Biology subjects

Tracy, J. I.

Publications and source records attributed to Tracy, J. I..

7 recordsLinked to original sources

bioRxiv2026

Structural and Functional Connectivity Predict the Effects of Direct Brain Stimulation on Memory

Intracranial stimulation can enhance episodic memory in humans; however, the behavioral effects vary substantially across individuals and stimulation sites. Here, we investigated whether the network embedding of a stimulation target, defined by MRI-based normative structural and functional connectivity, accounts for variability in stimulation-linked memory enhancement. We analyzed data from 50 adults with medically refractory epilepsy who underwent intracranial EEG monitoring and completed a verbal delayed free-recall task during stimulation of left temporal cortex sites across 61 sessions (39 closed-loop; 22 random). On average, closed-loop stimulation delivered during classifier-detected low-encoding states increased recall rates, whereas random stimulation produced no reliable benefit. Diffusion tractography from a normative database showed that sites yielding greater memory enhancement were characterized by stronger structural coupling to a distributed fronto-temporo-parietal network. Greater structure-function congruence with a normative verbal-encoding activation network predicted larger closed-loop memory benefit (Spearman {rho} = 0.58, P < 0.0001). Functional connectivity exhibited overlapping trends but did not yield robust regional associations after permutation correction. Multivariate Partial Least Squares Structural Equation Modeling further identified stimulation mode, baseline memory, and a structural profile factor as independent predictors of memory enhancement, with no independent contribution of functional connectivity. These findings indicate that reliable stimulation-driven memory improvement depends not only on the timing of stimulation, but also on whether the stimulated target is structurally embedded within an encoding-relevant network scaffold. Significance statementMemory enhancement through direct brain stimulation holds substantial clinical promise, yet inconsistent outcomes have limited its therapeutic translation. This study shows that the effectiveness of closed-loop brain stimulation for memory improvement is determined by the structural network architecture of the stimulation target. Sites more deeply embedded within white-matter pathways connecting a distributed verbal encoding network yield the greatest mnemonic benefits when stimulation is delivered adaptively during poor encoding states. These findings establish a principled, network-based rationale for precision-guided neuromodulation: optimizing both the targets structural embedding and the timing of stimulation delivery are necessary and complementary conditions for reliable, individualized memory enhancement.

neuroscience↗

bioRxiv2026

Mapping Individualized Dual-Axis Network Topology in Focal Epilepsy: Divergent Alterations in System Integrity, Integration, and Clinical Correlates

Focal epilepsy is increasingly recognized as a disorder of distributed brain systems, yet characterizations of patient-specific alterations in network organization that are clinically meaningful remain limited. Here, we used resting-state functional MRI to introduce an overlap-permitting individualized network-estimation framework anchored to normative references to derive two complementary, system-level axes of topology: (1) network correspondence, indexing the expression of canonical networks and the fidelity of intrinsic system boundaries, and (2) k-hubness, indexing cross-system integration and multi-functionality through multi-network participation. We used a large presurgical focal epilepsy cohort (305 patients, including temporal and extratemporal epilepsy; 224 healthy participants) and an independent multi-syndrome validation cohort spanning focal and common generalized and childhood epilepsy syndromes (903 patients; 666 healthy participants), to show: (1) correspondence disruption of both canonical and non-normative networks constitutes a broadly shared system-level endpoint that displays heterogeneity across individuals and differential impacts on cognition, (2) k-hubness reconfigurations reflect lateralized and syndrome-dependent redistributions of cross-system integration, demonstrating epilepsys impact on the functional multiplicity inherent to specific brain areas. These complementary axes shared variance yet showed dissociable clinical associations, with correspondence preferentially relating to neurocognitive deficits and k-hubness aligning with epilepsy clinical features. Accordingly, these axes demonstrate the presence of distinct topological phenotypes, providing clinically relevant, reproducible patient-level signatures that explain both the syndrome-specific and common effects of seizures on the organization and integration of canonical and individualized brain systems.

neuroscience↗

bioRxiv2024

Normative and individual, non-normative intrinsic networks and the transition to impaired cognition

Despite their temporal lobe pathology, a significant subgroup of temporal lobe epilepsy (TLE) patients are able to maintain normative cognitive functioning. Here, we identify TLE patients with intact versus impaired cognitive profiles, and interrogate for the presence of both normative and highly individual intrinsic connectivity networks(ICN) - all towards understanding the transition from impaired to intact neurocognitive status. We retrospectively investigated data from 88 TLE patients and matched 91 healthy controls with resting-state functional MRI. Functional MRI data were decomposed using independent component analysis to obtain individualized ICNs. Here, we calculated the degree of match between individualized ICNs and canonical ICNs (e.g., Yeo et.al 17 resting-state network) and divided each participants ICNs into normative or non-normative status based on the degree of match. We found that the individualized networks matched the canonical networks less well in the cognitively impaired compared to the cognitively intact TLE patients. The cognitively impaired patients showed significant abnormalities in the profiles of both normative and non-normative networks, whereas the intact patients showed abnormalities only in non-normative networks. At the same time, we found normative networks held a strong, positive association with the neuropsychological measures, with this association negative in non-normative networks. We were able to provide the initial data demonstrating that significant cognitive deficits are associated with the status of highly-individual ICNs, making clear that the transition from intact to impaired cognitive status is not simply the result of disruption to normative brain networks.

neuroscience↗

bioRxiv2021

Pathological and metabolic underpinnings of energetic inefficiency in temporal lobe epilepsy

The human brain consumes a disproportionate amount of energy to generate neural dynamics. Yet precisely how energetic processes are altered in neurological disorders remains far from understood. Here, we use network control theory to profile the brains energy landscape, describing the rich dynamical repertoire supported by the structural connectome. This approach allows us to estimate the energy required to activate a circuit, and determine which regions most support that activation. Focusing on temporal lobe epilepsy (TLE), we show that patients require more control energy to activate the limbic network than healthy volunteers, especially ipsilateral to the seizure focus. Further, greater energetic costs are largely localized to the ipsilateral temporo-limbic regions. Importantly, the energetic imbalance between ipsilateral and contralateral temporo-limbic regions is tracked by asymmetric metabolic patterns, which in turn are explained by asymmetric gray matter volume loss. In TLE, failure to meet the extra energy demands may lead to suboptimal brain dynamics and inadequate activation. Broadly, our investigation provides a theoretical framework unifying gray matter integrity, local metabolism, and energetic generation of neural dynamics.

neuroscience↗

bioRxiv2019

Tonic resting-state hubness supports high-frequency activity defined verbal-memory encoding network in epilepsy

High-frequency gamma activity of verbal-memory encoding using invasive-electroencephalogram coupled has laid the foundation for numerous studies testing the integrity of memory in diseased populations. Yet, the functional connectivity characteristics of networks subserving these HFA-memory linkages remains uncertain. By integrating this electrophysiological biomarker of memory encoding from IEEG with resting-state BOLD fluctuations, we estimated the segregation and hubness of HFA-memory regions in drug-resistant epilepsy patients and matched healthy controls. HFA-memory regions express distinctly different hubness compared to neighboring regions in health and in epilepsy, and this hubness was more relevant than segregation in predicting verbal memory encoding. The HFA-memory network comprised regions from both the cognitive control and primary processing networks, validating that effective verbal-memory encoding requires multiple functions, and is not dominated by a central cognitive core. Our results demonstrate a tonic intrinsic set of functional connectivity, which provides the necessary conditions for effective, phasic, task-dependent memory encoding.\n\nHighlightsO_LIHigh frequency memory activity in IEEG corresponds to specific BOLD changes in resting-state data.\nC_LIO_LIHFA-memory regions had lower hubness relative to control brain nodes in both epilepsy patients and healthy controls.\nC_LIO_LIHFA-memory network displayed hubness and participation (interaction) values distinct from other cognitive networks.\nC_LIO_LIHFA-memory network shared regional membership and interacted with other cognitive networks for successful memory encoding.\nC_LIO_LIHFA-memory network hubness predicted both concurrent task (phasic) and baseline (tonic) verbal-memory encoding success.\nC_LI

neuroscience↗

bioRxiv2019

Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia--thalamus network with resting-state functional magnetic resonance imaging in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for over one year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of \"disconnection\" simulations, we showed that these changes in interactive profiles of the basal ganglia--thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between the basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

neuroscience↗

bioRxiv2018

Predictive control of electrophysiological network architecture using direct, single-node neurostimulation in humans

Chronically implantable neurostimulation devices are becoming a clinically viable option for treating patients with neurological disease and psychiatric disorders. Neurostimulation offers the ability to probe and manipulate distributed networks of interacting brain areas in dysfunctional circuits. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. By integrating multi-modal intracranial recordings and diffusion tensor imaging from patients with drug-resistant epilepsy, we test hypothesized structural and functional rules that predict altered patterns of synchronized local field potentials. We demonstrate the ability to predictably reconfigure functional interactions depending on stimulation strength and location. Stimulation of areas with structurally weak connections largely modulates the functional hubness of downstream areas and concurrently propels the brain towards more difficult-to-reach dynamical states. By using focal perturbations to bridge large-scale structure, function, and markers of behavior, our findings suggest that stimulation may be tuned to influence different scales of network interactions driving cognition.

neuroscience↗