Publications by authors named "Ashan Veerakumar"

4 Publications

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Field potential 1/ activity in the subcallosal cingulate region as a candidate signal for monitoring deep brain stimulation for treatment-resistant depression.

J Neurophysiol 2019 09 17;122(3):1023-1035. Epub 2019 Jul 17.

Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia.

Subcallosal cingulate cortex deep brain stimulation (SCC-DBS) is an experimental therapy for treatment-resistant depression (TRD). Refinement and optimization of SCC-DBS will benefit from increased study of SCC electrophysiology in context of ongoing high-frequency SCC-DBS therapy. The study objective was a 7-mo observation of frequency-domain 1/ slope in off-stimulation local field potentials (SCC-LFPs) alongside standardized measurements of depression severity in 4 patients undergoing SCC-DBS. SCC was implanted bilaterally with a combined neurostimulation-LFP recording system. Following a 1-mo off-stimulation postoperative phase with multiple daily recordings, patients received bilateral SCC-DBS therapy (130 Hz, 90 μs) and weekly resting-state SCC-LFP recordings over a 6-mo treatment phase. 1/ slopes for each time point were estimated via linear regression of log-transformed Welch periodograms. General linear mixed-effects models were constructed to estimate pretreatment sources of 1/ slope variance, and 95% bootstrap confidence intervals were constructed to estimate treatment phase 1/ slope association with treatment response (50% decrease in preimplantation symptom severity). Results show the time of recording was a prominent source of pretreatment 1/ slope variance bilaterally, with increased 1/ slope magnitude observed during night hours (2300-0659). Increase in right 1/ slope was observed in the setting of treatment response, with bootstrap analysis supporting this observation in 3 of 4 subjects. We conclude that 1/ slope can be measured longitudinally in a combined SCC-DBS/LFP recording system and likely conforms to known 1/ circadian variability. The preliminary evidence of 1/ slope increase during treatment response suggests a potential utility as a candidate biomarker for ongoing development of adaptive TRD-neuromodulation strategies. In four patients with treatment-resistant depression undergoing therapeutic deep brain stimulation (DBS), we present the first longitudinal observations of local field potentials (LFP) from the subcallosal cingulate region outside the postoperative period. Specifically, our results demonstrate that frequency-domain 1/ activity is measurable in a combined DBS-LFP recording system and that right hemisphere recordings appear sensitive to mood state, thus suggesting a potential readout suitable for consideration in ongoing efforts to develop adaptive DBS delivery systems.
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http://dx.doi.org/10.1152/jn.00875.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766743PMC
September 2019

Test-retest reliability of a stimulation-locked evoked response to deep brain stimulation in subcallosal cingulate for treatment resistant depression.

Hum Brain Mapp 2018 12 18;39(12):4844-4856. Epub 2018 Aug 18.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.

Deep brain stimulation (DBS) to the subcallosal cingulate cortex (SCC) is an emerging therapy for treatment resistant depression. Precision targeting of specific white matter fibers is now central to the model of SCC DBS treatment efficacy. A method to confirm SCC DBS target engagement is needed to reduce procedural variance across treatment providers and to optimize DBS parameters for individual patients. We examined the reliability of a novel cortical evoked response that is time-locked to a 2 Hz DBS pulse and shows the propagation of signal from the DBS target. The evoked response was detected in four individuals as a stereotyped series of components within 150 ms of a 6 V DBS pulse, each showing coherent topography on the head surface. Test-retest reliability across four repeated measures over 14 months met or exceeded standards for valid test construction in three of four patients. Several observations in this pilot sample demonstrate the prospective utility of this method to confirm surgical target engagement and instruct parameter selection. The topography of an orbital frontal component on the head surface showed specificity for patterns of forceps minor activation, which may provide a means to confirm DBS location with respect to key white matter structures. A divergent cortical response to unilateral stimulation of left (vs. right) hemisphere underscores the need for feedback acuity on the level of a single electrode, despite bilateral presentation of therapeutic stimulation. Results demonstrate viability of this method to explore patient-specific cortical responsivity to DBS for brain-circuit pathologies.
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http://dx.doi.org/10.1002/hbm.24327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427067PMC
December 2018

Versatile genetic assembly system (VEGAS) to assemble pathways for expression in S. cerevisiae.

Nucleic Acids Res 2015 Jul 8;43(13):6620-30. Epub 2015 May 8.

Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York City, NY 10016, USA Institute for Systems Genetics, New York University Langone School of Medicine, New York City, NY 10016, USA High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

We have developed a method for assembling genetic pathways for expression in Saccharomyces cerevisiae. Our pathway assembly method, called VEGAS (Versatile genetic assembly system), exploits the native capacity of S. cerevisiae to perform homologous recombination and efficiently join sequences with terminal homology. In the VEGAS workflow, terminal homology between adjacent pathway genes and the assembly vector is encoded by 'VEGAS adapter' (VA) sequences, which are orthogonal in sequence with respect to the yeast genome. Prior to pathway assembly by VEGAS in S. cerevisiae, each gene is assigned an appropriate pair of VAs and assembled using a previously described technique called yeast Golden Gate (yGG). Here we describe the application of yGG specifically to building transcription units for VEGAS assembly as well as the VEGAS methodology. We demonstrate the assembly of four-, five- and six-gene pathways by VEGAS to generate S. cerevisiae cells synthesizing β-carotene and violacein. Moreover, we demonstrate the capacity of yGG coupled to VEGAS for combinatorial assembly.
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http://dx.doi.org/10.1093/nar/gkv466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513848PMC
July 2015

Baclofen dosage after traumatic spinal cord injury: a multi-decade retrospective analysis.

Clin Neurol Neurosurg 2015 Feb 6;129:50-6. Epub 2014 Dec 6.

The Johns Hopkins Hospital, Department of Neurosurgery, Meyer Bldg, Room 8-181, 600 N. Wolfe Street, Baltimore 21287, USA. Electronic address:

Objectives: To perform an analysis of oral baclofen dosage in patients with traumatic spinal cord injuries over time and to ascertain the clinical determinants of long-term baclofen dosage trends.

Study Design: Retrospective cohort study of patient records from the PM&R units at the Johns Hopkins Bayview Medical Center and the Johns Hopkins Hospital.

Subjects: A total of 115 PM&R patients suffering spinal cord injury due to trauma leading to either complete or incomplete paralysis. The modes of injury included were motor vehicle accidents (MVA) (n=39), gunshot wounds (GSW) (n=55), falls (n=17), diving (n=2), workplace (n=1) and swimming (n=1) accidents. The location of injury in the spinal cord was categorized into either cervical (n=52), thoracic (n=59), lumbar (n=2), or unspecified (n=2).

Results: From time of injury, an aggregate of all dosage assignments for each patient demonstrated a significant yearly increase in baclofen dosage (1.26 mg/year, p<0.01). Baclofen dosage for MVA cases were seen to rise at 4.99 mg/year (p<0.0001). Kaplan-Meier analysis revealed that GSW patients received their first baclofen dosage earlier than MVA patients (log-rank p<0.05, unadjusted).

Conclusions: We observed a marginal increase in baclofen dosage over nearly 25 years in a single provider's patient database and observed different timings of first dose between two causes of traumatic SCI. These results provide an estimate of baclofen dosage trends over time after spinal cord injury and may be useful for patient counseling or as a method to assess costs of providing SCI patient care.
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http://dx.doi.org/10.1016/j.clineuro.2014.11.023DOI Listing
February 2015