Changes in functional and structural brain connectivity following bilateral hand transplantation
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2024-12-01
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As a surgical treatment following amputation or loss of an upper limb, nearly 200 hand transplantations have been completed to date. We report here a magnetic resonance imaging (MRI) investigation of functional and structural brain connectivity for a bilateral hand transplant patient (female, 60 years of age), with a preoperative baseline and three postoperative testing sessions each separated by approximately six months. We used graph theoretical analyses to estimate connectivity within and between modules (networks of anatomical nodes), particularly a sensorimotor network (SMN), from resting-state functional MRI and structural diffusion-weighted imaging (DWI). For comparison, corresponding MRI measures of connectivity were obtained from 10 healthy, age-matched controls, at a single testing session. The patient's within-module functional connectivity (both SMN and non-SMN modules), and structural within-SMN connectivity, were higher preoperatively than that of the controls, indicating a response to amputation. Postoperatively, the patient's within-module functional connectivity decreased towards the control participants' values, across the 1.5 years postoperatively, particularly for hand-related nodes within the SMN module, suggesting a return to a more canonical functional organization. Whereas the patient's structural connectivity values remained relatively constant postoperatively, some evidence suggested that structural connectivity supported the postoperative changes in within-module functional connectivity.
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Madden, David J, Jenna L Merenstein, Todd B Harshbarger and Linda C Cendales (2024). Changes in functional and structural brain connectivity following bilateral hand transplantation. NeuroImage: Reports, 4(4). pp. 100222–100222. 10.1016/j.ynirp.2024.100222 Retrieved from https://hdl.handle.net/10161/32168.
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David Joseph Madden
My research focuses primarily on the cognitive neuroscience of aging: the investigation of age-related changes in perception, attention, and memory, using both behavioral measures and neuroimaging techniques, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI).
The behavioral measures have focused on reaction time, with the goal of distinguishing age-related changes in specific cognitive abilities from more general effects arising from a slowing in elementary perceptual processes. The cognitive abilities of interest include selective attention as measured in visual search tasks, semantic and episodic memory retrieval, and executive control processes.
The behavioral measures are necessary to define the cognitive abilities of interest, and the neuroimaging techniques help define the functional neuroanatomy of those abilities. The PET and fMRI measures provide information regarding neural activity during cognitive performance. DTI is a recently developed technique that images the structural integrity of white matter. The white matter tracts of the brain provide critical pathways linking the gray matter regions, and thus this work will complement the studies using PET and fMRI that focus on gray matter activation.
A current focus of the research program is the functional connectivity among regions, not only during cognitive task performance but also during rest. These latter measures, referred to as intrinsic functional connectivity, are beginning to show promise as an index of overall brain functional efficiency, which can be assessed without the implementation of a specific cognitive task. From DTI, information can be obtained regarding how anatomical connectivity constrains intrinsic functional connectivity. It will be important to determine the relative influence of white matter pathway integrity, intrinsic functional connectivity, and task-related functional connectivity, as mediators of age-related differences in behavioral measures of cognitive performance.
Ultimately, the research program can help link age-related changes in cognitive performance to changes in the structure and function of specific neural systems. The results also have implications for clinical translation, in terms of the identification of neural biomarkers for the diagnosis of neural pathology and targeting rehabilitation procedures.
Jenna Merenstein
My research uses MRI to study the effect of healthy brain aging on numerous cognitive abilities, especially memory and attention. I also use MRI to study the structural and functional brain properties that differentiate Alzheimer's disease from healthy aging. I obtained my Ph.D. in Cognitive Neuroscience in April 2022 from Dr. Lani Bennett's lab at the University of California, Riverside. I am currently a Postdoctoral Associate working in the Brain Imaging and Analysis Center (BIAC) with Dr. David Madden.
Todd B Harshbarger
Linda Carime Cendales
Vascularized composite allotransplantation (VCA) refers to the transplantation of multiple tissues, such as skin, muscle, tendon, nerve, and/or bone, as a functional unit (e.g. a hand, an abdominal wall). Several recent advances in clinical organ transplant immunosuppression and experimental VCA have now made it feasible to consider clinical VCA for functional restoration in patients with the loss of one or both hands or large tissue defects that may not be reconstructed with autologous tissue. My research facilitates the translation of VCA from the bench to the bedside.
Our group has established preclinical models to understand VCA rejection in different tissues and to use that insight to minimize immunosuppression in VCA recipients who participate in clinical trials. We also organized the first public international consensus discussions conference in VCA at the Ninth Banff Conference on Allograft Pathology in Spain in 2007 resulting in the Banff VCA 2007 classification for skin allograft pathology. Additionally, we established a VCA Consortium to enable the comprehensive analysis of samples from patients in VCA clinical trials around the country.
Based on our studies of different immunosuppressive regimens in primates, we have been the first to show that belatacept prevents rejection in VCA in primates and controls rejection in humans. We are currently investigating this approach in a clinical trial of hand transplant recipients (NCT02310867). This clinical trial aims to determine the safety and efficacy of hand transplantation as a treatment for patients with limb loss. This study will also test the efficacy of belatacept to prevent rejection of the transplanted hand. We are also currently investigating in a clinical trial the efficacy of abdominal wall transplantation for the reconstruction of abdominal wall defects (NCT03310905).
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