Biology subjects

Linn, G.

Publications and source records attributed to Linn, G..

7 recordsLinked to original sources

bioRxiv2026

Dose-dependent power and connectivity modulation of low frequency oscillations through transcranial magnetic stimulation in non-human primates.

Transcranial magnetic stimulation (TMS) is a powerful non-invasive tool for safely modulating neural activity in humans. In particular, the left dorsolateral prefrontal cortex (DLPFC) is a common target site for clinical interventions in disorders such as treatment-resistant depression. Yet, clinical trials investigating the efficacy of TMS often lack neural markers of target engagement of the DLPFC. Local field potentials (LFPs), such as prefrontal theta oscillations, have been implicated in the clinical symptoms of these disorders. However, non-invasive electroencephalography (EEG) recordings in humans are limited by their spatial resolution and challenges of interpreting EEG signals. In this study, we investigate the effects of single-pulse TMS applied to the left prefrontal cortex in non-human primates on LFPs recorded through intracranial EEG. Compared to sham TMS, the intensity of active TMS pulses scaled with LFP power changes in a 1-13 Hz range at contacts close to the stimulation site in the prefrontal cortex (e.g., caudate nucleus, anterior cingulate cortex, insular cortex) as well as contacts that were more distal (e.g., posterior cingulate cortex, temporal lobe). To test how TMS modulates connectivity between these regions, we conducted a phase-based connectivity analysis. TMS pulses initially enhanced and then disrupted connectivity at 1-13 Hz between the stimulation site and other contacts. Connectivity rebounded approximately 1500 ms post-stimulation. Only the initial enhancement in connectivity scaled with TMS intensity. Our results demonstrate a dose-dependent power modulation of low frequency LFPs across prefrontal, parietal and temporal cortical regions by single pulses. Furthermore, they show that TMS applied over the left prefrontal cortex can enhance and interrupt short- and long-range connectivity. Our study advances the understanding of the effects of TMS on brain oscillations and connectivity with direct relevance for clinical applications in neuromodulation therapies.

neuroscience↗

bioRxiv2024

Layer-specific dynamics of local field potentials in monkey V1 during electrical stimulation

The mammalian neocortex, organized into six cellular layers or laminae, forms a cortical network within layers. Layer specific computations are crucial for sensory processing of visual stimuli within primary visual cortex. Laminar recordings of local field potentials (LFPs) are a powerful tool to study neural activity within cortical layers. Electric brain stimulation is widely used in basic neuroscience and in a large range of clinical applications. However, the layer-specific effects of electric stimulation on LFPs remain unclear. To address this gap, we conducted laminar LFP recordings of the primary visual cortex in monkeys while presenting a flash visual stimulus. Simultaneously, we applied a low frequency sinusoidal current to the occipital lobe with offset frequency to the flash stimulus repetition rate. We analyzed the modulation of visual-evoked potentials with respect to the applied phase of the electric stimulation. Our results reveal that only the deeper layers, but not the superficial layers, show phase-dependent changes in LFP components with respect to the applied current. Employing a cortical column model, we demonstrate that these in vivo observations can be explained by phase-dependent changes in the driving force within neurons of deeper layers. Our findings offer crucial insight into the selective modulation of cortical layers through electric stimulation, thus advancing approaches for more targeted neuromodulation.

biophysics↗

bioRxiv2023

Experimental validation of computational models for the prediction of phase distribution during multi-channel transcranial alternating current stimulation

Transcranial alternating current stimulation (tACS) is a widely used noninvasive brain stimulation (NIBS) technique to affect neural activity. Neural oscillations exhibit phase-dependent associations with cognitive functions, and tools to manipulate local oscillatory phases can affect communication across remote brain regions. A recent study demonstrated that multi-channel tACS can generate electric fields with a phase gradient or traveling waves in the brain. Computational simulations using phasor algebra can predict the phase distribution inside the brain and aid in informing parameters in tACS experiments. However, experimental validation of computational models for multi-phase tACS is still lacking. Here, we develop such a framework for phasor simulation and evaluate its accuracy using in vivo recordings in nonhuman primates. We extract the phase and amplitude of electric fields from intracranial recordings in two monkeys during multi-channel tACS and compare them to those calculated by phasor analysis using finite element models. Our findings demonstrate that simulated phases correspond well to measured phases (r = 0.9). Further, we systematically evaluated the impact of accurate electrode placement on modeling and data agreement. Finally, our framework can predict the amplitude distribution in measurements given calibrated tissues conductivity. Our validated general framework for simulating multi-phase, multi-electrode tACS provides a streamlined tool for principled planning of multi-channel tACS experiments.

bioengineering↗

bioRxiv2022

Mesoscale neural effects of transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent direct neural mechanisms, i.e., due to electric field or connectivity, and peripheral sensory co-stimulation effects remain debated. Understanding how TMS stimulation parameters affect brain responses is vital for the rational design of TMS protocols. Studying these mechanisms in humans is challenging due to the limited spatiotemporal resolution of available non-invasive neuroimaging methods. Here, we leverage invasive recordings of local field potentials in non-human primates to study TMS mesoscale responses. We demonstrate that early TMS-evoked potentials show a sigmoidal dose-response with stimulation intensity. We further show that stimulation responses are spatially specific. We employ several control conditions to dissociate direct neural responses from auditory and somatosensory co-activation. These results provide crucial evidence regarding TMS neural effects at the brain circuit level. Our findings are highly relevant for interpreting human TMS studies and biomarker developments for TMS target engagement in clinical applications.

neuroscience↗

bioRxiv2018

Gradients of connectivity distance in the cerebral cortex of the macaque monkey

Cortical connectivity conforms to a series of organizing principles that are common across species. Spatial proximity, similar cortical type, and similar connectional profile all constitute factors for determining the connectivity between cortical regions. We previously demonstrated another principle of connectivity that is closely related to the spatial layout of the cerebral cortex. Using functional connectivity from resting-state fMRI in the human cortex, we found that the further a region is located from primary cortex, the more distant are its functional connections with other areas of the cortex. However, it remains unknown whether this relationship between cortical layout and connectivity extends to other primate species. Here, we investigated this relationship using both resting-state functional connectivity as well as gold-standard tract-tracing connectivity in the macaque monkey cortex. For both measures of connectivity, we found a gradient of connectivity distance extending between primary and frontoparietal regions. As in the human cortex, the further a region is located from primary areas, the stronger its connections to distant portions of the cortex, with connectivity distance highest in frontal and parietal regions. The similarity between the human and macaque findings provide evidence for a phylogenetically conserved relationship between the spatial layout of cortical areas and connectivity.

neuroscience↗

bioRxiv2018

Electric field dynamics in the brain during multi-electrode transcranial electric stimulation

Neural oscillations play a crucial role in communication between remote brain areas. Transcranial electric stimulation with alternating currents (TACS) can manipulate these brain oscillations in a non-invasive manner. Of particular interest, TACS protocols using multiple electrodes with phase shifted stimulation currents were developed to alter the connectivity between two or more brain regions. Typically, an increase in coordination between two sites is assumed when they experience an in-phase stimulation and a disorganization through an anti-phase stimulation. However, the underlying biophysics of multi-electrode TACS has not been studied in detail, thus limiting our ability to develop a mechanistic understanding. Here, we leverage direct invasive recordings from two non-human primates during multi-electrode TACS to show that the electric field magnitude and phase depend on the phase of the stimulation currents in a non-linear manner. Further, we report a novel phenomenon of a \"traveling wave\" stimulation where the location of the electric field maximum changes over the stimulation cycle. Our results provide a basis for a mechanistic understanding of multi-electrode TACS, necessitating the reevaluation of previously published studies, and enable future developments of novel stimulation protocols.

neuroscience↗

bioRxiv2017

Delineating the macroscale areal organization of the macaque cortex in vivo

Complementing longstanding traditions centered around histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP) provides the opportunity to overcome critical barriers in translational research. Here, we establish the data and scanning conditions for achieving reproducible, stable and internally valid areal parcellations in individuals. We demonstrate that these functional boundaries serve as a functional fingerprint of the individual animals, and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing), though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHP, as well as provide insights into the impact of scan state and motivate efforts toward harmonizing protocols.

neuroscience↗