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...

ObjectivePatients with refractory epilepsy experience extensive and invasive clinical testing for seizure onset zones treatable by surgical resection. However, surgical resection can fail to provide therapeutic benefit, and patients with neocortical epilepsy have the poorest therapeutic outcomes. This case series studied patients with neocortical epilepsy who were referred for surgical treatment. Prior to surgery, patients volunteered for resting-state functional magnetic resonance imaging (rs-f...

Indirect speech acts-- responding "I forgot to wear my watch today" to someone who asked for the time -- are ubiquitous in daily conversation, but are understudied in current neurobiological models of language. To comprehend an indirect speech act like this one, listeners must not only decode the lexical-semantic content of the utterance, but also make a pragmatic, bridging inference. This inference allows listeners to derive the speakers true, intended meaning--in the above dialogue, for exampl...

ObjectiveWe evaluated whether the combination of epileptiform spikes and ripples (spike ripples) outperformed other leading biomarkers in identifying the epileptogenic zone across subjects in a multicenter international study. MethodsWe validated and applied an automated spike ripple detector on intracranial EEG recordings in subjects from 4 centers who subsequently underwent surgical resection with known 1-year seizure outcomes. We evaluated the spike ripple rate in subjects cured after resect...

Regaining the ability to express and understand language is a key milestone for patients recovering from severe traumatic brain injury (TBI). However, the neurobiological correlates of language recovery after TBI have not been identified. We explored whether recovery of language in patients with acute severe TBI is associated with functional MRI (fMRI) changes within and outside the canonical language network (i.e. bilateral superior temporal gyri [STG] and inferior frontal gyri [IFG]). We conse...

The logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills, resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through pre-determined networks. First, we used cross-sectional structural MRI data from individuals with lvPPA...

BackgroundDeep brain stimulation (DBS) has been investigated for patients with drug-resistant epilepsy who are not candidates for resective surgery. Because different types of epilepsy involve different brain networks, numerous DBS targets have been explored. MethodsTo provide a comprehensive overview of this expanding literature, we conducted a systematic review of studies for DBS in epilepsy, collecting data on surgical targets, individual disease characteristics, outcomes, and precise electr...

IMPORTANCEThe neurological substrates of visual creativity are unknown. We demonstrate the role of dorsomedial visual cortex in emergence of visual artistic creativity (VAC) in the setting of dementia. Our findings illuminate neural substrates of human creativity and suggest that hyperactivation of specific brain areas may manifest as enhanced cognitive or behavioral capacities. OBJECTIVETo determine the anatomical and physiological underpinnings of VAC in dementia. DESIGN, SETTING, AND PARTIC...

Background and ObjectivesWithin frontotemporal dementia (FTD), the behavioral variant (bvFTD) characterized by frontal atrophy, and semantic behavioral variant (sbvFTD) characterized by right anterior temporal lobe (rATL) atrophy, present diagnostic challenges due to overlapping symptoms and neuroanatomy. Accurate differentiation is crucial for clinical trial inclusion targeting TDP-43 proteinopathies. This study investigated whether automated speech analysis can distinguish between FTD-related ...

ObjectivesDeep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by (i) developing a structural MRI approach for CM visualisation, (ii) identifying the CMs neurophysiological characteristics, and (iii) mapping connectivity from CM-DBS sites using functional MRI (fMRI). MethodsNineteen patients with LGS (m...

Drug-resistant epilepsy affects tens of millions of people worldwide and is associated with considerable morbidity and mortality. Thalamic deep brain stimulation and cortical responsive neurostimulation are proven treatments for focal epilepsy. Both have been used to target a range of thalamic nuclei, yet the roles of these thalamic nuclei in focal seizure generation remain incompletely understood. Thirteen patients with drug-resistant focal epilepsy undergoing intracranial EEG were consented t...

In drug-resistant epilepsy patients who undergo anterior thalamic deep brain stimulation (ANT-DBS), efficacy is assessed months after therapy initiation and clinicians have no guidance when choosing stimulation parameters due to the lack of real-time biomarkers. Here, we identified acute and chronic suppression of slow gamma oscillations (SGOs) (20-50Hz) in the ANT as a novel electrophysiological biomarker correlated with therapeutic response. Through analysis of an ongoing prospective ANT-DBS p...

Mesial temporal lobe epilepsy (mTLE) is a common localization of drug-resistant epilepsy in adults. Patients often undergo intracranial EEG (iEEG) monitoring to confirm localization and determine candidacy for focal ablation or resection. Clinicians primarily base surgical decision-making on seizure onset patterns, with imaging abnormalities and information from interictal epileptiform discharge (spikes) used as ancillary data. How the morphology and timing of spikes within multi-electrode seque...

Learning objectiveTo validate a novel video-based emotion identification measure in persons with neurodegeneration and show correspondence to emotion-relevant brain systems BackgroundGiven advances in disease-modifying therapies for dementia, the dementia field needs objective, practical behavioral assessment tools for patient trial selection and monitoring. The Dynamic Affect Recognition Test (DART) was designed to remedy limitations of instruments typically used to measure emotion identificat...

ObjectiveThe effects of deep brain stimulation (DBS) manifest across multiple timescales, spanning seconds to months, and involve direct electrical effects, neuroplasticity, and network reorganization. In epilepsy, the delayed impact of DBS on seizures presents challenges for optimization. Single-pulse stimulation and resulting brain stimulation evoked potentials (BSEPs) provide a means to assess effective connectivity and network excitability. This study integrates BSEPs and short trials of DBS...

Thalamic stimulation has emerged as a promising neuromodulation target for treating disorders of consciousness. Impaired consciousness, a debilitating outcome in temporal lobe epilepsy (TLE) remains a central problem for patients whose seizures cannot be treated pharmacologically and cannot be stopped with conventional surgery or responsive hippocampal stimulation. Although prior studies suggest an essential role of the thalamic intralaminar central lateral (CL) nucleus in arousal and sleep, evi...

Despite the availability of more than 20 anti-seizure medications (ASMs), approximately half of patients with newly diagnosed epilepsy fail their first drug trial. Unfortunately, clinicians lack objective tools or consensus guidelines to match individual patients with the most effective therapy, frequently leading to years of uncontrolled seizures. Here, we developed machine learning models to utilize a single, baseline routine resting-state scalp EEG to forecast ASM efficacy. EEGs and treatment...

One-third of epilepsy patients do not fully respond to antiseizure medications (ASM), are not candidates for curative surgical interventions, or have unsuccessful surgical therapies. Safe and effective therapies remain limited for these treatment-resistant epilepsy (TRE) patients. Several palliative neurostimulation devices were approved by the US Food and Drug Administration (FDA) and other regulatory agencies: vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain sti...

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...

Logopenic Progressive Aphasia is a rare language disorder characterised by repetition and naming difficulties, reflecting the progressive degeneration of left-lateralized peri-sylvian temporal and inferior parietal regions. Mounting evidence suggests that cognitive impairments in this syndrome extend beyond the language domain to include episodic encoding and retrieval disturbances. To date, it remains unknown whether autobiographical memories from across the lifespan are also subject to decline...