Deep Brain Stimulation (DBS) surgeries are not new, although they were only granted approval in the U.S. by the U.S. Food and Drug Administration (FDA) in 2002 for advanced Parkinson’s Disease (PD). In 2016, DBS surgery was approved for earlier stages of PD. This does not mean that DBS surgery, generally considered minimally invasive, does not come without commensurate risks. The Mayo Clinic identifies DBS as a serious and potential risky procedure, whereby those eligible must carefully weigh pros and cons. The aim of this paper is to provide a general overview of deep brain stimulation surgery and to present the findings of available informational resources on 14 hospital and medical center web sites that were reviewed, pertaining to surgical procedures and policies: pre-operative to post-operative. The article focuses on critiquing available educational DBS materials and their adequacy in addressing potential risks of DBS surgery. The findings indicate that hospital informational resources on the DBS surgical technique reaffirm each other’s educational materials and that they positively inform patient decision-making. These factors can be linked to better post-operative recovery. However, the materials provided by the hospitals overemphasize the positive aspects of DBS with relatively little detail about potential side effects. This article also outlines the potential short-term and long-term side effects of DBS surgery as identified by the DBS educational literature found on the hospital web sites reviewed.
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Minimally invasive brain injections for viral-mediated transgenesis: New tools for behavioral genetics in sticklebacks
Behavioral genetics in non-model organisms is currently gated by technological limitations. However, with the growing availability of genome editing and functional genomic tools, complex behavioral traits such as social behavior can now be explored in diverse organisms. Here we present a minimally invasive neurosurgical procedure for a classic behavioral, ecological and evolutionary system: threespine stickleback ( Gasterosteus aculeatus ). Direct brain injection enables viral-mediated transgenesis and pharmaceutical delivery which bypasses the blood-brain barrier. This method is flexible, fast, and amenable to statistically powerful within-subject experimental designs, making it well-suited for use in genetically diverse animals such as those collected from natural populations. Developing this minimally invasive neurosurgical protocol required 1) refining the anesthesia process, 2) building a custom surgical rig, and 3) determining the normal recovery pattern allowing us to clearly identify warning signs of failure to thrive. Our custom-built surgical rig (publicly available) and optimized anesthetization methods resulted in high (90%) survival rates and quick behavioral recovery. Using this method, we detected changes in aggression from the overexpression of either of two different genes, arginine vasopressin ( AVP ) and monoamine oxidase ( MAOA ), in outbred animals in less than one month. We successfully used multiple promoters to drive expression, allowing for tailored expression profiles through time. In addition, we demonstrate that widely available mammalian plasmids work with this method, lowering the barrier of entry to the technique. By using repeated measures of behavior on the same fish before and after transfection, we were able to drastically reduce the necessary sample size needed to detect significant changes in behavior, making this a viable approach for examining genetic mechanisms underlying complex social behaviors.
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- Award ID(s):
- 1915134
- NSF-PAR ID:
- 10251016
- Editor(s):
- Fugmann, Sebastian D.
- Date Published:
- Journal Name:
- PLOS ONE
- Volume:
- 16
- Issue:
- 5
- ISSN:
- 1932-6203
- Page Range / eLocation ID:
- e0251653
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Understanding the basis of behavior requires dissecting the complex waves of gene expression that underlie how the brain processes stimuli and produces an appropriate response. In order to determine the dynamic nature of the neurogenomic network underlying mate choice, we use transcriptome sequencing to capture the female neurogenomic response in two brain regions involved in sensory processing and decision‐making under different mating and social contexts. We use differential coexpression (DC) analysis to evaluate how gene networks in the brain are rewired when a female evaluates attractive and nonattractive males, greatly extending current single‐gene approaches to assess changes in the broader gene regulatory network. We find the brain experiences a remarkable amount of network rewiring in the different mating and social contexts we tested. Further analysis indicates the network differences across contexts are associated with behaviorally relevant functions and pathways, particularly learning, memory and other cognitive functions. Finally, we identify the loci that display social context‐dependent connections, revealing the basis of how relevant neurological and metabolic pathways are differentially recruited in distinct social contexts. More broadly, our findings contribute to our understanding of the genetics of mating and social behavior by identifying gene drivers behind behavioral neural processes, illustrating the utility of DC analysis in neurosciences and behavior.
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ABSTRACT BACKGROUND AND PURPOSE Functional magnetic resonance imaging (fMRI) is becoming widely recognized as a key component of preoperative neurosurgical planning, although intraoperative electrocortical stimulation (ECS) is considered the gold standard surgical brain mapping method. However, acquiring and interpreting ECS results can sometimes be challenging. This retrospective study assesses whether intraoperative availability of fMRI impacted surgical decision‐making when ECS was problematic or unobtainable.
METHODS Records were reviewed for 191 patients who underwent presurgical fMRI with fMRI loaded into the neuronavigation system. Four patients were excluded as a bur‐hole biopsy was performed. Imaging was acquired at 3 Tesla and analyzed using the general linear model with significantly activated pixels determined via individually determined thresholds. fMRI maps were displayed intraoperatively via commercial neuronavigation systems.
RESULTS Seventy‐one cases were planned ECS; however, 18 (25.35%) of these procedures were either not attempted or aborted/limited due to: seizure (10), patient difficulty cooperating with the ECS mapping (4), scarring/limited dural opening (3), or dural bleeding (1). In all aborted/limited ECS cases, the surgeon continued surgery using fMRI to guide surgical decision‐making. There was no significant difference in the incidence of postoperative deficits between cases with completed ECS and those with limited/aborted ECS.
CONCLUSIONS Preoperative fMRI allowed for continuation of surgery in over one‐fourth of patients in which planned ECS was incomplete or impossible, without a significantly different incidence of postoperative deficits compared to the patients with completed ECS. This demonstrates additional value of fMRI beyond presurgical planning, as fMRI data served as a backup method to ECS.
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Abstract Understanding the genetic influences of traits of nonmodel organisms is crucial to understanding how novel traits arise. Do new traits require new genes or are old genes repurposed? How predictable is this process? Here, we examine this question for gene expression influencing parenting behavior in a beetle,
Nicrophorus vespilloides . Parental care, produced from many individual behaviors, should be influenced by changes of expression of multiple genes, and one suggestion is that the genes can be predicted based on knowledge of behavior expected to be precursors to parental care, such as aggression, resource defense, and mating on a resource. Thus, testing gene expression during parental care allows us to test expectations of this “precursor hypothesis” for multiple genes and traits. We tested for changes of the expression of serotonin, octopamine/tyramine, and dopamine receptors, as well as one glutamate receptor, predicting that these gene families would be differentially expressed during social interactions with offspring and associated resource defense. We found that serotonin receptors were strongly associated with social and aggression behavioral transitions. Octopamine receptors produced a complex picture of gene expression over a reproductive cycle. Dopamine was not associated with the behavioral transitions sampled here, while the glutamate receptor was most consistent with a behavioral change of resource defense/aggression. Our results generate new hypotheses, refine candidate lists for further studies, and inform the genetic mechanisms that are co‐opted during the evolution of parent–offspring interactions, a likely evolutionary path for many lineages that become fully social. The precursor hypothesis, while not perfect, does provide a starting point for identifying candidate genes. -
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Electroporation is an increasingly common technique used for exogenous gene expression in live animals, but protocols are largely limited to traditional laboratory organisms. The goal of this protocol is to test
in vivo electroporation techniques in a diverse array of tadpole species. We explore electroporation efficiency in tissue-specific cells of five species from across three families of tropical frogs: poison frogs (Dendrobatidae), cryptic forest/poison frogs (Aromobatidae), and glassfrogs (Centrolenidae). These species are well known for their diverse social behaviors and intriguing physiologies that coordinate chemical defenses, aposematism, and/or tissue transparency. Specifically, we examine the effects of electrical pulse and injection parameters on species- and tissue-specific transfection of plasmid DNA in tadpoles. After electroporation of a plasmid encoding green fluorescent protein (GFP), we found strong GFP fluorescence within brain and muscle cells that increased with the amount of DNA injected and electrical pulse number. We discuss species-related challenges, troubleshooting, and outline ideas for improvement. Extendingin vivo electroporation to non-model amphibian species could provide new opportunities for exploring topics in genetics, behavior, and organismal biology.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1371/journal.pone.0251653
