A tight relationship between BOLD fMRI activation/deactivation and increase/decrease in single neuron responses in human association cortex

Comparative studies across populations using functional magnetic resonance imaging (fMRI) rely on a similar relationship between blood oxygen level-dependent (BOLD) signal and neural activity. However, in elderly and patients with cerebrovascular disease, impaired cerebrovascular dynamics and neurovascular coupling may explain differences in BOLD contrast across populations and brain regions. The purpose of the study was to determine whether poststroke patients have regional heterogeneities of cerebrovascular reactivity (CVR) and their potential influence on voxel-wise motor-related BOLD signal. Using fMRI, 8 fully recovered patients from stroke in the frontal lobe without cortical lesion in the regions of interest located in the primary sensorimotor cortex (SMC), supplementary motor area (SMA), and cerebellum (CRB) were compared with 8 healthy subjects. Motor-related BOLD signal changes (%SC) were evaluated during simple unimanual and bimanual tasks, and CVR was evaluated during hyperventilation (HV). Analyses were performed using Lipsia software in SMC, SMA, and CRB. In controls, amplitudes of BOLD signal were symmetrical in all regions of interest during all motor tasks and HV. In patients, %SC was decreased in SMC and SMA of the lesioned hemisphere despite their apparent anatomical integrity for all tasks. Impaired CVR was a predictor of impaired motor-related BOLD response in the SMC during contralateral movements (beta=-1.87; R=-0.75; P=0.03). These preliminary findings suggest that CVR heterogeneities may account for task-related BOLD signal changes in patients after stroke.

Human Brain can be studied and analysed using neuroimages viz. MRI(Magnetic Resonance Imaging) / fMRI(Functional Magnetic Resonance Imaging) / PET(Positron Emission Tomography) / EEG(Electroencephalography) / MEG(Magnetoencephalography), which brings out the hidden information from it. Connectomes are graph like structure which represents complex brain network connectivity which are of two type's mainly structural connectivity and functional connectivity. Connectivity can be anatomical and functional properties of the brain. Nodes are voxels or Regions of Interest whereas edges are fibre bundles, temporal correlation between regions, in structural connectome and functional connectome respectively. This work focuses on functional connectivity analysis of brain network obtained through RS- fMRI images for identification of important regions in the human brain using image processing and graph theoretical approaches. The RS-fMRI images are obtained from 1000 Functional connectomes project and preprocessed using image processing techniques. Then the image is parcellated using AAL(Automated Anatomical Labeling) atlas and binary matrix is obtained. The graph is constructed from the derived matrix that exhibits functional connectivity between ROIs(Region of Interest). The various centrality measures (degree centrality, eigenvector centrality, betweenness centrality and closeness centrality) are used to identify the ROIs that act as provincial and/or connector hubs. The prominent provincial hubs are Rolandic Operculum, Thalamus, Insula, Hippocampus, Olfactory and connector hubs are Insula, Putamen, Occipital superior gyrus, Parietal Superior gyrus and Supramarginal gyrus. This work highlights the key regions in human brain which is involved in massive communication and information flow within the network.

The relationship between Blood-Oxygen-Level-Dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) and increases or decreases in neural firing rate across human brain regions, especially the association cortex, remains largely unknown. Here, we contrast direct measures of neuronal activity in two adjacent brain regions of the fusiform gyrus (FG) associated with fMRI increases (lateral FG portion) or decreases (medial FG portion) of the same category-selective neural activity. In both individual brains tested across multiple recording sessions, a frequency-tagging stimulation objectively identified a substantial proportion (about 70%) of face-selective neurons. While single-units recorded in the lateral FG showed a selective increase to faces, neurons localized in the medial FG decreased spiking activity selectively to faces. Beyond a relative reduction to faces compared to non-face objects, about a third of single neurons found in the medial FG showed genuine suppression of baseline spiking activity upon presentation of a face. These observations clarify the nature of face-selective neural activity in the human brain, which can be expressed both as increases and active suppressions of spiking activity, and, more generally, shed light on the physiological basis of the fMRI signal.

Impairments in social cognition have been described in schizophrenia and relate to core symptoms of the disorder. Social cognition is subserved by a network of brain regions, many of which have been implicated in schizophrenia. We hypothesized that deficits in connectivity between components of this social brain network may underlie the social cognition impairments seen in the disorder. We investigated brain activation and connectivity in a group of individuals with schizophrenia making social judgments of approachability from faces (n = 20), compared with a group of matched healthy volunteers (n = 24), using functional magnetic resonance imaging. Effective connectivity from the amygdala was estimated using the psychophysiological interaction approach. While making approachability judgments, healthy participants recruited a network of social brain regions including amygdala, fusiform gyrus, cerebellum, and inferior frontal gyrus bilaterally and left medial prefrontal cortex. During the approachability task, healthy participants showed increased connectivity from the amygdala to the fusiform gyri, cerebellum, and left superior frontal cortex. In comparison to controls, individuals with schizophrenia overactivated the right middle frontal gyrus, superior frontal gyrus, and precuneus and had reduced connectivity between the amygdala and the insula cortex. We report increased activation of frontal and medial parietal regions during social judgment in patients with schizophrenia, accompanied by decreased connectivity between the amygdala and insula. We suggest that the increased activation of frontal control systems and association cortex may reflect a compensatory mechanism for impaired connectivity of the amygdala with other parts of the social brain networks in schizophrenia.

Progesterone, or rather its neuroactive metabolite allopregnanolone, modulates amygdala activity and thereby influences anxiety. Cognition and, in particular, memory are also altered by allopregnanolone. In the present study, we investigated whether allopregnanolone modulates memory for biologically salient stimuli by influencing amygdala activity, which in turn may affect neural processes in other brain regions. A single progesterone dose was administered orally to healthy young women in a double-blind, placebo-controlled, crossover design, and participants were asked to memorize and recognize faces while undergoing functional magnetic resonance imaging. Progesterone decreased recognition accuracy without affecting reaction times. The imaging results show that the amygdala, hippocampus, and fusiform gyrus supported memory formation. Importantly, progesterone decreased responses to faces in the amygdala and fusiform gyrus during memory encoding, whereas it increased hippocampal responses. The progesterone-induced decrease in neural activity in the amygdala and fusiform gyrus predicted the decrease in memory performance across subjects. However, progesterone did not modulate the differential activation between subsequently remembered and subsequently forgotten faces in these areas. A similar pattern of results was observed in the fusiform gyrus and prefrontal cortex during memory retrieval. These results suggest that allopregnanolone impairs memory by reducing the recruitment of those brain regions that support memory formation and retrieval. Given the important role of the amygdala in the modulation of memory, these results suggest that allopregnanolone alters memory by influencing amygdala activity, which in turn may affect memory processes in other brain regions.

Cortex-based inter-subject analysis of iEEG and fMRI data sets: Application to sustained task-related BOLD and gamma responses

In functional magnetic resonance imaging (fMRI) studies that apply a “subsequent memory” approach, successful encoding is indicated by increased fMRI activity during the encoding phase for hits vs. misses, in areas underlying memory encoding such as the hippocampal formation. Signal-detection theory (SDT) can be used to analyze memory-related fMRI activity as a function of the participant’s memory trace strength (d′). The goal of the present study was to use SDT to examine the relationship between fMRI activity during incidental encoding and participants’ recognition performance. To implement a new approach, post-experimental group assignment into High- or Low Performers (HP or LP) was based on 29 healthy participants’ recognition performance, assessed with SDT. The analyses focused on the interaction between the factors group (HP vs. LP) and recognition performance (hits vs. misses). A whole-brain analysis revealed increased activation for HP vs. LP during incidental encoding for remembered vs. forgotten items (hits > misses) in the insula/temporo-parietal junction (TPJ) and the fusiform gyrus (FFG). Parameter estimates in these regions exhibited a significant positive correlation with d′. As these brain regions are highly relevant for salience detection (insula), stimulus-driven attention (TPJ), and content-specific processing of mnemonic stimuli (FFG), we suggest that HPs’ elevated memory performance was associated with enhanced attentional and content-specific sensory processing during the encoding phase. We provide first correlative evidence that encoding-related activity in content-specific sensory areas and content-independent attention and salience detection areas influences memory performance in a task with incidental encoding of facial stimuli. Based on our findings, we discuss whether the aforementioned group differences in brain activity during incidental encoding might constitute the basis of general differences in memory performance between HP and LP.

Face perception elicits activation within a distributed cortical network in the human brain. The network includes visual ("core") regions, as well as limbic and prefrontal ("extended") regions, which process invariant facial features and changeable aspects of faces, respectively. We used functional Magnetic Resonance Imaging and Dynamic Causal Modeling to investigate effective connectivity and functional organization between and within the core and the extended systems. We predicted a ventral rather than dorsal connection between the core and the extended systems during face viewing and tested whether valence and fame would alter functional coupling within the network. We found that the core system is hierarchically organized in a predominantly feed-forward fashion, and that the fusiform gyrus (FG) exerts the dominant influence on the extended system. Moreover, emotional faces increased the coupling between the FG and the amygdala, whereas famous faces increased the coupling between the FG and the orbitofrontal cortex. Our results demonstrate content-specific dynamic alterations in the functional coupling between visual-limbic and visual-prefrontal face-responsive pathways.

Objective To investigate the regional homogeneity (ReHo) changes of primary insomnia (PI) with cognitive impairment using resting-state fMRI. Methods Twenty-one patients with primary insomnia and cognitive impairment and 25 healthy volunteers matched with age, gender and education level were collected from Southwest Hospital of China from November 2014 to June 2015. Pittsburgh sleep quality index (PSQI), Montreal Cognitive Assessment (MoCA), Mini-mental State Examination (MMSE), Activity of Daily Living Scale (ADL), Hamilton depression scale (HAMD), and Hamilton Anxiety Scale (HAMA) were conducted to evaluate the sleep and cognitive conditions of all subjects. Independent sample t-test was performed to evaluate the significant difference of neuropsychology scores of two groups. ReHo of rs-fMRI were evaluated and compared between two groups using independent sample T-test, meanwhile, the partial correlation analysis was conducted in ReHo values of different brain regions and neuropsychology scores (age, gender and education level were regarded as covariates). Results Compared with normal controls, patients with primary insomnia and cognitive impairment showed significant higher PSQI score and lower MoCA and MMSE scores(P<0.05). The patient group also showed significant increased ReHo in the left medial temporal gyrus(54 voxels, t=3.14), left inferior temporal gyrus(76 voxels, t=4.80), right inferior temporal gyrus(84 voxels, t=4.30) and left parahippocampal gyrus(301 voxels, t=4.44) (P<0.05) and decreased ReHo in the left superior temporal lobe(79 voxels, t=-3.38), right fusiform gyrus(50 voxels, t=-3.17), right superior temporal gyrus(283 voxels, t=-5.34), right inferior frontal gyrus(56 voxels, t=-3.98), right anterior cingulate(233 voxels, t=-3.91), left parietal lobe angular gyrus(67 voxels, t=-3.27) and superior parietal lobule(65 voxels, t=-3.45) (P<0.05). The partial correlation analysis showed positive correlations between the ReHo values and PSQI scores of the left parahippocampal gyrus (R=0.771, P<0.01), negative correlations between the ReHo values and PSQI scores of the right anterior cingulate gyrus (R=-0.649, P<0.01) and positive correlations between the ReHo values and MoCA scores of the right anterior cingulate gyrus(R=0.555, P<0.05). Conclusions Patients with primary insomnia and cognitive impairment have ReHo alterations in various brain regions. The decreasing ReHo in the right anterior cingulate gyrus can reflect the level of sleep disorder and cognitive impairment, and increasing ReHo in the left parahippocampal gyrus can reflect the compensation of sleep disorders of PI. Key words: Sleep initiation and maintenance disorders; Magnetic resonance imaging; Cognition disorders

To prospectively identify brain regions in which task-related changes in activation during a memory encoding task, measured with functional magnetic resonance (MR) imaging, correlate with degree of memory impairment across Alzheimer disease (AD), mild cognitive impairment (MCI), and elderly control subjects. The institutional review board approved this HIPAA-compliant study, and each patient gave written informed consent. Seventy-five subjects (mean age, 72.9 years+/-7.2 [standard deviation]; 37 men, 38 women)-13 patients with mild AD, 34 individuals with amnestic MCI, and 28 healthy elderly control subjects-were imaged at 4.0 T during novel encoding (NE) and familiar encoding (FE) of face-name pairs presented within a block design for later retrieval. Blood oxygen level-dependent (BOLD) changes were assessed across the entire brain for each group. Between-subject analysis identified brain regions demonstrating a monotonic increase or decrease in activation magnitude, from control subjects to patients with MCI to patients with mild AD. BOLD response was also correlated with score on the delayed portion of the California Verbal Learning Test (CVLT). In controls, the task elicited positive activation (NE>FE) in the dorsolateral prefrontal, lateral parietal, and medial temporal regions, and negative activation (FE>NE) in the midline frontal and parietal regions. Along the spectrum from control subjects to patients with AD, there was decreasing activation in the medial temporal lobe (MTL), including the hippocampus and parahippocampal and fusiform gyri, and increasing activation in the posteromedial cortices (PMCs), primarily in the precuneus and posterior cingulate gyrus. Activation magnitude in the PMCs significantly (P<.001, r=-0.502) correlated with CVLT score. Compared with activation in the MTL, deactivation in the PMCs could be a more sensitive marker of early AD at functional MR imaging.

Dual coding of knowledge in the human brain.

ObjectivesBrain structural and functional abnormalities have been separately reported in patients with classic trigeminal neuralgia (CTN). However, whether and how the functional deficits are related to the structural alterations remains unclear. This study aims to investigate the anatomical and functional deficits in patients with CTN and explore their association.MethodsA total of 34 patients with CTN and 29 healthy controls (HCs) with age- and gender-matched were recruited. All subjects underwent structural and resting-state functional magnetic resonance imaging (fMRI) scanning and neuropsychological assessments. Voxel-based morphometry (VBM) was applied to characterize the alterations of gray matter volume (GMV). The amplitude of low-frequency fluctuation (ALFF) method was used to evaluate regional intrinsic spontaneous neural activity. Further correlation analyses were performed between the structural and functional changes and neuropsychological assessments.ResultsCompared to the HCs, significantly reduced GMV was revealed in the right hippocampus, right fusiform gyrus (FFG), and temporal-parietal regions (the left superior/middle temporal gyrus, left operculo-insular gyrus, left inferior parietal lobule, and right inferior temporal gyrus) in patients with CTN. Increased functional activity measured by zALFF was observed mainly in the limbic system (the bilateral hippocampus and bilateral parahippocampal gyrus), bilateral FFG, basal ganglia system (the bilateral putamen, bilateral caudate, and right pallidum), left thalamus, left cerebellum, midbrain, and pons. Moreover, the right hippocampus and FFG were the overlapped regions with both functional and anatomical deficits. Furthermore, GMV in the right hippocampus was negatively correlated with pain intensity, anxiety, and depression. GMV in the right FFG was negatively correlated with illness duration. The zALFF value in the right FFG was positively correlated with anxiety.ConclusionOur results revealed concurrent structural and functional changes in patients with CTN, indicating that the CTN is a brain disorder with structural and functional abnormalities. Moreover, the overlapping structural and functional changes in the right hippocampus and FFG suggested that anatomical and functional changes might alter dependently in patients with CTN. These findings highlight the vital role of hippocampus and FFG in the pathophysiology of CTN.

Basic emotional states (such as anger, fear, and joy) can be similarly conveyed by the face, the body, and the voice. Are there human brain regions that represent these emotional mental states regardless of the sensory cues from which they are perceived? To address this question, in the present study participants evaluated the intensity of emotions perceived from face movements, body movements, or vocal intonations, while their brain activity was measured with functional magnetic resonance imaging (fMRI). Using multivoxel pattern analysis, we compared the similarity of response patterns across modalities to test for brain regions in which emotion-specific patterns in one modality (e.g., faces) could predict emotion-specific patterns in another modality (e.g., bodies). A whole-brain searchlight analysis revealed modality-independent but emotion category-specific activity patterns in medial prefrontal cortex (MPFC) and left superior temporal sulcus (STS). Multivoxel patterns in these regions contained information about the category of the perceived emotions (anger, disgust, fear, happiness, sadness) across all modality comparisons (face-body, face-voice, body-voice), and independently of the perceived intensity of the emotions. No systematic emotion-related differences were observed in the overall amplitude of activation in MPFC or STS. These results reveal supramodal representations of emotions in high-level brain areas previously implicated in affective processing, mental state attribution, and theory-of-mind. We suggest that MPFC and STS represent perceived emotions at an abstract, modality-independent level, and thus play a key role in the understanding and categorization of others' emotional mental states.

Spiking Irregularity and Frequency Modulate the Behavioral Report of Single-Neuron Stimulation

Functional object use requires the integration of visuomotor representations processed in the dorsal visual pathway with representations of surface texture and material composition of objects, processed in the ventral visual pathway. Do regions in the ventral visual pathway project outputs to dorsal visual pathway action systems, or are the outputs of the dorsal visual pathway communicated to the ventral visual pathway to modulate processing? And what are the white matter pathways that mediate structural connectivity in support of functional object use? Here we show that the left inferior parietal cortex, a region within the dorsal visual pathway, exerts a direct effect on neural responses in ventral occipital-temporal cortex during visual processing of manipulable objects. We studied a series of consecutively enrolled participants in the pre-operative phase of their neurosurgical care (N = 109) with lesions principally distributed throughout the left hemisphere. Participants completed an object processing category localizer functional MRI experiment in which they viewed images of manipulable objects, animals, faces, and places. We then used Voxel-based Lesion-Activity Mapping (VLAM), a technique in which functional responses in a region-of-interest are used to predict variance in voxel-wise lesion incidence throughout the brain. In the VLAM analyses performed here, we found that lesions to the left anterior intraparietal sulcus and left supramarginal gyrus, two inferior parietal regions known to support object-directed grasping and manipulation, respectively, cause reduced neural responses for manipulable objects (compared to faces, places and animals) in the fusiform gyrus. Parietal lesions do not affect neural responses during visual processing of places in the same region of the fusiform gyrus, even though places elicit stronger responses in the fusiform gyrus than manipulable objects. Seventy-five of 109 participants took part in a common diffusion MRI protocol, permitting a connectome-wide analyses relating white matter fiber integrity to the strength of functional responses for manipulable objects in the left fusiform gyrus. This analysis demonstrated that the descending portion of the left arcuate fasciculus mediates parietal-totemporal lobe connectivity for manipulable objects, supporting the integration of action representations with conceptual and perceptual attributes of objects. By combining voxel-based and connectome-wide lesion-symptom mapping methods with functional MRI, we have demonstrated that structural connectivity to dorsal visual pathway areas supporting skilled manual action shape category-specific neural responses for manipulable objects within the ventral visual pathway.