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1.
Psychophysiology ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33037836

RESUMO

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

2.
Front Neurosci ; 14: 147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041747

RESUMO

There are bi-directional interactions between the autonomic nervous system (ANS) and pain. This is likely underpinned by a substantial overlap between brain areas of the central autonomic network and areas involved in pain processing and modulation. To date, however, relatively little is known about the neuronal substrates of the ANS-pain association. Here, we acquired resting state fMRI scans in 21 healthy subjects at rest and during tonic noxious cold stimulation. As indicators of autonomic function, we examined how heart rate variability (HRV) frequency measures were influenced by tonic noxious stimulation and how these variables related to participants' pain perception and to brain functional connectivity in regions known to play a role in both ANS regulation and pain perception, namely the right dorsal anterior cingulate cortex (dACC) and periaqueductal gray (PAG). Our findings support a role of the cardiac ANS in brain connectivity during pain, linking functional connections of the dACC and PAG with measurements of low frequency (LF)-HRV. In particular, we identified a three-way relationship between the ANS, cortical brain networks known to underpin pain processing, and participants' subjectively reported pain experiences. LF-HRV both at rest and during pain correlated with functional connectivity between the seed regions and other cortical areas including the right dorsolateral prefrontal cortex (dlPFC), left anterior insula (AI), and the precuneus. Our findings link cardiovascular autonomic parameters to brain activity changes involved in the elaboration of nociceptive information, thus beginning to elucidate underlying brain mechanisms associated with the reciprocal relationship between autonomic and pain-related systems.

3.
Eur J Pain ; 24(9): 1850-1861, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32648623

RESUMO

BACKGROUND: Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes varies between cohorts and may relate to the consequences of living with chronic-pain related comorbidities, such as anxiety and depression. Healthy volunteer studies provide opportunities to study the effects of tonic noxious stimulation independently of these sequelae. Connectivity changes in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how these and other connectivity networks, for example, those governing descending pain control are affected by the presence of tonic, noxious stimulation in healthy, pain-free individuals, remains unknown. METHOD: In 20 healthy volunteers, we assessed FC prior to, during, and following tonic cold painful stimulation in the ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG). We also recorded subjectively reported pain using a computerised visual analogue scale. RESULTS: We saw DMN FC changes during painful stimulation and that inter-network connectivity between the rAI with the vmPFC increased during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations persisted following noxious stimulation. FC changes related to the magnitude of individuals' subjectively reported pain. CONCLUSIONS: We demonstrate FC changes during and following tonic cold-pain in healthy participants. Similarities between our findings and reports of patients with chronic pain suggest that some FC changes observed in these patients may relate to the presence of an ongoing afferent nociceptive drive. SIGNIFICANCE: How pain-related resting state networks are affected by tonic cold-pain remains unknown. We investigated functional connectivity alterations during and following tonic cold pain in healthy volunteers. Cold pain perturbed the functional connectivity of the ventro-medial prefrontal cortex, anterior insula, and the periacquaductal grey area. These connectivity changes were associated with the magnitude of individuals' reported pain. We suggest that some connectivity changes described in chronic pain patients may be due to an ongoing afferent peripheral drive.

4.
Neuroimage ; 221: 117178, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707236

RESUMO

Functional neuroimaging techniques have provided great insight in the field of pain. Utilising these techniques, we have characterised pain-induced responses in the brain and improved our understanding of key pain-related phenomena. Despite the utility of these methods, there remains a need to assess the test retest reliability of pain modulated blood-oxygen-level-dependant (BOLD) MR signal across repeated sessions. This is especially the case for more novel yet increasingly implemented stimulation modalities, such as noxious pressure, and it is acutely important for multi-session studies considering treatment efficacy. In the present investigation, BOLD signal responses were estimated for noxious-pressure stimulation in a group of healthy participants, across two separate sessions. Test retest reliability of functional magnetic resonance imaging (fMRI) data and self-reported visual analogue scale measures were determined by the intra-class correlation coefficient. High levels of reliability were observed in several key brain regions known to underpin the pain experience, including in the thalamus, insula, somatosensory cortices, and inferior frontal regions, alongside "excellent" reliability of self-reported pain measures. These data demonstrate that BOLD-fMRI derived signals are a valuable tool for quantifying noxious responses pertaining to pressure stimulation. We further recommend the implementation of pressure as a stimulation modality in experimental applications.

5.
J Hypertens ; 38(8): 1420-1435, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32687269

RESUMO

OBJECTIVE: Spontaneous or experimentally induced high blood pressure (BP) is associated with reduced pain perception, known as BP-related hypoalgesia. Despite its clinical implications, such as the interference with early detection of myocardial infarction in 'at risk' groups, the size of the association between high BP and pain has not yet been quantified. Moreover, the distinct association between high BP and physiological or psychological components of pain has not yet been considered so far. The aim of this study was to overcome this gap by performing separate meta-analyses on nociceptive response versus quantifiable perceptual measures of pain in relation to high BP. METHODS: PubMed and Web of Knowledge databases were searched for English language studies conducted in humans. Fifty-nine studies were eligible for the analyses. Pooled effect sizes (Hedges' g) were compared. Random effect models were used. Results show that higher BP is significantly associated with lower nociceptive response (g = 0.38; k = 6) and reduced pain perception, assessed by quantifiable measures (g = 0.48; k = 59). RESULTS: The association between BP and pain perception, derived from highly heterogeneous studies, was characterized by significant publication bias. BP assessment, pain assessment, site of pain stimulation, percentage of female participants in the sample, and control for potential confounders were significant moderators. CONCLUSION: Current meta-analytic results confirm the presence of BP-related hypoalgesia and point towards the need for a better understanding of its underlying mechanisms.

6.
Hum Brain Mapp ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

7.
Psychiatry Res Neuroimaging ; 295: 111020, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-31790922

RESUMO

Perseverative cognition (i.e. rumination and worry) describes intrusive, uncontrollable, repetitive thoughts. These negative affective experiences are accompanied by physiological arousal, as if the individual were facing an external stressor. Perseverative cognition is a transdiagnostic symptom, yet studies of neural mechanisms are largely restricted to specific clinical populations (e.g. patients with major depression). The present study applied activation likelihood estimation (ALE) meta-analyses to 43 functional neuroimaging studies of perseverative cognition to elucidate the neurobiological substrates across individuals with and without psychopathological conditions. Task-related and resting state functional connectivity studies were examined in separate meta-analyses. Across task-based studies, perseverative cognition engaged medial frontal gyrus, cingulate gyrus, insula, and posterior cingulate cortex. Resting state functional connectivity studies similarly implicated posterior cingulate cortex together with thalamus and anterior cingulate cortex (ACC), yet the involvement of ACC distinguished between perseverative cognition in healthy controls (HC) and clinical groups. Perseverative cognition is accompanied by the engagement of prefrontal, insula and cingulate regions, whose interaction may support the characteristic conjunction of self-referential and affective processing with (aberrant) cognitive control and embodied (autonomic) arousal. Within this context, ACC engagement appears critical for the pathological expression of rumination and worry.


Assuntos
Encéfalo/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Ruminação Cognitiva/fisiologia , Adulto , Nível de Alerta/fisiologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino
8.
Neuroimage ; 191: 380-391, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30798009

RESUMO

In Generalized Anxiety Disorder (GAD), fluctuations in ongoing thoughts (i.e., mind-wandering) often take the form of rigid and intrusive perseverative cognition, such as worry. Here, we sought to characterise the neural correlates of mind-wandering and perseverative cognition, alongside autonomic nervous system indices of central arousal, notably pupil dilation. We implemented a protocol incorporating the dynamic delivery of thought-probes within a functional neuroimaging task. Sixteen individuals with GAD and sixteen matched healthy controls (HC) underwent functional magnetic resonance imaging with concomitant pupillometry. Participants performed a series of low-demand tracking tasks, responding to occasional changes in a target stimulus. Such a task is typically accompanied by self-generated, off-task thinking. Thought-probes were triggered based on an individual's response time (RT) when responding to the change in the target. Subjective reports showed that long RT predicted off-task thinking/mind-wandering. Moreover, long RT and mind-wandering were also associated with larger pupil diameter. This effect was exaggerated in GAD patients during perseverative cognition. Within brain, during both pre-target periods and target events, there were distinct neural correlates for mind-wandering (e.g., anterior cingulate and paracingulate activation at target onset) and perseverative cognition (e.g., opposite patterns of activation in posterior cingulate and cerebellum at target onset in HC and GAD). Results suggest that not only attention systems but also sensory-motor cortices are important during off-task states. Interestingly, changes across the 'default mode network' also tracked fluctuations in pupillary size. Autonomic expression in pupillary changes mirrors brain activation patterns that occur during different forms of repetitive thinking.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Tempo de Reação/fisiologia , Adulto , Nível de Alerta/fisiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pupila
9.
Auton Neurosci ; 217: 41-48, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30704974

RESUMO

Generalized anxiety disorder (GAD) is associated with both autonomic dysfunction, notably decreased vagally-mediated heart rate variability (vmHRV), and neurostructural abnormalities. Regional differences in brain morphometry correlate with vmHRV in healthy individuals. Here, we tested the hypothesis that specific focal abnormalities in cortical structure in GAD underpin decreased vmHRV. Adult female patients with GAD (n = 17) and matched controls (n = 18) underwent structural magnetic resonance imaging after characterization of symptoms and quantification of resting vmHRV derived from continuous pulse oximetry. Cortical reconstruction was performed using the FreeSurfer image analysis suite. A priori analysis was conducted only within brain regions involved in vagal control of heart rate. Compared to controls, patients with GAD showed cortical thinning of the (i) left rostral anterior cingulate cortex, (ii) left medial orbitofrontal cortex, and (iii) right isthmus cingulate gyrus. Significant negative relationships were identified between the severity of anxiety symptoms and cortical thickness of the left medial orbitofrontal cortex and right isthmus cingulate gyrus. Compared to controls, patients with GAD showed decreased vmHRV at rest. In controls only, cortical thickness of the left caudal anterior cingulate cortex correlated positively with resting vmHRV. These results extend evidence in GAD for structural abnormalities within cortical areas implicated in emotion regulation and cognition. In addition, these findings may implicate abnormal integrity of anterior cingulate cortex in the psychophysiological expression of GAD and suggest that interventional targeting of this region may normalize autonomic function in GAD.


Assuntos
Transtornos de Ansiedade/patologia , Transtornos de Ansiedade/fisiopatologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Giro do Cíngulo/patologia , Córtex Pré-Frontal/patologia , Adulto , Transtornos de Ansiedade/diagnóstico por imagem , Regulação Emocional/fisiologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Frequência Cardíaca/fisiologia , Humanos , Imagem por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem
10.
Psychiatry Res Neuroimaging ; 281: 107-116, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30290286

RESUMO

Generalized anxiety disorder (GAD) has excessive anxiety and uncontrollable worry as core symptoms. Abnormal cerebral functioning underpins the expression and perhaps pathogenesis of GAD:. Studies implicate impaired communication between the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally investigate whether such network abnormalities are spatially restricted to this circuit or if the integrity of functional brain networks is globally disrupted in GAD. We acquired resting-state functional magnetic resonance imaging data from 16 GAD patients and 16 matched controls at baseline and after 1 year. Using network modeling and graph-theory, whole-brain connectivity was characterized from local and global perspectives. Overall lower global efficiency, indicating sub-optimal brain-wide organization and integration, was present in patients with GAD compared to controls. The amygdala and midline cortices showed higher betweenness centrality, reflecting functional dominance of these brain structures. Third, lower betweenness centrality and lower degree emerged for PFC, suggesting weakened inhibitory control. Overall, network organization showed impairments consistent with neurobiological models of GAD (involving amygdala, PFC, and cingulate cortex) and further pointed to an involvement of temporal regions. Such impairments tended to progress over time and predict anxiety symptoms. A graph-analytic approach represents a powerful approach to deepen our understanding of GAD.


Assuntos
Tonsila do Cerebelo/diagnóstico por imagem , Transtornos de Ansiedade/diagnóstico por imagem , Lobo Frontal/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Adulto , Tonsila do Cerebelo/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Feminino , Lobo Frontal/fisiopatologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia
11.
J Alzheimers Dis ; 63(2): 561-575, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29689722

RESUMO

Patients with amnestic mild cognitive impairment (aMCI) have higher probability to develop Alzheimer's disease (AD) than elderly controls. The detection of subtle changes in brain structure associated with disease progression and the development of tools to identify patients at high risk for dementia in a short time is crucial. Here, we used probabilistic white matter (WM) tractography to explore microstructural alterations within the main association, limbic, and commissural pathways in aMCI patients who converted to AD after 1 year follow-up (MCIconverters) and those who remained stable (MCIstable). Both diffusion tensor imaging (DTI) and quantitative magnetization transfer (qMT) parameters have been considered for a comprehensive pathophysiological characterization of the WM damage. Overall, tract-specific parameters derived from qMT and DTI at baseline were able to differentiate aMCI patients who converted to AD from those who remained stable in time. In particular, the qMT exchange rate, RMB0, of the right uncinate fasciculus was significantly decreased in MCIconverters, whereas fractional anisotropy was significantly decreased in the bilateral superior cingulum in MCIconverters compared to MCIstable. These results confirm the involvement of WM and particularly of association fibers in the progression of AD, highlighting disconnection as a potential mechanism.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão , Substância Branca/diagnóstico por imagem , Idoso , Imagem de Tensor de Difusão/métodos , Progressão da Doença , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Prognóstico
12.
Neuroimage Clin ; 17: 882-892, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29527493

RESUMO

Background: The Cognitive Avoidance Theory of Worry argues that worry is a cognitive strategy adopted to control the physiological arousal associated with anxiety. According to this theory, pathological worry, as in Generalized Anxiety Disorder (GAD), is verbal in nature, negative and abstract, rather than concrete. Neuroimaging studies link the expression of worry to characteristic modes of brain functional connectivity, especially in relation to the amygdala. However, the distinctive features of worry (verbal, abstract, negative), and their relationship to physiological arousal, have not so far been mapped to brain function. Methods: We addressed this omission by undertaking a resting-state functional magnetic resonance neuroimaging study of 19 patients with GAD and 21 controls, before and after induction of perseverative cognitions, while measuring emotional bodily arousal from heart rate (HR). Seed-based analyses quantified brain changes in whole brain functional connectivity from the amygdala. Results: In GAD, the induction increased negative thoughts and their verbal content. In line with predictions, the verbal expression of worry in GAD was associated with higher HR at baseline and attenuated HR increases after induction of perseverative cognitions. Within brain, the increased use of words during worry, and the associated dampening of HR after induction were mediated by the strength of functional connectivity between the amygdala and default mode network 'hubs' and the opercular cortex. The negative content of worry was further related to functional communication between amygdala and cingulo-opercular and temporal cortices. Conclusions: Findings provide a neurobiological basis for the impact of verbal worry on HR in GAD.


Assuntos
Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Emoções/fisiologia , Comportamento Verbal/fisiologia , Adulto , Transtornos de Ansiedade/psicologia , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Oxigênio/sangue , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas , Inquéritos e Questionários , Vocabulário , Adulto Jovem
13.
Cortex ; 99: 200-212, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29253783

RESUMO

Information processing, particularly of salient emotional stimuli, is influenced by cardiovascular afferent signals. Carotid baroreceptors signal the state of cardiovascular arousal to the brain, controlling blood pressure and heart rate via the baroreflex. Animal studies suggest a lateralization of this effect: Experimental stimulation of the right carotid sinus has a greater impact on heart rate when compared to left-sided stimulation. We tested, in humans, whether the processing of emotional information from faces was differentially affected by right versus left carotid afferents. To achieve so, we used an automated neck suction device to stimulate the carotid mechanoreceptors in the carotid sinus (parasympathetic pathway) synchronously with functional magnetic resonance imaging (fMRI) acquisition whilst participants were engaged in an emotional rating task of fearful and neutral faces. We showed that both right and left carotid stimulation (CS) influenced brain activity within opercular regions, although a stronger activation was observed within left insula during right stimulation compared to left stimulation. As regards the processing of fearful faces, right, but not left carotid stimulation attenuated the perceived intensity of fear, and (albeit to a lesser extent) enhanced intensity ratings of neutral faces. Mirroring the behavioural effects, there was a significant expression-by-stimulation interaction for right carotid stimulation only, when bilateral amygdala responses were attenuated to fear faces and amplified to neutral faces. Individual differences in basal heart rate variability (HRV) predicted the extent to which right carotid stimulation attenuated amygdala responses during fear processing. Our study provides unique evidence for lateralized viscerosensory effects on brain systems supporting emotional processing.


Assuntos
Tonsila do Cerebelo/fisiologia , Seio Carotídeo , Córtex Cerebral/fisiologia , Medo/fisiologia , Pressorreceptores/fisiologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Barorreflexo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Córtex Cerebral/diagnóstico por imagem , Emoções/fisiologia , Feminino , Lateralidade Funcional , Neuroimagem Funcional , Frequência Cardíaca , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
14.
Neurosci Biobehav Rev ; 74(Pt B): 330-341, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27185286

RESUMO

Given the intrinsic connection between the brain and the heart, a recent body of research emerged with the aim to influence cardiovascular system functioning by non-invasive brain stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Despite the implications of cardiovascular activity modulation for therapeutic purposes, such effects of NIBS have not yet been quantified. The aim of this study was to meta-analyze studies on NIBS effects on blood pressure (BP), heart rate (HR) and its variability (HRV). PubMed and Scopus databases were searched for English language studies conducted in humans. Twenty-nine studies were eligible for the analyses. Pooled effect sizes (Hedges' g) were compared. Random effect models were used. NIBS was effective in reducing HR (g=0.17) and enhancing HRV (g=0.30). A marginal effect emerged for BP (g=0.21). Significant moderators were the stimulation technique and the site of stimulation. Results show that NIBS affects cardiovascular and autonomic nervous system activity, confirming a potential pathogenic brain-heart pathway to cardiovascular disease.


Assuntos
Encéfalo , Doenças Cardiovasculares , Coração , Humanos , Idioma , Estimulação Transcraniana por Corrente Contínua , Estimulação Magnética Transcraniana
15.
Front Hum Neurosci ; 10: 553, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27853428

RESUMO

Excessive and uncontrollable worry is a defining feature of Generalized Anxiety Disorder (GAD). An important endeavor in the treatment of pathological worry is to understand why some people are unable to stop worrying once they have started. Worry perseveration is associated with a tendency to deploy goal-directed worry rules (known as "as many as can" worry rules; AMA). These require attention to the goal of the worry task and continuation of worry until the aims of the "worry bout" are achieved. This study examined the association between the tendency to use AMA worry rules and neural and autonomic responses to a perseverative cognition induction. To differentiate processes underlying the AMA worry rule use from trait worry, we also examined the relationship between scores on the Penn State Worry Questionnaire (PSWQ) and neural and autonomic responses following the same induction. We used resting-state functional magnetic resonance brain imaging (fMRI) while measuring emotional bodily arousal from heart rate variability (where decreased HRV indicates stress-related parasympathetic withdrawal) in 19 patients with GAD and 21 control participants. Seed-based analyses were conducted to quantify brain changes in functional connectivity (FC) with the amygdala. The tendency to adopt an AMA worry rule was associated with validated measures of worry, anxiety, depression and rumination. AMA worry rule endorsement predicted a stronger decrease in HRV and was positively associated with increased connectivity between right amygdala and locus coeruleus (LC), a brainstem noradrenergic projection nucleus. Higher AMA scores were also associated with increased connectivity between amygdala and rostral superior frontal gyrus. Higher PSWQ scores amplified decreases in FC between right amygdala and subcallosal cortex, bilateral inferior frontal gyrus, middle frontal gyrus, and areas of parietal cortex. Our results identify neural mechanisms underlying the deployment of AMA worry rules. We propose that the relationship between AMA worry rules and increased connectivity between the amygdala and prefrontal cortex (PFC) represents attempts by high worriers to maintain arousal and distress levels in order to feel prepared for future threats. Furthermore, we suggest that neural mechanisms associated with the PSWQ represent effortful inhibitory control during worry. These findings provide unique information about the neurobiological processes that underpin worry perseveration.

16.
PLoS One ; 11(10): e0163980, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27788143

RESUMO

Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients' cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptoms.


Assuntos
Encéfalo/patologia , Rede Nervosa/patologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Feminino , Heterozigoto , Homozigoto , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Rede Nervosa/fisiopatologia , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Descanso/fisiologia
17.
Soc Cogn Affect Neurosci ; 11(11): 1719-1728, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27369066

RESUMO

Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Rede Nervosa/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Nível de Alerta/fisiologia , Sistema Nervoso Autônomo/fisiopatologia , Progressão da Doença , Dominância Cerebral/fisiologia , Emoções/fisiologia , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética/métodos , Masculino , Adulto Jovem
18.
Biol Psychol ; 119: 31-41, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27345596

RESUMO

Generalized anxiety disorder (GAD) is characterized by difficulties in inhibiting both perseverative thoughts (worry and rumination) and autonomic arousal. We investigated the neurobiological substrates of such abnormal inhibitory processes, hypothesizing aberrant functional coupling within 'default mode' (DMN) and autonomic brain networks. Functional imaging and heart rate variability (HRV) data were acquired from GAD patients and controls during performance of three tracking tasks interspersed with a perseverative cognition (PC) induction. After detection of infrequent target stimuli, activity within putative DMN hubs was suppressed, consistent with a redirection of attentional resources from internal to external focus. This magnitude of activity change was attenuated in patients and individuals with higher trait PC, but was predicted by individual differences in HRV. Following the induction of PC in controls, this pattern of neural reactivity became closer to that of GAD patients. Results support, at a neural level, the association between cognitive inflexibility and autonomic rigidity.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Cognição/fisiologia , Inibição Psicológica , Análise e Desempenho de Tarefas , Adulto , Transtornos de Ansiedade/psicologia , Nível de Alerta/fisiologia , Atenção/fisiologia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Feminino , Frequência Cardíaca/fisiologia , Humanos , Imagem por Ressonância Magnética , Masculino
19.
J Alzheimers Dis ; 51(2): 377-89, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26890769

RESUMO

This longitudinal study investigates the modifications in structure and function occurring to typical Alzheimer's disease (AD) brains over a 2-year follow-up, from pre-dementia stages of disease, with the aim of identifying biomarkers of prognostic value. Thirty-one patients with amnestic mild cognitive impairment were recruited and followed-up with clinical, neuropsychological, and MRI assessments. Patients were retrospectively classified as AD Converters or Non-Converters, and the data compared between groups. Cross-sectional MRI data at baseline, assessing volume and functional connectivity abnormalities, confirmed previous findings, showing a more severe pattern of regional grey matter atrophy and default-mode network disconnection in Converters than in Non-Converters. Longitudinally, Converters showed more grey matter atrophy in the frontotemporal areas, accompanied by increased connectivity in the precuneus. Discriminant analysis revealed that functional connectivity of the precuneus within the default mode network at baseline is the parameter able to correctly classify patients in Converters and Non-Converters with high sensitivity, specificity, and accuracy.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Idoso , Atrofia , Mapeamento Encefálico , Estudos Transversais , Análise Discriminante , Progressão da Doença , Feminino , Seguimentos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Prognóstico , Descanso
20.
J Alzheimers Dis ; 50(2): 591-604, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26836635

RESUMO

Behavioral disorders and psychological symptoms (BPSD) in Alzheimer's disease (AD) are known to correlate with grey matter (GM) atrophy and, as shown recently, also with white matter (WM) damage. WM damage and its relationship with GM atrophy are reported in AD, reinforcing the interpretation of the AD pathology in light of a disconnection syndrome. It remains uncertain whether this disconnection might account also for different BPSD observable in AD. Here, we tested the hypothesis of different patterns of association between WM damage of the corpus callosum (CC) and GM atrophy in AD patients exhibiting one of the following BPSD clusters: Mood (i.e., anxiety and depression; ADmood), Frontal (i.e., dishinibition and elation; ADfrontal), and Psychotic (delusions and hallucinations; ADpsychotic) related symptoms, as well as AD patients without BPSD. Overall, this study brings to light the strict relationship between WM alterations in different parts of the CC and GM atrophy in AD patients exhibiting BPSD, supporting the hypothesis that such symptoms are likely to be caused by characteristic patterns of neurodegeneration of WM and GM, rather than being a reactive response to accumulation of cognitive disabilities, and should therefore be regarded as potential markers of diagnostic and prognostic value in AD.


Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Encéfalo/patologia , Substância Cinzenta/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Atrofia/patologia , Depressão/complicações , Depressão/patologia , Depressão/psicologia , Feminino , Alucinações/complicações , Alucinações/patologia , Alucinações/psicologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
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