Previous Neuroimaging Evidence Research Articles

Testing the effect of high-definition transcranial direct current stimulation of the insular cortex to modulate decision-making and executive control.

Previous neuroimaging evidence highlighted the role of the insular and dorsal anterior cingulate cortex (dACC) in conflict monitoring and decision-making, thus supporting the translational implications of targeting these regions in neuro-stimulation treatments for clinical purposes. Recent advancements of targeting and modeling procedures for high-definition tDCS (HD-tDCS) provided methodological support for the stimulation of otherwise challenging targets, and a previous study confirmed that cathodal HD-tDCS of the dACC modulates executive control and decision-making metrics in healthy individuals. On the other hand, evidence on the effect of stimulating the insula is still needed. We used a modeling/targeting procedure to investigate the effect of stimulating the posterior insula on Flanker and gambling tasks assessing, respectively, executive control and both loss and risk aversion in decision-making. HD-tDCS was applied through 6 small electrodes delivering anodal, cathodal or sham stimulation for 20 min in a within-subject offline design with three separate sessions. Bayesian statistical analyses on Flanker conflict effect, as well as loss and risk aversion, provided moderate evidence for the null model (i.e., absence of HD-tDCS modulation). These findings suggest that further research on the effect of HD-tDCS on different regions is required to define reliable targets for clinical applications. While modeling and targeting procedures for neuromodulation in clinical research could lead to innovative protocols for stand-alone treatment, or possibly in combination with cognitive training, assessing the effectiveness of insula stimulation might require sensitive metrics other than those investigated here.

Altered dynamic brain activity and functional connectivity in thyroid-associated ophthalmopathy.

Although previous neuroimaging evidence has confirmed the brain functional disturbances in thyroid-associated ophthalmopathy (TAO), the dynamic characteristics of brain activity and functional connectivity (FC) in TAO were rarely concerned. The present study aims to investigate the alterations of temporal variability of brain activity and FC in TAO using resting-state functional magnetic resonance imaging (rs-fMRI). Forty-seven TAO patients and 30 age-, gender-, education-, and handedness-matched healthy controls (HCs) were enrolled and underwent rs-fMRI scanning. The dynamic amplitude of low-frequency fluctuation (dALFF) was first calculated using a sliding window approach to characterize the temporal variability of brain activity. Based on the dALFF results, seed-based dynamic functional connectivity (dFC) analysis was performed to identify the temporal variability of efficient communication between brain regions in TAO. Additionally, correlations between dALFF and dFC and the clinical indicators were analyzed. Compared with HCs, TAO patients displayed decreased dALFF in the left superior occipital gyrus (SOG) and cuneus (CUN), while showing increased dALFF in the left triangular part of inferior frontal gyrus (IFGtriang), insula (INS), orbital part of inferior frontal gyrus (ORBinf), superior temporal gyrus (STG) and temporal pole of superior temporal gyrus (TPOsup). Furthermore, TAO patients exhibited decreased dFC between the left STG and the right middle occipital gyrus (MOG), as well as decreased dFC between the left TPOsup and the right calcarine fissure and surrounding cortex (CAL) and MOG. Correlation analyses showed that the altered dALFF in the left SOG/CUN was positively related to visual acuity (r = .409, p = .004), as well as the score of QoL for visual functioning (r = .375, p = .009). TAO patients developed abnormal temporal variability of brain activity in areas related to vision, emotion, and cognition, as well as reduced temporal variability of FC associated with vision deficits. These findings provided additional insights into the neurobiological mechanisms of TAO.

Altered neurovascular coupling in thyroid-associated ophthalmopathy: A combined resting-state fMRI and arterial spin labeling study.

Besides the well-documented ophthalmic manifestations, thyroid-associated ophthalmopathy (TAO) is believed to be related to emotional and psychological abnormalities. Given the previous neuroimaging evidence, we hypothesized that TAO patients would have altered neurovascular coupling associated with clinical-psychiatric disturbances. This study was to investigate neurovascular coupling changes in TAO by combining resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL) techniques. Amplitude of low-frequency fluctuation (ALFF) was calculated from rs-fMRI, and cerebral blood flow (CBF) was computed from ASL in 37 TAO patients and 21 healthy controls (HCs). Global neurovascular coupling was assessed by across-voxel CBF-ALFF correlation, and regional neurovascular coupling was evaluated by CBF/ALFF ratio. Auxiliary analyses were performed using fractional ALFF (fALFF) and regional homogeneity (ReHo) as rs-fMRI measures. Compared with HCs, TAO patients showed significantly reduced global CBF-ALFF coupling. Moreover, TAO patients exhibited decreased CBF/ALFF ratio in the left lingual gyrus (LG)/fusiform gyrus (FFG), and increased CBF/ALFF ratio in the bilateral precuneus (PCu). In TAOs, CBF/ALFF ratio in the left LG/FFG was positively correlated with visual acuity, while CBF/ALFF ratio in the bilateral PCu was negatively correlated with Montreal Cognitive Assessment score. The auxiliary analyses showed trends of reduced global neurovascular coupling (i.e., CBF-fALFF correlation and CBF-ReHo correlation), as well as significant altered regional neurovascular coupling (i.e., CBF/fALFF ratio and CBF/ReHo ratio) in several brain regions. These findings indicated that TAO patients had altered neurovascular coupling in the visual and higher-order cognitive cortices. The neurovascular decoupling might be a possible neuropathological mechanism of TAO.

High-definition transcranial direct current stimulation of the dorsal anterior cingulate cortex modulates decision-making and executive control.

Previous neuroimaging evidence highlights the translational implications of targeting the dorsal anterior cingulate cortex (dACC), i.e. a key node of the networks underlying conflict monitoring and decision-making, in brain stimulation treatments with clinical or rehabilitative purposes. While the optimized modelling of "high-definition" current flows between multiple anode-cathode pairs might, in principle, allow to stimulate an otherwise challenging target, sensitive benchmark metrics of dACC neuromodulation are required to assess the effectiveness of this approach. On this basis, we aimed to assess the modulatory effect of anodal and cathodal high-definition tDCS (HD-tDCS) of the dACC on different facets of executive control and decision-making in healthy young individuals. A combined modelling/targeting procedure provided the optimal montage for the maximum intensity of dACC stimulation with six small "high-definition" electrodes delivering anodal, cathodal or sham HD-tDCS for 20min in a within-subject design with three separate sessions. Following stimulation, participants performed Flanker and gambling tasks unveiling individual differences in executive control and both loss- and risk-aversion in decision-making, respectively. Compared to both anodal and sham conditions, cathodal dACC stimulation significantly affected task performance by increasing control over the Flanker conflict effect, and both loss and risk-aversion in decision-making. By confirming the feasibility and effectiveness of dACC stimulation with HD-tDCS, these findings highlight the implications of modelling and targeting procedures for neuromodulation in clinical research, whereby innovative protocols might serve as treatment addressing dysfunctional dACC activity, or combined with cognitive training, to enhance higher-order executive functioning in different neuropsychiatric conditions.

Sparse Interpretation of Graph Convolutional Networks for Multi-Modal Diagnosis of Alzheimer's Disease.

The interconnected quality of brain regions in neurological disease has immense importance for the development of biomarkers and diagnostics. While Graph Convolutional Network (GCN) methods are fundamentally compatible with discovering the connected role of brain regions in disease, current methods apply limited consideration for node features and their connectivity in brain network analysis. In this paper, we propose a sparse interpretable GCN framework (SGCN) for the identification and classification of Alzheimer's disease (AD) using brain imaging data with multiple modalities. SGCN applies an attention mechanism with sparsity to identify the most discriminative subgraph structure and important node features for the detection of AD. The model learns the sparse importance probabilities for each node feature and edge with entropy, ℓ 1, and mutual information regularization. We then utilized this information to find signature regions of interest (ROIs), and emphasize the disease-specific brain network connections by detecting the significant difference of connectives between regions in healthy control (HC), and AD groups. We evaluated SGCN on the ADNI database with imaging data from three modalities, including VBM-MRI, FDG-PET, and AV45-PET, and observed that the important probabilities it learned are effective for disease status identification and the sparse interpretability of disease-specific ROI features and connections. The salient ROIs detected and the most discriminative network connections interpreted by our method show a high correspondence with previous neuroimaging evidence associated with AD.

Task-Dependent Recruitment of Modality-Specific and Multimodal Regions during Conceptual Processing.

Conceptual knowledge is central to cognitive abilities such as word comprehension. Previous neuroimaging evidence indicates that concepts are at least partly composed of perceptual and motor features that are represented in the same modality-specific brain regions involved in actual perception and action. However, it is unclear to what extent the retrieval of perceptual–motor features and the resulting engagement of modality-specific regions depend on the concurrent task. To address this issue, we measured brain activity in 40 young and healthy participants using functional magnetic resonance imaging, while they performed three different tasks—lexical decision, sound judgment, and action judgment—on words that independently varied in their association with sounds and actions. We found neural activation for sound and action features of concepts selectively when they were task-relevant in brain regions also activated during auditory and motor tasks, respectively, as well as in higher-level, multimodal regions which were recruited during both sound and action feature retrieval. For the first time, we show that not only modality-specific perceptual–motor areas but also multimodal regions are engaged in conceptual processing in a flexible, task-dependent fashion, responding selectively to task-relevant conceptual features.

Structural Alterations in Large-scale Brain Networks and Their Relationship with Sleep Disturbances in the Adolescent Population

Although sleep disturbances are highly prevalent in adolescents, neuroimaging evidence on the effects of sleep disturbances on their developing brains remains limited. Therefore, we explored gray matter volumes (GMVs) at the whole-brain level and investigated their relationship to sleep disturbances in a sample of Korean adolescents in the general population. We recruited participants from one middle school and high school. All participants and their legal guardians gave informed consent before participating in our study. We used component 5 of the Pittsburgh Sleep Quality Index to measure sleep disturbances and conducted a voxel-based morphometry-DARTEL procedure to measure GMVs. We performed partial correlation analyses to examine whether the GMVs were associated with sleep disturbances. A total of 56 adolescents participated in this study. Our results revealed that GMVs in multiple global regions were negatively correlated with sleep disturbances. Moreover, most of these identified regions belong to large-scale brain networks categorized by functional neuroimaging studies. We found an association between regional GMVs in multiple global regions involved in large-scale networks and the severity of sleep disturbances in the adolescent population. Based on this evidence and previous neuroimaging evidence, we suggest that structural alterations in the networks may be linked to sleep disturbances.

Decreased amygdala functional connectivity in adolescents with autism: A resting-state fMRI study

The human brain undergoes dramatic changes in amygdala-related functional connectivity network during adolescence. Given that the amygdala is a vital component of the “social brain”, the Amygdala Theory of Autism has been proposed to account for atypical patterns of socio-emotional behavior in autism. Most of the previous neuroimaging evidence has concentrated on local functional or structural abnormalities of the amygdala in relation to social deficits in autism, rather than on its integrated role as part of larger brain networks. To examine whether functional integration pattern of the amygdala is altered in autism, the current study examined sixty-five adolescent subjects (30 autism and 35 healthy controls, 12–18 years old) from two independent datasets (UCLA and Leuven) of the Autism Brain Imaging Data Exchange. Whole-brain resting-state functional connectivity maps seeded in the amygdala were calculated and compared between patient and control groups. Compared with healthy controls, adolescents with autism showed decreased functional connectivity between the amygdala and subcortical regions in both datasets, including the bilateral thalamus and right putamen. These findings support the Amygdala Theory of Autism, demonstrating altered functional connectivity pattern associated with the amygdala in autism, and provide new insights into the pathophysiology of autism.

Alcohol Hits You When It Is Hard: Intoxication, Task Difficulty, and Theta Brain Oscillations.

BackgroundAlcohol intoxication is known to impair decision making in a variety of situations. Previous neuroimaging evidence suggests that the neurofunctional system subserving controlled processing is especially vulnerable to alcohol in conflict‐evoking tasks. The present study investigated the effects of moderate alcohol intoxication on the spatiotemporal neural dynamics of event‐related total theta (4 to 7 Hz) power as a function of task difficulty.MethodsTwo variants of the Simon task manipulated incongruity via simple spatial stimulus‐response mismatch and, in a more difficult version, by combining spatial and semantic interference. Healthy social drinkers participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. Whole‐head magnetoencephalography (MEG) signals were acquired and event‐related total theta power was calculated on each trial with Morlet wavelets. MEG sources were estimated using anatomically constrained, noise‐normalized, spectral dynamic statistical parametric mapping.ResultsLonger reaction times and lower accuracy confirmed the difficulty manipulation. Response conflict (incongruity) increased and alcohol intoxication decreased event‐related theta power overall during both tasks bilaterally in the medial and ventrolateral prefrontal cortices. However, alcohol‐induced theta suppression was selective for conflict only in the more difficult task which engaged the dorsal anterior cingulate (dAC) and anterior inferolateral prefrontal cortices. Theta power correlated negatively with drinking levels and disinhibition, suggesting that cognitive control is susceptible in more impulsive individuals with higher alcohol intake.ConclusionsThe spatiotemporal theta profile across the 2 tasks supports the concept of a rostrocaudal activity gradient in the medial prefrontal cortex that is modulated by task difficulty, with the dAC as the key node in the network subserving cognitive control. Conflict‐related theta power was selectively reduced by alcohol only under the more difficult task which is indicative of the alcohol‐induced impairment of conflict monitoring and top‐down regulation. Compromised executive control under alcohol may underlie a range of adverse effects including reduced competency in conflict‐inducing or complex situations.

Reduced after-effects following podokinetic adaptation in people with Parkinson's disease and freezing of gait

IntroductionGait dysfunction is common in people with Parkinson's disease (PD). Freezing of gait (FOG) is one such gait disturbance that significantly impacts mobility and quality of life in PD. Recent evidence suggests that cerebellar connectivity may differ in people with PD and FOG (PD+FOG) relative to those without FOG (PD-FOG). Investigation of gait adaptation, or the ability to change gait patterns in response to external perturbations, is cerebellum-dependent, is a practical means of probing cerebellar integrity and may provide additional insights regarding the FOG phenomenon. MethodsIn this study, we investigated gait adaptation in PD and FOG by measuring after-effects, namely whole-body rotation, following stepping on a rotating disc in PD+FOG compared to PD-FOG and older healthy adults. We refer to the period of stepping on the rotating disc as the podokinetic (PK) stimulation and after-effects as podokinetic after-rotation (PKAR). Our primary measure of adaptation was the magnitude and rate of decay of the after-effects. ResultsWe noted that PKAR was diminished in PD+FOG compared to the other groups, indicating reduced storage of the adapted gait pattern in PD+FOG. In the PD groups, FOG explained about 20% of the variability in peak velocity. Furthermore, these differences were independent of stepping cadence or motor sign severity. ConclusionOur results show that gait adaptation is impaired in PD+FOG, suggesting the cerebellum may be differentially impacted in PD+FOG compared to PD-FOG. This supports previous neuroimaging evidence of cerebellar dysfunction in PD+FOG. Overall, these data further our understanding of gait deficits in PD+FOG.

Response inhibition failure to visual stimuli paired with a "single-type" stressor in PTSD patients: an fMRI pilot study.

Patients with post-traumatic stress disorder (PTSD) tend to misinterpret innocuous stimuli as potential threats, possibly due to a conditioning provoked by traumatic episodes. Previous neuroimaging evidence has shown an abnormal activation of the amygdala and prefrontal cortex in PTSD patients during fear conditioning and extinction. Nevertheless, the effects of a single-type adverse stressor on that circuit remain poorly explored. We tested the hypothesis that a single-type adverse episode is able to affect the prefrontal cortex and amygdala response to conditioned stimuli. To test this hypothesis, fMRI recordings were performed in PTSD patients and trauma-exposed controls during the observation of neutral and negative paired or non-paired pictures with an adverse stimulus by means of a single association. Results showed that left amygdala activation during negative reinforced stimuli was correlated with the score of PTSD clinical scale across all subjects. Furthermore, in the traumatized non-PTSD group, the activation of the dorso-medial prefrontal cortex and bilateral amygdala was lower during the observation of the reinforced (CS(+)) versus non-reinforced pictures (CS(-)) in response to emotionally negative stimuli. This was not the case in the PTSD patients. These results suggest that in PTSD patients, a single-episode conditioning unveils the failure of an inhibitory mechanism moderating the activity of the prefrontal cortex and amygdala in response to adverse and neutral stimuli.

Stimulating the Brain's Language Network: Syntactic Ambiguity Resolution after TMS to the Inferior Frontal Gyrus and Middle Temporal Gyrus

The posterior middle temporal gyrus (MTG) and inferior frontal gyrus (IFG) are two critical nodes of the brain's language network. Previous neuroimaging evidence has supported a dissociation in language comprehension in which parts of the MTG are involved in the retrieval of lexical syntactic information and the IFG in unification operations that maintain, select, and integrate multiple sources of information over time. In the present investigation, we tested for causal evidence of this dissociation by modulating activity in IFG and MTG using an offline TMS procedure: continuous theta-burst stimulation. Lexical-syntactic retrieval was manipulated by using sentences with and without a temporarily word-class (noun/verb) ambiguity (e.g., run). In one group of participants, TMS was applied to the IFG and MTG, and in a control group, no TMS was applied. Eye movements were recorded and quantified at two critical sentence regions: a temporarily ambiguous region and a disambiguating region. Results show that stimulation of the IFG led to a modulation of the ambiguity effect (ambiguous-unambiguous) at the disambiguating sentence region in three measures: first fixation durations, total reading times, and regressive eye movements into the region. Both IFG and MTG stimulation modulated the ambiguity effect for total reading times in the temporarily ambiguous sentence region relative to the control group. The current results demonstrate that an offline repetitive TMS protocol can have influences at a different point in time during online processing and provide causal evidence for IFG involvement in unification operations during sentence comprehension.

P 46. Featural and Configural processing of faces are dissociated in the dorsolateral prefrontal cortex: A TMS study

Facial recognition relies on distinct and parallel types of processing: featural processing focuses on the individual components of a face (e.g., the shape or the size of the eyes), whereas configural (or “relational”) processing considers the spatial interrelationships among the single facial components (e.g., distance of the mouth from the nose). Previous neuroimaging evidence has suggested that featural and configural processes may rely on different brain circuits. By using rTMS, here we show for the first time a double dissociation in dorsolateral prefrontal cortex for different aspects of face processing. Twelve participants were asked to perform a same-different judgment task (“Jane faces” task, Mondloch et al., 2002, Perception 31:553–66) on two shortly consecutive presented faces. Two sets of stimuli (faces differing either for featural or configural aspects) were run separately to allow time for each style of processing to emerge. Triple-pulse TMS was delivered between 100 and 150 ms after the onset of the second face stimulus over the left middle frontal gyrus, the right middle frontal gyrus, or the vertex, in addition to a condition where no TMS was administered. TMS over the left middle frontal gyrus selectively disrupted featural processing, whereas TMS over the right frontal gyrus selectively interfered with configural processing of faces. By establishing a causal link between activation in left and right prefrontal areas and different modes of face processing, our data extend previous neuroimaging evidence and may have important implications in the study of face-processing deficits, such as those manifested in prosopagnosia and autistic spectrum disorders.

Processing of featural and configural aspects of faces is lateralized in dorsolateral prefrontal cortex: A TMS study

Facial recognition relies on distinct and parallel types of processing: featural processing focuses on the individual components of a face (e.g., the shape or the size of the eyes), whereas configural (or "relational") processing considers the spatial interrelationships among the single facial components (e.g., distance of the mouth from the nose). Previous neuroimaging evidence has suggested that featural and configural processes may rely on different brain circuits. By using rTMS, here we show for the first time a double dissociation in dorsolateral prefrontal cortex for different aspects of face processing: in particular, TMS over the left middle frontal gyrus (BA8) selectively disrupted featural processing, whereas TMS over the right inferior frontal gyrus (BA44) selectively interfered with configural processing of faces. By establishing a causal link between activation in left and right prefrontal areas and different modes of face processing, our data extend previous neuroimaging evidence and may have important implications in the study of face-processing deficits, such as those manifested in prosopagnosia and autistic spectrum disorders.

Minimizing motor mimicry by myself: Self-focus enhances online action-control mechanisms during motor contagion

Ideomotor theory of human action control proposes that activation of a motor representation can occur either through internally-intended or externally-perceived actions. Critically, sometimes these alternatives of eliciting a motor response may be conflicting, for example, when intending one action and perceiving another, necessitating the recruitment of enhanced action-control to avoid motor mimicry. Based on previous neuroimaging evidence, suggesting that reduced mimicry is associated with self-related processing, we aimed to experimentally enhance these action-control mechanisms during motor contagion by inducing self-focus. In two within-subjects experiments, participants had to enforce their action intention against an external motor contagion tendency under heightened and normal self-focus. During high self-focus participants showed reduced motor mimicry, induced either by mirror self-observation or self-referential judgments. This indicates that a self-focus provoking situation can enhance online action-control mechanisms, needed to resist unintentional motor contagion tendencies and thereby enables a modulation of automatic mirroring responses.

Functional Neuroanatomy of Meaning Acquisition from Context

An important issue in language learning is how new words are integrated in the brain representations that sustain language processing. To identify the brain regions involved in meaning acquisition and word learning, we conducted a functional magnetic resonance imaging study. Young participants were required to deduce the meaning of a novel word presented within increasingly constrained sentence contexts that were read silently during the scanning session. Inconsistent contexts were also presented in which no meaning could be assigned to the novel word. Participants showed meaning acquisition in the consistent but not in the inconsistent condition. A distributed brain network was identified comprising the left anterior inferior frontal gyrus (BA 45), the middle temporal gyrus (BA 21), the parahippocampal gyrus, and several subcortical structures (the thalamus and the striatum). Drawing on previous neuroimaging evidence, we tentatively identify the roles of these brain areas in the retrieval, selection, and encoding of the meaning.