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OBJECTIVE: Postictal psychiatric symptoms (PPS) are a relatively common but understudied phenomenon in epilepsy. The mechanisms by which seizures contribute to worsening in psychiatric symptoms are unclear. We aimed to identify PPS prospectively during and after admission to the epilepsy monitoring unit (EMU) in order to characterize the postictal physiologic changes leading to PPS. METHODS: We prospectively enrolled patients admitted to the EMU and administered repeat psychometric questionnaires during and after their hospital stay in order to assess for postictal exacerbations in four symptom complexes: anger/hostility, anxiety, depression, and paranoia. Electroclinical and electrographic seizures were identified from the EEG recordings, and seizure durations were measured. The severity of postictal slowing was calculated as the proportion of postictal theta/delta activity in the postictal EEG relative to the preictal EEG using the Hilbert transform. RESULTS: Among 33 participants, 8 demonstrated significant increases in at least one of the four symptoms (the PPS+ group) within three days following the first seizure. The most common PPS was anger/hostility, experienced by 7/8 participants with PPS. Among the 8 PPS+ participants, four experienced more than one PPS. As compared to those without PPS (the PPS- group), the PPS+ group demonstrated a greater degree of postictal EEG slowing at 10 min (p = 0.022) and 20 min (p = 0.05) following seizure termination. They also experienced significantly more seizures during the study period (p = 0.005). There was no difference in seizure duration between groups. SIGNIFICANCE: Postictal psychiatric symptoms including anger/hostility, anxiety, depression, and paranoia may be more common than recognized. In particular, postictal increases in anger and irritability may be particularly common. We provide physiological evidence of a biological mechanism as well as a demonstration of the use of quantitative electroencephalography toward a better understanding of postictal neurophysiology.
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Eletroencefalografia , Convulsões , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Convulsões/fisiopatologia , Convulsões/psicologia , Adulto Jovem , Estudos Prospectivos , Inquéritos e Questionários , Ansiedade/fisiopatologia , Epilepsia/fisiopatologia , Epilepsia/psicologia , Epilepsia/complicações , Transtornos Mentais/fisiopatologia , Escalas de Graduação Psiquiátrica , Transtornos Paranoides/fisiopatologia , Transtornos Paranoides/psicologia , Depressão/fisiopatologia , Depressão/etiologia , Psicometria , IdosoRESUMO
The effects of transcranial focused ultrasound (FUS) stimulation of the primary somatosensory cortex and its thalamic projection (i.e., ventral posterolateral nucleus) on the generation of electroencephalographic (EEG) responses were evaluated in healthy human volunteers. Stimulation of the unilateral somatosensory circuits corresponding to the non-dominant hand generated EEG evoked potentials across all participants; however, not all perceived stimulation-mediated tactile sensations of the hand. These FUS-evoked EEG potentials (FEP) were observed from both brain hemispheres and shared similarities with somatosensory evoked potentials (SSEP) from median nerve stimulation. Use of a 0.5 ms pulse duration (PD) sonication given at 70% duty cycle, compared to the use of 1 and 2 ms PD, elicited more distinctive FEP peak features from the hemisphere ipsilateral to sonication. Although several participants reported hearing tones associated with FUS stimulation, the observed FEP were not likely to be confounded by the auditory sensation based on a separate measurement of auditory evoked potentials (AEP) to tonal stimulation (mimicking the same repetition frequency as the FUS stimulation). Off-line changes in resting-state functional connectivity (FC) associated with thalamic stimulation revealed that the FUS stimulation enhanced connectivity in a network of sensorimotor and sensory integration areas, which lasted for at least more than an hour. Clinical neurological evaluations, EEG, and neuroanatomical MRI did not reveal any adverse or unintended effects of sonication, attesting its safety. These results suggest that FUS stimulation may induce long-term neuroplasticity in humans, indicating its neurotherapeutic potential for various neurological and neuropsychiatric conditions.
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Mãos , Sensação , Humanos , Sensação/fisiologia , Potenciais Evocados Auditivos , Potenciais Somatossensoriais Evocados/fisiologia , Sonicação/métodos , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiologiaRESUMO
OBJECTIVE: The association between postictal electroencephalogram (EEG) suppression (PES), autonomic dysfunction, and Sudden Unexpected Death in Epilepsy (SUDEP) remains poorly understood. We compared PES on simultaneous intracranial and scalp-EEG and evaluated the association of PES with postictal heart rate variability (HRV) and SUDEP outcome. METHODS: Convulsive seizures were analyzed in patients with drug-resistant epilepsy at 5 centers. Intracranial PES was quantified using the Hilbert transform. HRV was quantified using root mean square of successive differences of interbeat intervals, low-frequency to high-frequency power ratio, and RR-intervals. RESULTS: There were 64 seizures from 63 patients without SUDEP and 11 seizures from 6 SUDEP patients. PES occurred in 99% and 87% of seizures on intracranial-EEG and scalp-EEG, respectively. Mean PES duration in intracranial and scalp-EEG was similar. Intracranial PES was regional (<90% of channels) in 46% of seizures; scalp PES was generalized in all seizures. Generalized PES showed greater decrease in postictal parasympathetic activity than regional PES. PES duration and extent were similar between patients with and without SUDEP. CONCLUSIONS: Regional intracranial PES can be present despite scalp-EEG demonstrating generalized or no PES. Postictal autonomic dysfunction correlates with the extent of PES. SIGNIFICANCE: Intracranial-EEG demonstrates changes in autonomic regulatory networks not seen on scalp-EEG.
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Epilepsia , Disautonomias Primárias , Morte Súbita Inesperada na Epilepsia , Humanos , Eletrocorticografia , Eletroencefalografia , Convulsões/diagnóstico , Morte Súbita/etiologiaRESUMO
Cognitive control involves flexibly combining multiple sensory inputs with task-dependent goals during decision making. Several tasks involving conflicting sensory inputs and motor outputs have been proposed to examine cognitive control, including the Stroop, Flanker, and multi-source interference task. Because these tasks have been studied independently, it remains unclear whether the neural signatures of cognitive control reflect abstract control mechanisms or specific combinations of sensory and behavioral aspects of each task. To address these questions, we record invasive neurophysiological signals from 16 patients with pharmacologically intractable epilepsy and compare neural responses within and between tasks. Neural signals differ between incongruent and congruent conditions, showing strong modulation by conflicting task demands. These neural signals are mostly specific to each task, generalizing within a task but not across tasks. These results highlight the complex interplay between sensory inputs, motor outputs, and task demands underlying cognitive control processes.
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Cognição , Humanos , Cognição/fisiologia , Tempo de Reação/fisiologiaRESUMO
Deficits in cognitive control-that is, in the ability to withhold a default pre-potent response in favour of a more adaptive choice-are common in depression, anxiety, addiction and other mental disorders. Here we report proof-of-concept evidence that, in participants undergoing intracranial epilepsy monitoring, closed-loop direct stimulation of the internal capsule or striatum, especially the dorsal sites, enhances the participants' cognitive control during a conflict task. We also show that closed-loop stimulation upon the detection of lapses in cognitive control produced larger behavioural changes than open-loop stimulation, and that task performance for single trials can be directly decoded from the activity of a small number of electrodes via neural features that are compatible with existing closed-loop brain implants. Closed-loop enhancement of cognitive control might remediate underlying cognitive deficits and aid the treatment of severe mental disorders.
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Estimulação Encefálica Profunda , Humanos , Encéfalo , Próteses e Implantes , CogniçãoRESUMO
Low-intensity transcranial focused ultrasound (tFUS) offers new functional neuromodulation opportunities, enabling stimulation of cortical as well as deep brain areas with high spatial resolution. Brain stimulation of awake sheep, in the absence of the confounding effects of anesthesia on brain function, provides translational insight into potential human applications with safety information supplemented by histological analyses. We examined the effects of tFUS pulsing parameters, particularly regarding pulse durations (PDs), on stimulating the cortical motor area (M1) and its thalamic projection in unanesthetized, awake sheep (n = 8). A wearable tFUS headgear, custom-made for individual sheep, enabled experiments to be conducted without using anesthesia. FUS stimuli, each 200 ms long, were delivered to the M1 and the thalamus using three different PDs (0.5, 1, and 2 ms) with the pulse repetition frequency (PRF) adjusted to maintain a 70% duty cycle at a derated in situ spatial-peak temporal-average intensity (Ispta) of 3.6 W/cm2. Efferent electromyography (EMG) responses to stimulation were quantified from both hind limbs. Group-averaged EMG responses from each of the hind limbs across the experimental conditions revealed selective responses from the hind limb contralateral to sonication. The use of 0.5 and 1 ms PDs generated higher EMG signal amplitudes compared to those obtained using a 2 ms PD. Faster efferent response was also observed from thalamic stimulation than that from stimulating the M1. Post-sonication behavioral observation and histological assessment performed 24 h and 1 month after sonication were not indicative of any abnormalities. The results suggest the presence of pulsing scheme-dependent effects of tFUS on brain stimulation and attest its safety in awake large animals.
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Córtex Motor , Vigília , Humanos , Animais , Ovinos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Córtex Motor/fisiologia , Frequência CardíacaRESUMO
BACKGROUND: Electrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses. OBJECTIVE: To better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated. METHODS: We measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites). RESULTS: Increasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation. CONCLUSION: These results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.
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Córtex Cerebral , Substância Branca , Encéfalo , Córtex Cerebral/fisiologia , Estimulação Elétrica/métodos , Potenciais Evocados/fisiologia , HumanosRESUMO
The ability to distinguish between negative, positive and neutral valence is a key part of emotion perception. Emotional valence has conceptual meaning that supersedes any particular type of stimulus, although it is typically captured experimentally in association with particular tasks. We sought to identify neural encoding for task-invariant emotional valence. We evaluated whether high-gamma responses (HGRs) to visually displayed words conveying emotions could be used to decode emotional valence from HGRs to facial expressions. Intracranial electroencephalography was recorded from 14 individuals while they participated in two tasks, one involving reading words with positive, negative, and neutral valence, and the other involving viewing faces with positive, negative, and neutral facial expressions. Quadratic discriminant analysis was used to identify information in the HGR that differentiates the three emotion conditions. A classifier was trained on the emotional valence labels from one task and was cross-validated on data from the same task (within-task classifier) as well as the other task (between-task classifier). Emotional valence could be decoded in the left medial orbitofrontal cortex and middle temporal gyrus, both using within-task classifiers and between-task classifiers. These observations suggest the presence of task-independent emotional valence information in the signals from these regions.
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Emoções , Expressão Facial , Emoções/fisiologia , Humanos , Estimulação Luminosa , Leitura , Lobo TemporalRESUMO
Ultrasound is an important theragnostic modality in modern medicine. Technical advancement of both acoustic focusing and transcranial delivery have enabled administration of ultrasound waves to localized brain areas with few millimeters of spatial specificity and penetration depth sufficient to reach the thalamus. Transcranial focused ultrasound (tFUS) given at a low acoustic intensity has been shown to increase or suppress the excitability of region-specific brain areas. The neuromodulatory effects can outlast the sonication, suggesting the possibility of inducing neural plasticity needed for neurorehabilitation. Increasing numbers of studies have shown the efficacy and excellent safety profile of the technique, yet comparisons among the safety-related parameters have not been compiled. This review aims to provide safety information and perspectives of tFUS brain stimulation. First, the acoustic parameters most relevant to thermal/mechanical tissue damage are discussed along with regulated parameters for existing ultrasound therapies/diagnostic imaging. Subsequently, the parameters used in studies of large animals, non-human primates, and humans are surveyed and summarized in terms of the acoustic intensity and the mechanical index. The pulse-mode operation and the use of low ultrasound frequency for tFUS-mediated brain stimulation warrant the establishment of new safety guidelines/recommendations for the use of the technique among healthy volunteers, with additional cautionary requirements for its clinical translation.
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OBJECTIVE: Trauma-focused cognitive-behavioral therapy (CBT) is an important component of evidence-based treatment for posttraumatic stress disorder (PTSD), but the efficacy of treatment varies from individual to individual. It is hypothesized that some of this variability is derived from interindividual differences in the brain's intrinsic response to trauma-related stimuli and in activity of executive functional regions. The authors sought to characterize these differences using functional MRI (fMRI) in patients about to undergo CBT for PTSD. METHODS: Blood-oxygenation-level-dependent signal was measured in 12 individuals with PTSD related to sexual and/or physical trauma while they read words with positive, neutral, and negative content. Some negative words had PTSD-related themes, while others did not. It was hypothesized that PTSD-related words would evoke emotional processes likely to be engaged by the CBT process and would be most likely to activate brain circuitry important for CBT success. RESULTS: A group-level analysis showed that the rostral dorsomedial prefrontal cortex (rdmPFC) was activated to a greater degree in response to PTSD-related words compared with other word types. This activation was strongest among patients with the best CBT responses, particularly in the latter part of the task, when differences between individuals were most pronounced. CONCLUSIONS: The rdmPFC activation observed in this study may reflect the engagement of neural processes involved in introspection and self-reflection. CBT may be more effective for individuals with a greater ability to engage these processes.
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Encéfalo/patologia , Terapia Cognitivo-Comportamental , Córtex Pré-Frontal/patologia , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Targeted interrogation of brain networks through invasive brain stimulation has become an increasingly important research tool as well as therapeutic modality. The majority of work with this emerging capability has been focused on open-loop approaches. Closed-loop techniques, however, could improve neuromodulatory therapies and research investigations by optimizing stimulation approaches using neurally informed, personalized targets. Implementing closed-loop systems is challenging particularly with regard to applying consistent strategies considering inter-individual variability. In particular, during intracranial epilepsy monitoring, where much of this research is currently progressing, electrodes are implanted exclusively for clinical reasons. Thus, detection and stimulation sites must be participant- and task-specific. The system must run in parallel with clinical systems, integrate seamlessly with existing setups, and ensure safety features are in place. In other words, a robust, yet flexible platform is required to perform different tests with a single participant and to comply with clinical requirements. In order to investigate closed-loop stimulation for research and therapeutic use, we developed a Closed-Loop System for Electrical Stimulation (CLoSES) that computes neural features which are then used in a decision algorithm to trigger stimulation in near real-time. To summarize CLoSES, intracranial electroencephalography (iEEG) signals are acquired, band-pass filtered, and local and network features are continuously computed. If target features are detected (e.g. above a preset threshold for a certain duration), stimulation is triggered. Not only could the system trigger stimulation while detecting real-time neural features, but we incorporated a pipeline wherein we used an encoder/decoder model to estimate a hidden cognitive state from the neural features. CLoSES provides a flexible platform to implement a variety of closed-loop experimental paradigms in humans. CLoSES has been successfully used with twelve patients implanted with depth electrodes in the epilepsy monitoring unit. During cognitive tasks (N=5), stimulation in closed loop modified a cognitive hidden state on a trial by trial basis. Sleep spindle oscillations (N=6) and sharp transient epileptic activity (N=9) were detected in near real-time, and stimulation was applied during the event or at specified delays (N=3). In addition, we measured the capabilities of the CLoSES system. Total latency was related to the characteristics of the event being detected, with tens of milliseconds for epileptic activity and hundreds of milliseconds for spindle detection. Stepwise latency, the actual duration of each continuous step, was within the specified fixed-step duration and increased linearly with the number of channels and features. We anticipate that probing neural dynamics and interaction between brain states and stimulation responses with CLoSES will lead to novel insights into the mechanism of normal and pathological brain activity, the discovery and evaluation of potential electrographic biomarkers of neurological and psychiatric disorders, and the development and testing of patient-specific stimulation targets and control signals before implanting a therapeutic device.
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Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Processamento de Sinais Assistido por Computador , Encéfalo/fisiologia , Eletroencefalografia , Humanos , Neuroestimuladores Implantáveis , Neurônios/fisiologia , SoftwareRESUMO
OBJECTIVE: To examine the relationship between scalp EEG biomarkers of hyperexcitability in Alzheimer disease (AD) and to determine how these electric biomarkers relate to the clinical expression of seizures in AD. METHODS: In this cross-sectional study, we performed 24-hour ambulatory scalp EEGs on 43 cognitively normal elderly healthy controls (HC), 41 participants with early-stage AD with no history or risk factors for epilepsy (AD-NoEp), and 15 participants with early-stage AD with late-onset epilepsy related to AD (AD-Ep). Two epileptologists blinded to diagnosis visually reviewed all EEGs and annotated all potential epileptiform abnormalities. A panel of 9 epileptologists blinded to diagnosis was then surveyed to generate a consensus interpretation of epileptiform abnormalities in each EEG. RESULTS: Epileptiform abnormalities were seen in 53% of AD-Ep, 22% of AD-NoEp, and 4.7% of HC. Specific features of epileptiform discharges, including high frequency, robust morphology, right temporal location, and occurrence during wakefulness and REM, were associated with clinical seizures in AD. Multiple EEG biomarkers concordantly demonstrated a pattern of left temporal lobe hyperexcitability in early stages of AD, whereas clinical seizures in AD were often associated with bitemporal hyperexcitability. Frequent small sharp spikes were specifically associated with epileptiform EEGs and thus identified as a potential biomarker of hyperexcitability in AD. CONCLUSION: Epileptiform abnormalities are common in AD but not all equivalent. Specific features of epileptiform discharges are associated with clinical seizures in AD. Given the difficulty recognizing clinical seizures in AD, these EEG features could provide guidance on which patients with AD are at high risk for clinical seizures.
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Doença de Alzheimer/epidemiologia , Doença de Alzheimer/fisiopatologia , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Convulsões/epidemiologia , Convulsões/fisiopatologia , Idoso , Biomarcadores , Estudos Transversais , Eletroencefalografia , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
Lateralized periodic discharges (LPDs) are a rare type of epileptiform activity. The authors of this brief report describe the association of LPDs with acute catastrophic depression in a previously healthy patient who had a series of neurobiological insults caused by a stroke and its treatment that led to the development of significant psychopathology. Through this case of new and debilitating depression that followed a recent stroke, subsequent development of LPDs, and treatment with levetiracetam, the authors highlight the complex interplay of structural, electrophysiologic, and pharmacologic factors in the pathogenesis of poststroke depression and the crucial role of having a broad biopsychosocial assessment for optimal diagnosis and management.
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Anticonvulsivantes/efeitos adversos , Transtorno Depressivo Maior/induzido quimicamente , Transtorno Depressivo Maior/diagnóstico , Epilepsia/tratamento farmacológico , Acidente Vascular Cerebral/diagnóstico , Idoso , Transtorno Depressivo Maior/fisiopatologia , Eletroencefalografia , Feminino , HumanosRESUMO
BACKGROUND: The biological mechanisms by which efavirenz (EFV) causes central nervous system (CNS) effects are unclear. The objective of this pilot study was to elucidate the mechanisms underlying these CNS effects by correlating well-described neuropsychological (NP) changes with neurometabolites and immunologic markers following switch off EFV. SETTING: Two single-arm parallel switch studies among HIV-infected adults in Boston, USA, from 2015 to 2017. METHODS: Twenty asymptomatic HIV-infected adults on EFV-containing regimens were switched to an integrase strand transfer inhibitor-based regimen for 8 weeks. NP assessments were conducted before and after switch and correlated with neurometabolite changes measured using magnetic resonance spectroscopy and immunological markers. All pre-EFV and post-EFV measures were evaluated using matched-paired analyses. RESULTS: NP testing demonstrated improvement in the domains of mood, cognition, and sleep off EFV. Magnetic resonance spectroscopy revealed decreases in the neurometabolite glutathione level (P = 0.03), a marker of oxidative stress after switch. Inhibitory neuronal activity as reflected by gamma-amino butyric acid levels increased (P = 0.03), whereas excitatory neurotransmitters glutamine + glutamate (Glx) and aspartate decreased (P = 0.04, 0.001). Switching off EFV was also associated with changes in inflammatory markers; plasma markers sCD14 (P = 0.008) decreased, whereas I-FABP and TNFRI levels increased (P = 0.05, 0.03). Cellular markers CD4 and CD8 HLA-DR-/CD38 subsets both increased (P = 0.05, 0.02). CONCLUSIONS: Even asymptomatic participants showed improvements in NP parameters when switched off EFV. These improvements were associated with decreased CNS oxidative stress and excitatory neuronal activity. Changes in immune activation biomarkers suggested overall decreased inflammation. EFV may exert CNS effects through oxidative and inflammatory pathways, providing insight into possible mechanisms of EFV neurotoxicity.
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Fármacos Anti-HIV/farmacologia , Benzoxazinas/farmacologia , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Inibidores de Integrase de HIV/farmacologia , Adulto , Alcinos , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Biomarcadores , Boston , Ciclopropanos , Feminino , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Glutationa/metabolismo , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuropsicologia , Estresse Oxidativo , Projetos Piloto , Receptores Tipo I de Fatores de Necrose Tumoral , Ácido gama-Aminobutírico/metabolismoRESUMO
OBJECTIVES: In patients who do not achieve seizure freedom on low-dose first-line monotherapy antiepileptic drug (AED), the current practice is to increase the AED to higher doses. For patients who fail low dose levetiracetam (LEV), a reasonable alternative to increasing dosage may be the addition of a low-dose adjunctive AED. METHODS: In this open-label, pilot trial, low-dose lacosamide (200 mg/d) was added to adult patients with breakthrough seizures on low-dose monotherapy LEV (≤1500 mg/d). Comparison was made with a retrospective historical control cohort in whom the dose of LEV was raised after a breakthrough seizure. The main objectives were to determine efficacy effect size and tolerability. RESULTS: Twenty patients were recruited in the prospective polytherapy cohort, of whom 19 received at least 1 dose of adjunctive AED; the monotherapy cohort consisted of 36 patients. Six-month seizure freedom was achieved in 9 of 19 patients in the polytherapy cohort and in 15 of 36 patients in the monotherapy cohort (hazard ratio for seizure occurrence for polytherapy relative to monotherapy was 0.76; 95% confidence interval, 0.35-1.65; P = 0.49). There were treatment emergent adverse effects in 11 patients (61.1%) in the polytherapy cohort and 26 (72.2%) in the monotherapy cohort. Greater number of patients in the monotherapy cohort experienced irritability/depression (33.3% vs 5.6%, P < 0.05). CONCLUSIONS: Low-dose polytherapy with LEV and lacosamide was well tolerated and efficacious. Further studies are needed to determine whether this is a reasonable alternative to high-dose LEV monotherapy.
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Acetamidas/uso terapêutico , Anticonvulsivantes/uso terapêutico , Piracetam/análogos & derivados , Convulsões/tratamento farmacológico , Adulto , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Lacosamida , Levetiracetam , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Piracetam/uso terapêuticoRESUMO
In this study, healthy volunteers were scanned using functional magnetic resonance imaging (fMRI) to investigate the neural systems involved in processing the threatening content conveyed via visually presented "threat words." The neural responses elicited by these words were compared to those elicited by matched neutral control words. The results demonstrate that linguistic threat, when presented in written form, can selectively engage areas of lateral temporal and inferior frontal cortex, distinct from the core language areas implicated in aphasia. Additionally, linguistic threat modulates neural activity in visceral/emotional systems (amygdala, parahippocampal gyrus and periaqueductal gray), and at earlier stages of the visual-linguistic processing stream involved in visual word form representations (ventral occipitotemporal cortex). We propose a model whereby limbic activation modulates activity at multiple nodes along the visual-linguistic-semantic processing stream, including a perisylvian "semantic access network" involved in decoding word meaning, suggesting a dynamic interplay between feedforward and feedback processes.
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Tonsila do Cerebelo/fisiologia , Medo , Neocórtex/fisiologia , Semântica , Adolescente , Adulto , Afasia/fisiopatologia , Mapeamento Encefálico , Feminino , Lobo Frontal/fisiologia , Voluntários Saudáveis , Humanos , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Giro Para-Hipocampal/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Percepção Visual/fisiologia , Adulto JovemRESUMO
Persecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social "real world" and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal-parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia.
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Delusões/metabolismo , Medo/fisiologia , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/metabolismo , Desempenho Psicomotor/fisiologia , Esquizofrenia/metabolismo , Adulto , Estudos de Coortes , Delusões/diagnóstico , Delusões/psicologia , Emoções/fisiologia , Medo/psicologia , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto JovemRESUMO
Psychogenic nonepileptic seizures (PNES) can present emergently and are often mistaken for epileptic seizures. PNES emergencies have not been well studied, and yet there are associated serious morbidities, particularly when patients are seen in an emergency setting and are misdiagnosed. PNES may be prolonged, mimicking status epilepticus, a condition we refer to as nonepileptic psychogenic status (NEPS), and patients may receive aggressive and unnecessary medical treatments that can lead to serious iatrogenic complications, including death. NEPS is also associated with an increased risk of self-harm, including suicide attempts, and may indicate a serious comorbid psychiatric illness. In addition to iatrogenic complications of PNES, accidents and injuries are an underrecognized source of morbidity. PNES may also present during medical procedures, which may not only interfere with their completion, but may alarm practitioners who, fearing liability, may initiate further medical evaluations and treatments. When PNES occur during pregnancy, patients may be misdiagnosed with eclampsia and their offspring delivered prematurely. They also risk being placed on medications that are harmful to the fetus. Increased awareness of PNES is necessary to prevent iatrogenic harm and to identify underlying psychiatric illnesses that carry their own risks. As yet, data available to guide treatment are scant, and further study is needed.
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Transtorno Conversivo/diagnóstico , Emergências , Epilepsia/diagnóstico , Transtornos Somatoformes/diagnóstico , Adulto , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Comorbidade , Transtorno Conversivo/psicologia , Transtorno Conversivo/terapia , Diagnóstico Diferencial , Eletroencefalografia/efeitos dos fármacos , Serviço Hospitalar de Emergência , Epilepsia/psicologia , Epilepsia/reabilitação , Epilepsia/terapia , Feminino , Humanos , Gravidez , Transtornos Somatoformes/psicologia , Transtornos Somatoformes/terapia , Procedimentos DesnecessáriosAssuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Piracetam/análogos & derivados , Complicações na Gravidez/induzido quimicamente , Psicoses Induzidas por Substâncias/fisiopatologia , Adulto , Anticonvulsivantes/administração & dosagem , Comorbidade , Epilepsia/epidemiologia , Feminino , Humanos , Levetiracetam , Piracetam/administração & dosagem , Piracetam/efeitos adversos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Psicoses Induzidas por Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
INTRODUCTION: Occipital lobe seizures are a recognized manifestation of diabetic nonketotic hyperglycemia, though not as common as focal motor seizures. Occipital lobe white matter T2 hypointensity may suggest this diagnosis. METHODS: We present a case of a 66-year-old man with hyperglycemia-related occipital lobe seizures who presented with confusion, intermittent visual hallucinations, and homonymous hemianopia. RESULTS: Magnetic resonance imaging showed subcortical T2 hypointensity within the left occipital lobe with adjacent leptomeningeal enhancement. These findings were transient with disappearance in a follow-up MRI. The EEG captured frequent seizures originating in the left occipital region. HbA1c level was 13.4% on presentation, and finger stick blood glucose level was 400 mg/dl. CONCLUSION: Hyperglycemia should be considered in the etiology of differential diagnosis of patients with visual abnormalities suspicious for seizures, especially when the MRI shows focal subcortical T2 hypointensity with or without leptomeningeal enhancement.