Biology subjects

Halpern, A. R.

Publications and source records attributed to Halpern, A. R..

8 recordsLinked to original sources

bioRxiv2026

Decoding Individual Musical Pitches in Perception and Imagery using Evoked Theta and Beta Power in EEG

Imagery evokes perceptual-like experiences and recruits similar neural activity to perception. In music, this shared activity has already been established in secondary auditory cortex, yet the nature of the representation is not fully understood; specifically, it is not clear whether the identity of individual imagined pitches can be decoded from brain activity. Using temporal lobe EEG channels, we examined the shared evoked patterns of musical pitch perception and imagery, and decoded individual imagined pitches from evoked oscillatory power across three conditions (Perception, Imagery, Random Pitch). Twenty-two participants heard the opening tones of a familiar melody, imagined its continuation, and judged whether a final probe tone matched the original note; a random-pitch condition served as a control. Replicating previous findings, the evoked perceptual pattern was reinstated during imagery, particularly in the right temporal channels, which showed stronger event-related potential correlations and a larger mismatch negativity to the probe tone than the left. A multiclass support vector machine decoded individual pitch identity from evoked oscillatory power (phase-locked activity time-locked to each tone onset) exceeding chance in all conditions, with accuracy higher for Perception and Imagery than Random Pitch. The optimal oscillatory bands differed across conditions: theta-beta gave the highest accuracy for Perception and Imagery, theta-alpha for the Random Pitch. These results demonstrate that individual pitch information is present during both perception and imagery, and that the theta-beta signature shared by the predictive contexts, distinct from the control, suggests a contribution of predictive processing. Significance StatementMusical imagery -- the experience of "hearing" music in the minds ear -- recruits brain activity resembling perception, yet whether the pitch specific information during imagery can be read out from this activity has remained unknown. Using EEG, we show for the first time that individual imagined pitches can be decoded from evoked oscillatory power, and that perception and imagery share a spectral signature (theta-beta) absent from a non-predictive random-pitch control. This dissociation indicates that imagined pitch reflects top-down predictions reactivating sensory representations, consistent with a predictive-coding view of imagery. These findings clarify the oscillatory basis of musical imagery and establish that its specific content is recoverable from non-invasive signals, informing future imagery-based brain-computer interfaces.

neuroscience↗

bioRxiv2025

A Shared Neural Network for Highly Liked and Disliked Music

Music research has increasingly focused on neural responses to naturalistic stimuli. The neural correlates of music-induced peak moments of pleasure (e.g., chills) have been well-studied; data on other types of aesthetic responses, such as judgments of beauty, goodness, or liking are sparse. Among these, liking is of particular interest given its complex nature and its ubiquity in everyday--and musical--experiences. In this functional magnetic resonance imaging (fMRI) study, 26 participants listened to musical excerpts while continuously rating how much they liked the music. In addition, subjects provided an overall liking judgment at the end of each musical piece. Participants musical preferences manifested remarkably early and were sustained over time, with the value of the continuous rating at the end of each piece showing the strongest correlation with the overall ratings. At the neural level, highly liked and disliked musical pieces activated a shared neural network previously associated with the processing of both positive and negative emotional stimuli. This network encompassed the anterior cingulate cortex, limbic system, basal ganglia, and precuneus. These activations reflected individual differences, such that participants with greater trait-level responsiveness to artistic stimuli showed stronger engagement of this network while listening to music. Finally, the default-mode network was associated with the slope of the continuous ratings, suggesting that the faster participants liked a musical excerpt, the more disengaged this network became. In linking behavior and brain function to better characterize the way humans make aesthetic judgments of music the data support a model in which preferences and aesthetic choices are modulated by brain circuits associated with emotion and reward.

neuroscience↗

bioRxiv2023

Three-dimensional single-cell transcriptome imaging of thick tissues

Multiplexed error-robust fluorescence in-situ hybridization (MERFISH) allows genome-scale imaging of RNAs in individual cells in intact tissues. To date, MERFISH has been applied to image thin tissue samples of [~]10-{micro}m thickness. Here, we present a thick-tissue three-dimensional (3D) MERFISH imaging method, which uses confocal microscopy for optical sectioning, deep learning for increasing imaging speed and quality, as well as sample preparation and imaging protocol optimized for image registration of thick samples. We demonstrated 3D MERFISH on mouse brain tissue sections of up to 200 {micro}m thickness with high detection efficiency and accuracy. We anticipate that 3D thick-tissue MERFISH imaging will broaden the scope of questions that can be addressed by spatial genomics.

neuroscience↗

bioRxiv2021

Versatile, do-it-yourself, low-cost spinning disk confocal microscope

Confocal microscopy is an invaluable tool for 3D imaging of biological specimens, however, accessibility is often limited to core facilities due to the high cost of the hardware. We describe an inexpensive do-it-yourself (DIY) spinning disk confocal microscope (SDCM) module based on a commercially fabricated chromium photomask that can be added on to a laser-illuminated epifluorescence microscope. The SDCM achieves strong performance across a wide wavelength range (~400-800 nm) as demonstrated through a series of biological imaging applications that include conventional microscopy (immunofluorescence, small-molecule stains, and fluorescence in situ hybridization) and super-resolution microscopy (single-molecule localization microscopy and expansion microscopy). This low-cost and simple DIY SDCM is well-documented and should help increase accessibility to confocal microscopy for researchers.

biophysics↗

bioRxiv2021

The Giardia lamellipodium-like ventrolateral flange supports attachment and rapid cytokinesis

Attachment to the intestinal epithelium is critical to the lifestyle of the ubiquitous parasite Giardia lamblia. The microtubule cytoskeleton plays a well characterized role in attachment via the ventral adhesive disc, whereas the role of the unconventional actin cytoskeleton is controversial. We identified a novel actin associated protein with putative WH2-like actin binding domains we named Flangin. Flangin complexes with Giardia actin and is enriched in the ventrolateral flange (VLF), a lamellipodium-like membrane protrusion at the interface between parasites and attached surfaces. Live imaging revealed that the VLF grows to ~1 m in width after cytokinesis, then remains size-uniform in interphase, grows during mitosis, and is resorbed during cytokinesis. A Flangin truncation mutant stabilizes the VLF and blocks cytokinesis, indicating that the VLF is a membrane reservoir supporting rapid myosin-independent cytokinesis in Giardia. Rho family GTPases are important regulators of membrane protrusions, GlRac, the sole Rho family GTPase in Giardia, was localized to the VLF. Knockdown of Flangin, actin, and GlRac result in VLF formation defects indicating a conserved role for GlRac and actin in forming membrane protrusions, despite the absence of canonical actin binding proteins that link Rho GTPase signaling to lamellipodia formation. Flangin-depleted parasites challenged with fluid shear force in flow chambers had a reduced ability to remain attached, indicating a role for the VLF in attachment. This secondary attachment mechanism complements the microtubule based adhesive ventral disc, a feature that is particularly important during mitosis when the parental ventral disc begins disassembly in preparation for cytokinesis. ImportanceThe ventrolateral flange (VLF) is a lamellipodium-like structure found at the host-parasite interface that has long been thought to be involved in parasite attachment. The proteins responsible for building the VLF have remained unidentified precluding manipulation of the VLF to determine its role in Giardia biology. We identified Flangin, a novel actin associated protein that localizes to the VLF, implicating Giardia actin in VLF formation. We demonstrate that: 1.) Flangin, actin, and GlRac are required for VLF formation, 2.) the VLF serves as a membrane reservoir to support Giardias incredibly fast cytokinesis, and 3) the VLF augments attachment, which is critical to parasitism. The microtubule-based adhesive ventral disc and the actin-based ventrolateral flange represent redundant means of maintaining attachment, the presence of redundant systems illustrate the importance of attachment to the lifestyle of this ubiquitous parasite.

cell biology↗

bioRxiv2020

Mapping the contents of consciousness during musical imagery

Humans can internally represent auditory information without an external stimulus. When imagining music, how similar are unfolding neural representations to those during the original perceived experience? Can rhythmic motion influence the neural representation of music during imagery as during perception? Participants first memorized six one-minute-long instrumental musical pieces with high accuracy. Functional MRI data were collected during: 1) silent imagery of melodies to the beat of a visual metronome; 2) same but while tapping to the beat; and 3) passive listening. During imagery, inter-subject comparison showed that melody-specific temporal response patterns were reinstated in right associative auditory cortices. When tapping accompanied imagery, the melody-specific neural patterns were extended to associative cortices bilaterally. These results indicate that the specific contents of conscious experience are encoded similarly during imagery and perception in the dynamic activity of auditory cortices. Furthermore, rhythmic motion can enhance the reinstatement of neural patterns associated with the experience of complex sounds, in keeping with models of motor to sensory influences in auditory processing.

neuroscience↗

bioRxiv2020

Multiplexed single-cell profiling of chromatin states at genomic loci by expansion microscopy

Proper regulation of genome architecture and activity is essential for the development and function of multicellular organisms. Histone modifications, acting in combination, specify these activity states at individual genomic loci. However, the methods used to study these modifications often require either a large number of cells or are limited to targeting one histone mark at a time. Here, we developed a new method called Single Cell Evaluation of Post-TRanslational Epigenetic Encoding (SCEPTRE) that uses Expansion Microscopy (ExM) to visualize and quantify multiple histone modifications at non-repetitive genomic regions in single cells at a spatial resolution of ~75 nm. Using SCEPTRE, we distinguished multiple histone modifications at a single housekeeping gene, quantified histone modification levels at multiple developmentally-regulated genes in individual cells, and identified a relationship between histone H3K4 trimethylation and the loading of paused RNA polymerase II at individual loci. Thus, SCEPTRE enables multiplexed detection of combinatorial chromatin states at single genomic loci in single cells.

genomics↗

bioRxiv2019

Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues

Recent advances in optical clearing and light-sheet microscopy have provided unprecedented access to structural and molecular information from intact tissues. However, current light-sheet microscopes have imposed constraints on the size, shape, number of specimens, and compatibility with various clearing protocols. Here we present a multi-immersion open-top light-sheet microscope that enables simple mounting of multiple specimens processed with a variety of protocols, which will facilitate wider adoption by preclinical researchers and clinical laboratories. One Sentence SummaryGlaser et al. describe a multi-immersion open-top light-sheet microscope that enables simple and high-throughput imaging of large numbers of preclinical and clinical specimens prepared with a variety of clearing protocols.

bioengineering↗