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1.
Drug Alcohol Depend ; 259: 111288, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648721

RESUMO

BACKGROUND: Cocaine consumption is associated with reduced attentional event-related potentials (ERPs), namely P3a and P3b, indicating bottom-up and top-down deficits respectively. At cognitive level, these impairments are larger for faster routes of administration (e.g., smoked cocaine [SC]) than slower routes (e.g., insufflated cocaine [IC]). Here we assess these ERPs considering the route of cocaine administration. We hypothesized that SC dependent (SCD) would exhibit reduced amplitude of the P3a, while both SCD and IC dependent (ICD) would show reduced amplitude of the P3b. METHODS: We examined 25 SCD, 22 ICD matched by poly-consumption profiles, and 25 controls matched by demographic variables. We combined EEG data from the Global-Local task with behavioral data from attentional cognitive tasks. RESULTS: At the behavioral level, SCD exhibited attentional deficits in both bottom-up and top-down processes, while ICD only showed a tendency for top-down deficits. The amplitude of P3a and P3b was lower in Users groups. We observed subtle route-based differences, with larger differences in the P3a for SCD and in the P3b for ICD. Neurophysiological and behavioral data converged, with the P3a associated to bottom-up performance and P3b to top-down. CONCLUSIONS: Different routes of administration lead to distinct attentional neurocognitive profiles. Specifically, SCD showed greater attentional impairment, mainly at bottom-up/P3a, while ICD showed a trend of top-down/P3b deficits. These findings emphasize the crucial role of considering the route of administration in both clinical and research settings and support the use of attentional ERPs as valid measures for assessing attentional deficits in substance Dependence.


Assuntos
Atenção , Transtornos Relacionados ao Uso de Cocaína , Eletroencefalografia , Potenciais Evocados , Testes Neuropsicológicos , Humanos , Masculino , Adulto , Feminino , Atenção/efeitos dos fármacos , Atenção/fisiologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Potenciais Evocados/fisiologia , Potenciais Evocados/efeitos dos fármacos , Cocaína/administração & dosagem , Potenciais Evocados P300/fisiologia , Potenciais Evocados P300/efeitos dos fármacos , Adulto Jovem , Pessoa de Meia-Idade
2.
J Psychopharmacol ; 35(12): 1488-1495, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34330170

RESUMO

BACKGROUND: Cognitive decline after oral administration of sedatives, such as benzodiazepines, is a serious side effect. Suvorexant, an orexin receptor antagonist, has a favorable tolerability and a limited side-effect profile. AIM: The purpose of this study was to estimate the cognitive decline 1 day after oral medication with lormetazepam, a benzodiazepine, and suvorexant by comparing mismatch negativity (MMN) and P300 reflecting auditory discrimination function. METHODS: Sixty healthy subjects (42 males) were randomly assigned to three groups receiving suvorexant 20 mg, lormetazepam 2 mg, or placebo in this double-blind, randomized control study. Event-related potential recordings during an auditory oddball task and a digit symbol substitution test (DSST) were performed 1 day after oral administration. RESULTS: MMN, on the day after oral administration, was significantly attenuated in the lormetazepam group compared with the other two groups, but there was no difference between the suvorexant and placebo groups. No significant difference was found in P300 amplitudes and DSST scores among the three groups. CONCLUSION: These findings suggest that suvorexant, unlike benzodiazepine, is not associated with cognitive deficits, as revealed by MMN but not P300. This study shows a neurophysiological difference in the effects of suvorexant and benzodiazepine on cognitive function.


Assuntos
Percepção Auditiva/efeitos dos fármacos , Azepinas/farmacologia , Benzodiazepinas/farmacologia , Disfunção Cognitiva/induzido quimicamente , Discriminação Psicológica/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Lorazepam/análogos & derivados , Antagonistas dos Receptores de Orexina/farmacologia , Triazóis/farmacologia , Adulto , Azepinas/administração & dosagem , Azepinas/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Eletroencefalografia , Potenciais Evocados P300/efeitos dos fármacos , Feminino , Humanos , Lorazepam/administração & dosagem , Lorazepam/efeitos adversos , Lorazepam/farmacologia , Masculino , Antagonistas dos Receptores de Orexina/administração & dosagem , Antagonistas dos Receptores de Orexina/efeitos adversos , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Adulto Jovem
3.
Clin Neurophysiol ; 131(12): 2841-2850, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33137574

RESUMO

OBJECTIVE: Parkinson's Disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. Cognitive impairments have been reported using the event-related potential (ERP) technique. Patients show reduced novelty P3 (nP3) amplitudes in oddball experiments, a response to infrequent, surprising stimuli, linked to the orienting response of the brain. The nP3 is thought to depend on dopaminergic neuronal pathways though the effect of dopaminergic medication in PD has not yet been investigated. METHODS: Twenty-two patients with PD were examined "on" and "off" their regular dopaminergic medication in a novelty 3-stimulus-oddball task. Thirty-four healthy controls were also examined over two sessions, but received no medication. P3 amplitudes were compared throughout experimental conditions. RESULTS: All participants showed sizeable novelty difference ERP effects, i.e. ndP3 amplitudes, during both testing sessions. An interaction of diagnosis, medication and testing order was also found, indicating that dopaminergic medication modulated ndP3 in patients with PD across the two testing sessions: We observed enhanced ndP3 amplitudes from PD patients who were off medication on the second testing session. CONCLUSION: Patients with PD 'off' medication showed ERP evidence for repetition-related enhancement of novelty responses. Dopamine depletion in neuronal pathways that are affected by mid-stage PD possibly accounts for this modulation of novelty processing. SIGNIFICANCE: The data in this study potentially suggest that repetition effects on novelty processing in patients with PD are enhanced by dopaminergic depletion.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Potenciais Evocados P300/fisiologia , Doença de Parkinson/fisiopatologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Estimulação Acústica/métodos , Idoso , Dopaminérgicos/farmacologia , Dopaminérgicos/uso terapêutico , Neurônios Dopaminérgicos/efeitos dos fármacos , Eletroencefalografia/métodos , Potenciais Evocados P300/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Desempenho Psicomotor/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos
4.
J Neurovirol ; 26(6): 870-879, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32910431

RESUMO

Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the criteria for a minimal hepatic encephalopathy. Their liver function was compensated. We then disentangled potential cognitive changes associated with a sustained virologic response at 12 weeks (SVR-12), following treatment with direct antiviral agents (DAAs). We studied 23 selected HCV patients with a battery of standard neuropsychological tests, and with recordings of the P300 wave, a cerebral potential of "cognitive" significance. There was a baseline evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant (p < 0.05) cognitive impairment in the HCV group, which involved episodic and working memory, attention, visuospatial and verbal abilities, executive functions, and logic reasoning. The P300 latency was significantly (p < 0.05) delayed in the group. At T1, we observed some significant (p < 0.05) HCV recovery in given test domains, e.g., memory, executive functions, and reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV patients exhibited subtle cognitive defects, somehow independent of their liver condition, possibly linked to direct or indirect brain involvement by the virus. These defects partly recovered following the SVR-12, as achieved through DAAs. The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs can have a role in the early preservation of cognition in HCVs.


Assuntos
Antivirais/uso terapêutico , Encéfalo/virologia , Disfunção Cognitiva/diagnóstico , Hepatite C Crônica/diagnóstico , Fígado/virologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Idoso , Atenção/efeitos dos fármacos , Atenção/fisiologia , Encéfalo/efeitos dos fármacos , Estudos de Casos e Controles , Cognição/efeitos dos fármacos , Cognição/fisiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/virologia , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados P300/fisiologia , Função Executiva/efeitos dos fármacos , Função Executiva/fisiologia , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/psicologia , Hepatite C Crônica/virologia , Humanos , Fígado/efeitos dos fármacos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Hepatopatia Gordurosa não Alcoólica/psicologia , Hepatopatia Gordurosa não Alcoólica/virologia , Resposta Viral Sustentada
5.
Hum Brain Mapp ; 41(17): 4982-4996, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32820851

RESUMO

The concept of self and self-referential processing has a growing explanatory value in psychiatry and neuroscience, referring to the cognitive organization and perceptual differentiation of self-stimuli in health and disease. Conditions in which selfhood loses its natural coherence offer a unique opportunity for elucidating the mechanisms underlying self-disturbances. We assessed the psychoactive effects of psilocybin (230 µg/kg p.o.), a preferential 5-HT1A/2A agonist known to induce shifts in self-perception. Our placebo-controlled, double-blind, within-subject crossover experiment (n = 17) implemented a verbal self-monitoring task involving vocalizations and participant identification of real-time auditory source- (self/other) and pitch-modulating feedback. Subjective experience and task performance were analyzed, with time-point-by-time-point assumption-free multivariate randomization statistics applied to the spatiotemporal dynamics of event-related potentials. Psilocybin-modulated self-experience, interacted with source to affect task accuracy, and altered the late phase of self-stimuli encoding by abolishing the distinctiveness of self- and other-related electric field configurations during the P300 timeframe. This last effect was driven by current source density changes within the supragenual anterior cingulate and right insular cortex. The extent of the P300 effect was associated with the intensity of psilocybin-induced feelings of unity and changed meaning of percepts. Modulations of late encoding and their underlying neural generators in self-referential processing networks via 5-HT signaling may be key for understanding self-disorders. This mechanism may reflect a neural instantiation of altered self-other and relational meaning processing in a stimulus-locked time domain. The study elucidates the neuropharmacological foundation of subjectivity, with implications for therapy, underscoring the concept of connectedness.


Assuntos
Percepção Auditiva/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Giro do Cíngulo/efeitos dos fármacos , Córtex Insular/efeitos dos fármacos , Psilocibina/farmacologia , Autoimagem , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Percepção Social , Adulto , Estudos Cross-Over , Método Duplo-Cego , Eletroencefalografia , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Masculino , Percepção da Altura Sonora/efeitos dos fármacos , Psilocibina/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Agonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Adulto Jovem
6.
Int J Psychophysiol ; 151: 49-58, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32087182

RESUMO

Rinsing the mouth with a carbohydrate solution has been suggested as a means to enhance aspects of both physical and cognitive performance. However, evidence in support of these assertions is relatively weak. The purpose of this study was to investigate the effects of a carbohydrate mouth rinse solution on motor speed, inhibition, and sustained attention as indexed by both behavioral and neuroelectric measures. Using a double-blind, placebo-controlled, within-subjects crossover design, 50 college-aged young adults performed a battery of cognitive tasks both before and after rinsing their mouth for 10 s with 20 mL of either a carbohydrate mouth rinse solution or a sensory-matched placebo control solution. A simple tapping task was used as a measure of motor speed, a modified Eriksen flanker task was used to index inhibition, and a rapid visual information processing task was used as a measure of sustained attention. Participants demonstrated longer reaction times in the Flanker task after rinsing their mouths with the carbohydrate mouth rinse, relative to pretest. No differences in reaction time were observed for the placebo control condition. P3 latency in the Flanker task as an index of attentional processing speed was shorter at posttest than at pretest in the placebo control - but not the carbohydrate mouth rinse - condition. These results suggest that despite claims of cognitive enhancement, carbohydrate mouth rinses do not appear to alter motor speed, inhibition, or sustained attention as compared to a placebo control in non-physically-fatigued college-aged adults.


Assuntos
Atenção/efeitos dos fármacos , Carboidratos/farmacologia , Potenciais Evocados/efeitos dos fármacos , Inibição Psicológica , Antissépticos Bucais/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , Adulto , Método Duplo-Cego , Eletroencefalografia , Potenciais Evocados P300/efeitos dos fármacos , Feminino , Humanos , Masculino , Adulto Jovem
7.
Cancer Chemother Pharmacol ; 85(1): 61-67, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31745592

RESUMO

PURPOSE: Chemotherapy-related cognitive impairments in breast cancer patients were usually reported through cognitive questionnaires or scales which may be subjective and insensitive. This study is to assess the effect of chemotherapy on cognitive function in breast cancer patients stratified by age using objective electrophysiological measure, the P300 component of event-related potentials (ERPs) with a large sample size. METHODS: Totally, 529 primary breast cancer patients, including 178 cases at initial diagnosis stage and before chemotherapy (Group1), 167 cases during chemotherapy (Group2), and 184 cases post chemotherapy and during follow-up period (Group3), were examined with ERPs (P300 component) to assess the effect of chemotherapy on their cognitive function. RESULTS: There were significant differences of P300 latency in Group2 (364.74 ± 15.73 ms) and Group3 (364.02 ± 17.12 ms, mean follow-up period of 2.42 years) compared with Group1 (355.13 ± 19.47 ms, P < 0.001), respectively. With further age stratification: in patients of < 50 years, P300 latency was significantly prolonged in Group2 and Group3 compared with Group1 (P < 0.001), respectively; in patients of 50-59 years, P300 latency was significantly prolonged in Group2 compared with Group1 (P < 0.05), but without difference in Group1 and Group3 (P>0.05); In patients of ≥ 60 years, there were no differences of P300 latency among three the groups (P>0.05). CONCLUSIONS: It is first suggested by our objective detection data that the side effect of chemotherapy on cognitive functions in breast cancer patients may decrease with age. Electrophysiological cognitive impairments mainly occur in younger breast cancer patients undergoing chemotherapy and would last for years after chemotherapy, which highlights the importance of early intervention for those patients, especially in younger patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Sobreviventes de Câncer/estatística & dados numéricos , Disfunção Cognitiva/patologia , Potenciais Evocados P300/efeitos dos fármacos , Neoplasias da Mama/patologia , Disfunção Cognitiva/induzido quimicamente , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
8.
Sci Rep ; 9(1): 5967, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979930

RESUMO

This study aimed to explore the effects of radiochemotherapy on the neurocognitive function of patients with high-grade gliomas (HGG). The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), event-related potential P300 (ERP-P300), and specific MRI parameters were compared, and the associations between specific MRI parameters and different doses of radiation were determined for before and up to 12 months after radiotherapy. There were no significant differences in MMSE, MoCA, or ERP-P300 before and after radiotherapy. Compared with pre-radiochemotherapy, fractional anisotropy (FA) in the contralateral hippocampus decreased at 6 and 9 months after radiotherapy. FA in the ipsilateral hippocampus before radiochemotherapy decreased compared with 6 months after radiotherapy. Compared to the end of radiotherapy, as well as 3- and 6-months post-radiotherapy, the regional cerebral blood volume (rCBV) in the genu of the corpus was significantly lower at 12 months post-radiotherapy. Some MRI parameters in different regions of the brain were negatively correlated with the mean and maximum dose. There was no significant effect of radiochemotherapy on the neurocognitive functioning of patients with HGGs found before radiochemotherapy until 12 months after radiotherapy. The radiation-induced FA decrease in the bilateral hippocampus preceded cognitive dysfunction, and DTI of the hippocampus may provide a useful biomarker for predicting radiation-induced neurocognitive impairment in patients with HGGs.


Assuntos
Neoplasias Encefálicas/terapia , Encéfalo/diagnóstico por imagem , Quimiorradioterapia , Cognição , Glioma/terapia , Adolescente , Adulto , Idoso , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/psicologia , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/efeitos da radiação , Cognição/efeitos dos fármacos , Cognição/efeitos da radiação , Imagem de Tensor de Difusão/métodos , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados P300/efeitos da radiação , Feminino , Glioma/diagnóstico por imagem , Glioma/fisiopatologia , Glioma/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/efeitos da radiação , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Neuropsychopharmacology ; 44(6): 1062-1067, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30797222

RESUMO

Schizophrenia is a complex brain disease involving several neurotransmitter systems, including aberrant noradrenergic activity, which might underlie cognitive deficits. Clonidine is an α2A-agonist and previous research has demonstrated that single dosages of clonidine normalize sensori(motor) gating in schizophrenia. Currently, we investigated whether clonidine is able to normalize mismatch negativity (MMN) and P3a amplitude deficits in this same group of patients. This is important, since reports have shown that MMN amplitude is associated with cognitive functioning and daily life functions in schizophrenia. Twenty chronically ill, male schizophrenia patients were tested with the MMN paradigm from the Copenhagen Psychophysiological Test Battery (CPTB) on 5 occasions, separated by a week. Patients received randomized, yet balanced, either a placebo or a single dose (25, 50, 75 or 150 µg) of clonidine (each dose only once) on top of their usual medication on each occasion. Patients were matched on age and gender with 20 healthy controls (HC) who did not receive any treatment. We found decreased MMN and P3a amplitudes in our patients compared to HC. Although clonidine did neither significantly increase MMN nor P3a amplitude in our patients, it did increase certain levels of MMN and P3a amplitude such that these were not significantly different anymore from the healthy controls. Together with our previous reports indicating normalized sensori(motor) gating in the same patients following administration of clonidine, our results could be of potential high clinical relevance in treating schizophrenia. Future studies should focus on longer trial periods to investigate if clonidine also improves cognitive functioning in schizophrenia.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Percepção Auditiva/fisiologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Clonidina/farmacologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Esquizofrenia/fisiopatologia , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Adulto , Antipsicóticos/uso terapêutico , Clonidina/administração & dosagem , Eletroencefalografia , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados P300/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico
10.
Neurosci Lett ; 698: 121-125, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30639398

RESUMO

Despite the widespread use in clinical practice, little research has been done on mechanisms of sedation. In particular, little is known about the changes in the information processing of external stimuli in sedation. The aim of this study was to investigate the changes of event-related potential (ERP) in auditory passive oddball paradigm when the sedation was induced by sevoflurane inhalation. Electroencephalography (EEG) measurements were obtained for each subject using 32-channel EEG recording devices. Sevoflurane was administered at an initial concentration of 0.8 vol% to induce sedative state. Auditory stimulation based on the passive oddball paradigm was delivered to the subject via an earphone before and after sevoflurane administration. After ERP was extracted from the measured EEG, the topographic distribution of ERP, the temporal changes of ERP in each channel, and the statistical difference in ERP between awake and sedation were analyzed. In the awake state, P300 was observed at 320-360 ms latency, and P300 was concentrated in the frontal and central area. P300 amplitude was significantly decreased in sedation compared to awake. Sevoflurane-induced sedation caused a decrease in P300 amplitude. This result may reflect the weakening of the cognitive function governing attentional process and stimuli discrimination during sedation.


Assuntos
Estimulação Acústica , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados/efeitos dos fármacos , Sevoflurano/farmacologia , Estimulação Acústica/métodos , Adulto , Atenção/efeitos dos fármacos , Cognição/efeitos dos fármacos , Eletroencefalografia/métodos , Potenciais Evocados P300/fisiologia , Potenciais Evocados/fisiologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia
11.
Hum Psychopharmacol ; 34(1): e2684, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30488987

RESUMO

OBJECTIVE: The effects of GABA modulating drugs and nicotine, the prototypical nicotinic cholinergic agonist, on attention have been investigated using subcomponents of the P300 event-related potentials (ERP), which index involuntary (P3a) and voluntary attention (P3b). However, investigations into how such pharmacologic effects interact with genetic features in the GABA system remain unclear. This study examined the moderating effects of a single nucleotide polymorphism (rs7557793) in the glutamic acid decarboxylase 67 (GAD1) gene, which is implicated in the conversion of glutamate to GABA, on P300-indices of auditory attentional processing; the influence of nicotine administration was also assessed. METHODS: The effects of GAD1 genotype (TT/CC/CT) were examined on the P3a/b in response to an auditory selective attention task in healthy, nonsmoking male volunteers (N = 126; 18-40 years). Participants responded to rare target stimuli (P3b-eliciting) and ignored frequent nontarget stimuli as well as rare distractor stimuli (P3a-eliciting). In a subsample (N = 59), P3a/b profiles to acute nicotine (vs. placebo) administration were examined as a function of GAD1 genotype. As a secondary aim, earlier sensory processes were assessed with N200 ERP subcomponents elicited by novel (N2a) and target (N2b) auditory stimuli. RESULTS: GAD1 allelic variation moderated early sensory processes, enhancing N2a amplitudes in CT versus TT carriers. Further, TT homozygotes exhibited larger P3b amplitudes than CC homozygotes in the placebo versus nicotine condition. Regardless of genotype, nicotine versus placebo moderated the N200 ERP. CONCLUSION: These findings expand our knowledge regarding the attentional effects of GAD1 genetic variants in relation to nicotine.


Assuntos
Atenção/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Glutamato Descarboxilase/genética , Nicotina/farmacologia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Potenciais Evocados P300/fisiologia , Genótipo , Voluntários Saudáveis , Humanos , Masculino , Adulto Jovem , Ácido gama-Aminobutírico/fisiologia
12.
Neural Plast ; 2018: 4270263, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30410536

RESUMO

Event-related potentials (ERPs) and oscillations (EROs) provide powerful tools for studying the brain's synaptic function underlying information processing. The P300 component of ERPs indexing attention and working memory shows abnormal amplitude and latency in neurological and psychiatric diseases that are sensitive to pharmacological agents. In the active auditory oddball discriminant paradigm, behavior and auditory-evoked potentials (AEPs) were simultaneously recorded in awake rats to investigate whether P300-like potentials generated in rats responding to rare target oddball tones are sensitive to subcutaneous modulation of the cholinergic tone by donepezil (1 mg/kg) and scopolamine (0.64 mg/kg). After operant training, rats consistently discriminate rare target auditory stimuli from frequent irrelevant nontarget auditory stimuli by a higher level of correct lever presses (i.e., accuracy) in target trials associated with a food reward. Donepezil attenuated the disruptive effect of scopolamine on the level of accuracy and premature responses in target trials. Larger P300-like peaks with early and late components were revealed in correct rare target stimuli trials as compared to frequent tones. Donepezil enhanced the peak amplitude of the P300-like component to target stimuli and evoked slow theta and gamma oscillations, whereas scopolamine altered the amplitude of the P300-like component and EROs to target stimuli. Pretreatment with donepezil attenuated effects of scopolamine on the peak amplitude of the P300-like component and on EROs. This study provides evidence that AEP P300-like responses can be elicited by rats engaged in attentive and memory processing of target stimuli and outline the relevance of the cholinergic system in stimulus discrimination processing. The findings highlight the sensitivity of this translational index for investigating brain circuits and/or novel pharmacological agents, which modulate cholinergic transmission associated with increased allocation of attentional resources.


Assuntos
Percepção Auditiva/fisiologia , Colinérgicos/farmacologia , Neurônios Colinérgicos/fisiologia , Potenciais Evocados P300/fisiologia , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica/métodos , Animais , Percepção Auditiva/efeitos dos fármacos , Antagonistas Colinérgicos/farmacologia , Neurônios Colinérgicos/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Aprendizagem por Discriminação/efeitos dos fármacos , Aprendizagem por Discriminação/fisiologia , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Masculino , Ratos , Ratos Long-Evans
13.
Int J Psychophysiol ; 134: 30-43, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30253197

RESUMO

In this study we present the test-retest reliability of pre-intervention EEG/ERP (electroencephalogram/event-related potentials) data across four recording intervals separated by a washout period (18-22 days). POz-recording-reference EEG/ERP (28 sites, average reference) were recorded from thirty-two healthy male participants. Participants were randomly allocated into different intervention sequences, each with four intervention regimens: 10 mg vortioxetine, 20 mg vortioxetine, 15 mg escitalopram and Placebo. We report classical EEG spectra: δ (1-4 Hz), θ (4-8 Hz), α (8-12 Hz), ß (12-30 Hz), γ1 (30-45 Hz) and γ2 (45-80 Hz) of resting state and vigilance-controlled, and of auditory steady state response, as well as ERP components N100, P200 and P300 in auditory oddball task and error related negativity (ERN) and error positivity (Pe) in hybrid flanker task. Reliability was quantified using intra-class correlation coefficient (ICC). We found that θ, α and ß of continuous EEG were highly reliable (ICCs ≥ 0.84). Evoked power of other tasks demonstrated larger variability and less reliability compared to the absolute power of continuous EEG. Furthermore, reliabilities of ERP measures were lower compared to those of the EEG spectra. We saw fair to excellent reliability of the amplitude of the components such as Pe (0.60-0.82) and P300 (0.55-0.80). Moreover, blood tests confirmed that there was no measurable drug carry-over from the previous intervention. The results support that EEG/ERP is reliable across four recording intervals, thus it can be used to assess the effect of different doses and types of drugs with CNS effects.


Assuntos
Citalopram/farmacologia , Eletroencefalografia/normas , Potenciais Evocados/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Vortioxetina/farmacologia , Adulto , Ondas Encefálicas/efeitos dos fármacos , Ondas Encefálicas/fisiologia , Citalopram/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Eletroencefalografia/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados P300/fisiologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Humanos , Masculino , Reprodutibilidade dos Testes , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Fatores de Tempo , Vortioxetina/administração & dosagem , Adulto Jovem
14.
Alcohol ; 70: 1-10, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29705707

RESUMO

BACKGROUND: The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol-use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduce P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST). METHODS: One hundred forty-eight non-dependent moderate to heavy social drinkers, ages 21 to 27, participated in two single-blind, alcohol or placebo, counterbalanced sessions approximately 1 week apart. During each session, subjects performed an adaptive stop signal task (aSST) at 1) baseline, 2) upon reaching the target 60 mg/dL breath alcohol concentration or at the equivalent time during the placebo session, and 3) approximately 135 min later while the breath alcohol concentration was clamped. Here, we report on differences between baseline and first subsequent measurements across the experimental sessions. During each aSST run, the stop signal delay (SSD, the time between stop and go signals) adjusted trial-by-trial, based on the subject's performance. RESULTS: The aSST reliably generated a STOP P3 component that did not change significantly with repeated task performance. The pre-infusion SSD distribution was bimodal, with mean values several hundred msec apart (FAST: 153 msec and SLOW: 390 msec). This suggested different response strategies: FAST SSD favoring "going" over "stopping", and SLOW SSD favoring "stopping" over "going". Exposure to alcohol at 60 mg/dL differentially affected the amplitude and latency of the STOP P3 according to SSD group. Alcohol significantly reduced P3 amplitude in the SLOW SSD compared to the FAST SSD group, but significantly increased P3 latency in the FAST SSD compared to the SLOW SSD group. CONCLUSIONS: The aSST is a robust and sensitive task for detecting alcohol-induced changes in inhibition behavior as measured by the P3 component in a within-subject design. Alcohol was associated with P3 component changes, which varied by SSD group, suggesting a differential effect as a function of task strategy. Overall, the data support the potential utility of the aSST in the detection of alcohol response-related AUD risk.


Assuntos
Etanol/farmacologia , Potenciais Evocados P300/efeitos dos fármacos , Inibição Psicológica , Adulto , Potenciais Evocados P300/fisiologia , Feminino , Humanos , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Método Simples-Cego , Adulto Jovem
15.
Psychopharmacology (Berl) ; 235(2): 491-503, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29302713

RESUMO

RATIONALE: Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT2A receptors in information processing is less clear. OBJECTIVES: We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT2A/C agonistic properties, in healthy volunteers. METHODS: Twenty subjects (10M/10F) were given 0.26 mg/kg of psilocybin orally in a placebo-controlled, double-blind, cross-over design. ERPs (P300, MMN) were registered during the peak of intoxication. Correlations between measured electrophysiological variables and psilocin serum levels and neuropsychological effects were also analyzed. RESULTS: Psilocybin induced robust psychedelic effects and psychotic-like symptoms, decreased P300 amplitude (p = 0.009) but did not affect the MMN. Psilocybin's disruptive effect on P300 correlated with the intensity of the psychedelic state, which was dependent on the psilocin serum levels. We also observed a decrease in N100 amplitude (p = 0.039) in the P300 paradigm and a negative correlation between P300 and MMN amplitude (p = 0.014). CONCLUSIONS: Even though pre-attentive cognition (MMN) was not affected, processing at the early perceptual level (N100) and in higher-order cognition (P300) was significantly disrupted by psilocybin. Our results have implications for the role of 5-HT2A receptors in altered information processing in psychosis and schizophrenia.


Assuntos
Atenção/efeitos dos fármacos , Cognição/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Alucinógenos/farmacologia , Psilocibina/farmacologia , Estimulação Acústica/métodos , Adulto , Idoso , Atenção/fisiologia , Cognição/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Potenciais Evocados P300/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Psilocibina/efeitos adversos
16.
Basic Clin Pharmacol Toxicol ; 122(2): 245-252, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28869786

RESUMO

Event-related potentials (ERPs) are commonly used in Neuroscience research, particularly the P3 waveform because it is associated with cognitive brain functions and is easily elicited by auditory or sensory inputs. ERPs are affected by drugs such as lorazepam, which increase the latency and decrease the amplitude of the P3 wave. In this study, auditory-evoked ERPs were generated in 13 older healthy volunteers using an oddball tone paradigm, after administration of single 0.5 and 2 mg doses of lorazepam. Population pharmacokinetics (PK)/pharmacodynamics (PD) models were developed using nonlinear mixed-effects methods in order to assess the effect of lorazepam on the latency and amplitude of the P3 waveforms. The PK/PD models showed that doses of 0.3 mg of lorazepam achieved approximately half of the maximum effect on the latency of the P3 waveform. For P3 amplitude, half the maximum effect was achieved with a dose of 1.2 mg of lorazepam. The PK/PD models also predicted an efficacious dose range of lorazepam, which was close to the recommended therapeutic range. The use of longitudinal P3 latency data allowed better predictions of the lorazepam efficacious dose range than P3 amplitude or aggregate exposure-response data, suggesting that latency could be a more sensitive parameter for drugs with similar mechanisms of action as lorazepam and that time course rather than single time-point ERP data should be collected. Overall, the results suggest that P3 ERP waveforms could be used as potential non-specific biomarkers for functional target engagement for drugs with brain activity, and PK/PD models can aid trial design and choice of doses for development of new drugs with ERP activity.


Assuntos
Córtex Auditivo/efeitos dos fármacos , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacocinética , Lorazepam/administração & dosagem , Lorazepam/farmacocinética , Modelos Biológicos , Estimulação Acústica , Córtex Auditivo/fisiologia , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Tempo de Reação/efeitos dos fármacos , Método Simples-Cego
17.
Schizophr Res ; 195: 334-342, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28886890

RESUMO

Spectral entropy (SE) is a measurement from information theory field that provides an estimation of EEG regularity and may be useful as a summary of its spectral properties. Previous studies using small samples reported a deficit of EEG entropy modulation in schizophrenia during cognitive activity. The present study is aimed at replicating this finding in a larger sample, to explore its cognitive and clinical correlates and to discard antipsychotic treatment as the main source of that deficit. We included 64 schizophrenia patients (21 first episodes, FE) and 65 healthy controls. We computed SE during performance of an odd-ball paradigm, at the windows prior (-300 to 0ms) and following (150 to 450ms) stimulus presentation. Modulation of SE was defined as the difference between post- and pre-stimulus windows. In comparison to controls, patients showed a deficit of SE modulation over frontal and central regions, also shown by FE patients. Baseline SE did not differ between patients and controls. Modulation deficit was directly associated with cognitive deficits and negative symptoms, and inversely with positive symptoms. SE modulation was not related to antipsychotic doses. Patients also showed a smaller change of median frequency (i.e., smaller slowing of oscillatory activity) of the EEG from pre- to post-stimulus windows. These results support that a deficit of fast modulation contributes to cognitive deficits and symptoms in schizophrenia patients.


Assuntos
Transtornos Cognitivos/etiologia , Potenciais Evocados P300/fisiologia , Esquizofrenia/complicações , Adulto , Antipsicóticos/uso terapêutico , Mapeamento Encefálico , Eletroencefalografia , Entropia , Potenciais Evocados P300/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Análise de Componente Principal , Esquizofrenia/tratamento farmacológico , Análise Espectral , Adulto Jovem
18.
Neuroreport ; 29(3): 160-168, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29239976

RESUMO

Despite a wide range of reports on depression-induced P300 changes, it is still debatable whether P300 can return to a pattern characteristic of healthy individuals following antidepressant treatment. Thus, the present study aims to compare P300 and its underlying neural activation in depressed patients before and after antidepressant treatment to explore the brain regions related to pathogenesis and to evaluate the prognosis after treatment. P300 was evoked by the oddball auditory paradigm and collected from 14 sex-matched, age-matched, and education level-matched patients and controls. P300 was also collected in the same patients after treatment. sLORETA was used to explore the source activation of P300 components. Depressed patients before and after antidepressant treatment tended to show lower P300 amplitudes compared with healthy controls, and their P300 amplitudes of F3 electrodes were correlated negatively to their scores on the 24-item Hamilton Depression Rating Scale, the Snaith-Hamilton Pleasure Scale, and the nine-item Patient Health Questionnaire. P300 amplitudes of P4 electrodes were correlated negatively with their scores on the Dysfunctional Attitude Scale. P300 source activation of depressed patients before antidepressant treatment was reduced in the left superior parietal lobule and the precuneus compared with healthy controls and depressed patients after treatment. No difference was found between healthy controls and depressed patients after treatment. The left superior parietal lobule and the precuneus might be therapeutic targets of depression.


Assuntos
Antidepressivos/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/fisiopatologia , Potenciais Evocados P300/efeitos dos fármacos , Percepção Auditiva/efeitos dos fármacos , Percepção Auditiva/fisiologia , Mapeamento Encefálico , Eletroencefalografia , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
19.
Biomed Res ; 38(6): 371-374, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29225215

RESUMO

Interferon (IFN) has various side effects, including psychiatric symptoms. Event-related potentials are used as an electrophysiologic index of cognitive disorders. Auditory event-related potentials (P300) are often used in conditions in which cognitive ability is affected. In this study, we evaluated the association between P300, used to assess cognitive impairment, and neuropsychological side effects of IFN treatment in patients with chronic hepatitis C. Subjects were 20 patients with chronic hepatitis C; 13 patients were treated with peg IFN-α2b and ribavirin (riba group), and 7 patients were treated with peg IFN-α2a (alone group). P300 was performed on all patients before treatment and after 1 week, 4 weeks, 2 months, and 3 months of treatment. In addition, 10 patients of them completed the self-rating depression scale (SDS). P300 latency was significantly prolonged at all points of measurement during IFN treatment. No correlation between the change of SDS score and the change rate of P300 latency was shown. Six patients with neuropsychological symptom had a significantly increased change rate of P300 latency compared with patients without neuropsychological symptoms (P < 0.05). Based on P300 findings, this study suggests that patients with chronic hepatitis C treated with IFN may experience significant cognitive impairment.


Assuntos
Antivirais/efeitos adversos , Disfunção Cognitiva/etiologia , Hepatite C Crônica/complicações , Interferons/efeitos adversos , Idoso , Antivirais/uso terapêutico , Disfunção Cognitiva/diagnóstico , Potenciais Evocados P300/efeitos dos fármacos , Feminino , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Sorogrupo , Avaliação de Sintomas
20.
Epilepsia ; 58(5): 872-881, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28401986

RESUMO

OBJECTIVES: To investigate acoustic auditory processing in patients with recent infantile spasms (IS). METHODS: Patients (n = 22; 12 female; median age 8 months; range 5-11 months) had normal preceding development, brain magnetic resonance imaging (MRI), and neurometabolic testing (West syndrome of unknown cause, uWS). Controls were healthy babies (n = 22; 11 female; median age 6 months; range 3-12 months). Event-related potentials (ERPs) and psychometry (Bayley Scales of Infant Development, Second Edition, BSID-II) took place at a month following IS remission. RESULTS: Following a repeated pure tone, uWS patients showed less suppression of the N100 at the mid-temporal electrodes (p = 0.006), and a prolonged response latency (p = 0.019). Their novelty P300 amplitude over the mid-temporal electrodes was halved (p = 0.001). The peak of the novelty P300 to environmental broadband sounds emerged later over the left temporal lobe in patients (p = 0.015), the lag correlating with duration of spasms (r = 0.547, p = 0.015). BSID-II scores were lower in patients (p < 0.001), with no correlation to ERP. SIGNIFICANCE: Complex acoustic information is processed poorly following IS. This would impair language. Treatment did not reverse this phenomenon, but may have limited its severity. The data are most consistent with altered connectivity of the cortical acoustic processing areas induced by IS.


Assuntos
Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos/fisiologia , Espasmos Infantis/diagnóstico , Espasmos Infantis/fisiopatologia , Estimulação Acústica , Vias Auditivas/efeitos dos fármacos , Vias Auditivas/fisiopatologia , Percepção Auditiva/efeitos dos fármacos , Estudos de Casos e Controles , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Estudos Transversais , Eletroencefalografia , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados P300/fisiologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Feminino , Humanos , Lactente , Masculino , Prednisolona/uso terapêutico , Prognóstico , Estudos Prospectivos , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Processamento de Sinais Assistido por Computador , Espasmos Infantis/tratamento farmacológico , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/fisiologia , Gravação em Vídeo , Vigabatrina/uso terapêutico
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