex: A cross-species evaluation of reward-guided behavior

Efficient foraging is essential to survival and depends on frontal cortex in mammals. Because of its role in psychiatric disorders, frontal cortex and its contributions to reward procurement have been studied extensively in both rodents and non-human primates. How frontal cortex of these animal models compares is a source of intense debate. Here we argue that translating findings from rodents to non-human primates requires an appreciation of both the niche in which each animal forages as well as the similarities in frontal cortex anatomy and function. Consequently, we highlight similarities and differences in behavior and anatomy, before focusing on points of convergence in how parts of frontal cortex contribute to distinct aspects of foraging in rats and macaques, more specifically. In doing so, our aim is to emphasize where translation of frontal cortex function between species is clearer, where there is divergence, and where future work should focus. We finish by highlighting aspects of foraging for which have received less attention but we believe are critical to uncovering how frontal cortex promotes survival in each species

The drive to strive: goal generation based on current needs

Hungry animals are influenced by a multitude of different factors when foraging for sustenance. Much of the work on animal foraging has focused on factors relating to the amount of time and energy animals expend searching for and harvesting foods. Models that emphasize such factors have been invaluable in determining when it is beneficial for an animal to search for pastures new. When foraging, however, animals also have to determine how to direct their search. For what food should they forage? There is no point searching for more of a particular food when you are sated from eating it. Here we review work in macaques and humans that has sought to reveal the neural circuits critical for determining the subjective value of different foods and associated objects in our environment and tracking this value over time. There is mounting evidence that a network composed of the orbitofrontal cortex (OFC), amygdala and medial thalamus is critical for linking objects in the environment with food value and adjusting those valuations in real time based on current biological needs. Temporal inactivation studies have revealed that the amygdala and OFC play distinct, but complementary roles in this valuation process. Such a network for determining the subjective value of different foods and, by extension, associated objects, must interact with systems that determine where and for how long to forage. Only by efficiently incorporating these two factors into their decisions will animals be able to achieve maximal fitness

Oligomeric Aβ in the monkey brain impacts synaptic integrity and induces accelerated cortical aging

As the average age of the population continues to rise, the number of individuals affected with age-related cognitive decline and Alzheimer's disease (AD) has increased and is projected to cost more than $290 billion in the United States in 2019. Despite significant investment in research over the last decades, there is no effective treatment to prevent or delay AD progression. There is a translational gap in AD research, with promising drugs based on work in rodent models failing in clinical trials. Aging is the leading risk factor for developing AD and understanding neurobiological changes that affect synaptic integrity with aging will help clarify why the aged brain is vulnerable to AD. We describe here the development of a rhesus monkey model of AD using soluble oligomers of the amyloid beta (Aβ) peptide (AβOs). AβOs infused into the monkey brain target a specific population of spines in the prefrontal cortex, induce neuroinflammation, and increase AD biomarkers in the cerebrospinal fluid to similar levels observed in patients with AD. Importantly, AβOs lead to similar dendritic spine loss to that observed in normal aging in monkeys, but so far without detection of amyloid plaques or tau pathology. Understanding the basis of synaptic impairment is the most effective route to early intervention and prevention or postponement of age-related cognitive decline and transition to AD. These initial findings support the use of monkeys as a platform to understand age-related vulnerabilities of the primate brain and may help develop effective disease-modifying therapies for treatment of AD and related dementias

(A) Representative pictomicrographs of orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and sham lesions

<p><b>Copyright information:</b></p><p>Taken from "Distinct contributions of frontal areas to emotion and social behaviour in the rat"</p><p></p><p>The European Journal of Neuroscience 2007;26(8):2315-2326.</p><p>Published online Jan 2007</p><p>PMCID:PMC2228395.</p><p>© The Authors (2007). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd</p> Pictomicrographs of coronal sections (mm anterior to bregma) showing standard cell loss in representative OFC and ACC lesion animals compared with a sham lesion animal. Schematic coronal sections adapted from . AI, agranular insular cortex; AIv, agranular insular cortex ventral part; Cg1, cingulate cortex area 1; Cg2, cingulate area 2; DLO, dorsolateral orbital cortex; FrA, frontal association cortex; LO, lateral orbital cortex; M1, primary motor cortex; M2, secondary motor cortex; MO, medial orbital cortex; PL, prelimbic cortex; VO, ventral orbital cortex.(B) Reconstructions of the minimal (left), representative (centre) and maximal (right) OFC lesions. The size of the lesions in coronal sections between +5.2 mm and +2.2 mm anterior to bregma are illustrated.(C) Reconstructions of the minimal (left), representative (centre) and maximal (right) ACC lesions. The size of the lesions in coronal sections between +4.2 mm anterior to bregma and −0.26 mm posterior to bregma are illustrated. Dark shading represents areas of total cell loss. Light shading represents the lesion prenumba where cells were still present but were abnormal compared with those in sham lesion controls

The effect of excitotoxic orbitofrontal cortex (OFC) or anterior cingulate cortex (ACC) lesions on the successive alleys test

<p><b>Copyright information:</b></p><p>Taken from "Distinct contributions of frontal areas to emotion and social behaviour in the rat"</p><p></p><p>The European Journal of Neuroscience 2007;26(8):2315-2326.</p><p>Published online Jan 2007</p><p>PMCID:PMC2228395.</p><p>© The Authors (2007). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd</p> Mean (± SEM) time spent in each of the four sections of the apparatus. Section 1 was the least anxiogenic in character, while section 4 was the most