Changes in Brain Resting-state Functional Connectivity Associated with Peripheral Nerve Block: A Pilot Study.

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BACKGROUND: Limited information exists on the effects of temporary functional deafferentation (TFD) on brain activity after peripheral nerve block (PNB) in healthy humans. Increasingly, resting-state functional connectivity (RSFC) is being used to study brain activity and organization. The purpose of this study was to test the hypothesis that TFD through PNB will influence changes in RSFC plasticity in central sensorimotor functional brain networks in healthy human participants. METHODS: The authors achieved TFD using a supraclavicular PNB model with 10 healthy human participants undergoing functional connectivity magnetic resonance imaging before PNB, during active PNB, and during PNB recovery. RSFC differences among study conditions were determined by multiple-comparison-corrected (false discovery rate-corrected P value less than 0.05) random-effects, between-condition, and seed-to-voxel analyses using the left and right manual motor regions. RESULTS: The results of this pilot study demonstrated disruption of interhemispheric left-to-right manual motor region RSFC (e.g., mean Fisher-transformed z [effect size] at pre-PNB 1.05 vs. 0.55 during PNB) but preservation of intrahemispheric RSFC of these regions during PNB. Additionally, there was increased RSFC between the left motor region of interest (PNB-affected area) and bilateral higher order visual cortex regions after clinical PNB resolution (e.g., Fisher z between left motor region of interest and right and left lingual gyrus regions during PNB, -0.1 and -0.6 vs. 0.22 and 0.18 after PNB resolution, respectively). CONCLUSIONS: This pilot study provides evidence that PNB has features consistent with other models of deafferentation, making it a potentially useful approach to investigate brain plasticity. The findings provide insight into RSFC of sensorimotor functional brain networks during PNB and PNB recovery and support modulation of the sensory-motor integration feedback loop as a mechanism for explaining the behavioral correlates of peripherally induced TFD through PNB.





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Melton, M Stephen, Jeffrey N Browndyke, Todd B Harshbarger, David J Madden, Karen C Nielsen and Stephen M Klein (2016). Changes in Brain Resting-state Functional Connectivity Associated with Peripheral Nerve Block: A Pilot Study. Anesthesiology, 125(2). pp. 368–377. 10.1097/ALN.0000000000001198 Retrieved from

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M. Stephen Melton

Associate Professor of Anesthesiology

Jeffrey Nicholas Browndyke

Associate Professor of Psychiatry and Behavioral Sciences

Dr. Browndyke is an Associate Professor of Behavioral Health & Neurosciences in the Department of Psychiatry & Behavioral Sciences.  He has a secondary appointment as Assistant Professor of Cardiovascular & Thoracic Surgery.

Dr. Browndyke's research interests involve the use of advanced neurocognitive and neuroimaging techniques for perioperative contributions to delirium and later dementia risk, monitoring of late-life neuropathological disease progression, and intervention/treatment outcomes.  His research also involves novel telehealth methods for remote neurocognitive evaluation and implementation of non-invasive neuromodulatory techniques to assist in postoperative recovery and dementia risk reduction.

Dr. Browndyke's clinical expertise is focused upon geriatric neuropsychology with an emphasis in the assessment, diagnosis, and treatment of dementia and related disorders in adults and US veteran patient populations.


Todd B Harshbarger

Assistant Professor in Radiology

David Joseph Madden

Professor in Psychiatry and Behavioral Sciences

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.


Karen Cristina Nielsen

Associate Professor of Anesthesiology

* The Use of Advanced Regional Anesthesia for Ambulatory Surgery:
The unique use of single injection and continuous peripheral nerve blocks has tremendous advantages for outpatients. This is the major focus of the textbook " Ambulatory Anesthesia and Perioperative Analgesia" (Editors Susan M. Steele, Karen C. Nielsen, Stephen M. Klein).

* Ambulatory Anesthesiology Database:
The ambulatory anesthesia database collects outcomes data for regional and ambulatory anesthesia. This database has proved that valuable data can be collected in an ambulatory setting resulting in continuous quality improvement, providing improved support for research and publications.

* Continuous Peripheral Nerve Blockade in the Ambulatory Setting:
Major surgical procedures on healthy and high risk patients (ASA III and IV) can be performed in an ambulatory setting due to continuous regional anesthetic techniques.

* Continuous Peripheral Nerve Blockade in the Home Setting:
Major surgical procedures can be performed in an ambulatory setting under continuous peripheral nerve blocks. Patients can be discharged on the same day of surgery with disposable infusion pumps connected to peripheral nerve catheters for 3 -4 days. Patient selection and education are critical for the success of this home catheter program. Close patient follow-up is performed via telephone calls. Excellent pain management has been achieved, with improved cognitive function and sleep profile. No complications have been reported.

* The Use of Paravertebral Somatic Nerve Blockade Technique for Breast Cancer Surgery:
Benefits of regional anesthesia for breast cancer treatment include excellent analgesia, decreased incidence of postoperative nausea and
vomiting, faster recovery, preservation of immunologic function, decreasing hospital stay, and generating cost savings. Continuous paravertebral block techniques have been used to extend postoperative analgesia.

* Outcomes after Ambulatory Regional Anesthesia


Stephen Matthew Klein

Professor of Anesthesiology

As an active member in the Division of Ambulatory Anesthesia Department of Anesthesiology, Duke University Medical Center, I am involved in numerous educational and research endeavors with the goal to improve a patient's peri-operative experience. The group focuses on all aspects of outpatient surgery. These include preoperative education, advanced anesthetic techniques, prolonged pain management and improving operative outcome. The division maintains an active clinical practice at the Duke Ambulatory Surgery Center (ASC). The ASC is a unique academic outpatient center that administers care to over 6000 patients/year and has facilities for overnight patient observation and management. The facility, faculty and nursing consistently obtain outstanding ratings in patient care and satisfaction. As part of the educational mission of the center the division teaches resident physicians, fellows, and visiting faculty in the field of ambulatory and regional anesthesia. In addition, the center employs a full time registered nurse to coordinate, implement, and maintain the divisions protocols.

Using the divisions strength in regional anesthesia, state of the art facilities, combined with the resources of Duke University, the group has ongoing projects involved in (1) extending local anesthesia efficacy (2) development of new long acting local anesthetics (3) utilizing automated anesthesia information systems and outcomes data base to define patient outcome, satisfaction and economics (4) multi-drug therapy for reducing postoperative nausea (5) examining the efficacy of home infusion and health care for major surgery (6) redefining the scale, scope and postoperative care of ambulatory surgery.

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