Effective Connectivity within the Distributed Cortical Network for Face Perception

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.

Objective To investigate the characteristics of hypomanic symptoms (HS) to the brain neural activity in the resting-state of the patients with major depressive disorder (MDD). Methods Twenty-three patients from 54 patients with MDD were defined as MDD with HS because their HCL-32 scores were higher than or equal to 12. The rest 31 patients were defined as MDD patients without HS because of the lower scores. After checking the match of the factors such as gender and age et al, there were 19 MDD patients with HS, 19 patients without HS and 19 healthy controls in the final analysis. We analyzed the impact of HS to the regional brain function of the patients with MDD by amplitude of low-frequency fluctuation (ALFF). Results The patients with MDD had abnormal resting-state brain activity in a diffuse brain areas compared to healthy controls by the ALFF analysis. Compared to the patients without HS, the ALFF of the depressed MDD patients with HS were significantly higher in the bilateral orbitofrontal cortex (OFC; left OFC: MNI(x,y,z): - 34,56,- 10; t=5.26; right OFC: MNI(x,y,z): 20, 66, - 2; t=493) and superior frontal cortex (SFC; left SFC: MNI(x,y,z): -4, 66, 8; t=4.12; right SFC: MNI(x,y,z): 14, 56, 18, t=3.97, all P< 0.05); while lower in bilateral thalamus and left fusiform gyrus (P<0.05). Correlation analysis of ALFF at each voxel in the whole brain against the HCL-32 in the patients with MDD revealed significantly positive correlation in OFC (r=0.363, 0.426, 0.405, all P<0.05), negative correlation in left thalamus and left fusiform gyrus (r=- 0.352, P<0.05; r=- 0.468, P<0.01). Conclusions The study suggested that there were differences between the two subgroups patients with MDD defined by the HCL-32. Compared to the MDD without HS patients, MDD with HS patients showed increase ALFF in bilateral frontal cortex (especially the OFC), and decrease ALFF in left thalamus and left fusiform gyrus. These features may be regarded as the biomarker of the MDD patients who were positive to HCL-32 screening. Key words: Major depressive disorder; Hypomanic symptoms; Resting state; Functional magnetic resonance imaging; Amplitude of low-frequency fluctuation

BackgroundPrevious literature suggests that those with reading disability (RD) have more pronounced deficits during semantic processing in reading as compared to listening comprehension. This discrepancy has been supported by recent neuroimaging studies showing abnormal activity in RD during semantic processing in the visual but not in the auditory modality. Whether effective connectivity between brain regions in RD could also show this pattern of discrepancy has not been investigated.Methodology/Principal FindingsChildren (8- to 14-year-olds) were given a semantic task in the visual and auditory modality that required an association judgment as to whether two sequentially presented words were associated. Effective connectivity was investigated using Dynamic Causal Modeling (DCM) on functional magnetic resonance imaging (fMRI) data. Bayesian Model Selection (BMS) was used separately for each modality to find a winning family of DCM models separately for typically developing (TD) and RD children. BMS yielded the same winning family with modulatory effects on bottom-up connections from the input regions to middle temporal gyrus (MTG) and inferior frontal gyrus(IFG) with inconclusive evidence regarding top-down modulations. Bayesian Model Averaging (BMA) was thus conducted across models in this winning family and compared across groups. The bottom-up effect from the fusiform gyrus (FG) to MTG rather than the top-down effect from IFG to MTG was stronger in TD compared to RD for the visual modality. The stronger bottom-up influence in TD was only evident for related word pairs but not for unrelated pairs. No group differences were noted in the auditory modality.Conclusions/SignificanceThis study revealed a modality-specific deficit for children with RD in bottom-up effective connectivity from orthographic to semantic processing regions. There were no group differences in connectivity from frontal regions, suggesting that the core deficit in RD is not in top-down modulation.

Object recognition is traditionally viewed as a hierarchical, bottom-up neural process. This view has been challenged recently by theoretical models and by findings indicating that top-down processes are involved in facilitating recognition. However, how such high-level information can be activated quickly enough to facilitate the bottom-up processing is yet unknown. We propose that such top-down facilitation is triggered by magnocellular information projected early and rapidly to the orbitofrontal cortex. Using human neuroimaging, we show that stimuli designed to bias processing toward the magnocellular pathway differentially activated the orbitofrontal cortex compared with parvocellular-biased stimuli. Although the magnocellular stimuli had a lower contrast than the parvocellular stimuli, they were recognized faster and just as accurately. Moreover, orbitofrontal activity predicted the performance advantage for the magnocellular, but not for the parvocellular-biased, stimuli, whereas the opposite was true in the fusiform gyrus. Last, analyses of effective connectivity using dynamic causal modeling showed that magnocellular-biased stimuli significantly activated pathways from occipital visual cortex to orbitofrontal cortex and from orbitofrontal cortex to fusiform gyrus. Conversely, parvocellular-biased stimuli significantly activated a pathway from the occipital visual cortex to fusiform gyrus. Our findings support the proposal that fast magnocellular projections linking early visual and inferotemporal object recognition regions with the orbitofrontal cortex facilitate object recognition by enabling the generation of early predictions.

The human orbitofrontal cortex, ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex are involved in reward processing and thereby in emotion but are also implicated in episodic memory. To understand these regions better, the effective connectivity between 360 cortical regions and 24 subcortical regions was measured in 172 humans from the Human Connectome Project and complemented with functional connectivity and diffusion tractography. The orbitofrontal cortex has effective connectivity from gustatory, olfactory, and temporal visual, auditory, and pole cortical areas. The orbitofrontal cortex has connectivity to the pregenual anterior and posterior cingulate cortex and hippocampal system and provides for rewards to be used in memory and navigation to goals. The orbitofrontal and pregenual anterior cortex have connectivity to the supracallosal anterior cingulate cortex, which projects to midcingulate and other premotor cortical areas and provides for action-outcome learning including limb withdrawal or flight or fight to aversive and nonreward stimuli. The lateral orbitofrontal cortex has outputs to language systems in the inferior frontal gyrus. The medial orbitofrontal cortex connects to the nucleus basalis of Meynert and the pregenual cingulate to the septum, and damage to these cortical regions may contribute to memory impairments by disrupting cholinergic influences on the neocortex and hippocampus.

Outcome-guided behavior requires knowledge about the current value of expected outcomes. Such behavior can be isolated in the reinforcer devaluation task, which assesses the ability to infer the current value of specific rewards after devaluation. Animal lesion studies demonstrate that orbitofrontal cortex (OFC) is necessary for normal behavior in this task, but a causal role for human OFC in outcome-guided behavior has not been established. Here, we used sham-controlled, non-invasive, continuous theta-burst stimulation (cTBS) to temporarily disrupt human OFC network activity by stimulating a site in the lateral prefrontal cortex that is strongly connected to OFC prior to devaluation of food odor rewards. Subjects in the sham group appropriately avoided Pavlovian cues associated with devalued food odors. However, subjects in the stimulation group persistently chose those cues, even though devaluation of food odors themselves was unaffected by cTBS. This behavioral impairment was mirrored in changes in resting-state functional magnetic resonance imaging (rs-fMRI) activity such that subjects in the stimulation group exhibited reduced OFC network connectivity after cTBS, and the magnitude of this reduction was correlated with choices after devaluation. These findings demonstrate the feasibility of indirectly targeting the human OFC with non-invasive cTBS and indicate that OFC is specifically required for inferring the value of expected outcomes.

Studying task modulations of brain connectivity using functional magnetic resonance imaging (fMRI) is critical to understand brain functions that support cognitive and affective processes. Existing methods such as psychophysiological interaction (PPI) and dynamic causal modeling (DCM) usually implicitly assume that the connectivity patterns are stable over a block-designed task with identical stimuli. However, this assumption lacks empirical verification on high-temporal resolution fMRI data with reliable data-driven analysis methods. The present study performed a detailed examination of dynamic changes of functional connectivity (FC) in a simple block-designed visual checkerboard experiment with a sub-second sampling rate (TR = 0.645 s) by estimating time-varying correlation coefficient (TVCC) between BOLD responses of different brain regions. We observed reliable task-related FC changes (i.e., FCs were transiently decreased after task onset and went back to the baseline afterward) among several visual regions of the bilateral middle occipital gyrus (MOG) and the bilateral fusiform gyrus (FuG). Importantly, only the FCs between higher visual regions (MOG) and lower visual regions (FuG) exhibited such dynamic patterns. The results suggested that simply assuming a sustained FC during a task block may be insufficient to capture distinct task-related FC changes. The investigation of FC dynamics in tasks could improve our understanding of condition shifts and the coordination between different activated brain regions.

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.

It has recently been suggested that schizophrenia involves dysfunction in brain connectivity at a neural level, and a dysfunction in reward processing at a behavioral level. The purpose of the present study was to link these two levels of analyses by examining effective connectivity patterns between brain regions mediating reward learning in patients with schizophrenia and healthy, age-matched controls. To this aim, we used functional magnetic resonance imaging and galvanic skin recordings (GSR) while patients and controls performed an appetitive conditioning experiment with visual cues as the conditioned (CS) stimuli, and monetary reward as the appetitive unconditioned stimulus (US). Based on explicit stimulus contingency ratings, conditioning occurred in both groups; however, based on implicit, physiological GSR measures, patients failed to show differences between CS+ and CS− conditions. Healthy controls exhibited increased blood-oxygen-level dependent (BOLD) activity across striatal, hippocampal, and prefrontal regions and increased effective connectivity from the ventral striatum to the orbitofrontal cortex (OFC BA 11) in the CS+ compared to the CS− condition. Compared to controls, patients showed increased BOLD activity across a similar network of brain regions, and increased effective connectivity from the striatum to hippocampus and prefrontal regions in the CS− compared to the CS+ condition. The findings of increased BOLD activity and effective connectivity in response to the CS− in patients with schizophrenia offer insight into the aberrant assignment of motivational salience to non-reinforced stimuli during conditioning that is thought to accompany schizophrenia.

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.

Treatment of Psychiatric Symptoms Associated With a Frontal Lobe Tumor Through Surgical Resection

The aim of the study was to elucidate the correlation between spatially distinct brain areas with a full bladder from the perspective of functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) with simultaneous urodynamic testing in healthy volunteers. The brain regions with full and empty bladders were reported via rs-fMRI using a 3T magnetic resonance system. Then, we identified brain regions that are activated during bladder filling by calculating the amplitude of low-frequency fluctuation (ALFF) values using brain imaging software (DPABI and SPM8) and empirically derived six regions of interest (ROI) from analysis of activation were used as seeds for resting-state functional connectivity (rs-FC) analysis with the rest of the brain to examine differences in the two conditions. Statistical analysis was performed with a paired t-test and statistical significance was defined as a P < 0.01. Twenty-two healthy volunteers (11 men and 11 women) 35-64years of age were enrolled. The rs-fMRI scans of 22 healthy volunteers were analyzed. After motion correction, two subjects were excluded. Meaningful data were obtained on 20 of these subjects. Compared with an empty bladder, functional connection enhancement was noted mainly in the right inferior orbitofrontal cortex and bilateral calcarine gyrus, the left lingual gyrus, left fusiform gyrus, left superior occipital gyrus, right insula, right inferior temporal gyrus, superior parietal lobe, left insula, right lingual gyrus, right fusiform gyrus, left parahippocampal gyrus, right inferior temporal gyrus, superior parietal lobe, left calcarine gyrus, bilateral lingual gyrus, prefrontal cortex, including the middle frontal gyrus and superior frontal gyrus, the right middle temporal gyrus, bilateral posterior cingulate cortex, and right precuneus. The decrease in functional connection was mainly located in the right inferior orbitofrontal cortex, prefrontal cortex, including the superior frontal gyrus, orbitofrontal cortex, and anterior cingulate cortex, the left inferior orbitofrontal cortex, right insula, middle occipital gyrus, angular gyrus, inferior frontal gyrus, right insula, middle temporal gyrus, inferior parietal lobe, middle occipital gyrus, supplementary motor area, superior frontal gyrus, left insula, bilateral posterior cingulate cortex, bilateral precuneus, middle occipital gyrus, and right middle temporal lobe. There were significant changes in the functional connectivity of the brain between full and empty bladders in healthy volunteers, which suggests that the central neural processes involved in storage needs brain areas with integrated control. These findings are strong evidence for physicians to consider brain responses in urine storage and offer the provision of some normative data.

The role of negative affectivity and social inhibition in perceiving social threat: An fMRI study

PW01-147 - Diminished limbic activation associated with face perception in patients with schizophrenia

Effective connectivity, functional connectivity, and tractography were measured between 57 cortical frontal and somatosensory regions and the 360 cortical regions in the Human Connectome Project (HCP) multimodal parcellation atlas for 171 HCP participants. A ventral somatosensory stream connects from 3b and 3a via 1 and 2 and then via opercular and frontal opercular regions to the insula, which then connects to inferior parietal PF regions. This stream is implicated in "what"-related somatosensory processing of objects and of the body and in combining with visual inputs in PF. A dorsal "action" somatosensory stream connects from 3b and 3a via 1 and 2 to parietal area 5 and then 7. Inferior prefrontal regions have connectivity with the inferior temporal visual cortex and orbitofrontal cortex, are implicated in working memory for "what" processing streams, and provide connectivity to language systems, including 44, 45, 47l, TPOJ1, and superior temporal visual area. The dorsolateral prefrontal cortex regions that include area 46 have connectivity with parietal area 7 and somatosensory inferior parietal regions and are implicated in working memory for actions and planning. The dorsal prefrontal regions, including 8Ad and 8Av, have connectivity with visual regions of the inferior parietal cortex, including PGs and PGi, and are implicated in visual and auditory top-down attention.