Timothy J. Gardner's research while affiliated with University of Oregon and other places
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Publications (66)
This report describes a 3D microelectrode array integrated on a thin-film flexible cable for neural recording in small animals. The micro electrode array fabrication process integrates traditional silicon thin-film processing techniques and direct laser writing of 3D structures at micron resolution via two-photon lithography. While direct laser wri...
Songbirds provide a powerful model system for studying sensory-motor learning. However, many analyses of birdsong require time-consuming, manual annotation of its elements, called syllables. Automated methods for annotation have been proposed, but these methods assume that audio can be cleanly segmented into syllables, or they require carefully tun...
Musical and athletic skills are learned and maintained through intensive practice to enable precise and reliable performance for an audience. Consequently, understanding such complex behaviours requires insight into how the brain functions during both practice and performance. Male zebra finches learn to produce courtship songs that are more varied...
Miniaturized microscopes for head-mounted fluorescence imaging are powerful tools for visualizing neural activity during naturalistic behaviors, but the restricted field of view of first-generation "miniscopes" limits the size of neural populations accessible for imaging. Here we describe a novel miniaturized mesoscope offering cellular-resolution...
Songbirds provide an excellent model system for understanding sensorimotor learning. Many analyses of learning require annotating song, but songbirds produce more songs than can be annotated by hand. Existing methods for automating annotation are challenged by variable song, like that of Bengalese finches. For particularly complex song like that of...
The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanic...
Coordinated skills such as speech or dance involve sequences of actions that follow syntactic rules in which transitions between elements depend on the identities and order of past actions. Canary songs consist of repeated syllables called phrases, and the ordering of these phrases follows long-range rules¹ in which the choice of what to sing depen...
The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanic...
The change in residual stress in plasma enhanced chemical vapor deposition amorphous silicon carbide (a‐SiC:H) films exposed to air and wet ambient environments is investigated. A close relationship between stress change and deposition condition is identified from mechanical and chemical characterization of a‐SiC:H films. Evidence of amorphous sili...
Coordinated skills such as speech or dance involve sequences of actions that follow syntactic rules in which transitions between elements depend on past actions. Canary songs are comprised of repeated syllables, called phrases, and the ordering of these phrases follows long-range rules, where the choice of what to sing depends on song structure man...
Previously introduced bundles of hundreds or thousands of microfibers have the potential to extend optical access to deep brain regions, sampling fluorescence activity throughout a three-dimensional volume. Each fiber has a small diameter (
8
μ
m
) and follows a path of least resistance, splaying during insertion. By superimposing the fiber sen...
Microelectrode arrays that consistently and reliably record and stimulate neural activity under conditions of chronic implantation have so far eluded the neural interface community due to failures attributed to both biotic and abiotic mechanisms. Arrays with transverse dimensions of 10 µm or below are thought to minimize the inflammatory response;...
Objective:
Optical techniques for recording and manipulating neural activity have traditionally been constrained to superficial brain regions due to light scattering. New techniques are needed to extend optical access to large 3D volumes in deep brain areas, while retaining local connectivity.
Approach:
We have developed a method to implant bund...
Host encapsulation decreases the ability of chronically implanted microelectrodes to record or stimulate neural activity. The degree of foreign body response is thought to depend strongly on the cross-sectional dimensions of the electrode shaft penetrating neural tissue. Microelectrodes with cellular or sub-cellular scale shaft cross-sectional dime...
3D printing allows rapid fabrication of complex objects from digital designs. One 3D-printing process, direct laser writing, polymerises a light-sensitive material by steering a focused laser beam through the shape of the object to be created. The highest-resolution direct laser writing systems use a femtosecond laser to effect two-photon polymeris...
3D printing allows rapid fabrication of complex objects from digital designs. One 3D-printing process, direct laser writing, polymerises a light-sensitive material by steering a focused laser beam through the shape of the object to be created. The highest-resolution direct laser writing systems use a femtosecond laser to effect two-photon polymeris...
Host encapsulation decreases the ability of chronically implanted microelectrodes to record or stimulate neural activity. The degree of foreign body response is thought to depend strongly on the cross-sectional dimensions of the electrode shaft penetrating neural tissue. Microelectrodes with cellular or sub-cellular scale shaft cross-sectional dime...
Objectives:
Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational, and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume...
Objective:
Foreign body response to indwelling cortical microelectrodes limits the reliability of neural stimulation and recording, particularly for extended chronic applications in behaving animals. The extent to which this response compromises the chronic stability of neural devices depends on many factors including the materials used in the ele...
Objective:
Most preparations for making neural recordings degrade over time and eventually fail due to insertion trauma and reactive tissue response. The magnitudes of these responses are thought to be related to the electrode size (specifically, the cross-sectional area), the relative stiffness of the electrode, and the degree of tissue tolerance...
The song of the adult male zebra finch is strikingly stereotyped. Efforts to understand motor output, pattern generation, and learning have taken advantage of this consistency by investigating the bird’s ability to modify specific parts of song under external cues, and by examining timing relationships between neural activity and vocal output. Such...
Online resources.
Where to find the datasets and software introduced in this paper, with an overview of how to install and use the packages.
(PDF)
Sparse sequences of neuronal activity are fundamental features of neural circuit computation; however, the underlying homeostatic mechanisms remain poorly understood. To approach these questions, we have developed a method for cellular-resolution imaging in organotypic cultures of the adult zebra finch brain, including portions of the intact song c...
Objective:
The vision of bioelectronic medicine is to treat disease by modulating the signaling of visceral nerves near various end organs. In small animal models, the nerves of interest can have small diameters and limited surgical access. New high-resolution methods for building nerve interfaces are desirable. In this study, we present a novel n...
Objective:
Fluorescence imaging through head-mounted microscopes in freely behaving animals is becoming a standard method to study neural circuit function. Flexible, open-source designs are needed to spur evolution of the method.
Approach:
We describe a miniature microscope for single-photon fluorescence imaging in freely behaving animals. The d...
Most preparations for making neural recordings degrade over time and eventually fail due to insertion trauma and reactive tissue response. The magnitudes of these responses are thought to be related to the electrode size (specifically, the cross-sectional area) and the relative stiffness of the electrode material. Carbon fiber ultramicroelectrodes...
Summary of training.The success of operant training was determined on the basis of the d-prime score. When d’ is greater than 1, the bird was deemed successful in learning the task. In this table, the number of birds that succeeded in operant training for click sequence discrimination (d’ > 1) out of the total number of birds is shown. For example,...
Source data for ROC curve.This zip file contains spike-timing data used for the ROC analysis shown in Figure 4b. Spike times of 10 different cells recorded in primary or secondary auditory areas are included in folders with corresponding names. For simple visualization of spike rasters, Matlab source code (DataLoad.m) is also provided.DOI:
http://d...
Click-sequence audio files.
We provide audio files of all the click sequences used in this study in .wav format. The last number of the file name corresponds to the index of click sequence. For example, Clk_Sequence_1.wav contains audio data for sequence 1.
DOI:
http://dx.doi.org/10.7554/eLife.18205.024
Motor skills can be maintained for decades, but the biological basis of this memory persistence remains largely unknown. The zebra finch, for example, sings a highly stereotyped song that is stable for years, but it is not known whether the precise neural patterns underlying song are stable or shift from day to day. Here we demonstrate that the pop...
Stereotyped sequences of neural activity are thought to underlie reproducible behaviors and cognitive processes ranging from memory recall to arm movement. One of the most prominent theoretical models of neural sequence generation is the synfire chain, in which pulses of synchronized spiking activity propagate robustly along a chain of cells connec...
Author Summary
“Time cells” can be found throughout the vertebrate forebrain in various species and behavioral contexts. These neurons fire sparsely at precise times during a stereotyped behavior; however, how a neural circuit supports this remarkable property is not known. Here, we describe that the premotor neuronal circuit that is required in bi...
We propose a time-frequency representation based on the ridges of the continuous chirplet transform to identify both fast transients and components with well-defined instantaneous frequency in noisy data. At each chirplet modulation rate, every ridge corresponds to a territory in the time-frequency plane such that the territories form a partition o...
Objective:
Chronic neural recording in behaving animals is an essential method for studies of neural circuit function. However, stable recordings from small, densely packed neurons remains challenging, particularly over time-scales relevant for learning.
Approach:
We describe an assembly method for a 16-channel electrode array consisting of carb...
Using cross-validation to verify PST fits. To select the parameters used in the PST algorithm, we used a 10-fold cross-validation procedure repeated 3 times (with different data splits). As a measure of model performance we used average negative log-likelihood. Here we show cross-validation results as a function of the PST parameter . This paramete...
Full song barcodes for the examples given in
Fig. 1
and
Fig. 7
allow for direct visualization of long-range rules. These barcodes represent the full song sequence corresponding to the examples given in Fig. 1 and Fig. 7. A, Barcodes for the example from Fig. 1a centered on the first occurrence of the black phrase. B, Barcodes for the example in Fig...
Supplementary
Materials and Methods
.
(DOCX)
Some syllables have context-dependent transitional forms.
A, shown on the left are two example sonograms of the same phrase with different preceding phrases. In the two contexts, the first syllable of the phrase has a different transitional form (highlighted by the red and blue boxes). The image on the right is a color channel merge of two spectral...
Transition probabilities and number of transitions to accompany Fig. 7. The 95% confidence intervals are given in brackets below the transition probabilities and were estimated using a bootstrap procedure with a case resampling scheme. That is, the transition probabilities were estimated after randomly resampling the data with replacement. The conf...
Summary statistics for similarity scores for duration groups (for each syllable type, scores were computed referenced to the spectral density image from the group marked*). STD, standard deviation.
(DOCX)
The total number of phrases analyzed by each observer for individual birds. The bottom row contains the repertoire size for each bird.
(DOCX)
PSTs for the 4 birds not shown in
Fig. 5
.
(TIFF)
Phrase durations for all 6 birds analyzed. Each row corresponds to a different bird (same order as Fig. S11), and each group of points indicates the duration of a different phrase type. The colors (arbitrarily chosen) indicate different preceding phrase types. Abrupt changes in duration distribution that co-occur with color changes reveal a context...
Shown are the transition probabilities from two different phrases sung by the same bird as a function of repetition number.
Left: as phrase X is repeated, the most probable phrase transition from X to G decays, while the transition to S increases. Right: the opposite effect is seen in the same bird. The most probable transition, from H to X, increa...
Sample series of song bouts from a single canary, separate from the bird used for Audio S1.
(MP3)
Spectral density images demonstrate that syllables occurring in different contexts are highly similar.
A, Spectral density images of syllables with different surrounding phrases reveal acoustic similarity. As in Fig. 3a, spectral density images were computed for matching syllables that occur in different contexts; that is, different surrounding phr...
Summary statistics for similarity scores for sequence groups (for each syllable type, scores were computed referenced to the spectral density image from the group marked*). STD, standard deviation.
(DOCX)
Transition probabilities demonstrating alternative paths for prediction suffix trees (PSTs) shown in Fig. 5 and Fig. S8. The sequence DABN comes from the top PST in Fig. 5, HX from the bottom PST in Fig. 5, and ZGKLH from the bottom left PST in Fig. S8.
(DOCX)
Probabilistic finite automata (PFA) for all 6 birds analyzed. For visualization, all edges where p<.05 have been removed, and all edges where p<.2 are shown in thin light gray lines. Each PFA is completely determined by its corresponding PST. From top to bottom, the PFAs correspond to the PST shown in: the top left of Fig. S8; top right of Fig. S8;...
Sample series of song bouts from a single canary.
(MP3)
Author Summary
Bird songs range in form from the simple notes of a Chipping Sparrow to the complex repertoire of the nightingale. Recent studies suggest that bird songs may contain non-adjacent dependencies where the choice of what to sing next depends on the history of what has already been produced. However, the complexity of these rules has not...
Many signals cannot be resolved in time and frequency with a single time-scale of analysis and multi-band representations are needed that can adapt to the local signal content. Using a newly developed contour-based representation of signals, we show that efficient multi-band representations arise when long-range, structurally stable shapes are enha...
Time courses of spectral variance for all shams. All conventions follow Figure S1.
(TIF)
Time courses of spectral feature variance for all normal-hearing birds subject to transections–each bird is shown in a separate plot. All points are labeled relative to the day of the transection. Most birds show a significant increase in spectral variability at the first time point after surgery, followed by a rapid recovery. To compute spectral v...
Stereotyped sequences of neural activity underlie learned vocal behavior in songbirds; principle neurons in the cortical motor nucleus HVC fire in stereotyped sequences with millisecond precision across multiple renditions of a song. The geometry of neural connections underlying these sequences is not known in detail though feed-forward chains are...
Time courses of spectral variance for all transections on deafened birds. The transection related increase in spectral variability is less consistent in this group of birds. A trend towards increasing variability over time suggests that the acute recovery from transection is superimposed on a deafening related increase in variability. All conventio...
Time courses for number of detected songs for each bird (shown by different line colors) in the control and three experimental groups. Songs were detected through an automated survey (see Materials and Methods), time points are labeled relative to the day of the transection (“Pre” is the median of all points before the transection, and Post 6-End i...
Many signals are naturally described by continuous contours in the time-frequency plane, but standard time-frequency methods disassociate continuous structures into isolated “atoms” of energy. Here we propose a method that represents any discrete time-series as a set of time-frequency contours. The edges of the contours are defined by fixed points...
Neural circuits underlying complex learned behaviors, such as speech in humans, develop under genetic constraints and in response to environmental influences. Little is known about the rules and mechanisms through which such circuits form. We argue that songbirds, with their discrete and well studied neural pathways underlying a complex and natural...
Citations
... [201][202][203][204] The generally studied silicate materials is the ORMOCER ® (Organic Modified Ceramic), which has been applied in numerous photonic applications, and also as a scaffold for cell growth and biomolecule immobilization applications. [205][206][207][208][209] Combining silicon alkoxides with monomers and other metal alkoxides makes the modification of the material properties possible for specific TPL applications, such as the silicon-zirconium hybrid SZ2080™, which is a transparent, biocompatible, and mechanically stable hybrid that can be used for complex 3D structures without shrinkage ( Figure 3f). [119,[210][211][212][213][214][215][216] So far, different variants of silicon-zirconium composites have been investigated. ...
... 48 Researchers have used PAFs to cluster vocalisations of zebra finches (Taeniopygia 49 guttata) [18], baboons (Papio ursinus) [19], bottlenose dolphins (Tursiops 50 truncatus) [20], gibbons (Hylobates funereus) [21], and mice (Mus musculus) [22,23]. 51 For instance, Elie et al. [18] used 22 PAFs extracted using the Biosound package [24] to 52 cluster zebra finch (Taeniopygia guttata) vocalisations, Sainburg et al. [25] used 18 53 features from the same package to visualise and cluster vocalisations from 20 species, 54 Clink and Klinck [21] used Mel Frequency Cepstral Coefficients (MFCCs) to cluster 55 gibbon (Hylobates funereus) calls by individual, and Van Segbroeck et al. [22] used a 56 gammatone filterbank to cluster mice (Mus musculus) vocalisations. Alternatively, to 57 capture spectro-temporal variations, the concatenation of consecutive spectrogram 58 frames can be used [25,26]. ...
... However, it is still unclear how various neurotransmitters, hormones and neurotrophins regulate songbird singing behavior through related neural pathways. Optogenetics, chemogenetics and other targeted neural pathway manipulation techniques can be a key link between behavior and neural activity (Singh Alvarado et al., 2021). In the meantime, the related cell types and gene expression patterns of birds and mammals were compared by single-cell sequencing technology to reveal their evolutionary analogy (Colquitt et al., 2021). ...
... While cellular-resolution devices typically offer small fields of view (FOVs) covering less than one vertebra, large-FOV microscopes ('macroscopes') provide limited spatiotemporal resolution, sensitivity and contrast or are incompatible with use in freely moving mice 2,5,6 . Wearable widefield macroscopes with millimeter-sized FOVs have recently been developed [7][8][9][10] . Still, none offer the combined cellular resolution, frame rates, sensitivity and weights necessary for spinal cord imaging in mice. ...
... Fixed and sectioned tissues, rather than entire brains, still dominate studies of zebra finch song system projections. Though not a new technique in itself, organotypic brain slices have been recently used to image the finch brain at a higher resolution, including functional imaging using calcium sensors (Shen et al., 2017). The use of brain slices allows better access to tissues for specific labeling of structures and may prove useful for introducing other biosensors or looking at glial function. ...
... The same tools can be applied to differentiating between individuals in the same recording environment (e.g., Adi et al., 2010;Mielke and Zuberbühler, 2013). Most recent approaches rely on deep neural networks to detect vocalizations in noisy environments (e.g., Stowell et al., 2019;Cohen et al., 2020a). Current neural networks generally rely on some combination of convolutional filters in the temporal-frequency space of spectrograms (Convolutional Neural Networks or CNNs, Figure 3B) and temporal-recurrence (Recurrent Neural Networks, or RNNs, Figure 3C). ...
... Time-points at Days 1, 3, and 7 were considered sufficient given the regenerative capacity of musculoskeletal tissues and the decreased time-to-stability this imparts for implantable devices. [27][28][29][30] The rat was placed into a clear chamber and allowed to move freely. Video with simultaneous recording shows that movement of the implanted muscle group was associated with increased signal (Video S1, Supporting Information). ...
... No other mammalian species produce vocalizations that are as richly structured as human language. Many songbird species could produce songs that have complex syntax with syllable sequences following certain rules [1][2][3][4], which are flexible in different contexts [5]. Therefore, songbirds have been widely studied as an animal model to investigate the evolution and neural mechanisms of complex vocal sequencing [6,7]. ...
... A number of recording channels can be increased using hundreds of splayed microfibers, each following a path of least resistance through tissue. 356 More recently, a proof-of-principle demonstration of deep brain imaging has been achieved by scanning the excitation beam through an implanted multimodal optical fiber to form an image (Sec. 4.4). ...
... In addition to improvements in materials for SLA, there are also great opportunities in the customization of 3D printers. In a system similar to a two-photon DLW system, Pearre et al. (122) used resonant mirrors to speed up printing but maintain 1-µm resolution. This printer was capable of creating approximately 400 × 400 x 400 µm 3 cubes in 25 s. ...
Reference: 3D Printed Microfluidics