RESUMO
Congenital sensory deprivation induces significant changes in the structural and functional organisation of the brain. These are well-characterised by cross-modal plasticity, in which deprived cortical areas are recruited to process information from non-affected sensory modalities, as well as by other neuroplastic alterations within regions dedicated to the remaining senses. Here, we analysed visual and auditory networks of congenitally deaf and hearing individuals during different visual tasks to assess changes in network community structure and connectivity patterns due to congenital deafness. In the hearing group, the nodes are clearly divided into three communities (visual, auditory and subcortical), whereas in the deaf group a fourth community consisting mainly of bilateral superior temporal sulcus and temporo-insular regions is present. Perhaps more importantly, the right lateral geniculate body, as well as bilateral thalamus and pulvinar joined the auditory community of the deaf. Moreover, there is stronger connectivity between bilateral thalamic and pulvinar and auditory areas in the deaf group, when compared to the hearing group. No differences were found in the number of connections of these nodes to visual areas. Our findings reveal substantial neuroplastic changes occurring within the auditory and visual networks caused by deafness, emphasising the dynamic nature of the sensory systems in response to congenital deafness. Specifically, these results indicate that in the deaf but not the hearing group, subcortical thalamic nuclei are highly connected to auditory areas during processing of visual information, suggesting that these relay areas may be responsible for rerouting visual information to the auditory cortex under congenital deafness.
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Córtex Auditivo , Surdez , Perda Auditiva Neurossensorial , Humanos , Surdez/diagnóstico por imagem , Audição , Córtex Auditivo/diagnóstico por imagem , Encéfalo , Órgãos dos Sentidos , Plasticidade NeuronalRESUMO
The perceived lack of control over the experience of pain is arguably-one major cause of agony and impaired life quality in patients with chronic pain disorders as fibromyalgia (FM). The way perceived control affects subjective pain as well as the underlying neural mechanisms have so far not been investigated in chronic pain. We used functional magnetic resonance imaging (fMRI) to examine the neural correlates of self-controlled compared to computer-controlled heat pain in healthy controls (HC, n = 21) and FM patients (n = 23). Contrary to HC, FM failed to activate brain areas usually involved in pain modulation as well as reappraisal processes (right ventrolateral (VLPFC), dorsolateral prefrontal cortex (DLPFC) and dorsal anterior cingulate cortex (dACC)). Computer-controlled (compared to self-controlled) heat revealed significant activations of the orbitofrontal cortex (OFC) in HC, whereas FM activated structures that are typically involved in neural emotion processing (amygdala, parahippocampal gyrus). Additionally, FM displayed disrupted functional connectivity (FC) of the VLPFC, DLPFC and dACC with somatosensory and pain (inhibition)-related areas during self-controlled heat stimulation as well as significantly decreased gray matter (GM) volumes compared to HC in DLPFC and dACC. The described functional and structural changes provide evidence for far-reaching impairments concerning pain-modulatory processes in FM. Our investigation represents a first demonstration of dysfunctional neural pain modulation through experienced control in FM according to the extensive functional and structural changes in relevant sensory, limbic and associative brain areas. These areas may be targeted in clinical pain therapeutic methods involving TMS, neurofeedback or cognitive behavioral trainings.
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Dor Crônica , Fibromialgia , Humanos , Fibromialgia/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal , Substância Cinzenta , Imageamento por Ressonância Magnética/métodosRESUMO
Real-time fMRI (rt-fMRI) enables self-regulation of neural activity in localized brain regions through neurofeedback. Previous studies showed successful up- and down-regulation of neural activity in the anterior cingulate cortex (ACC) and the insula (Ins) during nociceptive stimulation. Such self-regulation capacity is, however, variable across subjects, possibly related to the ability of cognitive top-down control of pain. Moreover, how specific brain areas interact to enable successful regulation of nociceptive processing and neurofeedback-based brain modulation is not well understood. A connectivity analysis framework in the frequency domain was used to examine the up- or down-regulation in the ACC and Ins and pain intensity and unpleasantness ratings were assessed. We found that successful up- and down-regulation was mediated by the ACC and by its functional connectivity with the Ins and secondary somatosensory cortex. There was no significant relationship between successful up- or downregulation and pain ratings. These findings demonstrate functional interactions between brain areas involved in nociceptive processing during regulation of ACC and Ins activity, and the relevance of the frequency domain connectivity analysis for real-time fMRI. Moreover, despite successful neural regulation, there was no change in pain ratings, suggesting that pain is a complex perception, which may be more difficult to modify than other sensory or emotional processes.
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Chronic pain may sap the motivation for positive events and stimuli. This may lead to a negative behavioural cycle reducing the establishment of appetitive habitual engagement. One potential mechanism for this might be biased learning. In our experiment, chronic back pain patients and healthy controls completed an appetitive Pavlovian-instrumental transfer procedure. We examined participants` behaviour and brain activity and reported pain, depression and anxiety. Patients showed reduced habitual behaviour and increased responses in the hippocampus than controls. This behavioural bias was related to motivational value and reflected in the updating of brain activity in prefrontal-striatal-limbic circuits. Moreover, this was influenced by pain symptom duration, depression and anxiety (explained variance: up to 50.7%). Together, findings identify brain-behaviour pathways for maladaptive habitual learning and motivation in chronic back pain, which helps explaining why chronic pain can be resistant to change, and where clinical characteristics are significant modulators.
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Dor nas Costas/fisiopatologia , Encéfalo/fisiologia , Dor Crônica/fisiopatologia , Condicionamento Psicológico , Aprendizagem/fisiologia , Motivação , Adulto , Dor nas Costas/psicologia , Estudos de Casos e Controles , Dor Crônica/psicologia , Feminino , Humanos , MasculinoRESUMO
Avoiding any harm, such as painful experiences, is an important ability for our physical and mental health. This avoidance behavior might be overactive under chronic pain, and the cortical and subcortical brain volumetry, which also often changes in chronic pain states, might be a significant correlate of this behavior. In the present study, we thus investigated the association between volumetric brain differences using 3 T structural magnetic resonance imaging and pain- versus pleasure-related approach-avoidance behavior using an Approach Avoidance Task in the laboratory in chronic back pain (N = 42; mean age: 51.34 years; 23 female) and healthy individuals (N = 43; mean age: 45.21 years; 15 female). We found significant differences in hippocampal, amygdala and accumbens volumes in patients compared to controls. The patients` hippocampal volume was significantly positively related to pain avoidance, the amygdala volume to positive approach, and the accumbens volume negatively to a bias to pain avoidance over positive approach. These associations were significantly moderated by pain symptom duration. Cortical structure may thus contribute to an overacting pain avoidance system in chronic back pain, and could, together with a reduction in approaching positive stimuli, be related to maladaptive choice and decision-making processes in chronic pain.
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Aprendizagem da Esquiva , Dor Crônica , Tonsila do Cerebelo/diagnóstico por imagem , Dor nas Costas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Dor Crônica/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Intracranial arachnoid cysts are usually benign congenital findings of neuroimaging modalities, sometimes however, leading to focal neurological and psychiatric comorbidities. Whether primarily clinically silent cysts may become causally involved in cognitive decline in old age is neither well examined nor understood. CASE PRESENTATION: A 66-year old caucasian man presenting with a giant left-hemispheric frontotemporal cyst without progression of size, presented with slowly progressive cognitive decline. Neuropsychological assessment revealed an amnestic mild cognitive impairment (MCI) without further neurological or psychiatric symptoms. The patient showed mild medio-temporal lobe atrophy on structural MRI. Diffusion tensor and functional magnetic resonance imaging depicted a rather sustained function of the strongly suppressed left hemisphere. Amyloid-PET imaging was positive for increased amyloid burden and he was homozygous for the APOEε3-gene. A diagnosis of MCI due to Alzheimer's disease was given and a co-morbidity with a silent arachnoid cyst was assumed. To investigate, if a potentially reduced CSF flow due to the giant arachnoid cyst contributed to the early manifestation of AD, we reviewed 15 case series of subjects with frontotemporal arachnoid cysts and cognitive decline. However, no increased manifestation of neurodegenerative disorders was reported. CONCLUSIONS: With this case report, we illustrate the necessity of a systematic work-up for neurodegenerative disorders in patients with arachnoid cysts and emerging cognitive decline. We finally propose a modus operandi for the stratification and management of patients with arachnoid cysts potentially susceptive for cognitive dysfunction.
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Doença de Alzheimer/diagnóstico por imagem , Cistos Aracnóideos/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Idoso , Doença de Alzheimer/etiologia , Cistos Aracnóideos/psicologia , Disfunção Cognitiva/etiologia , Humanos , Masculino , Testes Neuropsicológicos , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologiaRESUMO
While the pathophysiology of transient global amnesia (TGA) is not understood, due to the specific nature of the clinical deficits, transient dysfunction in the medial temporal lobe, especially in the hippocampus, is assumed; however, concomitant disturbances in other brain regions and in executive function have been postulated. In this study, a cohort of 16 patients was prospectively recruited from the emergency department for resting-state functional MRI (fMRI) during the acute stage of TGA, as confirmed by a standardized neuropsychological assessment. Twenty age- and sex-matched controls, as well as twenty patients with a history of TGA, were recruited for comparison. Functional data were processed using independent component analysis (ICA), allowing the complete automatic (data-driven) identification of spontaneous network dynamics. We documented a severe disturbance in anterograde episodic long-term memory in all patients. Group-based ICA of resting-state data in acute TGA patients versus that of controls and patients with a past TGA episode demonstrated reduced FC mainly of structures belonging to the executive network (EN), but also the hippocampus, confirming its pathophysiological involvement in the disorder, as well as areas belonging to the salience network and other subcortical regions. No significant differences were found when comparing connectivity in patients with a history of TGA and controls. Our findings strengthen previous empirical and theoretical accounts of hippocampal and executive dysfunction in TGA. The disruption of frontal, parietal and insular control regions, together with disruption in the hippocampus, provides a new interpretation for the pathophysiology and neuropsychological profile of this neurological disorder on a large-scale network level.
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Amnésia Global Transitória/fisiopatologia , Encéfalo/fisiopatologia , Vias Neurais/fisiopatologia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , DescansoRESUMO
Transcranial direct current stimulation (tDCS) is routinely used in basic and clinical research, but its efficacy has been challenged on a methodological, statistical and technical basis recently. The arguments against tDCS derive from an insufficient understanding of how this technique interacts with brain processes physiologically. Because of its potential as a central tool in neuroscience, it is important to clarify whether tDCS affects neuronal activity. Here, we investigate influences of offline tDCS on network architecture measured by functional magnetic resonance imaging. Applied to one network node only, offline tDCS affects the architecture of the entire functional network. Furthermore, offline tDCS exerts polarity-specific effects on the topology of the functional network attached. Our results confirm in a functioning brain and in a bias free and independent fashion that offline tDCS influences neuronal activity. Moreover, our results suggest that network-specific connectivity has an important role in improving our understanding of the effects of tDCS.
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Mapeamento Encefálico/métodos , Encéfalo , Estimulação Transcraniana por Corrente Contínua/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
Classical fear conditioning is an important mechanism to adequately respond and adapt to environmental threats and has been related to the development of fear and anxiety. Both cue and context conditioning have been studied but little is known about their relation to relevant resting state networks. The default mode network (DMN) has been reported to be involved in affective learning and described as facilitating a state of readiness in responding to environmental changes. We examined resting state brain connectivity patterns of the default mode network (DMN) in 119 healthy volunteers. Specifically, we carried out correlation analyses between the DMN and skin conductance responses (SCRs) as well as arousal, valence and contingency ratings during learning. In addition, we examined the role of trait anxiety. Two different DMN patterns were identified in which stronger connectivity was linked to lower differential SCRs during fear and anxiety learning. One was related to cue conditioning and involved the amygdala and the medial prefrontal cortex, and one was associated with context conditioning and included the hippocampal formation and sensorimotor areas. These results were replicated in an independent sample. Functional connectivity of the DMN with these key regions at rest was also predictive of trait anxiety but this association could not be replicated in the second sample. We showed that DMN connectivity is differently associated with cued versus contextual learning mechanisms. Uncovering individual differences in baseline network connectivity of the DMN with these key regions might lead to a better understanding of fear and anxiety. Such findings could indeed help to identify vulnerability factors linked to network alterations at rest with dysregulation of learning processes involved in the pathophysiology of stress and anxiety disorders.
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Ansiedade/fisiopatologia , Encéfalo/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Vias Neurais/fisiologia , Adolescente , Adulto , Sinais (Psicologia) , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Descanso , Adulto JovemRESUMO
Neuromodulation techniques such as transcranial direct current stimulation (tDCS) are routinely used for treating neurological and neuropsychiatric disorders, and for enhancement of cognitive abilities. Recently, their effectiveness in modulating behavioral and neural responses has been questioned. Here we use excitatory and inhibitory tDCS prior to a functional magnetic resonance imaging (fMRI) experiment to show that neural responses for an area's preferred stimuli depend on the polarity of stimulation. This is an important, yet overlooked, data point in demonstrating the effectiveness of these stimulation techniques. Our results show that response preferences in the target area are dependent on the polarity of the tDCS session preceding the fMRI experiment - these preferences are less distinct in the cathodal than in the anodal session. As such, we show unequivocally that tDCS modulates neural responses. This result is of the utmost importance in demonstrating the effectiveness of tDCS for clinical and experimental purposes.
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Lobo Parietal/fisiologia , Adolescente , Adulto , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Lobo Parietal/diagnóstico por imagem , Tempo de Reação/fisiologia , Estimulação Transcraniana por Corrente Contínua , Adulto JovemRESUMO
Fear acquisition and extinction have been demonstrated as core mechanisms for the development and maintenance of mental disorders, with different contributions of processing cues vs contexts. The hypothalamic peptide oxytocin (OXT) may have a prominent role in this context, as it has been shown to affect fear learning. However, investigations have focused on cue conditioning, and fear extinction. Its differential role for cue and context fear acquisition is still not known. In a randomized, double-blind, placebo (PLC)-controlled design, we administered an intranasal dose of OXT or PLC before the acquisition of cue and context fear conditioning in healthy individuals (n = 52), and assessed brain responses, skin conductance responses and self-reports (valence/arousal/contingency). OXT compared with PLC significantly induced decreased responses in the nucleus accumbens during early cue and context acquisition, and decreased responses of the anterior cingulate cortex and insula during early as well as increased hippocampal response during late context, but not cue acquisition. The OXT group additionally showed significantly higher arousal in late cue and context acquisition. OXT modulates various aspects of cue and context conditioning, which is relevant from a mechanism-based perspective and might have implications for the treatment of fear and anxiety.
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Condicionamento Clássico/efeitos dos fármacos , Sinais (Psicologia) , Medo/efeitos dos fármacos , Ocitocina/farmacologia , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Método Duplo-Cego , Imagem Ecoplanar , Extinção Psicológica/efeitos dos fármacos , Feminino , Resposta Galvânica da Pele/efeitos dos fármacos , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
Transient global amnesia (TGA) is a disorder with reversible anterograde disturbance of explicit memory, frequently preceded by an emotionally or physically stressful event. By using magnetic resonance imaging (MRI) following an episode of TGA, small hippocampal lesions have been observed. Hence it has been postulated that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus. In experimental studies, stress has been shown to affect both explicit and implicit learning-the latter defined as learning and memory processes that lack conscious awareness of the information acquired. To test the hypothesis that impairment of implicit learning in TGA is present and related to stress, we determined the effect of experimental exposure to stress on hippocampal activation patterns during an implicit learning paradigm in patients who suffered a recent TGA and healthy matched control subjects. We used a hippocampus-dependent aversive learning procedure (context conditioning with the phases habituation, acquisition, and extinction) during functional MRI following experimental stress exposure (socially evaluated cold pressor test). After a control procedure, controls showed successful learning during the acquisition phase, indicated by increased valence, arousal and contingency ratings to the paired (CON+) vs. the non-paired (CON-) conditioned stimulus, and successful extinction of the conditioned responses. Following stress, acquisition was still successful, however extinction was impaired with persistently increased contingency ratings. In contrast, TGA patients showed impairment of conditioned responses and insufficient extinction after the control procedure, indicated by a lack of significant differences between CON+ and CON- for valence and arousal ratings after the acquisition phase and by significantly increased contingency ratings after the extinction. After stress, aversive learning was not successful with non-significant ratings of all parameters. Concerning brain activation patterns after the control procedure, controls showed increased hippocampal response during acquisition after the control procedure. This was not seen after stress exposure. In TGA patients, we observed an increased response in the right ventral striatum in the acquisition phase following stress. These findings suggest that alterations in implicit learning processes, including impaired hippocampal and increased striatal responses, might play a role in TGA pathophysiology, partly related to acute stress.
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BACKGROUND: Posttraumatic stress disorder (PTSD) might be maintained by deficient extinction memory. We used a cued fear conditioning design with extinction and a post-extinction phase to provoke the return of fear and examined the role of the interplay of amygdala, hippocampus and prefrontal regions. METHODS: We compared 18 PTSD patients with two healthy control groups: 18 trauma-exposed subjects without PTSD (nonPTSD) and 18 healthy controls (HC) without trauma experience. They underwent a three-day ABC-conditioning procedure in a functional magnetic resonance imaging scanner. Two geometric shapes that served as conditioned stimuli (CS) were presented in the context of virtual reality scenes. Electric painful stimuli were delivered after one of the two shapes (CS+) during acquisition (in context A), while the other (CS-) was never paired with pain. Extinction was performed in context B and extinction memory was tested in a novel context C. RESULTS: The PTSD patients showed significantly higher differential skin conductance responses than the non-PTSD and HC and higher differential amygdala and hippocampus activity than the HC in context C. In addition, elevated arousal to the CS+ during extinction and to the CS- throughout the experiment was present in the PTSD patients but self-reported differential valence or contingency were not different. During extinction recall, differential amygdala activity correlated positively with the intensity of numbing and ventromedial prefrontal cortex activity correlated positively with behavioral avoidance. CONCLUSIONS: PTSD patients show heightened return of fear in neural and peripheral measures. In addition, self-reported arousal was high to both danger (CS+) and safety (CS-) cues. These results suggest that a deficient maintenance of extinction and a failure to identify safety signals might contribute to PTSD symptoms, whereas non-PTSD subjects seem to show normal responses.
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Tonsila do Cerebelo/fisiopatologia , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Resposta Galvânica da Pele/fisiologia , Hipocampo/fisiopatologia , Rememoração Mental/fisiologia , Córtex Pré-Frontal/fisiologia , Trauma Psicológico/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Trauma Psicológico/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagemRESUMO
Exaggerated conditioned fear responses and impaired extinction along with amygdala overactivation have been observed in posttraumatic stress disorder (PTSD). These fear responses might be triggered by cues related to the trauma through higher-order conditioning, where reminders of the trauma may serve as unconditioned stimuli (US) and could maintain the fear response. We compared arousal, valence, and US expectancy ratings and BOLD brain responses using fMRI in 14 traumatized persons with PTSD and 14 without PTSD (NPTSD) and 13 matched healthy controls (HC) in a differential aversive conditioning paradigm. The US were trauma-specific pictures for the PTSD and NPTSD group and equally aversive and arousing for the HC; the conditioned stimuli (CS) were graphic displays. During conditioning, the PTSD patients compared to the NPTSD and HC indicated higher arousal to the conditioned stimulus that was paired with the trauma picture (CS+) compared to the unpaired (CS-), increased dissociation during acquisition and extinction, and failure to extinguish the CS/US-association compared to NPTSD. During early and late acquisition, the PTSD patients showed a significantly lower amygdala activation to CS+ versus CS- and a negative interaction between activation in the amygdala and dorsolateral prefrontal cortex (PFC), while NPTSD and HC displayed a negative interaction between amygdala and medial PFC. These findings suggest maladaptive anticipatory coping with trauma-related stimuli in patients with PTSD, indicated by enhanced conditioning, with related abnormal amygdala reactivity and connectivity, and delayed extinction.
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Tonsila do Cerebelo/fisiopatologia , Medo/fisiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Afeto , Nível de Alerta , Encéfalo/fisiopatologia , Mapeamento Encefálico , Condicionamento Clássico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estimulação LuminosaRESUMO
The neural circuits underlying fear learning have been intensively investigated in pavlovian fear conditioning paradigms across species. These studies established a predominant role for the amygdala in fear acquisition, while the ventromedial prefrontal cortex (vmPFC) has been shown to be important in the extinction of conditioned fear. However, studies on morphological correlates of fear learning could not consistently confirm an association with these structures. The objective of the present study was to investigate if interindividual differences in morphology of the amygdala and the vmPFC are related to differences in fear acquisition and extinction learning in humans. We performed structural magnetic resonance imaging in 68 healthy participants who underwent a differential cued fear conditioning paradigm. Volumes of subcortical structures as well as cortical thickness were computed by the semi-automated segmentation software Freesurfer. Stronger acquisition of fear as indexed by skin conductance responses was associated with larger right amygdala volume, while the degree of extinction learning was positively correlated with cortical thickness of the right vmPFC. Both findings could be conceptually replicated in an independent sample of 53 subjects. The data complement our understanding of the role of human brain morphology in the mechanisms of the acquisition and extinction of conditioned fear.
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Tonsila do Cerebelo/anatomia & histologia , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Individualidade , Córtex Pré-Frontal/anatomia & histologia , Adulto , Tonsila do Cerebelo/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Feminino , Resposta Galvânica da Pele , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/fisiologia , Adulto JovemRESUMO
BACKGROUND: Posttraumatic stress disorder (PTSD) is a frequent anxiety disorder with higher prevalence rates in female patients than in male patients (2.5:1). Association with a single nucleotide polymorphism (rs2267735) in the gene ADCYAP1R1 encoding the type I receptor (PAC1-R) of the pituitary adenylate cyclase activating polypeptide has been reported with PTSD in female patients. We sought to identify the neural correlates of the described PAC1-R effects on associative learning. METHODS: In a reverse genetic approach, we examined two independent healthy samples (N1 = 112, N2 = 73) using functional magnetic resonance imaging during cued and contextual fear conditioning. Skin conductance responses and verbal self-reports of arousal, valence, and contingency were recorded. RESULTS: We found that PAC1-R modulates the blood oxygenation level-dependent response of the hippocampus. Specifically, we observed decreased hippocampal activity during contextual, but not during cued, fear conditioning in female participants carrying the PAC1-R risk allele. We observed no significant differences in conditionability for skin conductance responses, verbal reports, or activation in other brain regions between the genotype groups in female participants. CONCLUSIONS: Our results suggest that impaired contextual conditioning in the hippocampal formation may mediate the association between PAC1-R and PTSD symptoms. Our findings potentially identify a missing link between the involvement of PAC1-R in PTSD and the well-established structural and functional hippocampal deficits in these patients.
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Medo/fisiologia , Hipocampo/fisiologia , Polimorfismo de Nucleotídeo Único , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/fisiologia , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Tonsila do Cerebelo/fisiologia , Mapeamento Encefálico , Condicionamento Clássico/fisiologia , Sinais (Psicologia) , Feminino , Resposta Galvânica da Pele , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Fatores SexuaisRESUMO
Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.
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Depressão/fisiopatologia , Depressão/psicologia , Recompensa , Adolescente , Adulto , Antecipação Psicológica , Aprendizagem por Associação/fisiologia , Feminino , Lobo Frontal/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Motivação , Núcleo Accumbens/fisiopatologia , Filosofia , Córtex Pré-Frontal/fisiopatologia , Punição/psicologia , Tempo de Reação , Estriado Ventral/fisiopatologia , Adulto JovemRESUMO
Many applications in MRI such as accelerated receive and transmit sequences require the synthesis of nonuniform 3-D gradient trajectories. Several methods have been proposed to design these gradient trajectories in a time-optimal manner, subject to hardware specific gradient magnitude and slew rate constraints. In this work a novel method is derived that designs time-optimal trajectories, solely based on a set of arbitrarily chosen control points in k-space. In particular, no path constraint is required for the k-space trajectory. It is shown that the above problem can be formulated as a constrained optimization problem. The fact that the objective function is derived in an analytic manner allows for designing time-optimal 3-D gradient trajectories within only few seconds without any significant numerical instabilities. The utilization of the shape of the trajectory--serving as a degree of freedom--results in significantly accelerated trajectories compared to current standard methods. This is proven in an extensive evaluation of the proposed method and in comparison with what can be considered the current Gold Standard method. The proposed Gradient Basis Function method provides significant benefits over current standard methods in terms of the duration of the trajectory (in average 9.2% acceleration), computation time (acceleration by at least 25% up to factors of 100), and robustness (no significant numerical instabilities).
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Algoritmos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
The aim of this study was the analysis of the effect of a learned increase in the dissociation between the rostral anterior cingulate cortex (rACC) and the left posterior insula (pInsL) on pain intensity and unpleasantness and the contribution of each region to the effect, exploring the possibility to influence the perception of pain with neurofeedback methods. We trained ten healthy subjects to increase the difference in the blood oxygenation level-dependent response between the rACC and pInsL to painful electric stimuli. Subjects learned to increase the dissociation with either the rACC (state 1) or the pInsL (state 2) being higher. For feedback we subtracted the signal of one region from the other and provided feedback in four conditions with six trials each yielding two different states: [rACC-pInsL increase (state 1), rACC-pInsL decrease (state 2), pInsL-rACC increase (state 2), pInsL-rACC decrease (state 1)]. Significant changes in the dissociation from trial one to six were seen in all conditions. There were significant changes from trial one to six in the pInsL in three of the four conditions, the rACC showed no significant change. Pain intensity or unpleasantness ratings were unrelated to the dissociation between the regions and the activation in each region. Learning success in the conditions did not significantly correlate and there was no significant correlation between the two respective conditions of one state, i.e., learning to achieve a specific state is not a stable ability. The pInsL seems to be the driving force behind changes in the learned dissociation between the regions. Despite successful differential modulation of activation in areas responsive to the painful stimulus, no corresponding changes in the perception of pain intensity or unpleasantness emerged. Learning to induce different states of dissociation between the areas is not a stable ability since success did not correlate overall or between two conditions of the the same state.
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Self-regulation of brain activation using real-time functional magnetic resonance imaging has been used to train subjects to modulate activation in various brain areas and has been associated with behavioral changes such as altered pain perception. The aim of this study was to assess the comparability of upregulation versus downregulation of activation in the rostral anterior cingulate cortex (rACC) and left posterior insula (pInsL) and its effect on pain intensity and unpleasantness. In a first study, we trained 10 healthy subjects to separately upregulate and downregulate the blood oxygenation level-dependent response in the rACC or pInsL (six trials on 4 days) in response to painful electrical stimulation. The participants learned to significantly downregulate activation in pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of one region and direction of the modulation was not significantly correlated with success in another condition, indicating that the ability to control pain-related brain activation is site-specific. Less covariation between the areas in response to the nociceptive stimulus was positively correlated with learning success. Upregulation or downregulation of either region was unrelated to pain intensity or unpleasantness; however, our subjects did not learn rACC upregulation, which might be important for pain control. A significant increase in pain unpleasantness was found during upregulation of pInsL when covariation with the rACC was low. These initial results suggest that the state of the network involved in the processing of pain needs to be considered in the modulation of pain-evoked activation and its behavioral effects.