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1.
World Neurosurg ; 133: 55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562962

RESUMO

Laughter has a major role in daily social interactions; consequently, its biologic bases have been previously studied. Nevertheless, its cerebral representation remains unclear. The most accepted hypothesis has postulated that laughter has 2 components: mirth, related to the temporal and frontal neocortical areas, and motor aspect, related to the limbic system and brainstem. Furthermore, in prior studies, laughter has been elicited during electric stimulation with depth electrodes in the supplementary motor area and the cingulum. This Video 1 reports resection of a right superior frontal gyrus diffuse astrocytoma (isocitrate dehydrogenase mutant, World Health Organization grade II) with awake intraoperative electric cortical and subcortical stimulation mapping. Diffusion tensor imaging (DTI) tractography, including all the tracts in relation to the tumor, was obtained preoperatively and postoperatively. Stimulation of the cingulum medially and inferiorly to the tumor elicited a patient's smile and laugh without mirth or merriment. Also, this point correlated with the reconstructed cingulum in the intraoperatively navigated DTI tractography. In conclusion, these findings support the anatomic subdivision of the laughter's mechanism and the role of the cingulum in its motor component. Furthermore, smiles and laughter could be useful functional landmarks to identify the cingulum during subcortical mapping. Although it remains unclear whether pursuing resection beyond this point would have caused permanent postoperative deficits, considering laughter's role in social interaction and other emotion-processing functions associated with the cingulum, in the future it could be potentially considered a functional limit of the resection of intrinsic tumors.


Assuntos
Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Giro do Cíngulo/fisiopatologia , Riso/fisiologia , Sorriso/fisiologia , Astrocitoma/patologia , Astrocitoma/fisiopatologia , Mapeamento Encefálico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Estimulação Elétrica , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Lobo Frontal/cirurgia , Humanos
2.
J Headache Pain ; 20(1): 103, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711415

RESUMO

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests principally as a suite of cognitive impairments, particularly in the executive domain. Executive functioning requires the dynamic coordination of neural activity over large-scale networks. It remains unclear whether changes in resting-state brain functional network connectivity and regional homogeneities (ReHos) underly the mechanisms of executive dysfunction evident in CADASIL patients. METHODS: In this study, 22 CADASIL patients and 44 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). Independent component analysis (ICA) was used to measure functional brain network connectivity, and ReHos were calculated to evaluate local brain activities. We used seed-based functional connectivity (FC) analyses to determine whether dysfunctional areas (as defined by ReHos) exhibited abnormal FC with other brain areas. Relationships among the mean intra-network connectivity z-scores of dysfunctional areas within functional networks, and cognitive scores were evaluated using Pearson correlation analyses. RESULTS: Compared to the controls, CADASIL patients exhibited decreased intra-network connectivity within the bilateral lingual gyrus (LG) and the right cuneus (CU) (thus within the visual network [VIN)], and within the right precuneus (Pcu), inferior frontal gyrus (IFG), and precentral gyrus (thus within the frontal network [FRN]). Compared to the controls, patients also exhibited significantly lower ReHos in the right precuneus and cuneus (Pcu/CU), visual association cortex, calcarine gyri, posterior cingulate, limbic lobe, and weaker FC between the right Pcu/CU and the bilateral parahippocampal gyrus (PHG), and between the right Pcu/CU and the right postcentral gyrus. Notably, the mean connectivity z-scores of the bilateral LG and the right CU within the VIN were positively associated with compromised attention, calculation and delayed recall as revealed by tests of the various cognitive domains explored by the Mini-Mental State Examination. CONCLUSIONS: The decreases in intra-network connectivity within the VIN and FRN and reduced local brain activity in the posterior parietal area suggest that patients with CADASIL may exhibit dysfunctional visuomotor behaviors (a hallmark of executive function), and that all visual information processing, visuomotor planning, and movement execution may be affected.


Assuntos
Encéfalo/diagnóstico por imagem , CADASIL/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Função Executiva , Adulto , Encéfalo/fisiopatologia , CADASIL/fisiopatologia , CADASIL/psicologia , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Cognição , Disfunção Cognitiva/psicologia , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Neuroimagem Funcional , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/fisiopatologia , Descanso , Córtex Visual/diagnóstico por imagem , Córtex Visual/fisiopatologia
3.
BMC Neurol ; 19(1): 237, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615444

RESUMO

BACKGROUND: The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls. METHODS: Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants. RESULTS: Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8-10 min of citalopram infusion. CONCLUSIONS: Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine.


Assuntos
Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/fisiopatologia , Serotonina/metabolismo , Adulto , Mapeamento Encefálico/métodos , Citalopram/farmacologia , Método Duplo-Cego , Feminino , Giro do Cíngulo/efeitos dos fármacos , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/farmacologia
4.
Neuropsychology ; 33(6): 795-807, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31448947

RESUMO

OBJECTIVE: Alcohol use disorder (AUD) and chronic pain are widespread conditions with extensive public health burden. This review seeks to describe neuroanatomical links and major mediating influences between AUD and chronic pain, in the service of identifying factors that predict the risk of chronic pain in precipitating or facilitating AUD. METHOD: We review the neural bases of pain and the influence of AUD on processes involved in pain perception. We propose potential mechanisms involved in the development of chronic pain in AUD, and we consider implications for pain management in recovery from AUD. RESULTS: Pain is a multidimensional and subjective experience that, in its acute form, is essential for survival, but in chronic form, pain is a disorder that negatively impacts quality of life. Neural substrates involved in initiating and maintaining chronic pain include dysfunction in descending pain pathways and reward network circuitry. AUD involves preoccupation or craving, intoxication, withdrawal, and negative affect. Neural substrates of AUD involve widespread mesocorticolimbic and cerebrocerebellar networks. Both conditions involve dysfunction of extended reward and oversight circuitry, particularly prefrontal cortex. CONCLUSIONS: The interrelationship between chronic pain and AUD resides in the intersection of etiological influences, mental experiences, and neurobiological processes. Characterization of the connection between brain and behavioral abnormalities in AUD's precipitation of chronic pain-and vice versa-allows for early detection and treatment of patients at risk for developing either or both of these conditions and for preemptive interventional approaches to reduce the risk of consequent vulnerabilities and harm. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Alcoolismo/fisiopatologia , Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Alcoolismo/reabilitação , Córtex Cerebral/fisiopatologia , Dor Crônica/terapia , Fissura , Giro do Cíngulo/fisiopatologia , Humanos , Vias Neurais , Manejo da Dor , Córtex Pré-Frontal/fisiopatologia , Qualidade de Vida , Recompensa
5.
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
6.
Nat Neurosci ; 22(8): 1223-1234, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31332372

RESUMO

Social deficit is a core clinical feature of autism spectrum disorder (ASD) but the underlying neural mechanisms remain largely unclear. We demonstrate that structural and functional impairments occur in glutamatergic synapses in the pyramidal neurons of the anterior cingulate cortex (ACC) in mice with a mutation in Shank3, a high-confidence candidate ASD gene. Conditional knockout of Shank3 in the ACC was sufficient to generate excitatory synaptic dysfunction and social interaction deficits, whereas selective enhancement of ACC activity, restoration of SHANK3 expression in the ACC, or systemic administration of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-positive modulator improved social behavior in Shank3 mutant mice. Our findings provide direct evidence for the notion that the ACC has a role in the regulation of social behavior in mice and indicate that ACC dysfunction may be involved in social impairments in ASD.


Assuntos
Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Giro do Cíngulo/patologia , Proteínas do Tecido Nervoso/genética , Comportamento Social , Animais , Dioxóis/farmacologia , Modelos Animais de Doenças , Ácido Glutâmico , Asseio Animal , Giro do Cíngulo/fisiopatologia , Relações Interpessoais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação/genética , Optogenética , Piperidinas/farmacologia , Células Piramidais/patologia , Receptores de AMPA/agonistas , Sinapses/patologia
7.
Soc Cogn Affect Neurosci ; 14(7): 777-787, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31269203

RESUMO

Mindfulness meditation training has been shown to increase resting-state functional connectivity between nodes of the frontoparietal executive control network (dorsolateral prefrontal cortex [DLPFC]) and the default mode network (posterior cingulate cortex [PCC]). We investigated whether these effects generalized to a Mindfulness-Based Stress Reduction (MBSR) course and tested for structural and behaviorally relevant consequences of change in connectivity. Healthy, meditation-naïve adults were randomized to either MBSR (N = 48), an active (N = 47) or waitlist (N = 45) control group. Participants completed behavioral testing, resting-state fMRI scans and diffusion tensor scans at pre-randomization (T1), post-intervention (T2) and ~5.5 months later (T3). We found increased T2-T1 PCC-DLPFC resting connectivity for MBSR relative to control groups. Although these effects did not persist through long-term follow-up (T3-T1), MBSR participants showed a significantly stronger relationship between days of practice (T1 to T3) and increased PCC-DLPFC resting connectivity than participants in the active control group. Increased PCC-DLPFC resting connectivity in MBSR participants was associated with increased microstructural connectivity of a white matter tract connecting these regions and increased self-reported attention. These data show that MBSR increases PCC-DLPFC resting connectivity, which is related to increased practice time, attention and structural connectivity.


Assuntos
Encéfalo/fisiologia , Função Executiva/fisiologia , Meditação/psicologia , Atenção Plena , Córtex Pré-Frontal/fisiologia , Adulto , Encéfalo/fisiopatologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Descanso , Substância Branca , Adulto Jovem
8.
Neural Plast ; 2019: 2057308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223307

RESUMO

Our previous studies have confirmed that electroacupuncture (EA) can effectively intervene in pain memory, but the neural mechanism involved remains unclear. In this study, we observed the effects of EA in regulating pain memory-related behaviors and synchronous neural oscillations in the rostral anterior cingulate cortex (rACC). During nociceptive behavioral testing, pain memory induced a nonpain stimulus that spurred a neural oscillatory reaction similar to that caused by pain stimuli in the rACC. After EA, nonpain stimuli did not induce decreased neural oscillatory activity in the rACC until the presentation of pain stimuli. During aversive behavioral testing, EA, through the downregulation of theta power, inhibited the retrieval of aversive memory and relieved pain memory-induced aversive behaviors. These changes of oscillatory activity may be the hallmarks of EA therapy for pain memory.


Assuntos
Comportamento Animal/fisiologia , Ondas Encefálicas/fisiologia , Eletroacupuntura , Giro do Cíngulo/fisiopatologia , Memória/fisiologia , Dor/fisiopatologia , Animais , Masculino , Nociceptividade/fisiologia , Limiar da Dor , Ratos , Ratos Sprague-Dawley
9.
JAMA Netw Open ; 2(6): e195578, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31167023

RESUMO

Importance: Hyperactivity in the subgenual cingulate cortex (SGC) is associated with major depressive disorder (MDD) and anticorrelated with activity in the dorsolateral prefrontal cortex (DLPFC). This association was found to be predictive of responsiveness to repetitive transcranial magnetic stimulation (rTMS) treatment. Such findings suggest that DLPFC-SGC connectivity is important for understanding both the therapeutic mechanism of rTMS in patients with MDD and the underlying pathophysiology of MDD. Objective: To evaluate SGC hyperactivity in patients with MDD before and after rTMS treatment. Design, Setting, and Participants: In this diagnostic study, among participants recruited from the adult and geriatric mood and anxiety services at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, who had participated in a randomized clinical trial, baseline SGC activity of patients with MDD was compared with healthy controls. In patients with MDD, SGC activity was compared before and after active or sham high-frequency rTMS treatment. Data collection started in July 2008 and concluded in March 2012. Neurophysiological data analysis started in January 2017 and ended in May 2018. Main Outcomes and Measures: Hyperactivity in the SGC before and after rTMS treatment was measured. Subgenual cingulate cortex hyperactivity activity was quantified using significant current density (SCD), and effective connectivity between the left DLPFC and SGC was computed using significant current scattering (SCS). Both measures were computed around TMS evoked potentials standard peak latencies prior to rTMS and after rTMS treatment, comparing patients with MMD treated with active and sham rTMS. Patients with MDD were assessed with the 17-item Hamilton Rating Scale for Depression. Results: Of 121 patients with MDD in the initial trial, 30 (15 [50.0%] women) were compared with 30 healthy controls (15 [50.0%] women) at rTMS treatment baseline. The mean (SD) age of the cohort with MDD was 39.1 (10.9) years, and the mean (SD) age of healthy controls was 37.0 (11.0) years. Following rTMS treatment, 26 patients with MDD who had active rTMS treatment (21.5%) were compared with 17 patients with MDD who had sham treatment (14.0%). At baseline, the SGC mean (SD) SCD and mean (SD) SCS at 200 milliseconds after TMS pulse were higher in participants with MDD compared with healthy controls (SCD: 1.04 × 10-6 [1.41 × 10-6] µA/mm2 vs 3.8 × 10-7 [7.8 × 10-7] µA/mm2; z = -2.95; P = .004; SCS: 0.87 [0.86] mm vs 0.54 [0.87] mm; z = -2.27; P = .02). Baseline source current density was able to classify MDD with 77% accuracy. Scores on the 17-item Hamilton Rating Scale for Depression were correlated with current density at the SGC (ρ = 0.41; P = .03). After rTMS treatment, SGC mean (SD) SCD and mean (SD) SCS at 200 milliseconds after rTMS pulse were attenuated to approximately the standard TMS-evoked potential latencies in the active rTMS group compared with the sham rTMS group (SCD: 1.57 × 10-7 [3.67 × 10-7] µA/mm2 vs 7.00 × 10-7 [7.51 × 10-7] µA/mm2; z = -2.91; P = .004; SCS: 0.20 [0.44] mm vs 0.74 [0.73] mm; z = -2.78; P = .006). Additionally, the SGC SCS change was correlated with symptom improvement on the 17-item Hamilton Rating Scale for Depression in the active rTMS group (ρ = 0.58; P = .047). Conclusions and Relevance: The findings of this study further implicate left DLPFC-SGC effective connectivity and SGC excitability in the pathophysiology of MDD and treatment with rTMS. These findings suggest that DLPFC-SGC connectivity may be a marker of rTMS treatment responsiveness. Trial Registration: ClinicalTrials.gov identifier: NCT01515215.


Assuntos
Transtorno Depressivo Maior/terapia , Giro do Cíngulo/fisiopatologia , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Adulto , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Resistente a Tratamento/fisiopatologia , Transtorno Depressivo Resistente a Tratamento/terapia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
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
11.
Photobiomodul Photomed Laser Surg ; 37(3): 133-141, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31050950

RESUMO

Objective: To examine the effects of transcranial and intranasal photobiomodulation (PBM) therapy, administered at home, in patients with dementia. Background: This study sought to replicate and build upon a previously published case series report describing improved cognitive function in five patients with mild-to-moderate dementia after 12 weeks of transcranial and intranasal near-infrared (NIR) PBM therapy. Materials and methods: Eight participants (mean age: 79.8 ± 5.8 years old) diagnosed with dementia by their physicians were randomized to 12 weeks of usual care (UC, n = 4) or home PBM treatments (n = 4). The NIR PBM treatments were administered by a study partner at home three times per week with the Vielight Neuro Gamma device. The participants were assessed with the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) subscale and the Neuropsychiatric Inventory (NPI) at baseline and 6 and 12 weeks, and with arterial spin-labeled perfusion magnetic resonance imaging (MRI) and resting-state functional MRI at baseline and 12 weeks. Results: At baseline, the UC and PBM groups did not differ demographically or clinically. However, after 12 weeks, there were improvements in ADAS-cog (group × time interaction: F1,6 = 16.35, p = 0.007) and NPI (group × time interaction: F1,6 = 7.52, p = 0.03), increased cerebral perfusion (group × time interaction: F1,6 = 8.46, p < 0.03), and increased connectivity between the posterior cingulate cortex and lateral parietal nodes within the default-mode network in the PBM group. Conclusions: Because PBM was well tolerated and associated with no adverse side effects, these results support the potential of PBM therapy as a viable home treatment for individuals with dementia.


Assuntos
Circulação Cerebrovascular/efeitos da radiação , Cognição/efeitos da radiação , Demência/terapia , Serviços de Assistência Domiciliar , Terapia com Luz de Baixa Intensidade , Idoso , Idoso de 80 Anos ou mais , Circulação Cerebrovascular/fisiologia , Cognição/fisiologia , Demência/fisiopatologia , Demência/psicologia , Feminino , Giro do Cíngulo/irrigação sanguínea , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Projetos Piloto , Resultado do Tratamento
12.
J Affect Disord ; 251: 280-286, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30953893

RESUMO

BACKGROUND: Aberrant functional and structural connectivity are considered to be involved in the underlying neural mechanism of generalized anxiety disorder (GAD). However, alterations in functional and structural interactions between the bilateral hemispheres are rarely examined. The current study aimed to characterized interhemispheric resting-state functional connectivity and white matter microstructural integrity of the corpus callosum in patients with GAD. METHODS: Resting-state Blood oxygen level-dependent and diffusion tensor image were acquired for patients with GAD and healthy subjects. The two groups were matched in age, gender, education years. The voxel-mirrored homotopic connectivity (VMHC) of whole brain and white matter integrity of the corpus callosum (CC) were compared between the two groups. Their correlations with clinical measures were further performed. RESULTS: Compare to controls, decreased resting-state VMHC were found in the precentral gyrus, middle cingulate gyrus and insula/putamen in patients with GAD. No regions of increased VMHC were detected in GAD. Compared to controls, GAD patients showed decreased fractional anisotropy (FA) values in CC2. In GAD group, further Pearson's correlation analyses showed that VMHC of the midcingulate gyrus positively correlated with FA of CC2, FA of CC2 negatively correlated with anxiety severity. Further mediation analyses demonstrated that attenuated VMHC in bilateral midcingulate gyrus partly mediated the association between white matter integrity of CC2 sub-region and anxiety severity. CONCLUSION: Our findings suggested impairment of interhemispheric coordination in GAD. Moreover, disrupted interhemispheric connectivity correlated with anxiety severity in GAD. Our findings provided a novel clue about the neural mechanism of GAD, and may contribute to further deep exploration and treatment of GAD. LIMITATIONS: The study was lack of comparison with non-GAD anxiety disorders.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Córtex Cerebral/fisiopatologia , Corpo Caloso/fisiopatologia , Adulto , Anisotropia , Transtornos de Ansiedade/diagnóstico por imagem , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/fisiologia , Imagem de Tensor de Difusão , Feminino , Giro do Cíngulo/fisiologia , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Valores de Referência
13.
Brain Topogr ; 32(5): 753-761, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31011853

RESUMO

Borderline personality disorder (BPD) is characterized by interpersonal disturbances and dysfunctional behavior such as non-suicidal self-injury (NSSI). We recently observed neural alterations in BPD during social inclusion by enhanced activations within the dorsomedial prefrontal cortex (dmPFC) and the posterior cingulate cortex (PCC). To examine the specificity of these neural alterations, we now investigated participants with NSSI but without BPD and compared them to BPD and healthy controls (HC). Considering the association between NSSI and BPD, we further examined neural commonalities during social inclusion. Fifteen females diagnosed with BPD, 16 with NSSI and 17 HC were investigated by fMRI and the cyberball paradigm, focusing on social inclusion (p < 0.05; FWE on cluster-level). To examine neural commonalities between BPD and NSSI compared to HC, we computed a conjunction analysis on neural activations under social inclusion. Significant increases in neural activation were observed in BPD within the dmPFC under social inclusion compared to NSSI and HC, whereas neural activations within the PCC did not differ between BPD and NSSI. The conjunction analysis revealed a common neurofunctional increase within the pregenual anterior cingulate cortex and the anterior insula in both, BPD and NSSI. We provide a further evidence regarding a disorder-specific neural reactivity within the dmPFC during social inclusion in BPD, whereas PCC activations may represent an unspecific neural alteration in BPD when compared to NSSI. In contrast, both clinical groups revealed a common neural increase within the salience network that may support the assumptions of a developmental continuum between these two psychiatric conditions.


Assuntos
Transtorno da Personalidade Borderline/fisiopatologia , Giro do Cíngulo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Comportamento Autodestrutivo/fisiopatologia , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino
14.
J Affect Disord ; 252: 365-372, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30999093

RESUMO

BACKGROUND: Major depressive disorder (MDD) is associated with a heavy disease burden due to the difficulty in diagnosing the disorder and the uncertainty of treatment outcomes. Previous studies have demonstrated the value of functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC) and the subgenual anterior cingulate cortex (sgACC) in the identification of MDD and the prediction of antidepressant efficacy. In the present study, we aimed to investigate whether FC is helpful in discriminating patients from healthy controls and in predicting treatment outcome. METHODS: Seventy-six medication-free patients with MDD and 28 healthy controls were enrolled in the study. Magnetoencephalography (MEG) and the Hamilton Rating Score for Depression (HRSD-17) were administered at baseline. Then, the HRSD-17 was assessed weekly until each patient met the remission criteria, defined as a total HRSD-17 score ≤ 7. Time-dependent Cox regression analysis was used to evaluate the association between FC and the incidence of remission. RESULTS: Healthy controls and MDD patients had opposite FC patterns; this may be helpful for identifying MDD (AUC = 0.8, p < 0.001, sensitivity 85.7%, specificity 67.9%). Alpha connectivity between the DLPFC and sgACC (HR 1.858, 95%CI 1.013-3.408, p = 0.045) was found to be an independent factor associated with better final antidepressant outcome. LIMITATIONS: This study was conducted in a small sample of subjects. Further, the direction of regulation between the DLPFC and sgACC was not considered. CONCLUSIONS: FC may help identify depression and may be related to the severity of depressive symptoms and predict the efficacy of antidepressant treatment.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Magnetoencefalografia/estatística & dados numéricos , Córtex Pré-Frontal/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Córtex Pré-Frontal/fisiopatologia , Análise de Regressão , Sensibilidade e Especificidade , Resultado do Tratamento
15.
Brain Dev ; 41(8): 735-739, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31005361

RESUMO

BACKGROUND: Non-paraneoplastic limbic encephalitis is characterized by attention deficit, loss of emotion control, and impaired memory. Viral infection can cause acute encephalitis in children, occasionally exhibiting clinical features of limbic dysfunction. However, how viral infection affects the limbic system remains to be elucidated. CASE DESCRIPTION: A 5-year-old Japanese boy was admitted to our hospital because of high fever and status epilepticus. After seizures were controlled by diazepam, he exhibited attention deficit, loss of emotion control, and impaired memory, suggesting acute limbic encephalitis. Since titers of antibodies against Coxsackie virus A10 were significantly elevated in the serum, we diagnosed him with non-paraneoplastic limbic encephalitis associated with the viral infection. Brain magnetic resonance imaging demonstrated involvement of anterior cingulate cortex as well as white matter of the frontal lobe in the acute period. After steroid pulse therapy, these brain lesions subsequently disappeared in a time-dependent manner, beginning with the frontal lobe white matter and extending to the anterior cingulate cortex, and his psychological symptoms also disappeared. CONCLUSION: To the best of our knowledge, this is the first report to show the involvement of the region from the anterior cingulate cortex to the frontal lobe white matter. Clinical features such as seizures, attention deficit, loss of emotion control, and impaired memory suggest that this viral limbic encephalitis possibly extended from the frontal white matter to the anterior cingulate cortex via inter-neuronal connections in a time-dependent manner.


Assuntos
Giro do Cíngulo/fisiopatologia , Encefalite Límbica/diagnóstico , Encefalite Límbica/fisiopatologia , Encéfalo/patologia , Pré-Escolar , Infecções por Coxsackievirus/diagnóstico , Encefalite/complicações , Enterovirus/patogenicidade , Humanos , Japão , Encefalite Límbica/imunologia , Imagem por Ressonância Magnética , Masculino , Convulsões/etiologia , Estado Epiléptico/complicações , Esteroides/uso terapêutico
16.
Neurobiol Learn Mem ; 161: 92-105, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30946882

RESUMO

Cocaine use disorder (CUD) is associated with prefrontal cortex dysfunction and cognitive deficits that may contribute to persistent relapse susceptibility. As the relationship between cognitive deficits, cortical abnormalities and drug seeking is poorly understood, development of relevant animal models is of high clinical importance. Here, we used an animal model to characterize working memory and reversal learning in rats with a history of extended access cocaine self-administration and prolonged abstinence. We also investigated immediate and long-term functional changes within the prelimbic cortex (PrL) in relation to cognitive performance and drug-seeking. Adult male rats underwent 6 days of short-access (1 h/day) followed by 12 days of long-access (6 h/day) cocaine self-administration, or received passive saline infusions. Next, rats were tested in delayed match-to-sample (DMS) and (non)match-to-sample (NMS) tasks, and finally in a single context + cue relapse test on day 90 of abstinence. We found that a history of chronic cocaine self-administration impaired working memory, though sparing reversal learning, and that the components of these cognitive measures correlated with later drug-seeking. Further, we found that dysregulated metabolic activity and mGlu5 receptor signaling in the PrL of cocaine rats correlated with past working memory performance and/or drug-seeking, as indicated by the analysis of cytochrome oxidase reactivity, mGlu5 and Homer 1b/c protein expression, as well as Arc mRNA expression in mGlu5-positive cells. These findings advocate for a persistent post-cocaine PrL dysfunction, rooted in ineffective compensatory changes and manifested as impaired working memory performance and hyperreactivity to cocaine cues. Considering the possible interplay between the neural correlates underlying post-cocaine cognitive deficits and drug-seeking, cognitive function should be evaluated and considered when developing neurobiologically-based treatments of cocaine relapse.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína/farmacologia , Disfunção Cognitiva , Inibidores da Captação de Dopamina/farmacologia , Giro do Cíngulo , Memória de Curto Prazo , Córtex Pré-Frontal , Receptor de Glutamato Metabotrópico 5/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Transtornos Relacionados ao Uso de Cocaína/complicações , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Ratos , Ratos Sprague-Dawley , Autoadministração
17.
Neurology ; 92(18): e2165-e2175, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30952795

RESUMO

OBJECTIVE: To compare the analgesic effects of stimulation of the anterior cingulate cortex (ACC) or the posterior superior insula (PSI) against sham deep (d) repetitive (r) transcranial magnetic stimulation (TMS) in patients with central neuropathic pain (CNP) after stroke or spinal cord injury in a randomized, double-blinded, sham-controlled, 3-arm parallel study. METHODS: Participants were randomly allocated into the active PSI-rTMS, ACC-rTMS, sham-PSI-rTMS, or sham-ACC-rTMS arms. Stimulations were performed for 12 weeks, and a comprehensive clinical and pain assessment, psychophysics, and cortical excitability measurements were performed at baseline and during treatment. The main outcome of the study was pain intensity (numeric rating scale [NRS]) after the last stimulation session. RESULTS: Ninety-eight patients (age 55.02 ± 12.13 years) completed the study. NRS score was not significantly different between groups at the end of the study. Active rTMS treatments had no significant effects on pain interference with daily activities, pain dimensions, neuropathic pain symptoms, mood, medication use, cortical excitability measurements, or quality of life. Heat pain threshold was significantly increased after treatment in the PSI-dTMS group from baseline (1.58, 95% confidence interval [CI] 0.09-3.06]) compared to sham-dTMS (-1.02, 95% CI -2.10 to 0.04, p = 0.014), and ACC-dTMS caused a significant decrease in anxiety scores (-2.96, 95% CI -4.1 to -1.7]) compared to sham-dTMS (-0.78, 95% CI -1.9 to 0.3; p = 0.018). CONCLUSIONS: ACC- and PSI-dTMS were not different from sham-dTMS for pain relief in CNP despite a significant antinociceptive effect after insular stimulation and anxiolytic effects of ACC-dTMS. These results showed that the different dimensions of pain can be modulated in humans noninvasively by directly stimulating deeper SNC cortical structures without necessarily affecting clinical pain per se. CLINICALTRIALSGOV IDENTIFIER: NCT01932905.


Assuntos
Córtex Cerebral/fisiopatologia , Estimulação Encefálica Profunda/métodos , Giro do Cíngulo/fisiopatologia , Neuralgia/terapia , Estimulação Magnética Transcraniana/métodos , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/fisiopatologia , Manejo da Dor/métodos , Medição da Dor , Resultado do Tratamento
18.
Bipolar Disord ; 21(6): 503-513, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31025452

RESUMO

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.


Assuntos
Afeto/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Atenção/fisiologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Emoções/fisiologia , Feminino , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Tálamo/fisiopatologia
19.
Transl Psychiatry ; 9(1): 136, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979866

RESUMO

Neuroimaging studies have shown topological disruptions of both functional and structural whole-brain networks in major depressive disorder (MDD). This study examined common and specific alterations between these two types of networks and whether the alterations were differentially involved in the two hemispheres. Multimodal MRI data were collected from 35 MDD patients and 35 healthy controls, whose functional and structural hemispheric networks were constructed, characterized, and compared. We found that functional brain networks were profoundly altered at multiple levels, while structural brain networks were largely intact in patients with MDD. Specifically, the functional alterations included decreases in intra-hemispheric (left and right) and inter-hemispheric (heterotopic) functional connectivity; decreases in local, global and normalized global efficiency for both hemispheric networks; increases in normalized local efficiency for the left hemispheric networks; and decreases in intra-hemispheric integration and inter-hemispheric communication in the dorsolateral superior frontal gyrus, anterior cingulate gyrus and hippocampus. Regarding hemispheric asymmetry, largely similar patterns were observed between the functional and structural networks: the right hemisphere was over-connected and more efficient than the left hemisphere globally; the occipital and partial regions exhibited leftward asymmetry, and the frontal and temporal sites showed rightward lateralization with regard to regional connectivity profiles locally. Finally, the functional-structural coupling of intra-hemispheric connections was significantly decreased and correlated with the disease severity in the patients. Overall, this study demonstrates modality- and hemisphere-dependent and invariant network alterations in MDD, which are helpful for understanding elaborate and characteristic patterns of integrative dysfunction in this disease.


Assuntos
Encéfalo/fisiopatologia , Conectoma , Transtorno Depressivo Maior/fisiopatologia , Vias Neurais/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Córtex Pré-Frontal/fisiopatologia
20.
J Affect Disord ; 250: 270-277, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30870777

RESUMO

BACKGROUND: Entropy analysis is a computational method used to quantify the complexity in a system, and loss of brain complexity is hypothesized to be related to mental disorders. Here, we applied entropy analysis to the resting-state functional magnetic resonance imaging (rs-fMRI) signal in subjects with late-life depression (LLD), an illness combined with emotion dysregulation and aging effect. METHODS: A total of 35 unremitted depressed elderly and 22 control subjects were recruited. Multiscale entropy (MSE) analysis was performed in the entire brain, 90 automated anatomical labeling-parcellated ROIs, and five resting networks in each study participant. LIMITATIONS: Due to ethical concerns, all the participants were under medication during the study. RESULTS: Regionally, subjects with LLD showed decreased entropy only in the right posterior cingulate gyrus but had universally increased entropy in affective processing (putamen and thalamus), sensory, motor, and temporal nodes across different time scales. We also found higher entropy in the left frontoparietal network (FPN), which partially mediated the negative correlation between depression severity and mental components of the quality of life, reflecting the possible neural compensation during depression treatment. CONCLUSION: MSE provides a novel and complementary approach in rs-fMRI analysis. The temporal-spatial complexity in the resting brain may provide the adaptive variability beneficial for the elderly with depression.


Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo/fisiopatologia , Imagem por Ressonância Magnética/métodos , Saúde Mental , Qualidade de Vida/psicologia , Idoso , Antidepressivos/uso terapêutico , Mapeamento Encefálico/métodos , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/psicologia , Entropia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Descanso/fisiologia , Tálamo/fisiopatologia
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