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1.
World Neurosurg ; 132: 314-320, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31449994

RESUMO

BACKGROUND: Whereas transient, self-limiting seizures are an infrequent but known complication of deep brain stimulation (DBS) implantation surgery, stimulation itself has occasionally been reported to result in seizure activity at delayed time points. The neural circuitry implicated in stimulation-induced seizures is unknown. CASE DESCRIPTION: A 47-year-old woman underwent chronic subcallosal cingulate DBS for treatment of refractory anorexia nervosa and experienced seizure with stimulation onset. Supratherapeutic voltage caused a generalized seizure. The patient subsequently experienced a full recovery. We reviewed the literature for other cases of delayed postoperative DBS seizures associated with stimulation. We also investigated whether the higher voltage may have recruited networks implicated in epilepsy. The supratherapeutic voltage stimulated a larger area and engaged vulnerable networks, including bilateral hippocampi, cingulate gyrus, and temporal lobes. Literature review identified 20 studies reporting delayed seizure after DBS surgery, 13 of which demonstrated a robust association with mostly nonmotor DBS stimulation. CONCLUSIONS: Nonmotor DBS targets, particularly in patients with epilepsy, may be more vulnerable to stimulation-induced seizures; as such, extra caution should be used when programming stimulation parameters at these DBS targets.


Assuntos
Anorexia Nervosa/terapia , Encéfalo/fisiopatologia , Estimulação Encefálica Profunda/efeitos adversos , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Encéfalo/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Humanos , Lamotrigina/uso terapêutico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia
2.
Exp Brain Res ; 237(9): 2367-2385, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31292696

RESUMO

The posterior cingulate cortex (PCC) has been implicated in a host of cognitive and behavioral processes in addition to serving as a central hub in the default mode network (DMN). Moreover, the PCC has been shown to be involved in a range of psychiatric and neurological disorders. However, very little is known about the specific activated/deactivated functional profiles of the PCC. Here, we employed a dual analytic approach using robust quantitative meta-analytical connectivity modeling (MACM) and ultra-high field, high resolution resting state functional magnetic resonance imaging (rs-fMRI) to identify state-specific functional activity patterns of the human PCC. The MACM results provided evidence for regions of convergence for PCC co-activation and co-deactivation (i.e., left medial frontal gyrus, left amygdala, and left anterior cingulate) as well as regions of divergence specific to either PCC activation (i.e., bilateral inferior frontal gyri) or PCC deactivation (i.e., left parahippocampal gyrus). In addition, exploratory MACMs on dorsal and ventral subregions of the PCC revealed differential functional activity patterns such as greater co-activation of the right PCC and left inferior parietal lobule with the dorsal PCC and greater co-activation of right precuneus with the ventral PCC. Resting state connectivity analyses showed widespread connectivity similar to that of the PCC co-activation-based MACM, but also demonstrated additional regions of activity, including bilateral superior parietal regions and right superior temporal regions. These analyses highlight the diverse neurofunctional repertoire of the human PCC, provide additional insight into its dynamic functional activity patterns as it switches between activated and deactivated states, and elucidates the cognitive processes that may be implicated in clinical populations.


Assuntos
Atenção/fisiologia , Córtex Cerebral/fisiologia , Conectoma , Giro do Cíngulo/fisiologia , Imagem por Ressonância Magnética , Rede Nervosa/fisiologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Conectoma/métodos , Giro do Cíngulo/diagnóstico por imagem , Humanos , Metanálise como Assunto , Modelos Teóricos , Rede Nervosa/diagnóstico por imagem
3.
Dev Cogn Neurosci ; 38: 100668, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31174061

RESUMO

Recent work has suggested atypical neural reward responses in individuals with Autism Spectrum Disorder (ASD), particularly for social reinforcers. Less is known about neural responses to restricted interests and few studies have investigated response to rewards in a learning context. We investigated neurophysiological differences in reinforcement learning between adolescents with ASD and typically developing (TD) adolescents (27 ASD, 31 TD). FMRI was acquired during a learning task in which participants chose one of two doors to reveal an image outcome. Doors differed in their probability of showing liked and not-liked images, which were individualized for each participant. Participants chose the door paired with liked images, but not the door paired with not-liked images, significantly above chance and choice allocation did not differ between groups. Interestingly, participants with ASD made choices less consistent with their initial door preferences. We found a neural prediction-error response at the time of outcome in the ventromedial prefrontal and posterior cingulate cortices that did not differ between groups. Together, behavioural and neural findings suggest that learning with individual interest outcomes is not different between individuals with and without ASD, adding to our understanding of motivational aspects of ASD.


Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Individualidade , Aprendizagem , Imagem por Ressonância Magnética/métodos , Córtex Pré-Frontal/diagnóstico por imagem , Adolescente , Transtorno do Espectro Autista/psicologia , Emoções/fisiologia , Feminino , Giro do Cíngulo/fisiologia , Humanos , Aprendizagem/fisiologia , Masculino , Motivação/fisiologia , Estimulação Luminosa/métodos , Córtex Pré-Frontal/fisiologia , Tempo de Reação/fisiologia , Recompensa , Adulto Jovem
4.
Biol Psychol ; 146: 107709, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31170437

RESUMO

Reward anticipation dysfunction is associated with major depressive disorder (MDD), but is not universally observed in individuals with MDD. Reward anticipation deficits have also been linked to childhood adversity (CA) and approach/avoidance traits. The present study evaluated whether severity of CA (as measured by the Childhood Trauma Questionnaire) and approach/avoidance traits predict individual differences in blood oxygen level dependent (BOLD) response to reward anticipation beyond MDD diagnosis alone. Participants were individuals with MDD (n = 23) and healthy controls (n = 27). Multiple regression was conducted using CTQ scores, trait approach/avoidance scores, and diagnosis to predict activation during reward anticipation in a monetary incentive delay fMRI task. Across groups, higher trait reward responsiveness predicted increased activation in the hippocampus, cingulate cortex, and medial frontal gyrus. Greater CTQ scores predicted increased reward network activation. Overall, CTQ and reward responsiveness scores predicted more variance in reward anticipation activation than diagnosis. These findings suggest that clinicians should assess history of childhood adversity and trait reward responsiveness when treating individuals with MDD.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Depressão/psicologia , Motivação/fisiologia , Recompensa , Adulto , Criança , Feminino , Giro do Cíngulo/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Individualidade , Imagem por Ressonância Magnética , Masculino , Análise Multivariada , Córtex Pré-Frontal/diagnóstico por imagem , Análise de Regressão , Adulto Jovem
5.
Psychopharmacology (Berl) ; 236(8): 2325-2336, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31201476

RESUMO

RATIONALE: Patients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function. OBJECTIVE: In this study, we investigate potential dopaminergic dysfunction during reward processing in the context of OCD. METHODS: We studied OCD patients (n = 18) and controls (n = 18) whilst they learned probabilistic associations between abstract stimuli and monetary rewards in the fMRI scanner involving administration (on separate visits) of a dopamine receptor agonist, pramipexole 0.5 mg; a dopamine receptor antagonist, amisulpride 400 mg; and placebo. We fitted a Q-learning computational model to fMRI prediction error responses; group differences were examined in anterior cingulate and nucleus accumbens regions of interest. RESULTS: There were no significant group, drug, or interaction effects in the number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups (p = 0.089, partial ƞ2 = 0.1). In the imaging results, there was a significant interaction of group by drug (p = 0.013, partial ƞ2 = 0.13). OCD patients showed abnormally strong cingulate signaling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride (p = 0.014, partial ƞ2 = 0.26, 1-ß error probability = 0.94). Exaggerated cingulate prediction error signaling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behavior in OCD. CONCLUSIONS: Our data support cingulate dysfunction during reward processing in OCD, and bidirectional remediation by dopaminergic modulation, suggesting that exaggerated cingulate error signals in OCD may be of dopaminergic origin. The results help to illuminate the mechanisms through which dopamine receptor antagonists achieve therapeutic benefit in OCD. Further research is needed to disentangle the different functions of dopamine receptor agonists and antagonists during bidirectional modulation of cingulate activation.


Assuntos
Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Recompensa , Adulto , Dopamina/metabolismo , Método Duplo-Cego , Feminino , Previsões , Giro do Cíngulo/metabolismo , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Transtorno Obsessivo-Compulsivo/metabolismo , Estimulação Luminosa/métodos
6.
Nat Commun ; 10(1): 1975, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036814

RESUMO

The default mode network (DMN) is associated with a wide range of brain functions. In humans, the DMN is marked by strong functional connectivity among three core regions: medial prefrontal cortex (mPFC), posterior parietal cortex (PPC), and the medial parietal and posterior cingulate cortex (PCC). Neuroimaging studies have shown that the DMN also exists in non-human primates, suggesting that it may be a conserved feature of the primate brain. Here, we found that, in common marmosets, the dorsolateral prefrontal cortex (dlPFC; peak at A8aD) has robust fMRI functional connectivity and reciprocal anatomical connections with the posterior DMN core regions (PPC and PCC), while the mPFC has weak connections with the posterior DMN core regions. This strong dlPFC but weak mPFC connectivity in marmoset differs markedly from the stereotypical DMN in humans. The mPFC may be involved in brain functions that are further developed in humans than in other primates.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Callithrix , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Lobo Parietal/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem
7.
Biomed Pharmacother ; 115: 108903, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054508

RESUMO

CD33 is a susceptibility locus for late-onset Alzheimer's disease (AD). However, how the neural mechanism of CD33 affects cognition in the AD spectrum population remains unclear. We aimed to investigate the primary and interactive effects of the CD33 (rs3865444) genotype on brain function in patients with AD using global functional connectivity density (gFCD) mapping via resting-state functional magnetic resonance imaging. Furthermore, we used a conditional process analysis to identify the relationship among the CD33 genotype, gFCD, and cognition performance across the AD spectrum population. Compared to cognitively normal (CN) and mild cognitively impaired (MCI) subjects, patients with AD showed higher gFCD in the default mode network, and the CD33 genotype primarily influenced brain function in the fronto-striatal circuit. Importantly, an interaction between the CD33 genotype and AD was observed in the parahippocampal gyrus. During disease progression, the gFCD trajectories of the CD33 A + allele gradually decreased, whereas those of the CD33 CC allele displayed an inverted U-shaped curve. Furthermore, gFCD in the dorsal anterior cingulate cortex positively mediated the relationship between the CD33 genotype and cognition, while gFCD in the precuneus bidirectionally moderated the mediation in the AD spectrum. These findings provide new insights into the neural mechanisms underlying the influence of the CD33 genotype on cognitive performance and highlight the importance of precise therapeutic strategies for high-risk AD populations.


Assuntos
Doença de Alzheimer/genética , Disfunção Cognitiva/genética , Giro do Cíngulo/fisiopatologia , Vias Neurais/fisiopatologia , Giro Para-Hipocampal/fisiopatologia , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Idoso , Doença de Alzheimer/fisiopatologia , Mapeamento Encefálico , Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Feminino , Genótipo , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Giro Para-Hipocampal/diagnóstico por imagem , Polimorfismo de Nucleotídeo Único
8.
PLoS One ; 14(4): e0215736, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002697

RESUMO

The present study employed functional magnetic resonance imaging (fMRI) to examine the characteristics of negative blood oxygen level-dependent (Negative BOLD) signals during motor execution. Subjects repeated extension and flexion of one of the following: the right hand, left hand, right ankle, or left ankle. Negative BOLD responses during hand movements were observed in the ipsilateral hemisphere of the hand primary sensorimotor area (SMI), medial frontal gyrus (MeFG), middle frontal gyrus (MFG), and superior frontal gyrus (SFG). Negative BOLD responses during foot movements were also noted in the bilateral hand SMI, MeFG, MFG, SFG, inferior frontal gyrus, middle temporal gyrus, parahippocampal gyrus, anterior cingulate cortex, cingulate gyrus (CG), fusiform gyrus, and precuneus. A conjunction analysis showed that portions of the MeFG and CG involving similar regions to those of the default mode network were commonly deactivated during voluntary movements of the right/left hand or foot. The present results suggest that three mechanisms are involved in the Negative BOLD responses observed during voluntary movements: (1) transcallosal inhibition from the contralateral to ipsilateral hemisphere in the SMI, (2) the deactivated neural network with several brain regions, and (3) the default mode network in the MeFG and CG.


Assuntos
Pé/fisiologia , Giro do Cíngulo/fisiologia , Mãos/fisiologia , Imagem por Ressonância Magnética/métodos , Movimento/fisiologia , Oxigênio/sangue , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico , Feminino , Pé/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Mãos/diagnóstico por imagem , Humanos , Masculino , Córtex Sensório-Motor/diagnóstico por imagem , Córtex Sensório-Motor/fisiologia , Adulto Jovem
9.
World Neurosurg ; 127: e957-e964, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30965169

RESUMO

BACKGROUND: Diagnosis of idiopathic normal pressure hydrocephalus is based in clinical data, radiologic variables, and invasive cerebrospinal fluid (CSF) testing, such as the lumbar infusion test. Several neuroimaging findings are inconclusively related to improvement after CSF shunt surgery. CSF tests are invasive and have complications. The aim of this study was to select radiologic variables related to a positive lumbar infusion test so as to avoid this test in patients. METHODS: Patients with possible idiopathic normal pressure hydrocephalus were reviewed. The collected radiologic data were cingulate sulcus sign, disproportionately enlarged subarachnoid space, callosal angle, and width of temporal horns. Two groups were established: group 1, comprising patients with resistance to CSF outflow <12 mm Hg/mL/minute, and group 2, comprising patients with resistance to CSF outflow >12 mm Hg/mL/minute. Negative and positive predictive values were determined. RESULTS: The study included 43 patients in group 1 and 64 patients in group 2. Group 2 significantly showed more acute callosal angle with higher accuracy cutoff value of 90.6°, lower width of temporal horns with higher accuracy cutoff value of 8 mm, and higher percentage of cingulate sulcus sign and disproportionately enlarged subarachnoid space. Matching the radiologic variables, positive predictive values were >80%; however, negative predictive values were low. CONCLUSIONS: Owing to high positive predictive values of matched radiological variables, the lumbar infusion test could be avoided in the diagnosis of idiopathic normal pressure hydrocephalus. However, when 1 or 2 of the variables are negative, this invasive test should be performed.


Assuntos
Corpo Caloso/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Espaço Subaracnóideo/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Derivações do Líquido Cefalorraquidiano/métodos , Corpo Caloso/cirurgia , Feminino , Giro do Cíngulo/cirurgia , Humanos , Hidrocefalia de Pressão Normal/cirurgia , Região Lombossacral , Imagem por Ressonância Magnética/métodos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Espaço Subaracnóideo/cirurgia , Lobo Temporal/cirurgia
10.
PLoS One ; 14(4): e0214917, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30947247

RESUMO

As a special kind of handwriting with a brush, Chinese calligraphic handwriting (CCH) requires a large amount of practice with high levels of concentration and emotion regulation. Previous studies have showed that long-term CCH training has positive effects physically (induced by handwriting activities) and psychologically (induced by the state of relaxation and concentration), the latter of which is similar to the effects of meditation. The aim of this study was to investigate the long-term CCH training effect on anxiety and attention, as well as brain structure. Participants were 32 individuals who had at least five years of CCH experience and 44 controls. Results showed that CCH training benefited individuals' selective and divided attention but did not decrease their anxiety level. Moreover, the VBM analysis showed that long-term CCH training was mainly associated with smaller grey matter volumes (GMV) in the right precuneus/posterior cingulate cortex (PCC). No brain areas showed larger GMV in the CCH group than the control group. Using two sets of regions of interest (ROIs), one related to meditation and the other to handwriting, ROI analysis showed significant differences between the CCH and the control group only at the meditation-related ROIs, not at the handwriting-related ROIs. Finally, for the whole sample, the GMV of both the whole brain and the PCC were negatively correlated with selective attention and divided attention. The present study was cross-sectional and had a relatively small sample size, but its results suggested that CCH training might benefit attention and influence particular brain structure through mental processes such as meditation.


Assuntos
Atenção/fisiologia , Giro do Cíngulo , Escrita Manual , Imagem por Ressonância Magnética , Lobo Parietal , Adolescente , Adulto , Mapeamento Encefálico , Criança , Pré-Escolar , Estudos Transversais , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Humanos , Masculino , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiologia
11.
Transl Psychiatry ; 9(1): 116, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30877271

RESUMO

The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram. In MDD patients during saline infusion, in contrast with controls, the DMN (i) did not include the precuneus that was instead part of an anti-correlated network but (ii) did include amygdala that was part of the anti-correlated network in controls. Citalopram infusion in MDD patients restored the pattern seen in controls under saline. In healthy controls, citalopram infusion disengaged the precuneus from the DMN and engaged the amygdala, partially reproducing the abnormalities seen under saline in MDD. In exploratory analyses within the MDD group, greater rumination self-ratings were associated with greater intra-network connectivity of the anterior cingulate cortex with the DMN. We hypothesise that, in MDD, disengagement of the precuneus from the DMN relates to overgeneral memory bias in rumination. The opposite effect, with greater engagement of the amygdala in the DMN, reflects the negative valence of rumination. Reversal of these abnormalities by citalopram suggests that they may be related to impaired serotonin function. That citalopram engaged the amygdala in the DMN in controls may relate to the paradoxical effects on aversive processing seen with acute SSRIs in healthy subjects.


Assuntos
Citalopram/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Giro do Cíngulo/fisiopatologia , Rede Nervosa/fisiopatologia , Administração Intravenosa , Adulto , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/efeitos dos fármacos , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Escalas de Graduação Psiquiátrica , Inibidores de Captação de Serotonina/administração & dosagem , Adulto Jovem
12.
Nat Commun ; 10(1): 1400, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30923310

RESUMO

Neuroimaging modalities such as MRI and EEG are able to record from the whole brain, but this comes at the price of either limited spatiotemporal resolution or limited sensitivity. Here, we show that functional ultrasound imaging (fUS) of the brain is able to assess local changes in cerebral blood volume during cognitive tasks, with sufficient temporal resolution to measure the directional propagation of signals. In two macaques, we observed an abrupt transient change in supplementary eye field (SEF) activity when animals were required to modify their behaviour associated with a change of saccade tasks. SEF activation could be observed in a single trial, without averaging. Simultaneous imaging of anterior cingulate cortex and SEF revealed a time delay in the directional functional connectivity of 0.27 ± 0.07 s and 0.9 ± 0.2 s for both animals. Cerebral hemodynamics of large brain areas can be measured at high spatiotemporal resolution using fUS.


Assuntos
Circulação Cerebrovascular , Cognição/fisiologia , Lobo Frontal/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Movimentos Sacádicos/fisiologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Ecoencefalografia , Movimentos Oculares/fisiologia , Lobo Frontal/fisiologia , Neuroimagem Funcional , Giro do Cíngulo/fisiologia , Macaca , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Análise e Desempenho de Tarefas , Ultrassonografia Doppler Transcraniana
13.
Mol Pain ; 15: 1744806919842483, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30900511

RESUMO

We explored the atypical functional connectivity between the anterior cingulate cortex and other brain areas in rats subjected to repeated meningeal nociception. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious rats. Rats were subdivided according to the frequency of the inflammatory soup infusions. Functional connectivity analysis seeded on the anterior cingulate cortex was performed on rats 21 days after inflammatory soup infusion. Glyceryl trinitrate was injected following baseline scanning in the low-frequency inflammatory soup group and magnetic resonance imaging data were acquired 1 h after the injection. The rats exhibited nociceptive behavior after high-frequency inflammatory soup infusion. The anterior cingulate cortex showed increased functional connectivity with the cerebellum in the inflammatory soup groups. The medulla showed increased functional connectivity with the anterior cingulate cortex in the ictal period in the low-frequency inflammatory soup rats. Several areas showed increased functional connectivity with the anterior cingulate cortex in the high-frequency inflammatory soup group, including the pontine tegmentum, midbrain, thalamus, corpus callosum, hippocampus, and retrosplenial, visual, sensory, and motor cortices. This study indicated that the medulla participates in the early stage of a migraine attack and may be associated with the initiation of migraine. Sensitization of the trigeminal nociceptive pathway might contribute to the cutaneous allodynia seen in chronic migraine. Brain areas important for memory function may be related to the chronification of migraine. Electrophysiological studies should examine those migraine-related areas and provide new targets for migraine treatment and prevention.


Assuntos
Encéfalo/metabolismo , Giro do Cíngulo/metabolismo , Cefaleia/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Cefaleia/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Ratos , Ratos Sprague-Dawley
14.
Psychiatry Res ; 275: 78-85, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30884334

RESUMO

Findings from in vivo brain proton magnetic resonance spectroscopy (1H MRS) and preclinical studies have suggested region- and medication status-dependent increases in glutamate (Glu) levels and deficiencies in glutathione (GSH) levels in schizophrenia. N-acetylcysteine (NAC), a GSH synthesis precursor, has demonstrated modest clinical benefit in schizophrenia. The objective of this study was to examine the effects of acute administration of NAC on GSH and Glu levels measured with 1H MRS in 19 patients with schizophrenia and 20 healthy control subjects. Levels of GSH were acquired in dorsal anterior cingulate cortex (dACC), and those of Glu in dACC and medial prefrontal cortex (mPFC), at baseline and 60 min following acute oral administration of 2400 mg of NAC. No differences in the levels of GSH or Glu were found at baseline or following NAC administration between patients with schizophrenia and control subjects in either of the targeted brain regions. Future studies measuring GSH levels in brain regions previously found to exhibit glutamatergic abnormalities or using genetic polymorphisms, while controlling for the age and medication status of the cohorts, are warranted to better identify groups of patients more likely to respond to NAC and its mode of action and mechanisms.


Assuntos
Acetilcisteína/farmacologia , Depuradores de Radicais Livres/farmacologia , Ácido Glutâmico/metabolismo , Glutationa/metabolismo , Giro do Cíngulo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Acetilcisteína/administração & dosagem , Adolescente , Adulto , Feminino , Depuradores de Radicais Livres/administração & dosagem , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Esquizofrenia/metabolismo , Adulto Jovem
15.
Brain Stimul ; 12(4): 877-892, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30904423

RESUMO

BACKGROUND: Electrical neuromodulation via implanted electrodes is used in treating numerous neurological disorders, yet our knowledge of how different brain regions respond to varying stimulation parameters is sparse. OBJECTIVE/HYPOTHESIS: We hypothesized that the neural response to electrical stimulation is both region-specific and non-linearly related to amplitude and frequency. METHODS: We examined evoked neural responses following 400 ms trains of 10-400 Hz electrical stimulation ranging from 0.1 to 10 mA. We stimulated electrodes implanted in cingulate cortex (dorsal anterior cingulate and rostral anterior cingulate) and subcortical regions (nucleus accumbens, amygdala) of non-human primates (NHP, N = 4) and patients with intractable epilepsy (N = 15) being monitored via intracranial electrodes. Recordings were performed in prefrontal, subcortical, and temporal lobe locations. RESULTS: In subcortical regions as well as dorsal and rostral anterior cingulate cortex, response waveforms depended non-linearly on frequency (Pearson's linear correlation r < 0.39), but linearly on current (r > 0.58). These relationships between location, and input-output characteristics were similar in homologous brain regions with average Pearson's linear correlation values r > 0.75 between species and linear correlation values between participants r > 0.75 across frequency and current values per brain region. Evoked waveforms could be described by three main principal components (PCs) which allowed us to successfully predict response waveforms across individuals and across frequencies using PC strengths as functions of current and frequency using brain region specific regression models. CONCLUSIONS: These results provide a framework for creation of an atlas of input-output relationships which could be used in the principled selection of stimulation parameters per brain region.


Assuntos
Tonsila do Cerebelo/fisiologia , Estimulação Encefálica Profunda/métodos , Eletrodos Implantados/tendências , Giro do Cíngulo/fisiologia , Núcleo Accumbens/fisiologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Estimulação Encefálica Profunda/instrumentação , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/diagnóstico por imagem , Primatas , Especificidade da Espécie , Técnicas Estereotáxicas/tendências
16.
Neuroimage Clin ; 22: 101731, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30831461

RESUMO

Post-traumatic stress disorder (PTSD) is characterized by intrusions, re-experiencing, avoidance and hyperarousal. These symptoms might be linked to dysfunction in core neurocognitive networks subserving self-referential mental processing (default mode network, DMN), detection of salient stimuli (salience network, SN) and cognitive dysfunction (central executive network, CEN). Resting state studies in adolescent PTSD are scarce and findings are inconsistent, probably due to differences in patient symptom severity. Resting state brain activity was measured in 14 adolescents with severe PTSD and 24 age-matched controls. Seed-based connectivity analyses were used to examine connectivity between the DMN and the whole brain, including regions from other networks (SN and CEN). The relationships of network properties with symptom dimensions (severity, anxiety and depression) and episodic memory were also examined. Analyses revealed decreased within-DMN connectivity (between PCC and occipital cortex) in patients compared to controls. Furthermore, within-DMN connectivity (between PCC and hippocampus) correlated negatively with symptom dimensions (severity and anxiety), while increased connectivity (DMN-SN and DMN-CEN) correlated positively with episodic memory measures. These abnormal network properties found in adolescent PTSD corroborate those previously reported in adult PTSD. Decreased within-DMN connectivity and disrupted DMN-SN and DMN-CEN coupling could form the basis for intrusive trauma recollection and impaired episodic autobiographical recall in PTSD.


Assuntos
Comportamento do Adolescente/psicologia , Giro do Cíngulo/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Imagem por Ressonância Magnética/tendências , Rede Nervosa/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Adolescente , Abuso Sexual na Infância/psicologia , Abuso Sexual na Infância/tendências , Feminino , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/psicologia
17.
Psychopharmacology (Berl) ; 236(7): 1985-1997, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30820633

RESUMO

RATIONALE: Anterior cingulate cortex (ACC) glutamatergic abnormalities are reported in treatment-resistant schizophrenia (TRS) and implicated in functional dysconnectivity and psychopathology. Preclinical evidence indicates riluzole reduces synaptic glutamate. However, it is unknown whether riluzole can modulate glutamate metabolite levels and associated functional connectivity in TRS. OBJECTIVES: To examine the relationship between glutamatergic function and cortical connectivity and determine if riluzole can modulate glutamate metabolite levels and cortical functional connectivity in TRS. METHODS: Nineteen TRS patients and 18 healthy volunteers (HV) underwent magnetic resonance imaging consisting of MR spectroscopy measuring ACC glutamate plus glutamine (Glx), fMRI measuring resting ACC-functional connectivity, and arterial spin labelling measuring regional cerebral blood flow (rCBF), and clinical measures. They then received 50 mg riluzole twice daily for 2 days when imaging was repeated. RESULTS: Baseline (pre-riluzole) Glx levels were correlated directly with negative symptom severity (r = 0.49; p = 0.03) and inversely with verbal learning in TRS (r = - 0.63; p = 0.002), but not HV (r = - 0.24; p = 0.41). Connectivity between the ACC and anterior prefrontal cortex (aPFC) was correlated with verbal learning in TRS (r = 0.49; p = 0.04), but not HV (r = 0.28; p = 0.33). There was a significant group × time interaction effect on Glx levels (p < 0.05) and on ACC connectivity to the aPFC (p < 0.05, FWE-corrected). Riluzole decreased Glx and increased ACC-aPFC connectivity in TRS relative to HV. Change in Glx correlated inversely with change in ACC-aPFC connectivity in TRS (r = - 0.52; p = 0.02) but not HV (r = 0.01; p = 0.98). Riluzole did not alter rCBF (p > 0.05), indicating absence of a non-specific blood flow effect. CONCLUSION: Results indicate glutamatergic function and cortical connectivity are linked to symptoms and cognitive measures and that it is possible to pharmacologically modulate them in TRS.


Assuntos
Ácido Glutâmico/metabolismo , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/metabolismo , Riluzol/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Psicologia do Esquizofrênico , Adulto , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/metabolismo , Humanos , Imagem por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Riluzol/farmacologia , Esquizofrenia/diagnóstico por imagem , Resultado do Tratamento , Adulto Jovem
18.
Psychiatry Res ; 274: 335-344, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30851596

RESUMO

Decreases in cortical volume (CV), thickness (CT) and surface area (SA) have been reported in individuals with schizophrenia by in vivo MRI studies. However, there are few studies that examine these cortical measures as potential biomarkers of treatment resistance (TR) and treatment response (NTR) in schizophrenia. This study used structural MRI to examine differences in CV, CT, and SA in 42 adults with schizophrenia (TR = 21, NTR = 21) and 23 healthy controls (HC) to test the hypothesis that individuals with TR schizophrenia have significantly greater reductions in these cortical measures compared to individuals with NTR schizophrenia. We found that individuals with TR schizophrenia showed significant reductions in CV and CT compared to individuals with NTR schizophrenia in right frontal and precentral regions, right parietal and occipital cortex, left temporal cortex and bilateral cingulate cortex. In line with previous literature, the temporal lobe and cingulate gyrus in both patient groups showed significant reductions of all three measures when compared to healthy controls. Taken together these results suggest that regional changes in CV and CT may index mechanisms specific to TR schizophrenia and potentially identify patients with TR schizophrenia for earlier treatment.


Assuntos
Córtex Cerebral/patologia , Imagem por Ressonância Magnética/métodos , Esquizofrenia/patologia , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia
19.
Neuroimage ; 189: 793-803, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30735826

RESUMO

Midlife obesity is a risk factor of late onset Alzheimer's disease (LOAD) but why this is the case remains unknown. As systemic inflammation is involved in both conditions, obesity-related neuroinflammation may contribute to damage in limbic structures important in LOAD. Here, we investigated the hypothesis that systemic inflammation would mediate central obesity related effects on limbic tissue microstructure in 166 asymptomatic individuals (38-71 years old). We employed MRI indices sensitive to myelin and neuroinflammation [macromolecular proton fraction (MPF) and kf] from quantitative magnetization transfer (qMT) together with indices from neurite orientation dispersion and density imaging (NODDI) to investigate the effects of central adiposity on the fornix, parahippocampal cingulum, uncinate fasciculus (compared with whole brain white matter and corticospinal tract) and the hippocampus. Central obesity was assessed with the Waist Hip Ratio (WHR) and abdominal visceral and subcutaneous fat area fractions (VFF, SFF), and systemic inflammation with blood plasma concentrations of leptin, adiponectin, C-reactive protein and interleukin 8. Men were significantly more centrally obese and had higher VFF than women. Individual differences in WHR and in VFF were negatively correlated with differences in fornix MPF and kf, but not with any differences in neurite microstructure. In women, age mediated the effects of VFF on fornix MPF and kf, whilst in men differences in the leptin and adiponectin ratio fully mediated the effect of WHR on fornix MPF. These results suggest that visceral fat related systemic inflammation may damage myelin-related properties of the fornix, a key limbic structure known to be involved in LOAD.


Assuntos
Adiposidade , Giro do Cíngulo/patologia , Hipocampo/patologia , Inflamação/complicações , Gordura Intra-Abdominal , Obesidade Abdominal/complicações , Caracteres Sexuais , Substância Branca/patologia , Adulto , Fatores Etários , Idoso , Feminino , Fórnice/diagnóstico por imagem , Fórnice/patologia , Giro do Cíngulo/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Inflamação/sangue , Inflamação/etiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fatores Sexuais , Substância Branca/diagnóstico por imagem
20.
J Affect Disord ; 248: 166-174, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30735853

RESUMO

BACKGROUND: Trauma-related diagnoses such as posttraumatic stress disorder (PTSD) are prevalent in veterans. The identification of mechanisms related to stress vulnerability and development of PTSD specifically in a veteran population may aid in the prevention of PTSD and identification of novel treatment targets. METHODS: Veterans with PTSD (n = 27), trauma-exposed veterans with no PTSD (TEC, n = 18) and non-trauma-exposed controls (NTEC, n = 28) underwent single-voxel proton (1H) magnetic resonance spectroscopy (MRS) at 3 Tesla in the dorsal anterior cingulate cortex (dACC) using a two-dimensional (2D) J-resolved point spectroscopy sequence in addition to completing a clinical battery. RESULTS: The PTSD and TEC groups demonstrated lower gamma-amino butyric acid (GABA)/H2O (p = 0.02) and glutamine (Gln)/H2O (p = 0.02) in the dACC as compared to the NTEC group. The PTSD group showed a trend towards higher Glu/GABA (p = 0.053) than the NTEC group. Further, GABA/H2O in the dACC correlated negatively with sleep symptoms in the PTSD group (p = 0.03) but not in the TEC and NTEC groups. LIMITATIONS: Cross-sectional study design, concomitant medications, single voxel measurement as opposed to global changes, absence of measure of childhood or severity of trauma and objective sleep measures, female participants not matched for menstrual cycle phase. CONCLUSIONS: Exposure to trauma in veterans may be associated with lower GABA/H2O and Gln/H2O in the dACC, suggesting disruption in the GABA-Gln-glutamate cycle. Further, altered Glu/GABA in the dACC in the PTSD group may indicate an excitatory-inhibitory imbalance. Further, lower GABA/H2O in the ACC was associated with poor sleep in the PTSD group. Treatments that restore GABAergic balance may be particularly effective in reducing sleep symptoms in PTSD.


Assuntos
Glutamina/metabolismo , Doenças Profissionais/metabolismo , Transtornos de Estresse Pós-Traumáticos/metabolismo , Veteranos/psicologia , Ácido gama-Aminobutírico/metabolismo , Adulto , Estudos Transversais , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Doenças Profissionais/diagnóstico por imagem , Doenças Profissionais/psicologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/psicologia , Estados Unidos
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