University of Indonesia

Neuroscientists have obtained the first direct recordings of the human brain in the minutes before and after a brain hub crucial for language meaning was surgically disconnected. The results reveal the importance of brain hubs in neural networks and the remarkable way in which the human brain attempts to compensate when a hub is lost, with immediacy not previously observed.  A University of Iowa-led team of international neuroscientists have obtained the first direct recordings of the human brain in the minutes before and after a brain hub crucial for language meaning was surgically disconnected. The results reveal the importance of brain hubs in neural networks and the remarkable way in which the human brain attempts to compensate when a hub is lost, with immediacy not previously observed. Hubs are critical for connectivity Hubs are everywhere. The hub of a bicycle wheel, with spokes shooting out from the center, keeps the wheel from collapsing when the bicycle is ridden. Airport hubs connect cities across the world. And social hubs like coffee shops or online social networks are places people gather for interaction. The human brain has hubs, too -- the intersection of many neuronal pathways that help coordinate brain activity required for complex functions like understanding and responding to speech. However, whether highly interconnected brain hubs are irreplaceable for certain brain functions has been controversial. By some accounts the brain, as an already highly interconnected neural network, can in principle immediately compensate for the loss of a hub, in the same way that traffic can be redirected around a blocked off city center. With a rare experimental opportunity, the UI neurosurgical and research teams led by Matthew Howard III, MD, professor and DEO of neurosurgery, and Christopher Petkov, PhD, professor and vice chair for research in neurosurgery, have achieved a breakthrough in understanding the necessity of a single hub. By obtaining evidence for what happens when a hub required for language meaning is lost, the researchers showed both the intrinsic importance of the hub as well as the remarkable and rapid ability of the brain to adapt and at least partially attempt to immediately compensate for its loss. The findings were reported recently in the journal Nature Communications. Evaluating the impact of losing a brain hub The study was conducted during surgical treatment of two patients with epilepsy. Both patients were undergoing procedures that required surgical removal of the anterior temporal lobe -- a brain hub for language meaning -- to allow the neurosurgeons access to a deeper brain area causing the patients' debilitating epileptic seizures. Before this type of surgery, neurosurgery teams often ask the patients to conduct speech and language tasks in the operating room as the team uses implanted electrodes to record activity from parts of the brain close to and distant from the planned surgery area. These recordings help the clinical team effectively treat the seizures while limiting the impact of the surgery on the patient's speech and language abilities. Typically, the recording electrodes are not needed after the surgical resection procedure and are removed. The innovation in this study was that the neurosurgery team was able to safely complete the procedure with the recording electrodes left in place or replaced to the same location after the procedure. This made it possible to obtain rare pre- and post-operative recordings allowing the researchers to evaluate signals from brain areas far away from the hub, including speech and language areas distant from the surgery site. Analysis of the change in responses to speech sounds before and after the loss of the hub revealed a rapid disruption of signaling and subsequent partial compensation of the broader brain network. "The rapid impact on the speech and language processing regions well removed from the surgical treatment site was surprising, but what was even more surprising was how the brain was working to compensate, albeit incompletely within this short timeframe," says Petkov, who also holds an appointment at Newcastle University Medical School in the UK. The findings disprove theories challenging the necessity of specific brain hubs by showing that the hub was important to maintain normal brain processing in language. "Neurosurgical treatment and new technologies continue to improve the treatment options provided to patients," says Howard, who also is a member of the Iowa Neuroscience Institute. "Research such as this underscores the importance of safely obtaining and comparing electrical recordings pre and post operatively, particularly when a brain hub might be affected." According to the researchers, the observation on the nature of the immediate impact on a neural network and its rapid attempt to compensate provides evidence in support of a brain theory proposed by Professor Karl Friston at University College London, which posits that any self-organizing system at equilibrium works towards orderliness by minimizing its free energy, a resistance of the universal tendency towards disorder. These neurobiological results following human brain hub disconnection were consistent with several predictions of this and related neurobiological theories, showing how the brain works to try to regain order after the loss of one of its hubs. In addition to Petkov and Howard, the research team included researchers in the UI Departments of Neurosurgery, Radiology, and Psychological and Brain Sciences, as well as colleagues from Newcastle University, UCL, and University of Cambridge in the UK, and from Carnegie Mellon University, University of Wisconsin-Madison, and Gonzaga University in the United States. The research was funded in part by grants from National Institutes of Health, the Wellcome Trust. and the European Research Council.

SPRINGFIELD, N.J., Dec. 12, 2022 /PRNewswire/ -- Evergreen Theragnostics has submitted a New Drug Application (NDA) for EVG-001 (Kit for preparation of Gallium-68 DOTATOC Injection), a radiopharmaceutical for imaging of neuroendocrine tumors using Positron Emission Tomography (PET), to the U.S. Food and Drug Administration (FDA). The FDA has accepted the application for review and granted a target approval date (PDUFA date) of July 20, 2023. "Gallium-68 DOTATOC imaging has been clinically used in Europe for well over a decade," said James Cook, President & CEO of Evergreen Theragnostics. "The University of Iowa took an important step in 2019 by gaining FDA approval for their own NDA for Gallium-68 DOTATOC, produced locally at the University of Iowa. If approved, this NDA will build on that by making Ga-68 DOTATOC imaging available nationwide for neuroendocrine tumor patients, in the form of an easy-to-use kit for radiopharmacies. We thank the University of Iowa for leading the way in this space, as well as for their support and contribution to this application." "It's very encouraging to see this move forward. The long-term goal of our work at the University of Iowa has always been to make Ga-68 DOTATOC more widely available to patients in the US," said John Sunderland, PhD, MBA, UI Professor of Radiology. "The efforts of Evergreen Theragnostics will almost certainly extend the availability of Gallium-68 DOTATOC to the neuroendocrine tumor patient population of the United States for future years to come, extending the primary vision of the researchers here at Iowa." "This filing represents the first NDA for Evergreen Theragnostics, and an important step forward as we broaden our portfolio of offerings," said Mr. Cook. "This significant achievement complements our ongoing commitment to our core CDMO (Contract Development and Manufacturing Organization) business." If approved, doses prepared using EVG-001 are expected to be available starting in Q3 2023 for purchase from Evergreen's radiopharmacy partners around the country. About Evergreen Theragnostics, Inc. Evergreen Theragnostics, established in 2019, is a US-based radiopharmaceutical company specialized in CDMO (Contract Development and Manufacturing Organization) services and commercialization of theragnostic radiopharmaceuticals. With a state-of-the-art global GMP facility in New Jersey, Evergreen provides highly reliable manufacturing services for therapeutic and centrally distributed diagnostic radiopharmaceuticals, from early development through commercialization. The company was founded by a team that brings a strong track record in theragnostic radiopharmaceutical commercialization, manufacturing process development, and regulatory affairs management. For more information, please visit . For further information, please contact: James Cook President & CEO [email protected] SOURCE Evergreen Theragnostics, Inc.

A new study that links the location of brain injury to levels of depression in patients following the injury has identified two distinct brain networks; one associated with increased depression symptoms and one associated with decreased depression symptoms. The large-scale study expands on previous findings and suggests that these brain networks might be potential targets for neuromodulation therapies to treat depression. A new study that links the location of brain injury to levels of depression in patients following the injury has identified two distinct brain networks; one associated with increased depression symptoms and one associated with decreased depression symptoms. The large-scale study led by researchers with University of Iowa Health Care expands on previous findings and suggests that these brain networks might be potential targets for neuromodulation therapies to treat depression. Neuromodulation therapies such as transcranial magnetic stimulation, or deep brain stimulation, are emerging as new non-pharmacological treatments for mood disorders. However, understanding which areas of the brain to target to get the best therapeutic effect is still limited. The new findings, which are published in the journal Brain, used brain imaging scans and depression scores from 526 patients who had acquired localized areas of brain injury from a stroke or other type of traumatic brain injury. A detailed statistical analysis of the patients' data allowed the researchers to correlate the brain lesion locations with levels of depression experienced by the patients in the months following the brain injury. "We found some really interesting results identifying specific brain structures that were associated with higher levels of depression post lesion, and surprisingly, also found some areas that were associated with lower-than-average levels of depression post lesion." says Nicholas Trapp, MD, UI assistant professor of psychiatry and lead author of the study. Risk and resilience networks in depression Using data from functional brain scans of healthy subjects to understand how these structures were interconnected, the researchers then discovered that the risk and resilience regions were not randomly scattered within the brain. Instead, regions most strongly associated with increased depression coincided with the nodes of the so-called salience network, which is involved in task reorientation, attention, and emotion processing. In contrast, peak resilience regions that were associated with less depression, were part of a network known as the default mode network, which is thought to be involved in introspection, or self-referential thinking. "Previous studies have suggested nodes of this network may be hyperactive in people with depression, who are prone to ruminating," says Trapp, who also is a member of the Iowa Neuroscience Institute. "It's possible that lesions within this network may alter that circuit in a way that leads people to report less depression." Patients whose brain lesions did not fall within either network had an average score of depression following their brain injury and provided a comparison group in the study. Strength in numbers The initial lesion mapping approach used by Trapp and his colleagues is a powerful tool for inferring if a brain region is required for a behavior, emotion, or cognitive ability. If damage to a specific area leads to loss of the ability, the area is most likely required for the ability. However, identifying an effect when the regions are spread across a network within the brain requires data from many patients, which may have hindered earlier smaller studies. Trapp and his team were able to conduct they study thanks to two large patient registries: the Iowa Neurological Patient Registry based at the UI, and the Vietnam head injury study, which is affiliated with researchers at Northwestern University. "Being able to identify these brain regions is really a product of having a large sample to study," Trapp says. "It's very challenging to recruit these patients and collect the data that's required. The decades of efforts here at the University of Iowa (establishing and maintaining the Iowa Neurological Patient Registry) positions us extremely well to do these types of studies." Potential new targets for neuromodulation Trapp hopes the findings will improve understanding of the causes of depression and potentially lead to better treatments. "This could open the doors to potential studies looking at deep brain stimulation, or non-invasive forms of stimulation like TMS, where we might be able to modulate the specific brain areas or networks that we've identified, to try to get antidepressant effect, or potentially other therapeutic effects," he says. In addition to Trapp, the UI research team included Aaron Boes, Joel Bruss, Kenneth Manzel, and Dan Tranel, of the UI Department of Neurology, and Jordan Grafman of the Shirley Ryan AbilityLab, at Northwestern University Feinberg School of Medicine in Chicago The study was funded in part by grants from the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the Kiwanis Neuroscience Research Foundation.