RESUMO
N-methyl-D-aspartate receptor (NMDAR) hypofunction is a leading pathophysiological model of schizophrenia. Resting-state functional magnetic resonance imaging (rsfMRI) studies demonstrate a thalamic dysconnectivity pattern in schizophrenia involving excessive connectivity with sensory regions and deficient connectivity with frontal, cerebellar, and thalamic regions. The NMDAR antagonist ketamine, when administered at sub-anesthetic doses to healthy volunteers, induces transient schizophrenia-like symptoms and alters rsfMRI thalamic connectivity. However, the extent to which ketamine-induced thalamic dysconnectivity resembles schizophrenia thalamic dysconnectivity has not been directly tested. The current double-blind, placebo-controlled study derived an NMDAR hypofunction model of thalamic dysconnectivity from healthy volunteers undergoing ketamine infusions during rsfMRI. To assess whether ketamine-induced thalamic dysconnectivity was mediated by excess glutamate release, we tested whether pre-treatment with lamotrigine, a glutamate release inhibitor, attenuated ketamine's effects. Ketamine produced robust thalamo-cortical hyper-connectivity with sensory and motor regions that was not reduced by lamotrigine pre-treatment. To test whether the ketamine thalamic dysconnectivity pattern resembled the schizophrenia pattern, a whole-brain template representing ketamine's thalamic dysconnectivity effect was correlated with individual participant rsfMRI thalamic dysconnectivity maps, generating "ketamine similarity coefficients" for people with chronic (SZ) and early illness (ESZ) schizophrenia, individuals at clinical high-risk for psychosis (CHR-P), and healthy controls (HC). Similarity coefficients were higher in SZ and ESZ than in HC, with CHR-P showing an intermediate trend. Higher ketamine similarity coefficients correlated with greater hallucination severity in SZ. Thus, NMDAR hypofunction, modeled with ketamine, reproduces the thalamic hyper-connectivity observed in schizophrenia across its illness course, including the CHR-P period preceding psychosis onset, and may contribute to hallucination severity.
Assuntos
Ketamina , Esquizofrenia , Glutamatos/efeitos adversos , Alucinações , Humanos , Ketamina/farmacologia , Lamotrigina/efeitos adversos , Imageamento por Ressonância Magnética , Receptores de N-Metil-D-Aspartato , Esquizofrenia/tratamento farmacológicoRESUMO
BACKGROUND: Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset. METHODS: Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups. RESULTS: Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups. CONCLUSIONS: PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages.
Assuntos
Transtornos Psicóticos , Esquizofrenia , Adolescente , Humanos , Estudos Transversais , Imageamento por Ressonância Magnética , Vias Neurais , TálamoRESUMO
The hallmark of resting EEG spectra are distinct rhythms emerging from a broadband, aperiodic background. This aperiodic neural signature accounts for most of total EEG power, although its significance and relation to functional neuroanatomy remains obscure. We hypothesized that aperiodic EEG reflects a significant metabolic expenditure and therefore might be associated with the default mode network while at rest. During eyes-open, resting-state recordings of simultaneous EEG-fMRI, we find that aperiodic and periodic components of EEG power are only minimally associated with activity in the default mode network. However, a whole-brain analysis identifies increases in aperiodic power correlated with hemodynamic activity in an auditory-salience-cerebellar network, and decreases in aperiodic power are correlated with hemodynamic activity in prefrontal regions. Desynchronization in residual alpha and beta power is associated with visual and sensorimotor hemodynamic activity, respectively. These findings suggest that resting-state EEG signals acquired in an fMRI scanner reflect a balance of top-down and bottom-up stimulus processing, even in the absence of an explicit task.
Assuntos
Encéfalo/fisiologia , Eletroencefalografia , Hemodinâmica , Imageamento por Ressonância Magnética , Rede Nervosa/fisiologia , Descanso/fisiologia , Adolescente , Adulto , Idoso , Circulação Cerebrovascular/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Mismatch negativity (MMN) is an event-related potential (ERP) component reflecting auditory predictive coding. Repeated standard tones evoke increasing positivity ('repetition positivity'; RP), reflecting strengthening of the standard's memory trace and the prediction it will recur. Likewise, deviant tones preceded by more standard repetitions evoke greater negativity ('deviant negativity'; DN), reflecting stronger prediction error signaling. These memory trace effects are also evident in MMN difference wave. Here, we assess group differences and test-retest reliability of these indices in schizophrenia patients (SZ) and healthy controls (HC). METHODS: Electroencephalography was recorded twice, 2 weeks apart, from 43 SZ and 30 HC, during a roving standard paradigm. We examined ERPs to the third, eighth, and 33rd standards (RP), immediately subsequent deviants (DN), and the corresponding MMN. Memory trace effects were assessed by comparing amplitudes associated with the three standard repetition trains. RESULTS: Compared with controls, SZ showed reduced MMNs and DNs, but normal RPs. Both groups showed memory trace effects for RP, MMN, and DN, with a trend for attenuated DNs in SZ. Intraclass correlations obtained via this paradigm indicated good-to-moderate reliabilities for overall MMN, DN and RP, but moderate to poor reliabilities for components associated with short, intermediate, and long standard trains, and poor reliability of their memory trace effects. CONCLUSION: MMN deficits in SZ reflected attenuated prediction error signaling (DN), with relatively intact predictive code formation (RP) and memory trace effects. This roving standard MMN paradigm requires additional development/validation to obtain suitable levels of reliability for use in clinical trials.
Assuntos
Atenção/fisiologia , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Rememoração Mental/fisiologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Adulto JovemRESUMO
BACKGROUND: During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds. Previously, we found attenuated vocalization-related auditory cortical suppression in psychosis and a similar trend in the psychosis risk syndrome. Here, we report data from the final sample of early illness schizophrenia patients (ESZ), individuals at clinical high risk for psychosis (CHR), and healthy controls (HC). METHODS: Event-related potentials (ERP) were recorded from ESZ (n = 84), CHR (n = 71), and HC (n = 103) participants during a vocalization paradigm. The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Age effects on N1 suppression (Talk-Listen), Talk N1, and Listen N1 were compared across groups. N1 measures were adjusted for normal aging before testing for group differences. RESULTS: Both ESZ and CHR groups showed reduced Talk-Listen N1 suppression relative to HC, but did not differ from each other. Listen N1 was reduced in ESZ, but not in CHR, relative to HC. Deficient Talk-Listen N1 suppression was associated with greater unusual thought content in CHR individuals. N1 suppression increased with age in HC (12-36 years), and while CHR individuals showed a similar age-related increase, no such relationship was evident in ESZ. CONCLUSIONS: Putative efference copy/corollary discharge-mediated auditory cortical suppression during vocalization is deficient in ESZ and precedes psychosis onset, particularly in CHR individuals with greater unusual thought content. Furthermore, this suppression increases from adolescence through early adulthood, likely reflecting the effects of normal brain maturation. This maturation effect is disrupted in ESZ, presumably due to countervailing illness effects.
Assuntos
Córtex Auditivo/fisiopatologia , Ondas Encefálicas/fisiologia , Potenciais Evocados/fisiologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Percepção da Fala/fisiologia , Fala/fisiologia , Adolescente , Adulto , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Masculino , Risco , Adulto JovemRESUMO
We report a case of a 56 year old male in ventricular fibrillation (VF) cardiac arrest for a total of 2 hours and 50 minutes who was diagnosed with ST elevation myocardial infarction (STEMI) during a brief 10 min period of return of spontaneous circulation (ROSC). The patient underwent successful percutaneous coronary intervention (PCI) while receiving mechanical chest compressions for ongoing VF. Our case demonstrates the potential for neurologically intact survival in VF cardiac arrest patients despite prolonged periods of VF who are treated with mechanical CPR and intra-arrest PCI.
Assuntos
Reanimação Cardiopulmonar/instrumentação , Desfibriladores , Parada Cardíaca/terapia , Intervenção Coronária Percutânea , Sobrevida , Serviços Médicos de Emergência , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST , Fatores de Tempo , Resultado do Tratamento , Fibrilação Ventricular/terapiaRESUMO
Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers.
Assuntos
Encéfalo/metabolismo , Plasticidade Neuronal , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Adulto , Encéfalo/efeitos dos fármacos , Ciclosserina/farmacologia , Demografia , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Aprendizagem , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Estimulação Luminosa , Placebos , Transdução de Sinais/efeitos dos fármacos , Análise e Desempenho de Tarefas , Adulto JovemRESUMO
Auditory hallucinations, a hallmark symptom of psychosis, are experienced by most people with a diagnosis of schizophrenia at some point in their illness. Auditory hallucinations can be understood as a failure in predictive coding, whereby abnormalities in sensory/perceptual processing combine with biased cognitive processes to result in a dampening of normal prediction error signaling. In this paper, we used a roving mismatch negativity (MMN) paradigm to optimize evaluation of prediction error signaling and short-term neuroplasticity in 30 people with schizophrenia (n = 16 with and n = 14 without recent auditory hallucinations) and 20 healthy comparison participants. The recent hallucinations group exhibited an abnormal roving MMN profile [F(2,27) = 3.98, p = 0.03], significantly reduced prediction error signaling [t(28) = -2.25, p = 0.03], and a trend for diminished short-term neuroplasticity [t(28) = 1.80, p = 0.08]. There were no statistically significant differences between the healthy comparison group and the combined schizophrenia group on any of the roving MMN indices. These findings are consistent with a predictive coding account of hallucinations in schizophrenia, which posits reduced prediction error signaling in those who are prone to hallucinations. These results also suggest that plasticity-mediated formation and online updating of predictive coding models may also be disrupted in individuals with recent hallucinations.
Assuntos
Encéfalo/fisiopatologia , Alucinações , Plasticidade Neuronal , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Estimulação Acústica , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
Up to 50% of individuals with major depressive disorder (MDD) do not recover after two antidepressant medication trials, and therefore meet the criteria for treatment-resistant depression (TRD). Mindfulness-based cognitive therapy (MBCT) is one promising treatment; however, the extent to which MBCT influences clinical outcomes relative to baseline neural activation remains unknown. In the present study we investigated baseline differences in amygdala activation between TRD patients and healthy controls (HCs), related amygdala activation to depression symptoms, and examined the impacts of MBCT and amygdala activation on longitudinal depression outcomes. At baseline, TRD patients (n = 80) and HCs (n = 37) participated in a functional magnetic resonance imaging task in which they identified either the emotion (affect labeling) or the gender (gender labeling) of faces, or passively viewed faces (observing). The TRD participants then completed eight weeks of MBCT or a health enhancement program (HEP). Relative to HCs, the TRD patients demonstrated less amygdala activation during affect labeling, and marginally less during gender labeling. Blunted amygdala activation in TRD patients during affect labeling was associated with greater depression severity. MBCT was associated with greater depression reductions than was HEP directly following treatment; however, at 52 weeks the treatment effect was not significant, and baseline amygdala activation across the task conditions predicted depression severity in both groups. TRD patients have blunted amygdala responses during affect labeling that are associated with greater concurrent depression. Furthermore, although MBCT produced greater short-term improvements in depression than did HEP, overall baseline amygdala reactivity was predictive of long-term clinical outcomes in both groups.
Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Resistente a Tratamento/fisiopatologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Antidepressivos/uso terapêutico , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/terapia , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Feminino , Promoção da Saúde , Humanos , Imageamento por Ressonância Magnética , Masculino , Atenção Plena , Escalas de Graduação Psiquiátrica , Tempo de Reação , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Across the animal kingdom, sensations resulting from an animal's own actions are processed differently from sensations resulting from external sources, with self-generated sensations being suppressed. A forward model has been proposed to explain this process across sensorimotor domains. During vocalization, reduced processing of one's own speech is believed to result from a comparison of speech sounds to corollary discharges of intended speech production generated from efference copies of commands to speak. Until now, anatomical and functional evidence validating this model in humans has been indirect. Using EEG with anatomical MRI to facilitate source localization, we demonstrate that inferior frontal gyrus activity during the 300ms before speaking was associated with suppressed processing of speech sounds in auditory cortex around 100ms after speech onset (N1). These findings indicate that an efference copy from speech areas in prefrontal cortex is transmitted to auditory cortex, where it is used to suppress processing of anticipated speech sounds. About 100ms after N1, a subsequent auditory cortical component (P2) was not suppressed during talking. The combined N1 and P2 effects suggest that although sensory processing is suppressed as reflected in N1, perceptual gaps may be filled as reflected in the lack of P2 suppression, explaining the discrepancy between sensory suppression and preserved sensory experiences. These findings, coupled with the coherence between relevant brain regions before and during speech, provide new mechanistic understanding of the complex interactions between action planning and sensory processing that provide for differentiated tagging and monitoring of one's own speech, processes disrupted in neuropsychiatric disorders.
Assuntos
Córtex Auditivo/fisiologia , Fala/fisiologia , Adolescente , Adulto , Vias Auditivas/fisiologia , Percepção Auditiva , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Audição/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiologia , Percepção da Fala/fisiologia , Adulto JovemRESUMO
BACKGROUND: Sensory prediction allows the brain to anticipate and parse incoming self-generated sensory information from externally generated signals. Sensory prediction breakdowns may contribute to perceptual and agency abnormalities in psychosis (hallucinations, delusions). The pons, a central node in a cortico-ponto-cerebellar-thalamo-cortical circuit, is thought to support sensory prediction. Examination of pons connectivity in schizophrenia and its role in sensory prediction abnormalities is lacking. METHODS: We examined these relationships using resting-state functional magnetic resonance imaging and the electroencephalography-based auditory N1 event-related potential in 143 participants with psychotic spectrum disorders (PSPs) (with schizophrenia, schizoaffective disorder, or bipolar disorder); 63 first-degree relatives of individuals with psychosis; 45 people at clinical high risk for psychosis; and 124 unaffected comparison participants. This unique sample allowed examination across the psychosis spectrum and illness trajectory. Seeding from the pons, we extracted average connectivity values from thalamic and cerebellar clusters showing differences between PSPs and unaffected comparison participants. We predicted N1 amplitude attenuation during a vocalization task from pons connectivity and group membership. We correlated participant-level connectivity in PSPs and people at clinical high risk for psychosis with hallucination and delusion severity. RESULTS: Compared to unaffected comparison participants, PSPs showed pons hypoconnectivity to 2 cerebellar clusters, and first-degree relatives of individuals with psychosis showed hypoconnectivity to 1 of these clusters. Pons-to-cerebellum connectivity was positively correlated with N1 attenuation; only PSPs with heightened pons-to-postcentral gyrus connectivity showed this pattern, suggesting a possible compensatory mechanism. Pons-to-cerebellum hypoconnectivity was correlated with greater hallucination severity specifically among PSPs with schizophrenia. CONCLUSIONS: Deficient pons-to-cerebellum connectivity linked sensory prediction network breakdowns with perceptual abnormalities in schizophrenia. Findings highlight shared features and clinical heterogeneity across the psychosis spectrum.
Assuntos
Cerebelo , Eletroencefalografia , Alucinações , Imageamento por Ressonância Magnética , Ponte , Transtornos Psicóticos , Esquizofrenia , Humanos , Alucinações/fisiopatologia , Esquizofrenia/fisiopatologia , Esquizofrenia/complicações , Masculino , Feminino , Adulto , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/complicações , Ponte/fisiopatologia , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Vias Neurais/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Mobile health technology's impact on cardiovascular risk factor control is not fully understood. This study evaluates the association between interaction with a mobile health application and change in cardiovascular risk factors. METHODS AND RESULTS: Participants with hypertension with or without dyslipidemia enrolled in a workplace-deployed mobile health application-based cardiovascular risk self-management program between January 2018 and December 2022. Retrospective evaluation explored the influence of application engagement on change in blood pressure (BP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and weight. Multiple regression analyses examined the influence of guideline-based, nonpharmacological lifestyle-based digital coaching on outcomes adjusting for confounders. Of 102 475 participants, 49.1% were women. Median age was 53 (interquartile range, 43-61) years, BP was 134 (interquartile range, 124-144)/84 (interquartile range, 78-91) mm Hg, TC was 183 (interquartile range, 155-212) mg/dL, LDL-C was 106 (82-131) mg/dL, and body mass index was 30 (26-35) kg/m2. At 2 years, participants with baseline systolic BP ≥140 mm Hg reduced systolic BP by 18.6 (SEM, 0.3) mm Hg. At follow up, participants with baseline TC ≥240 mg/dL reduced TC by 65.7 (SEM, 4.6) mg/dL, participants with baseline LDL-C≥160 mg/dL reduced LDL-C by 66.6 (SEM, 6.2) mg/dL, and participants with baseline body mass index ≥30 kg/m2 lost 12.0 (SEM, 0.3) pounds, or 5.1% of body weight. Interaction with digital coaching was associated with greater reduction in all outcomes. CONCLUSIONS: A mobile health application-based cardiovascular risk self-management program was associated with favorable reductions in BP, TC, LDL-C, and weight, highlighting the potential use of this technology in comprehensive cardiovascular risk factor control.
Assuntos
Doenças Cardiovasculares , Fatores de Risco de Doenças Cardíacas , Autogestão , Telemedicina , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Autogestão/métodos , Adulto , Estudos Retrospectivos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/sangue , Dislipidemias/sangue , Dislipidemias/diagnóstico , Dislipidemias/terapia , Dislipidemias/epidemiologia , Aplicativos Móveis , Hipertensão/fisiopatologia , Hipertensão/terapia , Pressão Sanguínea/fisiologia , LDL-Colesterol/sangue , Comportamento de Redução do RiscoRESUMO
BACKGROUND: Gamma-band oscillations and their synchronization have been implicated in the coordination of activity between distributed neuronal assemblies in the service of sensory registration of stimuli and perceptual binding of their features. Prior electroencephalographic (EEG) studies of chronic schizophrenia patients have documented deficits in the magnitude and/or phase synchrony of stimulus-evoked gamma oscillations, findings that have been linked to neurotransmission abnormalities involving GABA and NMDA-glutamate receptors. However, it remains unclear whether these abnormalities are present at the onset of the illness, or indeed, whether they are present during the prodromal period preceding illness onset. Accordingly, we examined the magnitude and phase synchrony of the transient gamma-band response (GBR) elicited by an auditory stimulus in young patients with schizophrenia and in patients at clinical high risk for psychosis based on their manifestation of putatively prodromal symptoms. METHODS: EEG was recorded during an auditory oddball target detection task in three groups: young schizophrenia patients early in their illness (YSZ; n = 19), patients at clinical high risk for psychosis (CHR; n = 55), and healthy controls (HC; n = 42). Single-trial EEG epochs and the average event-related potential time-locked to standard tones from the oddball task were subjected to time-frequency decomposition using Morlet wavelet transformations. The GBR between 50 and 100 ms following the tone onset was quantified in terms of evoked power, total power, and the phase-locking factor (PLF) reflecting cross-trial phase synchrony. RESULTS: GBR evoked power was significantly reduced in YSZ (p < 0.01) and CHR (p < 0.05) patients, relative to HC. Similarly, GBR PLF was significantly reduced in YSZ (p < 0.01) and showed a marginal reduction in CHR patients (p = 0.057), relative to HC. GBR total power was not reduced in CHR patients (p = 0.68) and showed only a trend level reduction in YSZ (p = 0.072). Within the CHR group. there were no significant GBR differences between the patients who converted to a psychotic disorder and those who did not convert to psychosis during a 12-month follow-up period. CONCLUSION: Reductions in the transient auditory GBR, as reflected by evoked power and phase synchrony, are evident in the early stages of schizophrenia and appear to precede psychosis onset. However, the absence of total power GBR abnormalities in CHR patients, with only a trend toward reduction in YSZ patients, suggests that the magnitude of the GBR is intact early in the course
Assuntos
Sincronização Cortical/fisiologia , Potenciais Evocados Auditivos/fisiologia , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Estimulação Acústica , Adolescente , Adulto , Análise de Variância , Mapeamento Encefálico , Criança , Eletroencefalografia , Feminino , Humanos , Masculino , Análise de Componente Principal , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Fatores de Tempo , Adulto JovemRESUMO
Background. The auditory steady state response (ASSR) is generated in bilateral auditory cortex and is the most used electroencephalographic (EEG) or magnetoencephalographic measure of gamma band abnormalities in schizophrenia. While the finding of reduced 40-Hz ASSR power and phase consistency in schizophrenia have been replicated many times, the 40-Hz ASSR phase locking angle (PLA), which assesses oscillation latency or phase delay, has rarely been examined. Furthermore, whether 40-Hz ASSR phase delay in schizophrenia is lateralized or common to left and right auditory cortical generators is unknown. Methods. Previously analyzed EEG data recorded from 24 schizophrenia patients and 24 healthy controls presented with 20-, 30-, and 40-Hz click trains to elicit ASSRs were re-analyzed to assess PLA in source space. Dipole moments in the right and left hemisphere were used to assess both frequency and hemisphere specificity of ASSR phase delay in schizophrenia. Results. Schizophrenia patients exhibited significantly reduced (ie, phase delayed) 40-Hz PLA in the left, but not the right, hemisphere, but their 20- and 30-Hz PLA values were normal. This left-lateralized 40-Hz phase delay was unrelated to symptoms or to previously reported left-lateralized PLF reductions in the schizophrenia patients. Conclusions. Consistent with sensor-based studies, the 40-Hz ASSR source-localized to left, but not right, auditory cortex was phase delayed in schizophrenia. Consistent with prior studies showing left temporal lobe volume deficits in schizophrenia, our findings suggest sluggish entrainment to 40-Hz auditory stimulation specific to left auditory cortex that are distinct from well-established deficits in gamma ASSR power and phase synchrony.
Assuntos
Córtex Auditivo , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Potenciais Evocados Auditivos/fisiologia , Eletroencefalografia/métodos , Estimulação Acústica/métodos , PoliésteresRESUMO
BACKGROUND: Amplitude reduction of mismatch negativity (MMN), an event-related potential component indexing NMDA receptor-dependent auditory echoic memory and predictive coding, is widely replicated in schizophrenia. Time-frequency analyses of single-trial electroencephalography epochs suggest that theta oscillation abnormalities underlie MMN deficits in schizophrenia. However, this has received less attention in early schizophrenia (ESZ). METHODS: Patients with ESZ (n = 89), within 5 years of illness onset, and healthy control subjects (n = 105) completed an electroencephalography MMN paradigm (duration-deviant, pitch-deviant, duration + pitch double-deviant). Repeated measures analyses of variance assessed group differences in MMN, theta intertrial phase coherence (ITC), and theta total power from frontocentral electrodes, after normal age adjustment. Group differences were retested after covarying MMN and theta measures. RESULTS: Relative to healthy control subjects, patients with ESZ showed auditory deviance deficits. Patients with ESZ had MMN deficits for duration-deviants (p = .041), pitch-deviants (ps = .007), and double-deviants (ps < .047). Patients with ESZ had reduced theta ITC for standards (ps < .040) and duration-deviants (ps < .030). Furthermore, patients with ESZ had reduced theta power across deviants at central electrodes (p = .013). MMN group deficits were not fully accounted for by theta ITC and power, and neither were theta ITC group deficits fully accounted for by MMN. Group differences in theta total power were no longer significant after covarying for MMN. CONCLUSIONS: Patients with ESZ showed reduced MMN and theta total power for all deviant types. Theta ITC showed a relatively specific reduction for duration-deviants. Although MMN and theta ITC were correlated in ESZ, covarying for one did not fully account for deficits in the other, raising the possibility of their sensitivity to dissociable pathophysiological processes.
Assuntos
Esquizofrenia , Humanos , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica , Potenciais Evocados , EletroencefalografiaRESUMO
BACKGROUND: Individual variation in brain aging trajectories is linked with several physical and mental health outcomes. Greater stress levels, worry, and rumination correspond with advanced brain age, while other individual characteristics, like mindfulness, may be protective of brain health. Multiple lines of evidence point to advanced brain aging in schizophrenia (i.e., neural age estimate > chronological age). Whether psychological dimensions such as mindfulness, rumination, and perceived stress contribute to brain aging in schizophrenia is unknown. METHODS: We estimated brain age from high-resolution anatomical scans in 54 healthy controls (HC) and 52 individuals with schizophrenia (SZ) and computed the brain predicted age difference (BrainAGE-diff), i.e., the delta between estimated brain age and chronological age. Emotional well-being summary scores were empirically derived to reflect individual differences in trait mindfulness, rumination, and perceived stress. Core analyses evaluated relationships between BrainAGE-diff and emotional well-being, testing for slopes differences across groups. RESULTS: HC showed higher emotional well-being (greater mindfulness and less rumination/stress), relative to SZ. We observed a significant group difference in the relationship between BrainAge-diff and emotional well-being, explained by BrainAGE-diff negatively correlating with emotional well-being scores in SZ, and not in HC. That is, SZ with younger appearing brains (predicted age < chronological age) had emotional summary scores that were more like HC, a relationship that endured after accounting for several demographic and clinical variables. CONCLUSIONS: These data reveal clinically relevant aspects of brain age heterogeneity among SZ and point to case-control differences in the relationship between advanced brain aging and emotional well-being.
Assuntos
Atenção Plena , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Envelhecimento , EmoçõesRESUMO
Functional magnetic resonance imaging (fMRI) scanners are unavoidably loud and uncomfortable experimental tools that are necessary for schizophrenia (SZ) neuroscience research. The validity of fMRI paradigms might be undermined by well-known sensory processing abnormalities in SZ that could exert distinct effects on neural activity in the presence of scanner background sound. Given the ubiquity of resting-state fMRI (rs-fMRI) paradigms in SZ research, elucidating the relationship between neural, hemodynamic, and sensory processing deficits during scanning is necessary to refine the construct validity of the MR neuroimaging environment. We recorded simultaneous electroencephalography (EEG)-fMRI at rest in people with SZ (n = 57) and healthy control participants without a psychiatric diagnosis (n = 46) and identified gamma EEG activity in the same frequency range as the background sounds emitted from our scanner during a resting-state sequence. In participants with SZ, gamma coupling to the hemodynamic signal was reduced in bilateral auditory regions of the superior temporal gyri. Impaired gamma-hemodynamic coupling was associated with sensory gating deficits and worse symptom severity. Fundamental sensory-neural processing deficits in SZ are present at rest when considering scanner background sound as a "stimulus." This finding may impact the interpretation of rs-fMRI activity in studies of people with SZ. Future neuroimaging research in SZ might consider background sound as a confounding variable, potentially related to fluctuations in neural excitability and arousal.
Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Eletroencefalografia , Imageamento por Ressonância Magnética/métodos , Nível de Alerta , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodosRESUMO
BACKGROUND: Alterations in the brain's reward system may underlie motivation and pleasure deficits in schizophrenia (SZ). Neuro-oscillatory desynchronization in the alpha band is thought to direct resource allocation away from the internal state, to prioritize processing salient environmental events, including reward feedback. We hypothesized reduced reward-related alpha event-related desynchronization (ERD) in SZ, consistent with less externally focused processing during reward feedback. METHODS: Electroencephalography was recorded while participants with SZ (n = 54) and healthy control participants (n = 54) played a simple slot machine task. Total alpha band power (8-14 Hz), a measure of neural oscillation magnitude, was extracted via principal component analysis and compared between groups and reward outcomes. The clinical relevance of hypothesized alpha power alterations was examined by testing associations with negative symptoms within the SZ group and with trait rumination, dimensionally, across groups. RESULTS: A group × reward outcome interaction (p = .018) was explained by healthy control participants showing significant posterior-occipital alpha power suppression to wins versus losses (p < .001), in contrast to participants with SZ (p > .1). Among participants with SZ, this alpha ERD was unrelated to negative symptoms (p > .1). Across all participants, less alpha ERD to reward outcomes covaried with greater trait rumination for both win (p = .005) and loss (p = .002) outcomes, with no group differences in slope. CONCLUSIONS: These findings demonstrate alpha ERD alterations in SZ during reward outcome processing. Additionally, higher trait rumination was associated with less alpha ERD during reward feedback, suggesting that individual differences in rumination covary with external attention to reward processing, regardless of reward outcome valence or group membership.
Assuntos
Esquizofrenia , Humanos , Eletroencefalografia , Motivação , Recompensa , Psicologia do EsquizofrênicoRESUMO
Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps < .024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (ps < .048). There was also cortical thinning of rich-club regions in ESZ (ps < .013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n = 9) had fewer connections among rich-club regions (ps < .037) and greater modularity (ps < .037) compared to CHR-P non-converters (n = 19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (ps < .012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to psychosis.
Assuntos
Antipsicóticos , Conectoma , Transtornos Psicóticos , Esquizofrenia , Humanos , Adolescente , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/complicações , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/complicações , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagemRESUMO
Patients with depression who ruminate repeatedly focus on depressive thoughts; however, there are two cognitive subtypes of rumination, reflection and brooding, each associated with different prognoses. Reflection involves problem-solving and is associated with positive outcomes, whereas brooding involves passive, negative, comparison with other people and is associated with poor outcomes. Rumination has also been related to atypical functional hyperconnectivity between the default mode network and subgenual prefrontal cortex. Repetitive pulse transcranial magnetic stimulation of the prefrontal cortex has been shown to alter functional connectivity, suggesting that the abnormal connectivity associated with rumination could potentially be altered. This study examined potential repetitive pulse transcranial magnetic stimulation prefrontal cortical targets that could modulate one or both of these rumination subtypes. Forty-three patients who took part in a trial of repetitive pulse transcranial magnetic stimulation completed the Rumination Response Scale questionnaire and resting-state functional magnetic resonance imaging. Seed to voxel functional connectivity analyses identified an anticorrelation between the left lateral orbitofrontal cortex (-44, 26, -8; k = 172) with the default mode network-subgenual region in relation to higher levels of reflection. Parallel analyses were not significant for brooding or the RRS total score. These findings extend previous studies of rumination and identify a potential mechanistic model for symptom-based neuromodulation of rumination.