Gamma Oscillations in the Mouse Primary Visual Cortex as an Endophenotype of Schizophrenia

Gamma oscillations (20-50 Hz) are a robust component of brain activity associated with information processing, but are also part of the background spontaneous activity during various brain states including sleep and anesthesia. Our goal was to examine the changes in gamma oscillations that result from pharmacological and genetic manipulations of glutamatergic transmission which produce endophenotypes of schizophrenia. We recorded local field potentials (LFP) and single units through the depth of the mouse primary visual cortex in vivo and examined the alterations in gamma frequency activity under both normal and pathological conditions. Our results indicate that both in awake and anesthetized animals, baseline gamma frequency power in the LFP is increased throughout the cortical lamina, and the signal-to-noise ratio of gamma oscillations produced by a visual stimulus is diminished, most notably in the superficial layers. In addition, the entrainment of single units to the local oscillations in the LFP is reduced in the supragranular (L2/3) and infragranular (L5/6) layers. This work supports the hypothesis that alterations in glutamatergic transmission result in changes to gamma oscillations in primary sensory areas and is consistent with the hypothesis that these changes are associated with disrupted sensory perception

Penalized Orthogonal Iteration for Sparse Estimation of Generalized Eigenvalue Problem

We propose a new algorithm for sparse estimation of eigenvectors in generalized eigenvalue problems (GEP). The GEP arises in a number of modern data-analytic situations and statistical methods, including principal component analysis (PCA), multiclass linear discriminant analysis (LDA), canonical correlation analysis (CCA), sufficient dimension reduction (SDR) and invariant co-ordinate selection. We propose to modify the standard generalized orthogonal iteration with a sparsity-inducing penalty for the eigenvectors. To achieve this goal, we generalize the equation-solving step of orthogonal iteration to a penalized convex optimization problem. The resulting algorithm, called penalized orthogonal iteration, provides accurate estimation of the true eigenspace, when it is sparse. Also proposed is a computationally more efficient alternative, which works well for PCA and LDA problems. Numerical studies reveal that the proposed algorithms are competitive, and that our tuning procedure works well. We demonstrate applications of the proposed algorithm to obtain sparse estimates for PCA, multiclass LDA, CCA and SDR. Supplementary materials are available online

Miniature structured illumination microscope for in vivo 3D imaging of brain structures with optical sectioning

We present a high-resolution miniature, light-weight fluorescence microscope with electrowetting lens and onboard CMOS for high resolution volumetric imaging and structured illumination for rejection of out-of-focus and scattered light. The miniature microscope (SIMscope3D) delivers structured light using a coherent fiber bundle to obtain optical sectioning with an axial resolution of 18 &micro;m. Volumetric imaging of eGFP labeled cells in fixed mouse brain tissue at depths up to 260 &micro;m is demonstrated. The functionality of SIMscope3D to provide background free 3D imaging is shown by recording time series of microglia dynamics in awake mice at depths up to 120 &micro;m in the brain. &nbsp;</p

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9–11, 2023 in Gainesville, Florida with the theme of “Pushing the Forefront of Neuromodulation”. The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices

Characterizing Longitudinal Changes in the Impedance Spectra of In-Vivo Peripheral Nerve Electrodes

Characterizing the aging processes of electrodes in vivo is essential in order to elucidate the changes of the electrode&#8315;tissue interface and the device. However, commonly used impedance measurements at 1 kHz are insufficient for determining electrode viability, with measurements being prone to false positives. We implanted cohorts of five iridium oxide (IrOx) and six platinum (Pt) Utah arrays into the sciatic nerve of rats, and collected the electrochemical impedance spectroscopy (EIS) up to 12 weeks or until array failure. We developed a method to classify the shapes of the magnitude and phase spectra, and correlated the classifications to circuit models and electrochemical processes at the interface likely responsible. We found categories of EIS characteristic of iridium oxide tip metallization, platinum tip metallization, tip metal degradation, encapsulation degradation, and wire breakage in the lead. We also fitted the impedance spectra as features to a fine-Gaussian support vector machine (SVM) algorithm for both IrOx and Pt tipped arrays, with a prediction accuracy for categories of 95% and 99%, respectively. Together, this suggests that these simple and computationally efficient algorithms are sufficient to explain the majority of variance across a wide range of EIS data describing Utah arrays. These categories were assessed over time, providing insights into the degradation and failure mechanisms for both the electrode&#8315;tissue interface and wire bundle. Methods developed in this study will allow for a better understanding of how EIS can characterize the physical changes to electrodes in vivo

Longitudinal Functional Assessment of Brain Injury Induced by High-Intensity Ultrasound Pulse Sequences

Exposure of the brain to high-intensity stress waves creates the potential for long-term functional deficits not related to thermal or cavitational damage. Possible sources of such exposure include overpressure from blast explosions or high-intensity focused ultrasound (HIFU). While current ultrasound clinical protocols do not normally produce long-term neurological deficits, the rapid expansion of potential therapeutic applications and ultrasound pulse-train protocols highlights the importance of establishing a safety envelope beyond which therapeutic ultrasound can cause neurological deficits not detectable by standard histological assessment for thermal and cavitational damage. In this study, we assessed the neuroinflammatory response, behavioral effects, and brain micro-electrocorticographic (microECoG) signals in mice following exposure to a train of transcranial pulses above normal clinical parameters. We found that the HIFU exposure induced a mild regional neuroinflammation not localized to the primary focal site, and impaired locomotor and exploratory behavior for up to 1 month post-exposure. In addition, low frequency (delta) and high frequency (beta, gamma) oscillations recorded by ECoG were altered at acute and chronic time points following HIFU application. ECoG signal changes on the hemisphere ipsilateral to HIFU exposure are of greater magnitude than the contralateral hemisphere, and persist for up to three months. These results are useful for describing the upper limit of transcranial ultrasound protocols, and the neurological sequelae of injury induced by high-intensity stress waves

Increased Degradation Rates in the Components of the Mitochondrial Oxidative Phosphorylation Chain in the Cerebellum of Old Mice

Brain structures differ in the magnitude of age-related neuron loss with the cerebellum being more affected. An underlying cause could be an age-related decline in mitochondrial bioenergetics. Successful aging of mitochondria reflects a balanced turnover of proteins involved in mitochondrial biogenesis and mitophagy. Thus, an imbalance in mitochondrial turnover can contribute to the diminution of cellular function seen during aging. Mitochondrial biogenesis and mitophagy are mediated by a set of proteins including MFN1, MFN2, OPA1, DRP1, FIS1 as well as DMN1l and DNM1, all of which are required for mitochondrial fission. Using N15 labeling, we report that the turnover rates for DMN1l and FIS1 go in opposite directions in the cerebellum of 22-month-old C57BL6j mice as compared to 3-month-old mice. Previous studies have reported decreased turnover rates for the mitochondrial respiratory complexes of aged rodents. In contrast, we found increased turnover rates for mitochondrial proteins of the oxidative phosphorylation chain in the aged mice as compared to young mice. Furthermore, the turnover rate of the components that are most affected by aging –complex III components (ubiquinol cytochrome C oxidoreductase) and complex IV components (cytochrome C oxidase)– was significantly increased in the senescent cerebellum. However, the turnover rates of proteins involved in mitophagy (i.e., the proteasomal and lysosomal degradation of damaged mitochondria) were not significantly altered with age. Overall, our results suggest that an age-related imbalance in the turnover rates of proteins involved in mitochondrial biogenesis and mitophagy (DMN1l, FIS1) in conjunction with an age-related imbalance in the turnover rates of proteins of the complexes III and IV of the electron transfer chain, might impair cerebellar mitochondrial bioenergetics in old mice