Project description:How long neural information is stored in a local brain area reflects functions of that region and is often estimated by the magnitude of the autocorrelation of intrinsic neural signals in the area. Here, we investigated such intrinsic neural timescales in high-functioning adults with autism and examined whether local brain dynamics reflected their atypical behaviours. By analysing resting-state fMRI data, we identified shorter neural timescales in the sensory/visual cortices and a longer timescale in the right caudate in autism. The shorter intrinsic timescales in the sensory/visual areas were correlated with the severity of autism, whereas the longer timescale in the caudate was associated with cognitive rigidity. These observations were confirmed from neurodevelopmental perspectives and replicated in two independent cross-sectional datasets. Moreover, the intrinsic timescale was correlated with local grey matter volume. This study shows that functional and structural atypicality in local brain areas is linked to higher-order cognitive symptoms in autism.
Project description:Schizophrenia (SCZ) can be characterized as a basic self-disorder that is featured by abnormal temporal integration on phenomenological (experience) and psychological (information processing) levels. Temporal integration on the neuronal level can be measured by the brain's intrinsic neural timescale using the autocorrelation window (ACW) and power-law exponent (PLE). Our goal was to relate intrinsic neural timescales (ACW, PLE), as a proxy of temporal integration on the neuronal level, to temporal integration related to self-disorder on psychological (Enfacement illusion task in electroencephalography) and phenomenological (Examination of Anomalous Self-Experience [EASE]) levels. SCZ participants exhibited prolonged ACW and higher PLE during the self-referential task (Enfacement illusion), but not during the non-self-referential task (auditory oddball). The degree of ACW/PLE change during task relative to rest was significantly reduced in self-referential task in SCZ. A moderation model showed that low and high ACW/PLE exerted differential impact on the relationship of self-disorder (EASE) and negative symptoms (PANSS). In sum, we demonstrate abnormal prolongation in intrinsic neural timescale during self-reference in SCZ including its relation to basic self-disorder and negative symptoms. Our results point to abnormal relation of self and temporal integration at the core of SCZ constituting a "common currency" of neuronal, psychological, and phenomenological levels.
Project description:Language comprehension is compositional: individual words are combined structurally to form larger meaning representations. The neural basis for compositionality is at the center of a growing body of recent research. Previous work has largely used univariate analysis to investigate the question, a technique that could potentially lead to the loss of fined-grained information due to the procedure of averaging over neural responses. In a functional magnetic resonance imaging experiment, the present study examined different types of composition relations in Chinese phrases, using a 1-back composition relation probe (CRP) task and a 1-back word probe (WP) task. We first analyzed the data using the multivariate representation similarity analysis, which better captures the fine-grained representational differences in the stimuli. The results showed that the left angular gyrus (AG) represents different types of composition relations in the CRP task, but no brain areas were identified in the WP task. We also conducted a traditional univariate analysis and found greater activations in the bilateral inferior frontal gyrus in the CRP task relative to the WP task. We discuss the methodological and theoretical implications of our findings in the context of the larger language neural network identified in previous studies. Our findings highlight the role of left AG in representing and distinguishing fine-grained linguistic composition relations.
Project description:To elucidate the role of Tau isoforms and PTM stoichiometry in Alzheimer’s disease (AD), we generated a high resolution quantitative proteomic map of 88 PTMs on multiple isoforms of Tau isolated from the post-mortem human tissue from 49 AD and 42 control subjects. While Tau PTM maps reveal heterogeneity across subjects, a subset of PTMs display high occupancy and patient frequency for AD suggesting importance in disease. Unsupervised analyses indicate that PTMs occur in an ordered manner leading to Tau aggregation. The processive addition and minimal set of PTMs associated with seeding activity was further defined by the analysis of size fractionated Tau. To summarize, critical features within the Tau protein for disease intervention at different stages of disease are identified, including enrichment of 0N and 4R isoforms, underrepresentation of the C-terminal, an increase in negative charge in the PRR and a decrease in positive charge in the MBD.
Project description:Concepts bind together the features commonly associated with objects and events to form networks in long-term semantic memory. These conceptual networks are the basis of human knowledge and underlie perception, imagination, and the ability to communicate about experiences and the contents of the environment. Although it is often assumed that this distributed semantic information is integrated in higher-level heteromodal association cortices, open questions remain about the role and anatomic basis of heteromodal representations in semantic memory. Here we used combined neuroimaging evidence from functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to characterize the cortical networks underlying concept representation. Using a lexical decision task, we examined the processing of concepts in four semantic categories that varied on their sensory-motor feature associations (sight, sound, manipulation, and abstract). We found that the angular gyrus was activated across all categories regardless of their modality-specific feature associations, consistent with a heteromodal account for the angular gyrus. Exploratory analyses suggested that categories with weighted sensory-motor features additionally recruited modality-specific association cortices. Furthermore, DTI tractography identified white matter tracts connecting these regions of modality-specific functional activation with the angular gyrus. These findings are consistent with a distributed semantic network that includes a heteromodal, integrative component in the angular gyrus in combination with sensory-motor feature representations in modality-specific association cortices.
Project description:Direct eye contact between two individuals is a salient social behavior known to initiate and promote interpersonal interaction. However, the neural processes that underlie these live interactive behaviors and eye-to-eye contact are not well understood. The Dynamic Neural Coupling Hypothesis presents a general theoretical framework proposing that shared interactive behaviors are represented by cross-brain signal coherence. Using functional near-infrared spectroscopy (fNIRS) adapted for hyper scanning, we tested this hypothesis specifically for neural mechanisms associated with eye-to-eye gaze between human participants compared to similar direct eye-gaze at a dynamic video of a face and predicted that the coherence of neural signals between the two participants during reciprocal eye-to-eye contact would be greater than coherence observed during direct eye-gaze at a dynamic video for those signals originating in social and face processing systems. Consistent with this prediction cross-brain coherence was increased for signals within the angular gyrus (AG) during eye-to-eye contact relative to direct eye-gaze at a dynamic face video (p < 0.01). Further, activity in the right temporal-parietal junction (TPJ) was increased in the real eye-to-eye condition (p < 0.05, FDR corrected). Together, these findings advance a functional and mechanistic understanding of the AG and cross-brain neural coupling associated with real-time eye-to-eye contact.
Project description:The left angular gyrus (AG) is reliably activated across a wide range of semantic tasks, and is also a consistently reported component of the so-called default network that it is deactivated during all goal-directed tasks. We show here that there is only partial overlap between the semantic system and the default network in left AG and the overlap defines a reliable functional landmark that can be used to segregate functional subdivisions within AG. In 94 healthy human subjects, we collected functional magnetic resonance imaging (fMRI) data during fixation and eight goal directed tasks that involved semantic matching, perceptual matching or speech production in response to familiar or unfamiliar stimuli presented in either verbal (letters) or nonverbal (pictures) formats. Our results segregated three different left AG regions that were all activated by semantic relative to perceptual matching: (1) a midregion (mAG) that overlapped with the default network because it was deactivated during all tasks relative to fixation; (2) a dorsomesial region (dAG) that was more activated by all tasks relative to fixation; and (3) a ventrolateral region (vAG) that was only activated above fixation during semantic matching. By examining the effects of task and stimuli in each AG subdivision, we propose that mAG is involved in semantic associations regardless of the presence or absence of a stimulus; dAG is involved in searching for semantics in all visual stimuli, and vAG is involved in the conceptual identification of visual inputs. Our findings provide a framework for reporting and interpreting AG activations with greater definition.
Project description:ObjectiveSchizophrenia (SCH) is primarily diagnosed based on specific clinical symptoms, with the lack of any objective SCH-related biomarkers often resulting in patient misdiagnosis and the underdiagnosis of this condition. This study was developed to assess the utility of amplitude of low-frequency fluctuation (ALFF) values analyzed via support vector machine (SVM) methods as a means of diagnosing SCH.MethodsIn total, 131 SCH patients and 128 age- and gender-matched healthy control (HC) individuals underwent resting-state functional magnetic resonance imaging (rs-fMRI), with the resultant data then being analyzed using ALFF values and SVM methods.ResultsRelative to HC individuals, patients with SCH exhibited ALFF reductions in the left angular gyrus (AG), fusiform gyrus, anterior cingulate cortex (ACC), right cerebellum, bilateral middle temporal gyrus (MTG), and precuneus (PCu) regions. No SCH patient brain regions exhibited significant increases in ALFF relative to HC individuals. SVM results indicated that reductions in ALFF values in the bilateral PCu can be used to effectively differentiate between SCH patients and HCs with respective accuracy, sensitivity, and specificity values of 73.36, 91.60, and 54.69%.ConclusionThese data indicate that SCH patients may exhibit characteristic reductions in regional brain activity, with decreased ALFF values of the bilateral PCu potentially offering value as a candidate biomarker capable of distinguishing between SCH patients and HCs.
Project description:Music reduces pain in fibromyalgia (FM), a chronic pain disease, but the functional neural correlates of music-induced analgesia (MIA) are still largely unknown. We recruited FM patients (n = 22) who listened to their preferred relaxing music and an auditory control (pink noise) for 5 min without external noise from fMRI image acquisition. Resting state fMRI was then acquired before and after the music and control conditions. A significant increase in the amplitude of low frequency fluctuations of the BOLD signal was evident in the left angular gyrus (lAnG) after listening to music, which in turn, correlated to the analgesia reports. The post-hoc seed-based functional connectivity analysis of the lAnG showed found higher connectivity after listening to music with right dorsolateral prefrontal cortex (rdlPFC), the left caudate (lCau), and decreased connectivity with right anterior cingulate cortex (rACC), right supplementary motor area (rSMA), precuneus and right precentral gyrus (rPreG). Pain intensity (PI) analgesia was correlated (r = 0.61) to the connectivity of the lAnG with the rPreG. Our results show that MIA in FM is related to top-down regulation of the pain modulatory network by the default mode network (DMN).
Project description:Transcranial magnetic stimulation (TMS) is a non-invasive technique that can transiently interfere with local cortical functioning, thus enabling inferences of causal left AG involvement in higher functions from experimentation with healthy participants. Here, we examine 35 studies that measure behavioural outcomes soon after or during targeting TMS to the left AG, by design and as documented by individual magnetic resonance images, in healthy adult participants. The reviewed evidence suggests a specific causal involvement of the left AG in a wide range of tasks involving language, memory, number processing, visuospatial attention, body awareness and motor planning functions. These core findings are particularly valuable to inform theoretical models of the left AG role(s) in higher functions, due to the anatomical specificity afforded by the selected studies and the complementarity of TMS to different methods of investigation. In particular, the variety of the operations within and between functions in which the left AG appears to be causally involved poses a formidable challenge to any attempts to identify a single computational process subserved by the left AG (as opposed to just outlining a broad type of functional contribution) that could apply across thematic areas. We conclude by highlighting directions for improvement in future experimentation with TMS, in order to strengthen the available evidence, while taking into account the anatomical heterogeneity of this brain region.