Biology subjects

Jensen, M. A.

Publications and source records attributed to Jensen, M. A..

13 recordsLinked to original sources

bioRxiv2026

Insulotaxy: Navigating the Human Insula with a Novel Stereotactic Framework

IntroductionThe insula is an increasingly important target for functional neurosurgery given its involvement in a range of neurological and neuropsychiatric disorders, including epilepsy and chronic pain. As this practice evolves, optimal targeting will require standardized outcome measures that relate electrode or laser trajectory to postprocedural outcome. Traditional whole- brain registration approaches fail to capture the substantial person-to-person variability in insular gyral configuration, including the relative internal rotation of the insular gyri with respect to standard stereotactic space. ObjectiveWe propose and validate a stereotactic coordinate system based on local anatomical landmarks to facilitate surgical planning and standardized outcome assessment within the insular cortex. MethodsOur approach transforms brain MRI first into standard AC-PC space, and then into an insular-specific space defined by five anatomical landmarks: four points along the central sulcus of the insula and one point at the middle cerebral artery (MCA) bifurcation (at the limen insulae). The system calculates two angles - {theta} (axial) and {varphi} (sagittal) - between the AC-PC line and the insular axis, and the brain volume undergoes sequential rotation through these angles followed by translation to place the coordinate systems origin along the insular axis. ResultsIn a sample of 32 patients, the angle between the AC-PC line and the insular axis ranged from -17{degrees} to 17{degrees} in the axial plane ({theta}) and 31{degrees} to 69{degrees} in the sagittal plane ({varphi}). In the resulting coordinate system, the insular axis defines z = 0 and the MCA turning point defines y = 0. We developed a custom, open-access MATLAB graphical interface that allows intuitive implementation of this system for both surgical planning and postoperative analysis; implanted electrodes, laser fiber position, and ablation geometry can each be localized within this common space. As a demonstration of its utility for pooling data across subjects, we applied the transformation to a previously acquired intracranial electrophysiology dataset and found that anatomically consistent, effector-specific motor representations emerged across 18 subjects once electrode positions were expressed in insular-specific coordinates. ConclusionAs stereotactic surgery for insular targets becomes more common with expanding scientific inquiry, an insular-specific coordinate system may facilitate operative planning and functional mapping, and may help standardize outcome assessment across patients and institutions. SIGNIFICANCE STATEMENTThe insular cortex represents an increasingly important surgical target for therapeutic interventions, yet substantial person-to-person anatomical variability hampers standardized targeting and outcome comparison. The insula is simultaneously the subject of expanding scientific inquiry -- into interoception, pain, autonomic regulation, salience processing, and sensorimotor representation -- much of it now pursued through intracranial recording and stimulation in humans, where cohorts are small, electrode sampling is idiosyncratic, and progress therefore depends on pooling data across patients in a frame that respects insular gyral architecture. We present "Insulotaxy," a stereotactic coordinate system built from consistent, easily identifiable local anatomical landmarks that accounts for the insulas unique rotational relationship to standard brain coordinates. An open-source MATLAB tool transforms imaging into insular-specific coordinates, facilitating surgical planning for ablation and electrode placement while enabling standardized outcome reporting across institutions. By providing locally anchored, anatomically aligned coordinates rather than relying on whole-brain registration, this framework addresses a practical gap in functional neurosurgery and lays a foundation for pooling clinical and electrophysiological data as insular interventions become more prevalent.

neuroscience↗

bioRxiv2026

Attention reshapes the information dynamics of thalamic and cortical prediction-error learning

Prediction errors (PEs) drive perceptual learning by updating internal models of the sensory environment, yet it remains unclear how attention reshapes their representation across distributed thalamocortical circuits. Using intracranial stereoelectroencephalography (sEEG) from 17 patients performing a roving auditory oddball task under attended and unattended conditions, we quantified PE encoding using mutual information and co-information to capture redundant and synergistic PE representations. Attention modulated PE encoding in both the thalamus and the temporal cortex, but with distinct informational dynamics. Thalamic encoding showed a stable reduction of PE information during distraction, consistent with state-dependent thalamocortical gating. In contrast, the temporal cortex expressed two opposing learning trajectories during attended listening that converged once attention was diverted, revealing distinct cortical learning regimes rather than a uniform attentional effect. Attention further reorganized the informational content of cortical PE representations by altering the balance between redundant and synergistic information. A biologically constrained neural network showed that attention-dependent changes in inhibition and long-range connectivity reproduced these dynamics through Hebbian learning. Together, these findings suggest that attention regulates predictive learning not simply by changing the strength of PE responses, but by reshaping how distributed thalamocortical circuits represent and integrate sensory evidence over time.

neuroscience↗

bioRxiv2025

Light-orchestrated multi-step solid-phase picodroplet reactors

Picoliter droplet reactors, enabled by droplet microfluidics, are revolutionary tools for biochemical reactions with high efficiency, precision, and minimal reagent use. They excel in single-step reactions and reagent addition through droplet merging. Integrating reagent exchange and washing capabilities directly into these platforms may enable complex multi-step processes, such as de novo oligonucleotide synthesis and multiplex immunoassays. However, current picodroplet microfluidics, lacking such capabilities, remain critically deficient in executing multi-step processes. Here we introduce light-orchestrated solid-phase picodroplet reactors to overcome these limitations. Our platform employs optoelectronic tweezers to manipulate individual picodroplets and microbeads. Using this platform, we demonstrate an eight-step click chemistry-based DNA ligation synthesis cycle, with real-time in situ fluorescence detection of reaction products. This platform overcomes single-step limitations by achieving precise sequential encapsulation and decapsulation of beads with different reagent droplets, ensuring uniform reagent exposure and effective washing. Hence it mitigates reaction errors caused by nonuniform reagent exposure and trapped impurities in conventional bulk processing of microbeads. With minimal reagent consumption, real-time analysis, and programmable light- based control, the platform can potentially be scaled and fully automated into a universal and versatile picoliter-scale reagent handling robot for miniaturizing and streamlining workflows in synthetic biology, drug discovery, and beyond.

bioengineering↗

bioRxiv2025

The Human Insula Encodes Somatotopic Representation of Motor Execution with an Effector-Specific Connectomic Map to Primary Motor Cortex

Understanding motor representation in the human brain requires mapping beyond the primary motor cortex, into the distributed networks that coordinate complex movements. The insular cortex, a multifunctional hub buried within the Sylvian fissure, has been implicated in motor control through clinical observations and neuroimaging. Yet its precise relation to movement processing remains one of the least understood aspects of motor neurophysiology. To address this gap, we quantified electrophysiological changes from implanted depth electrodes in patients performing simple movement tasks combined with single-pulse electrical stimulation (SPES) to map functional connectivity. The movement data reveal distinct somatotopic representation bilaterally, as well as inter-effector regions that are active for different movement types. Hand representation is centered along the ventral aspect of the middle and posterior short gyri bilaterally, while tongue/mouth tuned sites cluster in the dorsal posterior short gyrus and the dorsal long gyri. Insular activity temporally follows the primary motor cortex (M1) and precedes movement onset. SPES revealed somatotopically-specific connectivity between corresponding sites in M1 and insula (hand-to-hand, tongue-to-tongue) and between bilateral insulae. These observations establish that somatotopy is a conserved property of distributed motor control incorporating the insula, with direct implications for basic and clinical neuroscience.

neuroscience↗

bioRxiv2025

Broadband synergy versus oscillatory redundancy in the visual cortex

The cortex generates diverse neural dynamics, ranging from broadband fluctuations to narrowband oscillations at specific frequencies. Here, we investigated whether broadband and oscillatory dynamics play different roles in the encoding and transmission of visual information. We used information-theoretical measures to dissociate neural signals sharing common information (i.e., redundancy) from signals encoding complementary information (i.e., synergy). We analyzed electrocorticography (ECoG) and local field potentials (LFP) in the visual cortex of human and non-human primates (macaque) to investigate the extent to which broadband signals (BB) and narrowband gamma (NBG) oscillations conveyed synergistic or redundant information about images. In both species, the information conveyed by BB signals was highly synergistic within and between visual areas. By contrast, the information carried by NBG was primarily redundant within and between the same visual areas. Finally, the information conveyed by BB signals emerged early after stimulus onset, while NBG sustained information at later time points. These results suggest a potential dual role of BB and NBG cortical dynamics in visual processing, with broadband dynamics supporting nonlinear pattern recognition and oscillations facilitating information maintenance across the cortex.

neuroscience↗

bioRxiv2024

Proper reference selection and re-referencing to mitigate bias in single pulse electrical stimulation data

Single pulse electrical stimulation experiments produce pulse-evoked potentials used to infer brain connectivity. The choice of recording reference for intracranial electrodes remains non-standardized and can significantly impact data interpretation. When the reference electrode is affected by stimulation or evoked brain activity, it can contaminate the pulse-evoked potentials recorded at all other electrodes and influence interpretation of findings. We highlight this specific issue in intracranial EEG datasets from two subjects recorded at separate institutions. We present several intuitive metrics to detect the presence of reference contamination and offer practical guidance on different mitigation strategies. Either switching the reference electrode or re-referencing to an adjusted common average effectively mitigated the reference contamination issue, as evidenced by increased variability in pulse-evoked potentials across the brain. Overall, we demonstrate the importance of clear quality checks and preprocessing steps that should be performed before analysis of single pulse electrical stimulation data. HighlightsO_LIA reference electrode close to active tissue can contaminate intracranial EEG signals C_LIO_LIInterpretation of pulse-evoked potentials can be biased by reference contamination C_LIO_LILow response variability between channels is indicative of reference contamination C_LIO_LIReference contamination can be resolved through data recollection or re-referencing C_LI

neuroscience↗

bioRxiv2024

Feasibility of Stereo EEG Based Brain Computer Interfacing in An Adult and Pediatric Cohort

IntroductionStereoelectroencephalography (sEEG) is a mesoscale intracranial monitoring method which records from the brain volumetrically with depth electrodes. Implementation of sEEG in BCI has not been well-described across a diverse patient cohort. MethodsAcross eighteen subjects, channels with high frequency broadband (HFB, 65-115Hz) power increases during hand, tongue, or foot movements during a motor screening task were provided real-time feedback based on these HFB power changes to control a cursor on a screen. ResultsSeventeen subjects established successful control of the overt motor BCI, but only nine were able to control imagery BCI with[≥] 80% accuracy. In successful imagery BCI, HFB power in the two target conditions separated into distinct subpopulations, which appear to engage unique subnetworks of the motor cortex compared to cued movement or imagery alone. ConclusionsEEG-based motor BCI utilizing overt movement and kinesthetic imagery is robust across patient ages and cortical regions with substantial differences in learning proficiency between real or imagined movement.

bioengineering↗

bioRxiv2024

Functional Mapping of Movement and Speech Using Task-Based Electrophysiological Changes in Stereoelectroencephalography

IntroductionStereoelectroencephalography (sEEG) has become the predominant method for intracranial seizure localization. When imaging, semiology, and scalp EEG are not in full agreement or definitively localizing, implanted sEEG recordings are used to test candidate seizure onset zones (SOZs). Discovered SOZs may then be targeted for resection, laser ablation, or neurostimulation. If a SOZ is eloquent, resection and ablation are both contraindicated, so identifying functional representation is crucial for therapeutic decision making. ObjectiveWe present a novel functional brain mapping technique that utilizes task-based electrophysiological changes in sEEG during behavioral tasks and test this in pediatric and adult patients. MethodssEEG was recorded in twenty patients with epilepsy, aged 6-39 (12 female, 18 of 20 patients < 21 years old), who underwent implanted monitoring to identify seizure onset. Each performed 1) visually cued simple repetitive movements of the hand, foot, or tongue while electromyography was recorded, and 2) simple picture naming or verb generation speech tasks while audio was recorded. Broadband changes in the power spectrum of the sEEG were compared between behavior and rest. ResultsElectrophysiological functional mapping of movement and/or speech areas was completed in all 20 patients. Eloquent representation was identified in both cortex and white matter, and generally corresponded to classically described functional anatomic organization as well as other clinical mapping results. Robust maps of brain activity were identified in healthy brain, regions of developmental or acquired structural abnormality, and SOZs. ConclusionTask based electrophysiological mapping using broadband changes in the sEEG signal reliably identifies movement and speech representation in pediatric and adult epilepsy patients.

neuroscience↗

bioRxiv2023

Distributed representations of prediction error signals across the cortical hierarchy are synergistic

An important question concerning inter-areal communication in the cortex is whether these interactions are synergistic, i.e. brain signals can either share common information (redundancy) or they can encode complementary information that is only available when both signals are considered together (synergy). Here, we dissociated cortical interactions sharing common information from those encoding complementary information during prediction error processing. To this end, we computed co-information, an information-theoretical measure that distinguishes redundant from synergistic information among brain signals. We analyzed auditory and frontal electrocorticography (ECoG) signals in five common awake marmosets performing two distinct auditory oddball tasks and investigated to what extent event-related potentials (ERP) and broadband (BB) dynamics encoded redundant and synergistic information during auditory prediction error processing. In both tasks, we observed multiple patterns of synergy across the entire cortical hierarchy with distinct dynamics. The information conveyed by ERPs and BB signals was highly synergistic even at lower stages of the hierarchy in the auditory cortex, as well as between auditory and frontal regions. Using a brain-constrained neural network, we simulated the spatio-temporal patterns of synergy and redundancy observed in the experimental results and further demonstrated that the emergence of synergy between auditory and frontal regions requires the presence of strong, long-distance, feedback and feedforward connections. These results indicate that the distributed representations of prediction error signals across the cortical hierarchy can be highly synergistic.

neuroscience↗

bioRxiv2022

Homunculus Interruptus: A motor association area in the depth of the central sulcus

Cells in the precentral gyrus of the human brain directly send signals to the periphery to generate movement and are topologically organized as a map of the body. We find that movement induced electrophysiological changes from implanted depth electrodes extend this map 3-dimensionally throughout the volume of the gyrus. Unexpectedly, this organization is interrupted by a motor association area in the depths of the central sulcus at its mid-lateral aspect that is active during many different types of movements from both sides of the body.

neuroscience↗

bioRxiv2021

An intrinsic endothelial dysfunction causes cerebral small vessel disease

Small Vessel Disease (SVD) is the leading cause of vascular dementia, causes a quarter of strokes, and worsens stroke outcomes(1, 2). The disease is characterised by cerebral small vessel and white matter pathology, but the underlying mechanisms are poorly understood. Classically, the microvascular and tissue damage has been considered secondary to extrinsic factors, such as hypertension, consisting of microvessel stiffening, impaired vasoreactivity and blood-brain barrier dysfunction identified in human sporadic SVDs. However, increasing evidence points to an underlying vulnerability to SVD-related brain damage, not just extrinsic factors. Here, in a novel normotensive transgenic rat model where the phospholipase flippase Atp11b is deleted, we show pathological, imaging and behavioural changes typical of those in human sporadic SVD, but that occur without hypertension. These changes are due to an intrinsic endothelial cell dysfunction, identified in vessels of the brain white matter and the retina, with pathological evidence of vasoreactivity and blood-brain barrier deficits, which precipitate a secondary maturation block in oligodendroglia and myelin disruption around the small vessels. This highlights that an intrinsic endothelial dysfunction may underlie vulnerability to human sporadic SVD, providing alternative therapeutic targets to prevent a major cause of stroke and dementia.

neuroscience↗

bioRxiv2021

Loss of KRASG12D feedback regulation involving splicing factor SRSF1 accelerates pancreatic cancer

The gene encoding KRAS GTPase is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC), triggering the formation of precursor lesions, i.e., acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). However, the majority of pancreatic cells from KC (LSL-KrasG12D/+; Pdx-1-Cre) mice expressing the KrasG12D mutation remain morphologically normal for a long time, suggesting the existence of compensatory feedback mechanisms that buffer aberrant KrasG12D signaling, and that additional steps are required for disrupting cell homeostasis and promoting transformation. Here we report a feedback mechanism in which the ubiquitously expressed splicing factor SRSF1--which is associated with cell transformation in multiple cell types--is downregulated in the majority of morphologically normal pancreas cells with the KrasG12D mutation. Conversely, increasing SRSF1 expression disrupts cell homeostasis by activating MAPK signaling, in part by regulating alternative splicing and mRNA stability of interleukin 1 receptor type 1 (Il1r1). This disruption in homeostasis in turn accelerates KrasG12D-mediated PDAC initiation and progression. Our results demonstrate the involvement of SRSF1 in the pancreatic-cell homeostatic response against the KrasG12D mutation, dysregulation of which facilitates PDAC initiation. One-Sentence SummarySplicing factor SRSF1 is involved in KRASG12D feedback regulation and pancreatic-cancer tumorigenesis.

cancer biology↗

bioRxiv2018

Free-running enzymatic oligonucleotide synthesis for data storage applications

Here we present preliminary results for a method of oligodeoxynucleotide synthesis using terminal deoxynucleotidyl transferase (TdT) to generate mixed base homopolymer runs of defined sequence. In a process we have termed Free-Running Synthesis (FRS), we allow TdT to freely add multiple bases of a given monomer. With this method, homopolymeric runs can be used for writing DNA in a data storage capacity, where a stretch of As, for example, will be read as a single base, and the transitions between successive homopolymer runs encodes information. As a proof-of-concept, we demonstrate homopolymer additions of A, C and T onto the 3 end of a 22 base initiator strand.

biochemistry↗