From evoked potentials to cortical currents: Resolving V1 and V2 components using retinotopy constrained source estimation without fMRI

Despite evoked potentials' (EP) ubiquity in research and clinical medicine, insights are limited to gross brain dynamics as it remains challenging to map surface potentials to their sources in specific cortical regions. Multiple sources cancellation due to cortical folding and cross‐talk obscures close sources, e.g. between visual areas V1 and V2. Recently retinotopic functional magnetic resonance imaging (fMRI) responses were used to constrain source locations to assist separating close sources and to determine cortical current generators. However, an fMRI is largely infeasible for routine EP investigation. We developed a novel method that replaces the fMRI derived retinotopic layout (RL) by an approach where the retinotopy and current estimates are generated from EEG or MEG signals and a standard clinical T1‐weighted anatomical MRI. Using the EEG‐RL, sources were localized to within 2 mm of the fMRI‐RL constrained localized sources. The EEG‐RL also produced V1 and V2 current waveforms that closely matched the fMRI‐RL's (n = 2) r_(1,198) = 0.99, P < 0.0001. Applying the method to subjects without fMRI (n = 4) demonstrates it generates waveforms that agree closely with the literature. Our advance allows investigators with their current EEG or MEG systems to create a library of brain models tuned to individual subjects' cortical folding in retinotopic maps, and should be applicable to auditory and somatosensory maps. The novel method developed expands EP's ability to study specific brain areas, revitalizing this well‐worn technique. Hum Brain Mapp 37:1696–1709, 2016. © 2016 Wiley Periodicals, Inc.     

Investigation of the electrophysiological correlates of negative BOLD response during intermittent photic stimulation: An EEG‐fMRI study

Although the occurrence of concomitant positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to visual stimuli is increasingly investigated in neuroscience, it still lacks a definite explanation. Multimodal imaging represents a powerful tool to study the determinants of negative BOLD responses: the integration of functional Magnetic Resonance Imaging (fMRI) and electroencephalographic (EEG) recordings is especially useful, since it can give information on the neurovascular coupling underlying this complex phenomenon. In the present study, the brain response to intermittent photic stimulation (IPS) was investigated in a group of healthy subjects using simultaneous EEG‐fMRI, with the main objective to study the electrophysiological mechanisms associated with the intense NBRs elicited by IPS in extra‐striate visual cortex. The EEG analysis showed that IPS induced a desynchronization of the basal rhythm, followed by the instauration of a novel rhythm driven by the visual stimulation. The most interesting results emerged from the EEG‐informed fMRI analysis, which suggested a relationship between the neuronal rhythms at 10 and 12 Hz and the BOLD dynamics in extra‐striate visual cortex. These findings support the hypothesis that NBRs to visual stimuli may be neuronal in origin rather than reflecting pure vascular phenomena. Hum Brain Mapp 37:2247–2262, 2016. © 2016 Wiley Periodicals, Inc.     

Abnormalities of the executive control network in multiple sclerosis phenotypes: An fMRI effective connectivity study

The Stroop interference task is a cognitively demanding task of executive control, a cognitive ability that is often impaired in patients with multiple sclerosis (MS). The aim of this study was to compare effective connectivity patterns within a network of brain regions involved in the Stroop task performance between MS patients with three disease clinical phenotypes [relapsing‐remitting (RRMS), benign (BMS), and secondary progressive (SPMS)] and healthy subjects. Effective connectivity analysis was performed on Stroop task data using a novel method based on causal Bayes networks. Compared with controls, MS phenotypes were slower at performing the task and had reduced performance accuracy during incongruent trials that required increased cognitive control. MS phenotypes also exhibited connectivity abnormalities reflected as weaker shared connections, presence of extra connections (i.e., connections absent in the HC connectivity pattern), connection reversal, and loss. In SPMS and the BMS groups but not in the RRMS group, extra connections were associated with deficits in the Stroop task performance. In the BMS group, the response time associated with correct responses during the congruent condition showed a positive correlation with the left posterior parietal → dorsal anterior cingulate connection. In the SPMS group, performance accuracy during the congruent condition showed a negative correlation with the right insula → left insula connection. No associations between extra connections and behavioral performance measures were observed in the RRMS group. These results suggest that, depending on the phenotype, patients with MS use different strategies when cognitive control demands are high and rely on different network connections. Hum Brain Mapp, 37:2293–2304, 2016. © 2016 Wiley Periodicals, Inc.     

Motor imagery of hand actions: Decoding the content of motor imagery from brain activity in frontal and parietal motor areas

How motor maps are organized while imagining actions is an intensely debated issue. It is particularly unclear whether motor imagery relies on action‐specific representations in premotor and posterior parietal cortices. This study tackled this issue by attempting to decode the content of motor imagery from spatial patterns of Blood Oxygen Level Dependent (BOLD) signals recorded in the frontoparietal motor imagery network. During fMRI‐scanning, 20 right‐handed volunteers worked on three experimental conditions and one baseline condition. In the experimental conditions, they had to imagine three different types of right‐hand actions: an aiming movement, an extension–flexion movement, and a squeezing movement. The identity of imagined actions was decoded from the spatial patterns of BOLD signals they evoked in premotor and posterior parietal cortices using multivoxel pattern analysis. Results showed that the content of motor imagery (i.e., the action type) could be decoded significantly above chance level from the spatial patterns of BOLD signals in both frontal (PMC, M1) and parietal areas (SPL, IPL, IPS). An exploratory searchlight analysis revealed significant clusters motor‐ and motor‐associated cortices, as well as in visual cortices. Hence, the data provide evidence that patterns of activity within premotor and posterior parietal cortex vary systematically with the specific type of hand action being imagined. Hum Brain Mapp 37:81–93, 2016. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals

Subthreshold depression (StD) is a highly prevalent condition associated with increased service utilization and social morbidity. Nevertheless, due to limitations in current diagnostic systems that set the boundary for major depressive disorder (MDD), very few brain imaging studies on the neurobiology of StD have been carried out, and its underlying neurobiological mechanism remains unclear. In recent years, accumulating evidence suggests that the disruption of the default mode network (DMN), a network involved in self-referential processing, affective cognition, and emotion regulation, is involved in major depressive disorder. Using independent component analysis, we investigated resting-state default mode network (DMN) functional connectivity (FC) changes in two cohorts of StD patients with different age ranges (young and middle-aged, n = 57) as well as matched controls (n = 79). We found significant FC increase between the DMN and ventral striatum (key region in the reward network), in both cohorts of StD patients in comparison with controls. In addition, we also found the FC between the DMN and ventral striatum was positively and significantly associated with scores on the Center for Epidemiologic Studies Depression Scale (CES-D), a measurement of depressive symptomatology. We speculate that this enhanced FC between the DMN and the ventral striatum may reflect a self-compensation to ameliorate the lowered reward function.     

Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation

Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6 ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2 h 45 min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response.     

Differential anterior prefrontal activation during the recognition stage of a spatial working memory task

Neuroimaging studies commonly show widespread activations in the prefrontal cortex during various forms of working memory and long-term memory tasks. However, the anterior prefrontal cortex (aPFC, Brodmann area 10) has been mainly associated with retrieval in episodic memory, and its role in working memory is less clear. We conducted an event-related functional magnetic resonance imaging study to examine brain activations in relation to recognition in a spatial delayed-recognition task. Similar to the results from previous findings, several frontal areas were strongly activated during the recognition phase of the task, including the aPFC, the lateral PFC and the anterior cingulate cortex. Although the aPFC was more active during the recognition phase, it was also active during the delay phase of the spatial working memory task. In addition, the aPFC showed greater activity in response to negative probes (non-targets) than to positive probes (targets). While our analyses focused on examining signal changes in the aPFC, other prefrontal regions showed similar effects and none of the areas were more active in response to the positive probes than to the negative probes. Our findings support the conclusion that the aPFC is involved in working memory and particularly in processes that distinguish target and non-target stimuli during recognition.     

Monetary incentives enhance processing in brain regions mediating top-down control of attention

To evaluate the effect of an abstract motivational incentive on top-down mechanisms of visual spatial attention, 10 subjects engaged in a target detection task and responded to targets preceded by spatially valid (predictive), invalid (misleading) or neutral central cues under three different incentive conditions: win money (WIN), lose money (LOSE), and neutral (neither gain nor lose). Activation in the posterior cingulate cortex was correlated with visual spatial expectancy, defined as the degree to which the valid cue benefited performance as evidenced by faster reaction times compared to non-directional cues. Winning and losing money enhanced this relationship via overlapping but independent limbic mechanisms. In addition, activity in the inferior parietal lobule was correlated with disengagement (the degree to which invalid cues diminished performance). This relationship was also enhanced by monetary incentives. Finally, incentive enhanced the relationship of activation in the visual cortex to visual spatial expectancy and disengagement for both types of incentive (WIN and LOSE). These results show that abstract incentives enhance neural processing within the attention network in a process- and valence-selective manner. They also show that different cognitive and motivational mechanisms may produce a common effect upon unimodal cortices in order to enhance processing to serve the current behavioral goal.