Examining the Neural Correlates of Error Awareness in a Large fMRI Study

Goal-directed behaviour is dependent upon the ability to detect errors and implement appropriate post-error adjustments. Accordingly, several studies have explored the neural activity underlying error-monitoring processes, identifying the insula cortex as crucial for error awareness and reporting mixed findings with respect to the anterior cingulate cortex. Variable patterns of activation have previously been attributed to insufficient statistical power. We therefore sought to clarify the neural correlates of error awareness in a large event-related functional magnetic resonance imaging (MRI) study. Four hundred and two healthy participants undertook the Error Awareness Task, a motor Go/No-Go response inhibition paradigm in which participants were required to indicate their awareness of commission errors. Compared to unaware errors, aware errors were accompanied by significantly greater activity in a network of regions including the insula cortex, supramarginal gyrus, and midline structures such as the anterior cingulate cortex and supplementary motor area. Error awareness activity was related to indices of task performance and dimensional measures of psychopathology in select regions including the insula, supramarginal gyrus and supplementary motor area. Taken together, we identified a robust and reliable neural network associated with error awareness.

Chronic Alcohol Dysregulates Glutamatergic Function in the Basolateral Amygdala in a Projection- and Sex-Specific Manner

Chronic intermittent ethanol (CIE) produces alcohol dependence, facilitates anxiety-like behavior, and increases post-CIE alcohol intake. The basolateral amygdala (BLA) is one of several brain regions that regulates anxiety-like behavior and alcohol intake through downstream projections. The BLA receives information from two distinct input pathways. Afferents from medial structures like the thalamus and prefrontal cortex enter the BLA through the stria terminalis whereas lateral cortical structures like the anterior insula cortex enter the BLA through the external capsule. CIE induces input- and sex-specific adaptations to glutamatergic function in the BLA. Previous studies sampled neurons throughout the BLA, but did not distinguish between projection-specific populations. The current study investigated BLA neurons that project to the NAC (BLA-NAC neurons) or the BNST (BLA-BNST neurons) as representative "reward" and "aversion" BLA neurons, and showed that CIE alters glutamatergic function and excitability in a projection- and sex-specific manner. CIE increases glutamate release from stria terminalis inputs only onto BLA-BNST neurons. At external capsule synapses, CIE increases postsynaptic glutamatergic function in male BLA-NAC neurons and female BLA-BNST neurons. Subsequent experiments demonstrated that CIE enhanced the excitability of male BLA-NAC neurons and BLA-BNST neurons in both sexes when glutamatergic but not GABAergic function was intact. Thus, CIE-mediated increased glutamatergic function facilitates hyperexcitability in male BLA-NAC neurons and BLA-BNST neurons of both sexes.

Role of anterior insula cortex in context-induced relapse of nicotine-seeking

Tobacco use is the leading cause of preventable death worldwide, and relapse during abstinence remains the key barrier to successful treatment of tobacco addiction. During abstinence, environmental contexts associated with nicotine use can induce craving and contribute to relapse. The insular cortex (IC) is thought to be a critical substrate of nicotine addiction and relapse. However, its specific role in context-induced relapse of nicotine-seeking is not fully known. In this study, we report a novel rodent model of context-induced relapse to nicotine-seeking after punishment-imposed abstinence, which models self-imposed abstinence through increasing negative consequences of excessive drug use. Using the neuronal activity marker Fos we find that the anterior (aIC), but not the middle or posterior IC, shows increased activity during context-induced relapse. Combining Fos with retrograde labelling of aIC inputs, we show projections to aIC from contralateral aIC and basolateral amygdala exhibit increased activity during context-induced relapse. Next, we used fiber photometry in aIC and observed phasic increases in aIC activity around nicotine-seeking responses during self-administration, punishment, and the context-induced relapse tests. Next, we used chemogenetic inhibition in both male and female rats to determine whether activity in aIC is necessary for context-induced relapse. We found that chemogenetic inhibition of aIC decreased context-induced nicotine-seeking after either punishment- or extinction-imposed abstinence. These findings highlight the critical role nicotine-associated contexts play in promoting relapse, and they show that aIC activity is critical for this context-induced relapse following both punishment and extinction imposed abstinence.

Dor nociplástica

A dor nociplástica é ligada à sensibilização central (SC) da dor, que é a amplificação da sinalização dos neurônios nociceptivos no sistema nervoso central à entrada somatossensorial aferente. Ocorre por alterações neuroplásticas associadas à atividade nervosa espontânea, campos receptivos expandidos e aumento da resposta neural na medula espinhal. Do ponto de vista neurobiológico, há um desequilíbrio entre neurotransmissores nociceptivos (substância P, glutamato) e antinociceptivos (serotonina, noradrenalina). Estudos funcionais de imagem cerebral demonstram atividade cerebral aumentada em áreas envolvidas na percepção da dor (ínsula, córtex cingulado anterior e córtex pré-frontal) e regiões não relacionadas à dor (núcleos do tronco cerebral, córtex frontal dorsolateral e córtex parietal). As principais características das síndromes nociplásticas são: predominância no sexo feminino, agregação familiar, longo tempo de evolução de dor multifocal, hiperalgesia, alodinia, coexistência de várias condições de dor crônica, alta frequência de comorbidades, presença de sensibilizadores psicológicos e pouca ou nenhuma resposta a tratamentos com ação periférica (anti-inflamatórios não esteroidais, glicocorticoides, injeções e cirurgias). Três aspectos clínicos são importantes na discriminação da dor centralizada: acometimento difuso, sem território neuroanatômico específico; intensidade desproporcional à natureza da lesão ou doença; e hipersensibilidade dos sentidos não relacionada ao sistema musculoesquelético. Entretanto, a presença de estímulo nociceptivo persistente, como pontos-gatilho miofascial ou doença que causa dor crônica como osteoartrite e artrite reumatoide, bem como existência de lesão neuropática, podem perpetuar o mecanismo de sensibilização central. O tratamento inclui medidas não farmacológicas (exercícios físicos, terapia cognitivo-comportamental, acupuntura) e farmacológicas (inibidores da recaptação de serotonina/noradrenalina, gabapentinoides, antidepressivos tricíclicos, tramadol, naltrexona). Unitermos: Dor nociplástica. Sensibilização central, somatossensorial. Dor crônica. Fibromialgia.

Quantitative Analysis of Synthetic Magnetic Resonance Imaging in Alzheimer’s Disease

Objectives: The purpose of this study was to evaluate the feasibility and whether synthetic MRI can benefit diagnosis of Alzheimer’s disease (AD).Materials and Methods: Eighteen patients and eighteen age-matched normal controls (NCs) underwent MR examination. The mini-mental state examination (MMSE) scores were obtained from all patients. The whole brain volumetric characteristics, T1, T2, and proton density (PD) values of different cortical and subcortical regions were obtained. The volumetric characteristics and brain regional relaxation values between AD patients and NCs were compared using independent-samples t-test. The correlations between these quantitative parameters and MMSE score were assessed by the Pearson correlation in AD patients.Results: Although the larger volume of cerebrospinal fluid (CSF), lower brain parenchymal volume (BPV), and the ratio of brain parenchymal volume to intracranial volume (BPV/ICV) were found in AD patients compared with NCs, there were no significant differences (p > 0.05). T1 values of right insula cortex and T2 values of left hippocampus and right insula cortex were significantly higher in AD patients than in NCs, but T1 values of left caudate showed a reverse trend (p < 0.05). As the MMSE score decreased in AD patients, the BPV and BPV/ICV decreased, while the volume of CSF and T1 values of bilateral insula cortex and bilateral hippocampus as well as T2 values of bilateral hippocampus increased (p < 0.05).Conclusion: Synthetic MRI not only provides more information to differentiate AD patients from normal controls, but also reflects the disease severity of AD.

Dysregulated anterior insula reactivity as robust functional biomarker for chronic pain – convergent evidence from neuroimaging meta-analysis

Neurobiological pain models propose that the transition from acute to chronic pain is accompanied by neuropathological adaptations that mediate progressive pain processing dysfunctions. In contrast, meta-analytic studies on neurofunctional dysregulations in chronic pain have not revealed convergent evidence for robust alterations during experimental pain induction. Against this background, the present neuroimaging meta-analysis combined three different meta-analytic approaches with stringent study selection criteria for case-control functional magnetic resonance imaging experiments during acute pain processing with a focus on chronic pain disorders (i.e., fibromyalgia, irritable bowel syndrome, chronic low back pain, neuropathic pain; n = 295 patients, n = 211 controls; 86 foci). Across the meta-analytic approaches, convergent neurofunctional dysregulations in chronic pain patients were observed in the left anterior insula cortex, with study characteristics indicating generalized pain processing abnormalities. Seed-based resting-state functional connectivity based on a large publicly available dataset combined with a meta-analytic task-based approach identified the anterior insular region as a key node of an extended bilateral insula-fronto-cingular network, resembling the salience network. Moreover, the meta-analytic decoding showed that this region presents a high probability to be specifically activated during pain-related processes. Together, the present findings indicate that dysregulated left anterior insular activity represents a robust neurofunctional maladaptation and potential treatment target in chronic pain disorders.

Clinical presentation of strokes confined to the insula: a systematic review of literature

Background and purpose The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive the appropriate treatment (e.g. thrombolysis). Methods We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords “insular stroke” and “insular infarction”, to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed. Results We identified 25 reports including a total of 49 patients (59.7 ± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache. Conclusions The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations.