Altered grid-like coding in early blind people.

Cognitive maps in the hippocampal-entorhinal system are central for the representation of both spatial and non-spatial relationships. Although this system, especially in humans, heavily relies on vision, the role of visual experience in shaping the development of cognitive maps remains largely unknown. Here, we test sighted and early blind individuals in both imagined navigation in fMRI and real-world navigation. During imagined navigation, the Human Navigation Network, constituted by frontal, medial temporal, and parietal cortices, is reliably activated in both groups, showing resilience to visual deprivation. However, neural geometry analyses highlight crucial differences between groups. A 60° rotational symmetry, characteristic of a hexagonal grid-like coding, emerges in the entorhinal cortex of sighted but not blind people, who instead show a 90° (4-fold) symmetry, indicative of a square grid. Moreover, higher parietal cortex activity during navigation in blind people correlates with the magnitude of 4-fold symmetry. In sum, early blindness can alter the geometry of entorhinal cognitive maps, possibly as a consequence of higher reliance on parietal egocentric coding during navigation.

Source space connectomics of neurodegeneration: One-metric approach does not fit all.

Brain functional connectivity in dementia has been assessed with dissimilar EEG connectivity metrics and estimation procedures, thereby increasing results' heterogeneity. In this scenario, joint analyses integrating information from different metrics may allow for a more comprehensive characterization of brain functional interactions in different dementia subtypes. To test this hypothesis, resting-state electroencephalogram (rsEEG) was recorded in individuals with Alzheimer's Disease (AD), behavioral variant frontotemporal dementia (bvFTD), and healthy controls (HCs). Whole-brain functional connectivity was estimated in the EEG source space using 101 different types of functional connectivity, capturing linear and nonlinear interactions in both time and frequency-domains. Multivariate machine learning and progressive feature elimination was run to discriminate AD from HCs, and bvFTD from HCs, based on joint analyses of i) EEG frequency bands, ii) complementary frequency-domain metrics (e.g., instantaneous, lagged, and total connectivity), and iii) time-domain metrics with different linearity assumption (e.g., Pearson correlation coefficient and mutual information). <10% of all possible connections were responsible for the differences between patients and controls, and atypical connectivity was never captured by >1/4 of all possible connectivity measures. Joint analyses revealed patterns of hypoconnectivity (patientsHCs) in both groups was mainly identified in frontotemporal regions. These atypicalities were differently captured by frequency- and time-domain connectivity metrics, in a bandwidth-specific fashion. The multi-metric representation of source space whole-brain functional connectivity evidenced the inadequacy of single-metric approaches, and resulted in a valid alternative for the selection problem in EEG connectivity. These joint analyses reveal patterns of brain functional interdependence that are overlooked with single metrics approaches, contributing to a more reliable and interpretable description of atypical functional connectivity in neurodegeneration.

Altered effective connectivity within the cingulo-frontal-parietal cognitive attention networks in chronic low back pain: a dynamic causal modeling study.

Dysfunction of the cingulo-frontal-parietal (CFP) cognitive attention network has been associated with the pathophysiology of chronic low back pain (cLBP). However, the direction of information processing within this network remains largely unknown. We aimed to study the effective connectivity among the CFP regions in 36 cLBP patients and 36 healthy controls by dynamic causal modeling (DCM). Both the resting-state and task-related (Multi-Source Interference Task, MSIT) functional magnetic resonance imaging (fMRI) data were collected and analyzed. The relationship between the effective connectivity of the CFP regions and clinical measures was also examined. Our results suggested that cLBP had significantly altered resting-state effective connectivity of the prefrontal cortex (PFC)-to-mid-cingulate cortex (MCC) (increased) and MCC-to-left superior parietal cortex (LPC) (decreased) pathways as compared with healthy controls. MSIT-related DCM suggested that the interference task could significantly increase the effective connectivity of the right superior parietal cortex (RPC)-to-PFC and RPC-to-MCC pathways in cLBP than that in healthy controls. The control task could significantly decrease the effective connectivity of the MCC-to-LPC and MCC-to-RPC pathways in cLBP than that in healthy controls. The endogenous connectivity of the PFC-to-RPC pathway in cLBP was significantly lower than that in healthy controls. No significant correlations were found between the effective connectivity within CFP networks and pain/depression scores in patients with cLBP. In summary, our findings suggested altered effective connectivity in multiple pathways within the CFP network in both resting-state and performing attention-demanding tasks in patients with cLBP, which extends our understanding of attention dysfunction in patients with cLBP.

Functional differentiation in the language network revealed by lesion-symptom mapping.

Theories of language organization in the brain commonly posit that different regions underlie distinct linguistic mechanisms. However, such theories have been criticized on the grounds that many neuroimaging studies of language processing find similar effects across regions. Moreover, condition by region interaction effects, which provide the strongest evidence of functional differentiation between regions, have rarely been offered in support of these theories. Here we address this by using lesion-symptom mapping in three large, partially-overlapping groups of aphasia patients with left hemisphere brain damage due to stroke (N = 121, N = 92, N = 218). We identified multiple measure by region interaction effects, associating damage to the posterior middle temporal gyrus with syntactic comprehension deficits, damage to posterior inferior frontal gyrus with expressive agrammatism, and damage to inferior angular gyrus with semantic category word fluency deficits. Our results are inconsistent with recent hypotheses that regions of the language network are undifferentiated with respect to high-level linguistic processing.

Changes of functional connectivity of the subgenual anterior cingulate cortex and precuneus after cognitive behavioral therapy combined with fluoxetine in young depressed patients with suicide attempt.

This single-center, randomized, single-blind, parallel-controlled study aimed to analyze the changes in resting-state functional connectivity (RSFC) in young patients with a suicide attempt caused by depression before and after cognitive-behavioral therapy (CBT) combined with fluoxetine or fluoxetine alone by functional magnetic resonance imaging (fMRI). Before treatment, functional connectivity of the right subgenual anterior cingulate cortex (R-sgACC), left subgenual anterior cingulate cortex (L-sgACC) and right precuneus (R-PCu) was lower in depressed patients with a suicide attempt than that of healthy controls. After treatment, compared with the fluoxetine group, functional connectivity between the R-sgACC and left posterior cerebellar lobe in the CBT group was increased, while this group also showed increased RSFC between the L-sgACC and right anterior cingulate cortex/ medial prefrontal cortex. On the contrary, the functional connectivity between the R-PCu and right parietal lobe was reduced (P < 0.001). It was also found there were some changes in different brain regions in pre- and post-treatment within both the CBT and MG group. The functional connectivity of the R-sgACC and the left posterior cerebellum lobe was negatively correlated with the SSI score. The functional connectivity of the R-PCu and right middle frontal cortex was negatively correlated with the HAMD score before treatment. After treatment, functional connectivity between the R-PCu and right superior frontal gyrus was positively correlated with the SSI scores in the CBT group. After 8 weeks of combined CBT, the strength of the functional connectivity in the bilateral sgACC and bilateral PCu was significantly changed.

Tonic somatosensory responses and deficits of tactile awareness converge in the parietal operculum.

Although clinical neuroscience and the neuroscience of consciousness have long sought mechanistic explanations of tactile-awareness disorders, mechanistic insights are rare, mainly because of the difficulty of depicting the fine-grained neural dynamics underlying somatosensory processes. Here, we combined the stereo-EEG responses to somatosensory stimulation with the lesion mapping of patients with a tactile-awareness disorder, namely tactile extinction. Whereas stereo-EEG responses present different temporal patterns, including early/phasic and long-lasting/tonic activities, tactile-extinction lesion mapping co-localizes only with the latter. Overlaps are limited to the posterior part of the perisylvian regions, suggesting that tonic activities may play a role in sustaining tactile awareness. To assess this hypothesis further, we correlated the prevalence of tonic responses with the tactile-extinction lesion mapping, showing that they follow the same topographical gradient. Finally, in parallel with the notion that visuotactile stimulation improves detection in tactile-extinction patients, we demonstrated an enhancement of tonic responses to visuotactile stimuli, with a strong voxel-wise correlation with the lesion mapping. The combination of these results establishes tonic responses in the parietal operculum as the ideal neural correlate of tactile awareness.

Altered Functional Connectivity Patterns of Parietal Subregions Contribute to Cognitive Dysfunction in Patients with White Matter Hyperintensities.

BACKGROUND: The white matter hyperintensities (WMHs) are considered as one of the core neuroimaging findings of cerebral small vessel disease and independently associated with cognitive deficit. The parietal lobe is a heterogeneous area containing many subregions and play an important role in the processes of neurocognition. OBJECTIVE: To explore the relationship between parietal subregions alterations and cognitive impairments in WHMs. METHODS: Resting-state functional connectivity (rs-FC) analyses of parietal subregions were performed in 104 right-handed WMHs patients divided into mild (n = 39), moderate (n = 37), and severe WMHs (n = 28) groups according to the Fazekas scale and 36 healthy controls. Parietal subregions were defined using tractographic Human Brainnetome Atlas and included five subregions for superior parietal lobe, six subregions for inferior parietal lobe (IPL), and three subregions for precuneus. All participants underwent a neuropsychological test battery to evaluate emotional and general cognitive functions. RESULTS: Differences existed between the rs-FC strength of IPL_R_6_2 with the left anterior cingulate gyrus, IPL_R_6_3 with the right dorsolateral superior frontal gyrus, and the IPL_R_6_5 with the left anterior cingulate gyrus. The connectivity strength between IPL_R_6_3 and the left anterior cingulate gyrus were correlated with AVLT-immediate and AVLT-recognition test in WMHs. CONCLUSION: We explored the roles of parietal subregions in WMHs using rs-FC. The functional connectivity of parietal subregions with the cortex regions showed significant differences between the patients with WMHs and healthy controls which may be associated with cognitive deficits in WMHs.

Brain Activity Response to Visual Cues for Gait Impairment in Parkinson's Disease: An EEG Study.

Background. Gait impairments are common in Parkinson's disease (PD) and increase falls risk. Visual cues can improve gait in PD, particularly freezing of gait (FOG), but mechanisms involved in visual cue response are unknown. This study aimed to examine brain activity in response to visual cues in people with PD who do (PD+FOG) and do not report FOG (PD-FOG) and explore relationships between attention, brain activity and gait. Methods. Mobile EEG measured brain activity during gait in 20 healthy older adults and 43 PD participants (n=22 PD+FOG, n=21 PD-FOG). Participants walked for 2-minutes with and without visual cues (transverse lines to step over). We report power spectral density (PSD) in Delta (1-4 Hz), Theta (4-7 Hz), Alpha (8-12 Hz), Beta (14-24 Hz) and Gamma (30-50 Hz) bands within clusters of similarly brain localized independent component sources. Results. PSDs within the parietal and occipital lobes were altered when walking with visual cues in PD, particularly in PD+FOG. Between group, differences suggested that parietal sources in PD, particularly with PD+FOG, had larger activity compared to healthy older adults when walking. Within group, visual cues altered brain activity in PD, particularly in PD+FOG, within visual processing brain regions. In PD participants, brain activity differences with cues correlated with gait improvements, and in PD+FOG those with worse attention required more visual attentional processing (reduced alpha PSD) in the occipital lobe. Conclusions. Visual cues improve gait and influence brain activity during walking in PD, particularly in PD+FOG. Findings may allow development of more effective therapeutics.

Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls.

Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD.

Modulation of Working Memory and Resting-State fMRI by tDCS of the Right Frontoparietal Network.

Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.

Altered mismatch response of inferior parietal lobule in amnestic mild cognitive impairment: A magnetoencephalographic study.

BACKGROUND: Mismatch negativity (MMN) reflects the functional integrity of sensory memory function. With the advantages of independence of individual's focused attention and behavioral cooperation, this neurophysiological signal is particularly suitable for investigating elderly with cognitive decline such as amnestic mild cognitive impairment (aMCI). However, the existing results remain substantially inconsistent whether these patients show deficits of MMN. In order to reconcile the previous disputes, the present study used magnetoencephalography combined with distributed source imaging methods to determine the source-level magnetic mismatch negativity (MMNm) in aMCI. METHODS: A total of 26 healthy controls (HC) and 26 patients with aMCI underwent an auditory oddball paradigm during the MEG recordings. MMNm amplitudes and latencies in the bilateral superior temporal gyrus, inferior frontal gyrus, and inferior parietal lobule (IPL) were compared between HC and aMCI groups. The correlations of MMNm responses with performance of auditory/verbal memory tests were examined. Finally, MMNm and its combination with verbal/auditory memory tests were submitted to receiver operating characteristic (ROC) curve analysis. RESULTS: Compared to HC, patients with aMCI showed significantly delayed MMNm latencies in the IPL. Among the patients with aMCI, longer MMNm latencies of left IPL were associated with lower scores of Chinese Version Verbal Learning Test (CVVLT). The ROC curve analysis revealed that the combination of MMNm latencies of left IPL and CVVLT scores yielded a moderate accuracy in the discrimination of aMCI from HC at an individual level. CONCLUSIONS: Our data suggest dysfunctional MMNm in patients with aMCI, particularly in the IPL.

Neural networks associated with quality of life in patients with Parkinson's disease.

INTRODUCTION: The neural underpinnings of health-related quality of life in Parkinson's disease remain unclear. This study was conducted to unravel which motor and non-motor symptoms in Parkinson's disease influence health-related quality of life and reveal neural networks most likely linked to it. METHODS: Comprehensive clinical assessments were conducted for 247 Parkinson's disease patients and image analyses were performed for 181 patients. Clinical scores commonly used to assess various symptoms related to health-related quality of life were investigated. Factor and resting-state functional magnetic resonance imaging analyses were reviewed to reveal health-related quality of life-associated brain networks. RESULTS: The Spearman's rank correlation coefficient for the Parkinson's disease Questionnaire-39 summary index was high in the Activities-specific Balance Confidence Scale, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 2, Freezing of Gait Questionnaire, and Self-reported Autonomic Symptoms in Parkinson's disease. Multiple regression and Random Forest regression analyses indicated that health-related quality of life-associated factors were Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 1, Depression Rating Scales, and the above-mentioned scales. The resting-state functional magnetic resonance imaging analysis revealed decreased functional connectivity between the anterior cingulate cortex and right temporo-parietal junction as health-related quality of life worsened. CONCLUSION: Fear of falling, daily living activities, gait freezing, and autonomic dysfunction have notable effects on health-related quality of life in Parkinson's disease. Brain networks consisting of the anterior cingulate cortex and temporo-parietal junction may be associated with the emotion-related and social factors of health-related quality of life in Parkinson's disease.

Rehabilitation of somatoparaphrenia with misoplegia: insights from a single case-pilot study.

Somatoparaphrenia lacka ownership of a paralyzed limb, i.e., the illusion that one's limbs belong to someone else. Somatoparaphrenia is one of the many forms of body misperceptions. We report a case of somatoparaphrenia with misoplegia, characterized by the absence of anosognosia for hemiplegia and personal neglect, following a surgical operation for left parietal meningioma. The patient received a novel multidisciplinary treatment, including motor rehabilitation training, traditional physiotherapy and robotic rehabilitation using the Hunova Movendo Technology and psychological counseling. At the end of the training, the patient improved in global cognitive functioning, mood, motor abilities, and the perception of herself and her body, reducing the sense of estrangement and repulsion in the lower right limb. Our result showed the importance of a specific neuropsychological assessment in patients with parietal brain lesions and the usefulness of an integrated psychological and motor approach in rehabilitating patients with somatoparaphrenia, primarily when associated with misoplegia.

Increased functional interaction within frontoparietal network during working memory task in major depressive disorder.

Abnormal fronto-parietal activation has been suggested as a neural underpinning of the working memory (WM) deficits in major depressive disorder (MDD). However, the potential interaction within the frontoparietal network during WM processing in MDD remains unclear. This study aimed to examine the role of abnormal functional interactions within frontoparietal network in the neuropathological mechanisms of WM deficits in MDD. A total of 40 MDD patients and 47 demographic matched healthy controls (HCs) were included. Functional magnetic resonance imaging and behavioral data were collected during numeric n-back tasks. The psychophysiological interaction and dynamic causal modelling methods were applied to investigate the connectivity within the frontoparietal network in MDD during n-back tasks. The psychophysiological interaction analysis revealed that MDD patients showed increased functional connectivity between the right inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (dlPFC) compared with HCs during the 2-back task. The dynamic causal modelling analysis revealed that MDD patients had significantly increased forward modulation connectivity from the right IPL to the right dlPFC than HCs during the 2-back task. Partial correlation was used to calculate the relationship between connective parameters and psychological variables in the MDD group, which showed that the effective connectivity from right IPL to right dlPFC was correlated negatively with the sensitivity index d' of WM performances and positively with the depressive severity in MDD group. In conclusion, the abnormal functional and effective connectivity between frontal and parietal regions might contribute to explain the neuropathological mechanism of working memory deficits in major depressive disorder.

Parieto-premotor functional connectivity changes during parietal lobe seizures are associated with motor semiology.

OBJECTIVES: Parietal lobe seizures (PLS) are characterized by multiple clinical manifestations including motor signs. The mechanisms underlying the occurrence of motor signs are poorly understood. The main objective of this work was to estimate the functional coupling of brain regions associated with this clinical presentation. METHODS: We retrospectively selected patients affected by drug-resistant epilepsy who underwent Stereoelectroencephalography (SEEG) for pre-surgical evaluation and in whom the seizure onset zone (SOZ) was located in the parietal cortex. The SOZ was defined visually and quantitatively by the epileptogenicity index (EI) method. Two groups of seizures were defined according to the presence ("motor seizures") or the absence ("non-motor seizures") of motor signs. Functional connectivity (FC) estimation was based on pairwise nonlinear regression analysis (h2 coefficient). To study FC changes between parietal, frontal and temporal regions, for each patient, z-score values of 16 cortico-cortical interactions were obtained comparing h2 coefficients of pre-ictal, seizure onset and seizure propagation periods. RESULTS: We included 22 patients, 13 with "motor seizures" and 9 with "non-motor seizures". Resective surgery was performed in 14 patients, 8 patients had a positive surgical outcome (Engel's class I and II). During seizure onset period, a decrease of FC was observed and was significantly more important (in comparison with background period) in "motor" seizures. This was particularly observed between parietal operculum/post-central gyrus (OP/PoCg) and mesial temporal areas. During seizure propagation, a FC increase was significantly more important (in comparison with seizure onset) in "motor seizures", in particular between lateral pre-motor (pmL) area and precuneus, pmL and superior parietal lobule (SPL) and between inferior parietal lobule (IPL) and supplementary motor area (SMA). CONCLUSIONS: Our study shows that motor semiology in PLS is accompanied by an increase of FC between parietal and premotor cortices, significantly different than what is observed in PLS without motor semiology. SIGNIFICANCE: Our results indicate that preferential routes of coupling between parietal and premotor cortices are responsible for the prominent motor presentation during PLS.

Increased Global-Brain Functional Connectivity Is Associated with Dyslipidemia and Cognitive Impairment in First-Episode, Drug-Naive Patients with Bipolar Disorder.

Objectives: Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way. Methods: A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls. Results: Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%). Conclusions: This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.

Focal atonic seizures originated in the posterior temporoparietal area: A case report.

Atonic seizures are typically observed in younger children with Lennox-Gastaut syndrome and have been rarely described in adults. Herein we present a case of the adolescent-onset drug-resistant focal epilepsy in a 31-year-old woman with focal atonic seizures originating in the left posterior temporoparietal area and manifesting without aura with abrupt impairment of consciousness and slow falling down. According to the video-EEG monitoring, the seizure began with the medium amplitude spikes principally at T5 area evolving onto the left centroparietal area, which was immediately followed by the diffuse suppression of the background EEG activity. The underlying mechanism might be related to high-frequency electrical stimulation of the negative motor areas within the inferior frontal gyrus or anterior to the supplementary sensorimotor area.

Seeing things differently: Gaze shapes neural signal during mentalizing according to emotional awareness.

Studies on social cognition often use complex visual stimuli to asses neural processes attributed to abilities like "mentalizing" or "Theory of Mind" (ToM). During the processing of these stimuli, eye gaze, however, shapes neural signal patterns. Individual differences in neural operations on social cognition may therefore be obscured if individuals' gaze behavior differs systematically. These obstacles can be overcome by the combined analysis of neural signal and natural viewing behavior. Here, we combined functional magnetic resonance imaging (fMRI) with eye-tracking to examine effects of unconstrained gaze on neural ToM processes in healthy individuals with differing levels of emotional awareness, i.e. alexithymia. First, as previously described for emotional tasks, people with higher alexithymia levels look less at eyes in both ToM and task-free viewing contexts. Further, we find that neural ToM processes are not affected by individual differences in alexithymia per se. Instead, depending on alexithymia levels, gaze on critical stimulus aspects reversely shapes the signal in medial prefrontal cortex (MPFC) and anterior temporoparietal junction (TPJ) as distinct nodes of the ToM system. These results emphasize that natural selective attention affects fMRI patterns well beyond the visual system. Our study implies that, whenever using a task with multiple degrees of freedom in scan paths, ignoring the latter might obscure important conclusions.

The neural substrates of diminished humor comprehension in schizophrenia and its relationship with psychopathology.

Patients with schizophrenia commonly revealed difficulties in understanding humor. Previous research suggested links between impaired humor comprehension, psychopathology symptoms and cognitive deficits. In this study, we investigated the associations between neural substrates of humor processing and psychopathology and cognition in schizophrenia. We assessed 25 schizophrenia outpatients in an functional magnetic resonance imaging (fMRI) procedure and 40 in an electroencephalography (EEG) procedure. A punchline­based humor comprehension task was used in which outpatients rated stories by their comprehensibility and funniness. The symptom severity and cognition were correlated with activation within the humor processing network using fMRI and effective connectivity using an EEG­based directed transfer function (DTF) method. More severe positive and disorganization symptoms were associated with impaired humor comprehension and with altered temporo­parietal effective connectivity during humor processing. More severe excitement and emotional reactivity symptoms were associated with increased activation in the bilateral frontal and temporo­parietal regions. Moreover, schizophrenia outpatients with better cognitive functioning were more accurate in humor comprehension that was associated with increased fronto­temporo­parietal activation and effective connectivity. We found the intensity of humor processing (fMRI) in schizophrenia is related to the level of cognitive abilities and the severity of schizophrenia psychopathology that is also reflected in altered effective connectivity (EEG­DTF) in the humor processing network.

Anomalous neurovascular coupling in patients with generalized anxiety disorder evaluated by combining cerebral blood flow and functional connectivity strength.

Coupling between neuronal activity and blood perfusion is termed neurovascular coupling, and it provides a new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in generalized anxiety disorder (GAD), whether anomalous neurovascular coupling would still be presented in such disease is hitherto unknown. In this study, the neuronal activity and blood supply were measured using the functional connectivity strength (FCS) and cerebral blood flow (CBF). The voxel-wise CBF-FCS correlations and CBF/FCS ratio were separately used to assess global and local neurovascular coupling in participants. Patients with GAD showed decreased voxel-wise CBF-FCS correlation, implicating global neurovascular decoupling. They also exhibited increased CBF/FCS ratio in the right superior parietal gyrus (SPG), and the enhanced CBF/FCS ratio in this region was negatively correlated with the self-esteem scores of GAD. The abnormal neurovascular coupling of GAD may indicate the disrupted balance between the intrinsic functional organization of the brain and corresponding blood perfusion of patients, and the abnormally increased local neurovascular coupling of the right SPG may be correlated with the abnormal self in GAD. These findings provide new information in understanding the brain dysfunction and abnormal cognition of GAD from the perspective of neurovascular coupling.