Vinh T. Nguyen

The superior temporal sulcus and the N170 during face processing: single trial analysis of concurrent EEG-fMRI

Face-selective neural signals have been reliably identified using both EEG and fMRI studies. These consist of the N170 component, a neural response peaking approximately 170ms after a face is presented, and face-selective activations in the fusiform face area (FFA), the occipital face area (OFA), and the superior temporal sulcus (STS). As most neuroimaging studies examine these face-selective processes separately, the relationship between the N170 neural response and activation in the fusiform gyrus is still debated. In this study, we concurrently measured EEG and fMRI responses to upright faces, inverted faces, and objects to examine this association. We introduce a method for single-trial estimation of N170 amplitudes and correlation of the trial-by-trial variation in N170 neural responses with fMRI BOLD responses. For upright faces, BOLD responses in the right STS were negatively correlated with N170 amplitudes, showing greater activation on trials in which N170 amplitudes were larger (more negative). For inverted faces, a medial region of the fusiform gyrus (mFG) was positively correlated with N170 amplitudes, showing greater activation on trials in which N170 amplitudes were smaller (less negative). This result points to the STS as a crucial region for generating the N170 associated with face perception, and suggests that the mFG is additionally recruited for processing inverted faces, particularly on trials in which N170 is small. Despite the different time resolution of fMRI and EEG signals, our single-trial estimation and EEG-fMRI correlation method can reveal associations between activation in face-selective brain regions and neural processes at 170ms associated with face perception.

A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields

Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas. DOI: http://dx.doi.org/10.7554/eLife.15252.001

The integration of the internal and external milieu in the insula during dynamic emotional experiences.

Whilst external events trigger emotional responses, interoception (the perception of internal physiological states) is fundamental to core emotional experience. By combining high resolution functional neuroimaging with concurrent physiological recordings, we investigated the neural mechanisms of interoceptive integration during free listening to an emotionally salient audio film. We found that cardiac activity, a key interoceptive signal, was robustly synchronised across participants and centrally represented in the posterior insula. Effective connectivity analysis revealed that the anterior insula, specifically tuned to the emotionally salient moments of the audio stream, serves as an integration hub of interoceptive processing: interoceptive states represented in the posterior insula are integrated with exteroceptive representations by the anterior insula to highlight these emotionally salient moments. Our study for the first time demonstrates the insular hierarchy for interoceptive processing during natural emotional experience. These findings provide an ecologically-valid framework for elucidating the neural underpinnings of emotional deficits in neuropsychiatric disorders.

Network dysfunction of emotional and cognitive processes in those at genetic risk of bipolar disorder

The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non-linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder.

Fusing concurrent EEG-fMRI with dynamic causal modeling: application to effective connectivity during face perception.

Despite the wealth of research on face perception, the interactions between core regions in the face-sensitive network of the visual cortex are not well understood. In particular, the link between neural activity in face-sensitive brain regions measured by fMRI and EEG markers of face-selective processing in the N170 component is not well established. In this study, we used dynamic causal modeling (DCM) as a data fusion approach to integrate concurrently acquired EEG and fMRI data during the perception of upright compared with inverted faces. Data features derived from single-trial EEG variability were used as contextual modulators on fMRI-derived estimates of effective connectivity between key regions of the face perception network. The overall construction of our model space was highly constrained by the effects of task and ERP parameters on our fMRI data. Bayesian model selection suggested that the occipital face area (OFA) acted as a central gatekeeper directing visual information to the superior temporal sulcus (STS), the fusiform face area (FFA), and to a medial region of the fusiform gyrus (mFG). The connection from the OFA to the STS was strengthened on trials in which N170 amplitudes to upright faces were large. In contrast, the connection from the OFA to the mFG, an area known to be involved in object processing, was enhanced for inverted faces particularly on trials in which N170 amplitudes were small. Our results suggest that trial-by-trial variation in neural activity at around 170 ms, reflected in the N170 component, reflects the relative engagement of the OFA to STS/FFA network over the OFA to mFG object processing network for face perception. Importantly, the DCMs predicted the observed data significantly better by including the modulators derived from the N170, highlighting the value of incorporating EEG-derived information to explain interactions between regions as a multi-modal data fusion method for combined EEG-fMRI.

Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms.

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting‐state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test–retest reliability of resting‐state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test–retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting‐state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting‐state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio–visual processing become more reliable, higher order brain networks, such as default mode and attention networks, but also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI. Hum Brain Mapp 38:2226–2241, 2017.

Out-of-sync: disrupted neural activity in emotional circuitry during film viewing in melancholic depression

While a rich body of research in controlled experiments has established changes in the neural circuitry of emotion in major depressive disorders, little is known as to how such alterations might translate into complex, naturalistic settings - namely involving dynamic multimodal stimuli with rich contexts, such as those provided by films. Neuroimaging paradigms employing dynamic natural stimuli alleviate the anxiety often associated with complex tasks and eschew the need for laboratory-style abstractions, hence providing an ecologically valid means of elucidating neural underpinnings of neuropsychiatric disorders. To probe the neurobiological signature of refined depression subtypes, we acquired functional neuroimaging data in patients with the melancholic subtype of major depressive disorder during free viewing of emotionally salient films. We found a marked disengagement of ventromedial prefrontal cortex during natural viewing of a film with negative emotional valence in patients with melancholia. This effect significantly correlated with depression severity. Such changes occurred on the background of diminished consistency of neural activity in visual and auditory sensory networks, as well as higher-order networks involved in emotion and attention, including bilateral intraparietal sulcus and right anterior insula. These findings may reflect a failure to re-allocate resources and diminished reactivity to external emotional stimuli in melancholia.

Distinct neurobiological signatures of brain connectivity in depression subtypes during natural viewing of emotionally salient films.

BACKGROUND Establishing an evidence-based diagnostic system informed by the biological (dys)function of the nervous system is a major priority in psychiatry. This objective, however, is often challenged by difficulties in identifying homogeneous clinical populations. Melancholia, a biological and endogenous subtype for major depressive disorder, presents a canonical test case in the search of biological nosology. METHOD We employed a unique combination of naturalistic functional magnetic resonance imaging (fMRI) paradigms - resting state and free viewing of emotionally salient films - to search for neurobiological signatures of depression subtypes. fMRI data were acquired from 57 participants; 17 patients with melancholia, 17 patients with (non-melancholic) major depression and 23 matched healthy controls. RESULTS Patients with melancholia showed a prominent loss of functional connectivity in hub regions [including ventral medial prefrontal cortex, anterior cingulate cortex (ACC) and superior temporal gyrus] during natural viewing, and in the posterior cingulate cortex while at rest. Of note, the default mode network showed diminished reactivity to external stimuli in melancholia, which correlated with the severity of anhedonia. Intriguingly, the subgenual ACC, a potential target for treating depression with deep brain stimulation (DBS), showed divergent changes between the two depression subtypes, with increased connectivity in the non-melancholic and decreased connectivity in the melancholic subsets. CONCLUSION These findings reveal neurobiological changes specific to depression subtypes during ecologically valid behavioural conditions, underscoring the critical need to respect differing neurobiological processes underpinning depressive subtypes.

Scene unseen: Disrupted neuronal adaptation in melancholia during emotional film viewing

Impairments in attention and concentration are distinctive features of melancholic depression, and may diminish the ability to shift focus away from internal dysphoric states. Disrupted brain networks may underlie the inability to effectively disengage from interoceptive signals in this disorder. This study investigates changes in effective connectivity between cortical systems supporting attention, interoception, and perception in those with melancholic depression when shifting attention from rest to viewing dynamic film stimuli. We hypothesised that those with melancholia would show impaired attentional shifting from rest to emotional film viewing, captured in neuronal states that differed little across conditions. Functional magnetic resonance imaging (fMRI) data were acquired from 48 participants (16 melancholic depressed, 16 non-melancholic depressed, and 16 healthy controls) at rest and whilst viewing emotionally salient movies. Using independent component analysis, we identified 8 cortical modes (default mode, executive control, left/right frontoparietal attention, left/right insula, visual and auditory) and studied their dynamics using dynamic causal modelling. Engagement with dynamic emotional material diminished in melancholia and was associated with network-wide increases in effective connectivity. Melancholia was also characterised by an increase in effective connectivity amongst cortical regions involved in attention and interoception when shifting from rest to negative film viewing, with the converse pattern in control participants. The observed involvement of attention- and insula-based cortical systems highlights a potential neurobiological mechanism for disrupted attentional resource allocation, particularly in switching between interoceptive and exteroceptive signals, in melancholia.

Safety of EEG-fMRI recordings in newborn infants at 3T: a study using a baby-size phantom.

OBJECTIVE We aimed to study EEG electrode temperatures during MRI recordings using a neonatal-size phantom to establish the safety of neonatal EEG-MRI. METHODS We constructed a phantom set-up for co-registration of EEG and MRI measurements with newborn size configurations. The set-up consisted of a spherical glass phantom fitted with a customised MRI-compatible 64-channel EEG cap and EEG amplifier. Temperatures were recorded during and after five different scanning sequences (two T2∗ sensitised BOLD fMRI, one T1-weighted and two T2-weighted spin echo) in five electrode locations using a thermistor that was integrated into the electrode housing. A temperature increase >4°C was defined a priori as the safety limit. RESULTS During fMRI and T1 sequences, none of the electrodes showed meaningful temperature changes. Only one MRI sequence (T2 with Max turbo factor 25; SAR 89%) caused temperature increase in one electrode (Fpz; +4.1°C) that slightly exceeded our predefined safety limit, while the conventional T2 sequence was within safety limits (up to +1.7°C). CONCLUSIONS Co-registration of EEG and fMRI can be considered safe in babies with respect to electrode heating, which is the primary safety concern. SIGNIFICANCE The present findings open up a possibility to commence studies where EEG and MRI/fMRI are co-registered in human babies. Such studies hold significant promise of a better understanding of the early development of brain function and neurovascular coupling.