An orexigenic subnetwork within the human hippocampus
Senior Author, Casey H. Halpern, MD
For our research published in Nature, we discovered disrupted connections between memory and appetite regulating brain circuits are directly proportional to body mass index, notably in patients who suffer from disordered or overeating that can lead to obesity, such as binge eating disorder. Individuals who are obese have impaired connections between the dorsolateral hippocampus and the lateral hypothalamus, which may impact their ability to control or regulate emotional responses when anticipating rewarding meals or treats.
These findings underscore that some individual’s brains can be fundamentally different in regions that increase the risk for obesity. Conditions like disordered eating and obesity are a lot more complicated than simply managing self-control and eating healthier. What these individuals need is not more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.
The hippocampus has never been targeted to treat obesity, or the disordered eating that can sometimes cause obesity. We hope to be able to use this research to both identify which individuals who are likely to develop obesity later in life, and to develop novel therapies – both invasive and not – to help improve function of this critical circuit that seems to go awry in patients who are obese.
Full Publication
Structural and functional integration of human forebrain organoids with the injured adult rat visual system
Senior Author, H. Isaac Chen, MD
Very few options exist to recover neurological function in patients who have sustained some form of brain damage. One promising approach to rebuilding brain circuitry is transplantation of structured neural tissues. Recently, significant progress has been made in generating brain organoids from human stem cell sources, including induced pluripotent stem cells derived from patients. These organoids mimic the architecture of the brain to a substantial degree.
The goal of this paper was to examine how well human brain organoids integrated with the brain of host animals after transplantation. Cavities in the visual cortex of young adult rats were made using suction, and organoids were immediately inserted into the cavities. At 1, 2, and 3 months after transplantation, robust organoid grafts were found. These grafts formed synaptic connections with the host brain, primarily with brain regions typically associated with the visual system. In particular, herpes simplex virus-based trans-synaptic tracing demonstrated synaptic connectivity between the host animal’s eye (retina) and the organoid graft. We also observed that visual stimulation of the host animal’s eye caused neuronal responses in the organoid graft. A subset of the organoid neurons exhibited orientation selectivity, a sophisticated feature of visual cortex neurons. These intriguing results show that brain organoids can structurally and functionally integrate with the brain, establishing the feasibility of neural transplantation for repairing the brain after injury.
Full Publication
Top-down control of exogenous attentional selection is mediated by beta coherence in prefrontal cortex
Senior Author, Bijan Pesaran, PhD
In the study, we sought to illuminate the neural mechanism that helps the brain decide whether to focus visual attention on a rewarding task or an alluring distraction. By analyzing neuron activity in animal models as they faced this kind of attentional conflict, we discovered that a pattern of coordinated activity called “beta bursts” in a set of neurons in the lateral prefrontal cortex (LPFC)—a section in the front of the brain responsible for motivation and rewards—appears to have a major role in keeping attention task-focused, essentially by suppressing the influence of the distracting stimulus. We believe that understanding prefrontal cortical mechanisms for suppressing distracting inputs may help develop novel treatments for a variety of mental health disorders involving attention disorders, cue-reactivity and other disorders of impulse control.
Full Publication