Biology subjects

Temel, Y.

Publications and source records attributed to Temel, Y..

10 recordsLinked to original sources

bioRxiv2026

High-Precision Event Synchronization for Chronic Deep Brain Stimulation Local Field Potential Recordings

BackgroundElectrophysiological recordings from chronically implanted Deep Brain Stimulation (DBS) electrodes can greatly advance understanding of disease and treatment mechanisms of motor and psychiatric disorders. The Medtronic Percept system allows for chronic recordings of local field potentials (LFP) from DBS target regions. However, these systems lack an inbuilt synchronization option to align LFP recordings to other recording modalities and consequently events in computerized tasks. ObjectiveWe propose and evaluate a synchronization method based on Transcutaneous Electrical Stimulation (TES) with low amplitudes to precisely align recorded LFP signals from the DBS electrodes to EEG recordings. MethodsThe TES-based synchronization approach was implemented and tested in 11 participants implanted with the Medtronic Percept for treatment of Parkinsons disease. ResultsThe proposed method provides high reliability, precise alignment and usability across all Medtronic Percept recording modes. Notably, the method enables recordings during adaptive DBS and with stimulation turned off. In this recording mode, LFP signals can be acquired from all recording contact pairs simultaneously, with a high signal-to-noise ratio. We provide detailed setup plans and share Python and Matlab scripts for signal alignment to enable easy application of our approach. ConclusionBy enabling reliable, well-aligned LFP recordings from all DBS contacts, our method provides a robust tool for studying neural dynamics and refining therapeutic interventions in diverse neurological conditions.

neuroscience↗

bioRxiv2025

Insular error network enables self-correcting intracranial brain-computer interface

Error recognition is fundamental to adaptive behavior, enabling rapid compensatory action when outcomes deviate from expectations. Central to this function are neural circuits for performance monitoring, encoding cognitive signals that could support more reliable neural interfaces. Here, we recorded intracranial electroencephalography (iEEG) in epilepsy patients to enable a motor brain-computer interface (BCI) while sampling error-related activity across a distributed network. Our work reveals high-frequency population dynamics emerging in the anterior insula and propagating to the prefrontal cortex as the interface fails to follow the users intention. We identify spatially organized insular responses to error processing and movement feedback, highlighting it as a heterogeneous hub linking action and outcome. Real-time integration of error responses enables a self-correcting neural interface that enhances usability by reducing the need for manual user intervention. Together, our work demonstrates a human intracranial BCI harnessing insular brain activity, integrating cognitive processes directly into device control.

neuroscience↗

bioRxiv2025

Decoding brain-wide signatures of uninformed choices for BCI assisted decision-making

Decision-making is an essential cognitive function. It can be impaired due to a number of neurological and psychiatric disorders as well as external factors such as time pressure or stress. To assist users during decision-making, we propose a decision-making brain computer interface (BCI) that can alert to uninformed decision-making, prompt additional information seeking and therefore improve decision-making quality. To this aim, we establish the feasibility of decoding uninformed decision-making from local field potentials recorded with implanted stereo-electroencephalography (sEEG) electrodes in 6 participants. We show that decoding of available information above chance level is possible for all participants, both after stimulus presentation, as well as before task response. Starting from stimulus onset, the temporal processing hierarchy of informed vs. uninformed decision-making spans from visual processing through hippocampal memory processes to frontal control network shifting. The anterior insula, known to be a decision-making hub, codes available information during the decision phase prior to button press. These results further elucidate the neural basis of coded information availability and confirm the feasibility of a decision-making BCI.

neuroscience↗

bioRxiv2025

Remote magnetomechanical neuromodulation uncovers a novel therapeutic mechanism for alleviating Parkinsonian symptoms in freely moving mice

To overcome the limitations of invasive neuromodulation systems, we introduce a wireless magnetomechanical approach for remote, minimally invasive deep brain stimulation (DBS) without chronically implanted electrodes. This method leverages biocompatible nanoscale magnetite nanodiscs (MNDs) with ground vortex magnetisation, which undergo in-plane transitions under low-frequency alternating magnetic fields, thereby generating localised piconewton-scale torques. These torques engage endogenous mechanosensory pathways to modulate neural activity, enabling reversible stimulation without the need for genetic modifications. Calcium imaging validated the rapid neuromodulatory effects of MNDs in vitro and ex vivo, which motivated the subsequent application of magnetomechanical DBS to the subthalamic nucleus in mice. We demonstrated the remote control of motor behaviour in wild-type mice and significant restoration of motor function in a severe hemiparkinsonian model. This study established the first wireless therapeutic magnetomechanical neuromodulation platform that leverages biocompatible nanomaterials and endogenous mechanosensory ion channels, representing a promising step toward untethered, clinically translatable neurotechnology.

neuroscience↗

bioRxiv2021

Rapid dynamic naturalistic monitoring of bradykinesia in Parkinson's disease using a wrist-worn accelerometer

IntroductionMotor fluctuations in Parkinsons disease are characterized by unpredictability in the timing and duration of dopaminergic therapeutic benefit on symptoms including bradykinesia and rigidity. These fluctuations significantly impair the quality of life of many Parkinsons patients. However, current clinical evaluation tools are not designed for the continuous, naturalistic (real-world) symptom monitoring needed to optimize clinical therapy to treat fluctuations. Although commercially available wearable motor monitoring, used over multiple days, can augment neurological decision making, the feasibility of rapid and dynamic detection of motor fluctuations is unclear. So far, applied wearable monitoring algorithms are trained on group data. Here, we investigate the influence of individual model training on short timescale classification of naturalistic bradykinesia fluctuations in Parkinsons patients using a single wrist-accelerometer. MethodsAs part of the Parkinson@Home study protocol, 20 Parkinson patients were recorded with bilateral wrist-accelerometers for a one hour OFF medication session and a one hour ON medication session during unconstrained activities in their own homes. Kinematic metrics were extracted from the accelerometer data from the bodyside with the largest unilateral bradykinesia fluctuations across medication states. The kinematic accelerometer features were compared over the whole one-hour recordings, and medication-state classification analyses were performed on one-minute segments of data. The influence of individual versus group model training, data window length, and total amount of training patients included in group model training on classification was analyzed. ResultsStatistically significant areas under the curves (AUCs) for medication induced bradykinesia fluctuation classification were seen in 85% of the Parkinson patients at the single minute timescale using the group models. Individually trained models performed at the same level as the group trained models (mean AUC both 0.70, +/- respectively 0.18 and 0.10) despite the small individual training dataset. AUCs of the group models improved as the length of the feature windows was increased to 300 seconds, and with additional training patient datasets. ConclusionMedication induced fluctuations in bradykinesia can be classified using wrist worn accelerometery at the time scale of a single minute. Rapid, naturalistic Parkinson motor monitoring has important clinical potential to evaluate dynamic symptomatic and therapeutic fluctuations and help tailor treatments on a fast timescale.

neuroscience↗

bioRxiv2021

Altered sleep intensity upon DBS to hypothalamic sleep-wake centers in rats

Deep brain stimulation (DBS) has been scarcely investigated in the field of sleep research. We hypothesize that DBS onto hypothalamic sleep- and wake-promoting centers will produce significant neuromodulatory effects, and potentially become a therapeutic strategy for patients suffering severe, drug-refractory sleep-wake disturbances. We aimed to investigate whether continuous electrical high-frequency DBS, such as that often implemented in clinical practice, in the ventrolateral preoptic nucleus (VLPO) or the perifornical area of the posterior lateral hypothalamus (PeFLH), significantly modulates sleep-wake characteristics and behavior. We implanted healthy rats with electroencephalographic/electromyographic electrodes and recorded vigilance states in parallel to bilateral bipolar stimulation of VLPO and PeFLH at 125 Hz at 90 A over 24 h to test the modulating effects of DBS on sleep-wake proportions, stability and spectral power in relation to baseline. We unexpectedly found that VLPO DBS at 125 Hz deepens slow-wave sleep as measured by increased delta power, while sleep proportions and fragmentation remain unaffected. Thus, the intensity, but not the amount of sleep or its stability, is modulated. Similarly, the proportion and stability of vigilance states remained altogether unaltered upon PeFLH DBS but, in contrast to VLPO, 125 Hz stimulation unexpectedly weakened SWS, evidenced by reduced delta power. This study provides novel insights into non-acute functional outputs of major sleep-wake centers in the rat brain in response to electrical high-frequency stimulation, a paradigm frequently used in human DBS. In the conditions assayed, while exerting no major effects on sleep-wake architecture, hypothalamic high-frequency stimulation arises as a provocative sleep intensity-modulating approach.

neuroscience↗

bioRxiv2020

The effect of noise trauma and high-frequency stimulation on thalamic sensory gating in rodents

BackgroundThe medial geniculate body (MGB) of the thalamus plays a central role in tinnitus pathophysiology. Breakdown of sensory gating in this part of the auditory thalamus is a potential mechanism underlying tinnitus. The alleviation of tinnitus-like behavior by high-frequency stimulation (HFS) of the MGB might mitigate dysfunctional sensory gating. ObjectiveThe study aims at exploring the role of the MGB in sensory gating as a mandatory relay area in auditory processing in noise-exposed and control subjects, and to assess the effect of MGB HFS on this function. MethodsNoise-exposed rats and controls were tested. Continuous auditory sequences were presented to allow assessment of sensory gating effects associated with pitch, binary grouping, and temporal regularity. Evoked potentials (EP) were recorded from the MGB and acquired before and after HFS (100 Hz). ResultsNoise-exposed rats showed differential modulation of MGB EP amplitudes, confirmed by significant main effects of stimulus type, pair position and temporal regularity. Noise-exposure selectively abolished the effect of temporal regularity on EP amplitudes. A significant three-way interaction between HFS phase, temporal regularity and rat condition (noise-exposed, control) revealed that only noise-exposed rats showed significantly reduced EP amplitudes following MGB HFS. ConclusionThis is the first report that shows thalamic filtering of incoming auditory signals based on different sound features. Noise-exposed rats further showed higher EP amplitudes in most conditions and did not differentiate the temporal regularity. Critically, MGB HFS was effective in reducing amplitudes of the EP responses in noise-exposed animals. HighlightsO_LIEP findings indicate sensory gating in the MGB in rats. C_LIO_LINoise exposure alters EP amplitudes in the MGB. C_LIO_LIHFS selectively suppresses EP responses in noise-exposed animals. C_LI

neuroscience↗

bioRxiv2020

Injectable Nanoelectrodes Enable Wireless Deep Brain Stimulation of Native Tissue in Freely Moving Mice

Devices that electrically modulate the central nervous system have enabled important breakthroughs in the management of neurological and psychiatric disorders. Such devices typically have centimeter-scale dimensions, requiring surgical implantation and wired-in powering. Using smaller, remotely powered materials could lead to less invasive neuromodulation. Herein, we present injectable magnetoelectric nanoelectrodes that wirelessly transmit electrical signals to the brain in response to an external magnetic field. Importantly, this mechanism of modulation requires no genetic modification of the brain, and allows animals to freely move during stimulation. Using these nanoelectrodes, we demonstrate neuronal modulation in vitro and in deep brain targets in vivo. We also show that local thalamic modulation promotes modulation in other regions connected via basal ganglia circuitry, leading to behavioral changes in mice. Magnetoelectric materials present a versatile platform technology for less invasive, deep brain neuromodulation.

bioengineering↗

bioRxiv2019

Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation-induced anticipatory fear in a rat model

BackgroundElectrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful tool for modelling anticipatory fear and agoraphobia.\n\nMethodsIn this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then used tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons.\n\nResultsAlthough acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, chronic administrations of both drugs were comparably effective. We found that the number of dopaminergic neurons in the ventral tegmental area (VTA) was lowered in both chronic buspirone and escitalopram groups. We showed a strong correlation between the number of dopaminergic neurons and freezing in the VTA. We further showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta in escitalopram and buspirone groups, respectively.\n\nLimitationsAlthough our data strongly hint to a role of dopaminergic mechanisms in the dlPAG induced fear response, more in-depth studies with larger sample sizes are needed to understand the neuronal mechanisms underlying the interactions between serotonergic drugs and dopaminergic cell number and fear behavior.\n\nConclusionChronic treatment with an SSRI and a 5-HT1A agonist decrease the number of dopaminergic neurons in the VTA. These effects seem to be associated with reduced dlPAG-induced anticipatory freezing behaviour.\n\nKey PointsO_LIChronic treatment of escitalopram and buspirone was effective in reducing dlPAG induced anticipatory freezing behaviour.\nC_LIO_LIThe number of dopaminergic neurons in the ventral tegmental area (VTA) was lowered in both chronic buspirone and escitalopram groups and was correlated to freezing.\nC_LIO_LIWe found positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta in escitalopram and buspirone groups, respectively.\nC_LI

neuroscience↗

bioRxiv2019

Cortico-basal white matter alterations occurring in Parkinson’s disease

Magnetic resonance imaging studies typically use standard anatomical atlases for identification and analyses of (patho-)physiological effects on specific brain areas; these atlases often fail to incorporate neuroanatomical alterations that may occur with both age and disease. The present study utilizes Parkinsons disease and age-specific anatomical atlases of the subthalamic nucleus for diffusion tractography, assessing tracts that run between the subthalamic nucleus and a-priori defined cortical areas known to be affected by Parkinsons disease. The results show that the strength of white matter fiber tracts appear to remain structurally unaffected by disease. Contrary to that, Fractional Anisotropy values were shown to decrease in Parkinsons disease patients for connections between the subthalamic nucleus and the pars opercularis of the inferior frontal gyrus, anterior cingulate cortex, the dorsolateral prefrontal cortex and the pre-supplementary motor, collectively involved in preparatory motor control, decision making and task monitoring. While the biological underpinnings of fractional anisotropy alterations remain elusive, they may nonetheless be used as an index of Parkinsons disease. Moreover, we find that failing to account for structural changes occurring in the subthalamic nucleus with age and disease reduce the accuracy and influence the results of tractography, highlighting the importance of using appropriate atlases for tractography.

neuroscience↗