Faculty Bibliography
Searched for:
Department/Unit:Neurology
Total Results:
24488
Hybrid spatial organization and evidence for magnitude-independent neural coding of linguistic information during sentence production
Humans are the only species with the ability to systematically combine words to convey an unbounded number of complex meanings. This process is guided by combinatorial processes whose underlying neural mechanisms remain obscured by inherent limitations of noninvasive brain measures and a near-total focus on comprehension paradigms. Here, we address these limitations with high-resolution neurosurgical recordings (electrocorticography) and a controlled sentence production experiment. We uncover distinct cortical networks encoding word-level and higher-order information. These networks exhibited a hybrid spatial organization: broadly distributed across traditional language areas but with focal concentrations of sensitivity to semantic and structural contrasts in canonical language regions. In contrast to previous comprehension-based findings, we find that these networks are largely nonoverlapping. Most notably, higher-order linguistic information showed an unexpected dissociation from local activity magnitude. This result establishes an operational dissociation between activity magnitude and information content, pointing toward a potentially distinct neural coding scheme for higher-order language, with important implications for the neurobiology of language.
PMID: 42555736
ISSN: 2375-2548
CID: 6070827
What Does α-Syn-SAA-Negative Parkinson's Disease Reveal About the Proposed "Biological Definition" of Parkinson's Disease? [Letter]
PMID: 42549779
ISSN: 1531-8257
CID: 6070805
Correction: The Roseto Study: Selection Bias Versus Social Support
[This corrects the article DOI: 10.7759/cureus.113024.].
PMID: 42564463
ISSN: 2168-8184
CID: 6070863
True vignettes: interesting, illustrative examples of behavioral abnormalities in people with Parkinson's disease
BACKGROUND/UNASSIGNED:Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurobehavioral disorders in which behavioral abnormalities are common but often not recognized. OBJECTIVE/UNASSIGNED:To bring to life the actual descriptions rendered by our patients of their unusual experiences. METHODS/UNASSIGNED:Members of the Parkinson Study Group were asked to provide illustrative examples of particularly memorable abnormal behaviors that their own PD patients or family members reported. RESULTS/UNASSIGNED:These recollections were deidentified and sorted into categories. These disorders include the classically described syndromes of Capgras, Cotard, Diogenes, Ekbom, Othello as well as overlap parasomnias, and impulse control disorders. CONCLUSION/UNASSIGNED:Patients with PD often have had unusual experiences that they may not share without inquiries by their healthcare providers, fearful of how they will be perceived. Sensitive inquiries are required to reveal these problems. We believe that reading about real experiences will help sensitize the reader.
PMCID:13183462
PMID: 42150593
ISSN: 1678-4227
CID: 6070912
Changes in effectiveness and safety in patients with Lennox-Gastaut syndrome transitioning from the fenfluramine randomized controlled trial to open-label extension study
In the phase 3 randomized controlled trial (RCT; NCT03355209) of fenfluramine in Lennox-Gastaut syndrome (LGS), patients in fenfluramine treatment groups (0.2 mg/kg/day, 0.7 mg/kg/day) experienced greater reduction from baseline in frequency of seizures associated with a fall versus placebo, which was sustained in the open-label extension (OLE) study (NCT03355209). In this post hoc analysis, trajectories of fenfluramine effectiveness and safety, along with dose changes over time, are described for patients with LGS randomized to placebo in RCT who switched to fenfluramine in OLE (PBO-FFA) and those who received fenfluramine in both RCT/OLE (FFA-FFA). Among patients who completed 12 months in OLE (N = 151), numerical improvements in effectiveness outcomes were seen in the PBO-FFA group (n = 59) after initiating fenfluramine and were similar to those in the FFA-FFA group (n = 92). Regression to the mean was not observed in the PBO-FFA group, suggesting that changes were due to fenfluramine. Incidence of the most commonly reported treatment-emergent adverse events increased in the PBO-FFA group after fenfluramine initiation but decreased in the FFA-FFA group in OLE. These data demonstrate rapid improvement in seizure frequency and global functioning in both groups with continued clinical improvement as the mean fenfluramine dose was increased. These results confirm that sustained fenfluramine treatment is effective and tolerable. PLAIN LANGUAGE SUMMARY: This study assessed the change over time in the number of seizures, overall improvement, and side effects in patients with LGS receiving placebo (no active medicine) or fenfluramine in a 14-week study; all patients later received fenfluramine in the extension study. Overall, the number of seizures (associated with a fall) decreased once patients initially receiving placebo changed to fenfluramine (optimal effect around Month 4 while receiving a higher dose), but as expected, common side effects were reported more frequently once patients began fenfluramine treatment. Patients, parents, and doctors should be aware of this time course to allow fenfluramine enough time to work.
PMCID:13431789
PMID: 42545895
ISSN: 2470-9239
CID: 6070798
SSRI/SNRI and long COVID in children and adolescents with neuropsychiatric conditions: a cohort study from the RECOVER Initiative
Long COVID has been an important health concern in children and adolescents, yet factors associated with its development remain incompletely understood. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are widely prescribed for pediatric neuropsychiatric conditions and may influence immune and autonomic pathways involved in postinfectious symptoms. Here we show associations between SSRI/SNRI use and long coronavirus disease (COVID)-related outcomes in a retrospective cohort of 110,955 children and adolescents with pre-existing neuropsychiatric conditions across 37 US health systems participating in the National Institutes of Health Researching COVID to Enhance Recovery consortium. SSRI/SNRI use was not associated with clinician-recorded long COVID diagnosis but showed heterogeneous associations with individual symptoms. Lower risks were observed for some symptoms, including fever, chills and hair loss, whereas higher risks were observed for neurological and systemic outcomes, including postural orthostatic tachycardia syndrome, cognitive dysfunction and fatigue. These findings suggest that antidepressant exposure may be associated with differing post-COVID symptom patterns in youth and warrant further investigation.
PMCID:13442008
PMID: 42564177
ISSN: 2731-6076
CID: 6070860
Loops all the way up: Recurrency as an implementation-first primitive for consciousness
Consciousness science is fragmented, and empirical investigations are largely confined within the framework of each theory of consciousness (ToC). Proliferating ToCs accumulate anomalies without progress, operating orthogonally. The principle of recurrency, functional and architectural, specifies a unifying, mechanistic scaffold for consciousness to arise. We show that all theories tacitly invoke feedback loops and can be re-expressed along a single axis of recursion. Four nested levels, viz., cellular, local inter-areal, global, and lateral, map onto state consciousness, phenomenal (P) content, conscious access (A), and phenomenal character, respectively, thus tying evolved anatomy to phenomenality. The classical P-A distinction dissolves into a graded cascade wherein deeper recursion expands the set of reportable, behaviour-driving variables. Recurrency, defined as structural, causal, and/or functional feedforward and feedback connections between elements within a system, is favoured in biological architectures, and supports the closed-loop interactions between brain, body, and environment that underlie adaptive behaviour and self-related processing. Disparities in the explanatory mechanisms across theories of consciousness can thus be resolved by converging onto this shared principle on the implementation axis, rather than deal with phenomenal-first or functional-first ontologies. The field urgently requires this implementation-first distillation that is biologically plausible, mechanistic, and empirically testable.
PMID: 42556031
ISSN: 1873-1457
CID: 6070829
Global Burden of Elevated LDL-C: Findings From the Global Burden of Disease Study 2023
IMPORTANCE/UNASSIGNED:Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C-related burden is critical for guiding prevention and treatment strategies. OBJECTIVES/UNASSIGNED:To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. DESIGN, SETTING, AND POPULATION/UNASSIGNED:This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. EXPOSURE/UNASSIGNED:Population-level LDL-C concentrations. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C-attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. RESULTS/UNASSIGNED:In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C-attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.
PMID: 42525403
ISSN: 1538-3598
CID: 6070510
Proteomic comparison of hippocampal neurofibrillary tangles in PART, intermediate Alzheimer's disease and advanced Alzheimer's disease
Alzheimer's disease (AD) is characterised by the intraneuronal aggregation of phosphorylated Tau (pTau) into neurofibrillary tangles and by the extracellular deposition of β-amyloid (Aβ). Tau pathology restricted to the hippocampal formation is frequently observed in the elderly brain in the absence of any Aβ deposition and considered as "primary age-related tauopathy" (PART). Here, we applied an unbiased proteomic approach to determine how concomitant Aβ pathology modifies the neurofibrillary tangle proteome. Neurofibrillary tangles were isolated by dissecting Tau pSer202/pThr205 "AT8" immunopositive neuronal profiles, combining chromogenic immunohistochemistry with laser capture microdissection, from hippocampal sections of 17 post-mortem brains spanning three groups: PART (n = 5; A0, B1-2, C0 scores), intermediate AD (n = 6; A1-2, B2-3, C1-2 scores) and advanced AD (n = 6; A3, B3, C3 scores). A label-free quantitative liquid chromatography-mass spectrometry based proteomic analysis, using data independent acquisition (DIA) on a Bruker timsTOF, was performed. A conserved core of 63 proteins was identified as enriched in tangles across all groups, mostly associated with "RNA binding" and "regulation of mRNA metabolic process", based on the Gene Ontology database. Group-specific signatures were also observed: 33 proteins were significantly enriched only in tangles collected from PART cases and were predominantly linked to "structural molecule activity", whereas Aβ-positive cases showed specific enrichment of "RNA binding" and "cytoplasmic translation" pathways-with intermediate AD cases displaying a transitional profile. Our findings are consistent with PART having distinct tangle proteomic features; however, the majority of its proteomic signature is in common with tangles within the AD continuum. By addressing how Aβ accumulation alters the tangle proteome, this study provides mechanistic insights into the expansion of Tau pathology, paving the way towards the identification of biomarkers and therapeutic strategies that would allow for stabilisation of Tau pathology in the elderly.
PMID: 42542447
ISSN: 1432-0533
CID: 6070502
Predictive acoustical processing in human cortical layers
In our dynamic environments, predictive processing is vital for auditory perception and its associated behaviors. Predictive coding formalizes inferential processes by implementing them as information exchange across cortical layers and areas. With laminar-specific blood oxygenation level-dependent imaging we measured responses to a cascading oddball paradigm, to ground predictive auditory processes on the mesoscopic human cortical architecture. Using a modeling approach, we derive putative changes in neural dynamics while accounting for draining effects. We show that the violations of predictions are potentially hierarchically organized and associated with responses in superficial layers of the planum polare and middle layers of the lateral temporal cortex. Moreover, we relate the updating of the brain's internal model to changes in deep layers. Our results support the role of temporal cortical architecture in the implementation of predictive coding and highlight the ability of laminar fMRI to investigate mesoscopic processes in a large extent of temporal areas.
PMID: 42191715
ISSN: 2041-1723
CID: 6070515
