In vivo optogenetics using a Utah Optrode Array with enhanced light output and spatial selectivity.

Optogenetics allows manipulation of neural circuits in vivo with high spatial and temporal precision. However, combining this precision with control over a significant portion of the brain is technologically challenging (especially in larger animal models). Here, we have developed, optimised, and tested in vivo, the Utah Optrode Array (UOA), an electrically addressable array of optical needles and interstitial sites illuminated by 181 µLEDs and used to optogenetically stimulate the brain. The device is specifically designed for non-human primate studies. Thinning the combined µLED and needle backplane of the device from 300 µm to 230 µm improved the efficiency of light delivery to tissue by 80%, allowing lower µLED drive currents, which improved power management and thermal performance. The spatial selectivity of each site was also improved by integrating an optical interposer to reduce stray light emission. These improvements were achieved using an innovative fabrication method to create an anodically bonded glass/silicon substrate with through-silicon vias etched, forming an optical interposer. Optical modelling was used to demonstrate that the tip structure of the device had a major influence on the illumination pattern. The thermal performance was evaluated through a combination of modelling and experiment, in order to ensure that cortical tissue temperatures did not rise by more than 1°C. The device was tested in vivo in the visual cortex of macaque expressing ChR2-tdTomato in cortical neurons. It was shown that the strongest optogenetic response occurred in the region surrounding the needle tips, and that the extent of the optogenetic response matched the predicted illumination profile based on optical modelling - demonstrating the improved spatial selectivity resulting from the optical interposer approach. Furthermore, different needle illumination sites generated different patterns of low-frequency potential (LFP) activity.

Overcoming the field-of-view to diameter trade-off in microendoscopy via computational optrode-array microscopy.

High-resolution microscopy of deep tissue with large field-of-view (FOV) is critical for elucidating organization of cellular structures in plant biology. Microscopy with an implanted probe offers an effective solution. However, there exists a fundamental trade-off between the FOV and probe diameter arising from aberrations inherent in conventional imaging optics (typically, FOV < 30% of diameter). Here, we demonstrate the use of microfabricated non-imaging probes (optrodes) that when combined with a trained machine-learning algorithm is able to achieve FOV of 1x to 5x the probe diameter. Further increase in FOV is achieved by using multiple optrodes in parallel. With a 1 × 2 optrode array, we demonstrate imaging of fluorescent beads (including 30 FPS video), stained plant stem sections and stained living stems. Our demonstration lays the foundation for fast, high-resolution microscopy with large FOV in deep tissue via microfabricated non-imaging probes and advanced machine learning.

Multisite microLED optrode array for neural interfacing.

We present an electrically addressable optrode array capable of delivering light to 181 sites in the brain, each providing sufficient light to optogenetically excite thousands of neurons in vivo, developed with the aim to allow behavioral studies in large mammals. The device is a glass microneedle array directly integrated with a custom fabricated microLED device, which delivers light to 100 needle tips and 81 interstitial surface sites, giving two-level optogenetic excitation of neurons in vivo. Light delivery and thermal properties are evaluated, with the device capable of peak irradiances > 80 mW / mm 2 per needle site. The device consists of an array of 181 80 µ m × 80 µ m 2 microLEDs, fabricated on a 150 - µ m -thick GaN-on-sapphire wafer, coupled to a glass needle array on a 150 - µ m thick backplane. A pinhole layer is patterned on the sapphire side of the microLED array to reduce stray light. Future designs are explored through optical and thermal modeling and benchmarked against the current device.

Depth-specific optogenetic control in vivo with a scalable, high-density µLED neural probe.

Controlling neural circuits is a powerful approach to uncover a causal link between neural activity and behaviour. Optogenetics has been widely adopted by the neuroscience community as it offers cell-type-specific perturbation with millisecond precision. However, these studies require light delivery in complex patterns with cellular-scale resolution, while covering a large volume of tissue at depth in vivo. Here we describe a novel high-density silicon-based microscale light-emitting diode (µLED) array, consisting of up to ninety-six 25 µm-diameter µLEDs emitting at a wavelength of 450 nm with a peak irradiance of 400 mW/mm(2). A width of 100 µm, tapering to a 1 µm point, and a 40 µm thickness help minimise tissue damage during insertion. Thermal properties permit a set of optogenetic operating regimes, with ~0.5 °C average temperature increase. We demonstrate depth-dependent activation of mouse neocortical neurons in vivo, offering an inexpensive novel tool for the precise manipulation of neural activity.

Saying the right thing at the right time: a view through the lens of the analytic process scales (APS).

Skillful psychoanalytic technique presumably involves knowing what to say, and when and how to say it. Does skillful technique have a positive impact upon the patient? The study described in this article relied on ratings by experienced psychoanalysts using the Analytic Process Scales (APS), a research instrument for assessing recorded psychoanalyses, in order to examine analytic interventions and patient productivity (greater understanding, affective engagement in the analytic process, and so on). In three analytic cases, the authors found significant correlations between core analytic activities (e.g., interpretation of defenses, transference, and conflicts) and patient productivity immediately following the intervention, but only if it had been skillfully carried out. Findings were independently replicated by psychology interns.

What happens in a psychoanalysis? A view through the lens of the analytic process scales (APS).

A group of experienced analysts has developed scales and a coding manual illustrated with clinical examples to evaluate recorded analyses and psychodynamic therapies. The analytic process scales (APS) assesses three dimensions: (1) the contribution of the analyst: helping to develop a relationship in which the analyst can provide clarification and interpretation of transference and resistance; (2) the contribution of the patient: the communication of experience and the expression of feeling in ways which provide information about needs, wishes and conflicts, accompanied by self-reflection; and (3) interactional characteristics of the emerging relationship, explored by studying sessions divided into psychoanalytically coherent segments. A preliminary study of nine sessions has established that the variables assessed by the APS can be rated reliably. Study of the analysts' contributions illuminated their varied and complex structure. Important differences emerged among the three patient-analyst pairs studied, and changes in scores over time tracked developments in the analytic work which would imply different treatment outcomes. The APS appears to be a reliable tool facilitating the systematic study of psychoanalyses.

A path-analytic strategy to analyze psychoanalytic treatment effects.

This paper introduces a path-analytic strategy to analyze psychoanalytic treatment effects. A simple causal model is used to analyze a well-known case study by Charles Brenner. Application of even this simple model to the case study sharpens causal inferences that may be validly made, highlights important aspects of the psychoanalytic process and builds a foundation for further model development.