Biology subjects

Teichert, T.

Publications and source records attributed to Teichert, T..

8 recordsLinked to original sources

bioRxiv2025

Aseptic, semi-sealed cranial chamber implants for chronic multi-channel neurochemical and electrophysiological neural recording in nonhuman primates

We developed an implantable neural interface for monitoring both chemical and electrical forms of brain activity in monkeys that maintains aseptic properties for year-long periods while leveraging the modular functions (e.g., sensor moveability) provided by a chamber system. Invasive electrophysiological recordings, especially in subcortical structures from nonhuman primates usually involves implanting electrodes into the brain through a skull-mounted chamber. These electrodes may be attached temporarily for several hours of recording, or permanently. Permanent attachments are favorable to allow for sealing the chamber completely from externally originating pathogenic species that can infiltrate and compromise the health of the animal. A sealed chamber also reduces the need for frequent chamber cleaning required to minimize the accumulation of pathogenic organisms. However, neurochemical measurements require specialized electrodes with extremely fragile carbon fiber tips and are not compatible with recently developed sealed chamber systems. Here, we leveraged osseointegrating materials and hermetic sealing strategies to enable both neurochemical and electrical neural activity measurements from a sealed chamber with an aspirating port for culturing chamber fluid to ensure an aseptic environment. The system was shown to provide successful recordings of neural activity in two monkeys while maintaining negative bacteria culture results for over a year post-implant.

neuroscience↗

bioRxiv2024

Volumetric mesoscopic electrophysiology: a new imaging modality for the non-human primate

The primate brain is a densely interconnected organ whose function is best understood by recording from the entire structure in parallel, rather than parts of it in sequence. However, available methods either have limited temporal resolution (functional magnetic resonance imaging), limited spatial resolution (macroscopic electroencephalography), or a limited field of view (microscopic electrophysiology). To address this need, we developed a volumetric, mesoscopic recording approach (MePhys) by tessellating the volume of a monkey hemisphere with 992 electrode contacts that were distributed across 62 chronically implanted multi-electrode shafts. We showcase the scientific promise of MePhys by describing the functional interactions of local field potentials between the more than 300,000 simultaneously recorded pairs of electrodes. We find that a subanesthetic dose of ketamine -believed to mimic certain aspects of psychosis- can create a pronounced state of functional disconnection and prevent the formation of stable large-scale intrinsic states. We conclude that MePhys provides a new and fundamentally distinct window into brain function whose unique profile of strengths and weaknesses complements existing approaches in synergistic ways.

neuroscience↗

bioRxiv2021

Long-term persistence of viral RNA and inflammation in the CNS of macaques exposed to aerosolized Venezuelan equine encephalitis virus.

Venezuelan equine encephalitis virus (VEEV) is a positively-stranded RNA arbovirus of the genus Alphavirus that causes encephalitis in humans. Cynomolgus macaques are a relevant model of the human disease caused by VEEV and are useful in exploring pathogenic mechanisms and the host response to VEEV infection. Macaques were exposed to small-particle aerosols containing virus derived from an infectious clone of VEEV strain INH-9813, a subtype IC strain isolated from a human infection. VEEV-exposed macaques developed a biphasic fever after infection similar to that seen in humans. Maximum temperature deviation correlated with the inhaled dose, but fever duration did not. Neurological signs, suggestive of virus penetration into the CNS, were predominantly seen in the second febrile period. Electroencephalography data indicated a statistically significant decrease in all power bands and circadian index during the second febrile period that returned to normal after fever resolved. Intracranial pressure increased late in the second febrile period. On day 6 post-infection macaques had high levels of MCP-1 and IP-10 chemokines in the CNS, as well as a marked increase of T lymphocytes and activated microglia. More than four weeks after infection, viral genomic RNA was found in the brain, cerebrospinal fluid and cervical lymph nodes. Pro-inflammatory cytokines & chemokines, infiltrating leukocytes and pathological changes were seen in the CNS tissues of macaques euthanized at these times. These data are consistent with persistence of virus replication and/or genomic RNA and potentially, inflammatory sequelae in the central nervous system after resolution of acute VEEV disease.

immunology↗

bioRxiv2021

Linear superposition of responses evoked by individual glottal pulses explain over 80% of the frequency following response to human speech in the macaque monkey

The frequency-following response (FFR) is a scalp-recorded electrophysiological potential that closely follows the periodicity of complex sounds such as speech. It has been suggested that FFRs reflect the linear superposition of responses that are triggered by the glottal pulse in each cycle of the fundamental frequency (F0 responses) and sequentially propagate through auditory processing stages in brainstem, midbrain, and cortex. However, this conceptualization of the FFR is debated, and it remains unclear if and how well a simple linear superposition can capture the spectro-temporal complexity of FFRs that are generated within the highly recurrent and non-linear auditory system. To address this question, we used a deconvolution approach to compute the hypothetical F0 responses that best explain the FFRs in rhesus monkeys to human speech and click trains with time-varying pitch patterns. The linear superposition of F0 responses explained well over 90% of the variance of click train steady state FFRs and well over 80% of mandarin tone steady state FFRs. The F0 responses could be measured with high signal-to-noise ratio and featured several spectro-temporally and topographically distinct components that likely reflect the activation of brainstem (<5ms; 200-1000 Hz), midbrain (5-15 ms; 100-250 Hz) and cortex (15-35 ms; ~90 Hz). In summary, our results in the monkey support the notion that FFRs arise as the superposition of F0 responses by showing for the first time that they can capture the bulk of the variance and spectro-temporal complexity of FFRs to human speech with time-varying pitch. These findings identify F0 responses as a potential diagnostic tool that may be useful to reliably link altered FFRs in speech and language disorders to altered F0 responses and thus to specific latencies, frequency bands and ultimately processing stages.

neuroscience↗

bioRxiv2021

Deconstructing the Cortical Sources of Frequency Following Responses to Speech: A Cross-species Approach

Time-varying pitch is a vital cue for human speech perception. Neural processing of time-varying pitch has been extensively assayed using scalp-recorded frequency-following responses (FFRs), an electrophysiological signal thought to reflect integrated phase-locked neural ensemble activity from subcortical auditory areas. Emerging evidence increasingly points to a putative contribution of auditory cortical ensembles to the scalp-recorded FFRs. However, the properties of cortical FFRs and precise characterization of laminar sources are still unclear. Here we used direct human intracortical recordings as well as extra- and intracranial recordings from macaques and guinea pigs to characterize the properties of cortical sources of FFRs to time-varying pitch patterns. We found robust FFRs in the auditory cortex across all species. We leveraged representational similarity analysis as a translational bridge to characterize similarities between the human and animal models. Laminar recordings in animal models showed FFRs emerging primarily from the thalamorecepient layers of the auditory cortex. FFRs arising from these cortical sources significantly contributed to the scalp-recorded FFRs via volume conduction. Our research paves the way for a wide array of studies to investigate the role of cortical FFRs in auditory perception and plasticity. Significance StatementFrequency following responses (FFRs) to speech are scalp-recorded neural signals that inform the fidelity of sound encoding in the auditory system. FFRs, long believed to arise from brainstem and midbrain, have shaped our understanding of sub-cortical auditory processing and plasticity. Non-invasive studies have shown cortical contributions to the FFRs, however, this is still actively debated. Here we employed direct cortical recordings to trace the cortical contribution to the FFRs and characterize the properties of these cortical FFRs. With extra-cranial and intra-cranial recordings within the same subjects we show that cortical FFRs indeed contribute to the scalp-recorded FFRs, and their response properties differ from the sub-cortical FFRs. The findings provide strong evidence to revisit and reframe the FFR driven theories and models of sub-cortical auditory processing and plasticity with careful characterization of cortical and sub-cortical components in the scalp-recorded FFRs.

neuroscience↗

bioRxiv2020

Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.

Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or therapeutics can mitigate CNS infection or disease in this model. The documentation of alphavirus encephalitis in animals relies on traditional physiological biomarkers and behavioral/neurological observations by veterinary staff; quantitative measurements such as electroencephalography (EEG) and intracranial pressure (ICP) can recapitulate underlying encephalitic processes. We detail a telemetry implantation method suitable for continuous monitoring of both EEG and ICP in awake macaques, as well as methods for collection and analysis of such data. We sought to evaluate whether changes in EEG/ICP suggestive of CNS penetration by virus would be seen after aerosol exposure of naive macaques to VEEV IC INH9813 or EEEV V105 strains compared to mock-infection in a cohort of twelve adult cynomolgus macaques. Data collection ran continuously from at least four days preceding aerosol exposure and up to 50 days thereafter. EEG signals were processed into frequency spectrum bands (delta: [0.4 - 4Hz); theta: [4 - 8Hz); alpha: [8-12Hz); beta: [12-30] Hz) and assessed for viral encephalitis-associated changes against robust background circadian variation while ICP data was assessed for signal fidelity, circadian variability, and for meaningful differences during encephalitis. Results indicated differences in delta, alpha, and beta band magnitude in infected macaques, disrupted circadian rhythm, and proportional increases in ICP in response to alphavirus infection. This novel enhancement of the cynomolgus macaque model offers utility for timely determination of onset, severity, and resolution of encephalitic disease and for the evaluation of vaccine and therapeutic candidates.

immunology↗

bioRxiv2020

A surface metric and software toolbox for EEG electrode grids in the macaque

BackgroundThe past years have seen increased appreciation of non-invasive extracranial electroencephalographic (EEG) recordings in non-human primates (NHP) as a tool for translational research. In humans, the international 10-20 system or extensions thereof provide standardized electrode positions that enable easy comparison of data between subjects and laboratories. In the NHP, no such generally accepted, standardized placement system is available. New MethodHere we introduce a surface metric and software package (NHP1020) that automates the planning of large, approximately evenly spaced electrode grids on the NHP skull. ResultsThe system is based on one CT and one MRI image and requires the user to specify two intracranial markers. Based on this, the software defines electrode positions on the brain surface using a surface-based spherical metric similar to the one used by the international 10-20 system. The electrode positions are then projected to the surface of the skull. Standardized electrode grids can be shared, imported or defined with few high-level commands. Existing MethodsNHP EEG electrodes are often placed on an individual basis relative to extracranial markers, or relative to underlying neural structures. Both approaches are time-consuming and require manual intervention. Furthermore, the use of extracranial markers in this species may be more problematic than in humans, because cranial muscles and ridges are larger and keep maturing long into adulthood thus potentially affecting electrode positions. ConclusionThe key advantage of the current approach is the automated and objective identification of corresponding electrode positions in different animals. Automation was made possible by the use of a two-dimensional metric on the brain surface which has a simpler, i.e., more convex and sphere-like anatomy than the skull. This enables fast and efficient planning, optimization and calculation of large electrode grids.

neuroscience↗

bioRxiv2019

Mismatch responses mediated by adaptation and deviance detection have complementary functional profiles that point to different auditory short-term memory systems

Mismatch negativity (MMN) is a macroscopic EEG deflection in response to rare or unexpected sounds. It has provided important insights into auditory short-term memory, pre-attentive guidance of attention, and their alteration in conditions such as schizophrenia. It remains unclear if MMN is caused by passive adaptation, active memory-comparison processes (deviance detection; DD), or a mix of both. To answer this question, macaque monkeys listened to a new paradigm that quantified both components of MMN. Micro- and macroscopic mismatch responses in the rhesus were dominated by adaptation at short latencies but included a smaller contribution of deviance detection at longer latencies. Most importantly, we show that mismatch responses mediated by adaptation have a short temporal scope and narrow frequency tuning while mismatch responses mediated by deviance detection have a longer temporal scope but broader frequency tuning. The different functional profiles point to the involvement of two distinct auditory short-term memory systems and complementary roles in the pre-attentive guidance of attention.

neuroscience↗