Implantation accuracy and operative variables in robot-assisted stereoelectroencephalography.

OBJECTIVE: The stereoelectroencephalography (SEEG) procedure provides a unique 3D overview of the seizure-onset zone. Although the success of SEEG relies on the accuracy of depth electrode implantation, few studies have investigated how different implantation techniques and operative variables affect accuracy. This study examined the effect of two different electrode implantation techniques (external vs internal stylet) on implantation accuracy while controlling for other operative variables. METHODS: The implantation accuracy of 508 depth electrodes from 39 SEEG cases was measured after coregistration of postimplantation CT or MR images with planned trajectories. Two different implantation techniques were compared: preset length with internal stylet use and measured length with external stylet use. Correlations between implantation accuracy and technique type, entry angle, intended implantation depth, and other operative variables were determined statistically using multiple regression analysis. RESULTS: Multiple regression analysis showed that the internal stylet technique exhibited a larger target radial error (p = 0.046) and angular deviation (p = 0.039) with a smaller depth error (p < 0.001) than the external stylet technique. Entry angle and implantation depth were positively correlated with target radial error (p = 0.007 and < 0.001, respectively) only for the internal stylet technique. CONCLUSIONS: Better target radial accuracy was achieved when an external stylet was used to open the intraparenchymal pathway for the depth electrode. In addition, more oblique trajectories were equally accurate to orthogonal ones with the usage of an external stylet, while more oblique trajectories were associated with larger target radial errors with the usage of an internal stylet (without an external stylet).

Spinal Metastases from Colorectal Cancer at Mass General Brigham: A Twenty-Year Case Series With Literature Review.

OBJECTIVE: We present an institutional case series of patients treated for colorectal carcinoma (CRC) spinal metastases to investigate the outcomes between no treatment, radiation, surgery, and surgery/radiation. METHODS: A retrospective cohort of patients with CRC spinal metastases presenting to affiliated institutions between 2001 and 2021 wereidentified. Information related to patient demographics, treatment modality, treatment outcomes, symptom improvement, and survival was collected by chart review. Overall survival (OS) was compared between treatments by log-rank significance testing. A literature review was conducted to identify other cases series of CRC patients with spinal metastases. RESULTS: Eighty-nine patients (mean age 58.5) with CRC spinal metastases across a mean of 3.3 levels met inclusion criteria: 14 (15.7%) received no treatment, 11 (12.4%) received surgery alone, 37 (41.6%) received radiation alone, and 27 (30.3%) received both radiation and surgery. Patients treated with combination therapy had the longest median OS of 24.7 months (range 0.6-85.9), which did not significantly differ from the median OS of 8.9 months (range 0.2-42.6) observed in patients who received no treatment (P = 0.075). Combination therapy provided objectively longer survival time in comparison to other treatment modalities but failed to reach statistical significance. The majority of patients that received treatment (n = 51/75, 68.0%) experienced some degree of symptomatic or functional improvement. CONCLUSIONS: Therapeutic intervention has the potential to improve the quality of life in patients with CRC spinal metastases. We demonstrate that surgery and radiation are useful options for these patients, despite their lack of objective improvement in OS.

Real-Time, In Vivo Measurement of Protein Kinase A Activity in Deep Brain Structures Using Fluorescence Lifetime Photometry (FLiP).

The biochemical state of neurons, and of cells in general, is regulated by extracellular factors, including neurotransmitters, neuromodulators, and growth hormones. Interactions of an animal with its environment trigger neuromodulator release and engage biochemical transduction cascades to modulate synapse and cell function. Although these processes are thought to enact behavioral adaption to changing environments, when and where in the brain they are induced has been mysterious because of the challenge of monitoring biochemical state in real time in defined neurons in behaving animals. Here, we describe a method allowing measurement of activity of protein kinase A (PKA), an important intracellular effector for neuromodulators, in freely moving mice. To monitor PKA activity in vivo, we use a genetically targeted sensor (FLIM-AKAR) and fluorescence lifetime photometry (FLiP). This article describes how to set up a FLiP system and obtain robust recordings of net PKA phosphorylation state in vivo. The methods should be generally useful to monitor other pathways for which fluorescence lifetime reporters exist. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Building a FLiP system Basic Protocol 2: FLIM-AKAR viral injection and fiber implantation for FLiP measurement Basic Protocol 3: Performing measurements using FLiP.

Cell-type-specific asynchronous modulation of PKA by dopamine in learning.

Reinforcement learning models postulate that neurons that release dopamine encode information about action and action outcome, and provide a teaching signal to striatal spiny projection neurons in the form of dopamine release1. Dopamine is thought to guide learning via dynamic and differential modulation of protein kinase A (PKA) in each class of spiny projection neuron2. However, the real-time relationship between dopamine and PKA in spiny projection neurons remains untested in behaving animals. Here we monitor the activity of dopamine-releasing neurons, extracellular levels of dopamine and net PKA activity in spiny projection neurons in the nucleus accumbens of mice during learning. We find positive and negative modulation of dopamine that evolves across training and is both necessary and sufficient to explain concurrent fluctuations in the PKA activity of spiny projection neurons. Modulations of PKA in spiny projection neurons that express type-1 and type-2 dopamine receptors are dichotomous, such that these neurons are selectively sensitive to increases and decreases, respectively, in dopamine that occur at different phases of learning. Thus, PKA-dependent pathways in each class of spiny projection neuron are asynchronously engaged by positive or negative dopamine signals during learning.