Brain Communications

BackgroundRecent work has delineated the semantic behavioral variant of frontotemporal dementia (sbvFTD; or right temporal variant of FTD, which is thought to preferentially impair semantic knowledge for emotional concepts. However, this proposed core feature has not yet been empirically validated, and no clinical tool exists to assess it. Establishing reliable markers is essential to clinically differentiate sbvFTD from behavioral variant FTD (bvFTD), which is critical given their overlapping b...

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) can reduce seizures in patients with drug-resistant epilepsy. However, seizure freedom is rare, and there is no early response biomarker to predict long-term seizure suppression. To evaluate a short-term biomarker of therapeutic response to DBS, we studied 18-minute trials of ANT stimulation in patients with drug-resistant epilepsy undergoing intracranial electroencephalography. We compared a standard high-frequency perio...

BackgroundEpilepsy affects approximately 50 million individuals worldwide, with nearly one-third developing drug-resistant epilepsy (DRE). The centromedian nucleus of the thalamus (CM) and the brainstem are integral components of seizure-modulating networks and represent promising targets for neuromodulation. This study aimed to map structural connectivity between CM and specific brainstem nuclei using probabilistic tractography and to evaluate whether connectivity patterns correlate with seizur...

About half of patients who undergo epilepsy surgery for drug-resistant epilepsy have seizure recurrence, supporting the need for approaches that more accurately identify the epileptogenic zone, defined as the brain areas whose removal causes cessation of seizures. Altered network connectivity has emerged as a candidate biomarker of the epileptogenic zone, but how connectivity is altered in the epileptogenic zone remains uncertain, with prior studies reporting inconsistent results. We hypothesize...

Despite promising results, it remains unclear how to optimally target and personalize closed-loop stimulation to ameliorate deficits in memory and other cognitive functions. We hypothesized that evoked connectivity - the measurement of neural pathway activation using single pulses of electrical stimulation - can guide patient-specific selection of stimulation location and parameters for memory. We characterized brain-wide evoked connectivity profiles of stimulation in memory-related brain region...

BackgroundClinical trajectories in functional neurological disorder (FND) are variable, and the mechanisms underlying this heterogeneity remain poorly understood. ObjectiveThis longitudinal study examined resting-state functional connectivity predictors and mechanisms of symptom change in FND. MethodsThirty-two adults with FND (motor and/or seizure phenotypes) completed baseline questionnaires and a functional MRI (fMRI) session, followed by naturalistic treatment for 6.8{+/-}0.8 months. All p...

Semantic cognition allows us to represent, process and manipulate verbal and nonverbal knowledge about the surrounding environment. Semantic cognition plays a critical role in language, communication and many nonverbal behaviours and can be disrupted by several neurological diseases, including stroke and dementias. Therefore for clinical practice, it is essential to evaluate semantic cognition and to do so using culturally-appropriate assessments (given that some facets of semantic knowledge and...

Although epilepsy surgery studies have proposed intracranial EEG-derived biomarkers for localizing seizure onset and anticipating postoperative outcomes, evaluation has often been limited to derivation cohorts using internal cross-validation. An influential notion holds that neurons distributed within the seizure onset zone (SOZ) frequently generate high-frequency activity (HFA) and that resection of such sites is associated with favorable postoperative seizure control. However, the extent to wh...

Epilepsy diagnosis and treatment monitoring are hindered by the episodic, heterogeneous expression of seizures and by normal-appearing scalp EEG in many patients. We previously described paroxysmal slow-wave events (PSWEs)--brief epochs of broadband slowing detectable on EEG. Here, using intracerebral and epidural recordings in a paraoxon rat model of temporal lobe epilepsy, we show that PSWEs arise preferentially in temporo-frontal networks, co-occur with global slowing, and increase during bot...

ObjectiveHigh-frequency oscillations (HFOs) are highly specific biomarkers of epileptogenic tissue, yet their noninvasive localization remains challenging due to their brief duration, low amplitude, and poor signal-to-noise ratio. Here, we introduce TH-DeepSIF, a transformer-based deep learning framework trained on biologically realistic neural mass model simulations, to robustly perform HFO source imaging from scalp EEG. MethodsTH-DeepSIF was evaluated in simulated single- and dual-source HFO ...

ObjectiveTo delineate the phenotype of juvenile myoclonic epilepsy (JME) with a focus on obsessive-compulsive personality disorder (OCPD) using multimodal psychiatric, neuropsychological, quantitative EEG (qEEG), and structural MRI markers within a predictive-processing/free-energy framework. MethodsWe prospectively studied 65 patients with JME and 68 matched healthy controls (HC). Participants completed DSM-IV SCID I/II interviews and a neuropsychological battery assessing working memory, psyc...

Effective connectivity of the human insula, mainly assessed at rest using cortico-cortical evoked potentials (CCEPs), is not yet fully characterized at high-resolution. Here, we significantly extend prior CCEP studies of the insula by leveraging an extensive multicenter CCEP database and fine-grained anatomical atlases of the insula. We analyzed CCEP datasets from 897 patients with refractory focal epilepsy (459 females, age: 26{+/-}14 years) explored by stereo electroencephalography and with a...

PurposeEvidence suggests the contralesional cortico-reticulospinal tract (cCRST) upregulates after stroke, and that this upregulation correlates with worse motor function, suggesting it may be harmful for walking recovery. However, this relationship may be confounded by the extent of ipsilesional corticospinal tract (CST) and CRST damage, which could cause both greater cCRST upregulation and worse walking function. No previous studies have tested whether this confounding relationship exists, nor...

Neuromodulation targeting thalamic nuclei is increasingly used to treat drug-resistant focal epilepsy, yet human intracranial EEG studies describing how thalamocortical interactions evolve across seizures remain limited. We aimed to define frequency-specific thalamocortical network dynamics from seizure onset to termination, compare thalamocortical and cortico-cortical network activation, and test whether thalamic EEG features can classify seizure state to inform closed-loop or adaptive thalamic...

ObjectiveQuantitative assessment of extent of tissue resection following epilepsy surgery requires accurate delineation of the resection cavity on postoperative MRI. Current methods for resection cavity masking are time-consuming and labour-intensive, while existing automated approaches exhibit variable segmentation accuracy, particularly on extra-temporal resections. We developed MELD-PostOp, a deep learning tool trained and evaluated on a large, international, heterogeneous cohort to automatic...

Epilepsy is among the most prevalent neurological disorders, affecting millions of individuals worldwide at every stage of life. Characterised by recurrent seizures, epilepsy can significantly disrupt daily functioning, education, employment, and overall quality of life. Despite advances in neuroimaging, current approaches often overlook the individualised nature of brain disruptions in epilepsy. Here, we introduce an individualised functional Magnetic Resonance Imaging (fMRI) framework, Adjuste...

Primary Progressive Aphasias (PPA) are a group of neurodegenerative disorders characterized by the gradual decline of language abilities. They are typically divided into three major clinical variants: the non-fluent (nfvPPA), the semantic (svPPA) and the logopenic (lvPPA) variant. Even with an extensive clinical examination, a correct differential diagnosis among variants can be difficult due to the overlapping of dysfunctional language features. In this context, the combination of Transcranial ...

BackgroundFunctional neurological disorder (FND) is associated with alterations in functional brain networks, yet relationships between peripheral autonomic physiology and brain architecture remain poorly characterized. This pilot study examined associations between cardiac autonomic metrics and resting-state functional connectivity (rsFC) in FND. MethodsTwenty females with FND and 23 age-matched female psychiatric controls (PCs) completed questionnaires, 10-min resting photoplethysmography rec...

BackgroundIdiopathic REM sleep behavior disorder (iRBD) and hyposmia are the strongest clinical indicators of prodromal Parkinsons disease, reflecting distinct proposed pathways of -synuclein pathology propagation. According to the body-first/brain-first model, iRBD represents a body-first phenotype with early brainstem involvement, whereas hyposmia may reflect a brain-first phenotype with early limbic involvement. We therefore hypothesized that these markers would show distinct fiber-specific w...

Epilepsy is one of the most prevalent neurological diseases, with 25-33% of patients developing drug-resistant epilepsy (DRE). The precise etiology of DRE remains unidentified. Recent studies have revealed an increase in tetraploid astrocytes in drug-resistant temporal lobe epilepsy (DR-TLE), a common subtype of DRE. This study aims to characterize the function of tetraploid astrocytes in the brain of subjects without central nervous system diseases and in DR-TLE. Cortical samples adjacent to th...