Specialized late cingulo-opercular network activation elucidates the mechanisms underlying decisions about ambiguity.

Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In the main study, the slow reveal task was administered to 32 young adults in the fMRI environment and BOLD time courses were extracted from regions of interest in three control networks. In a follow-up study, the task was administered to a larger, online sample (n = 81) using a more extended slow reveal design with additional unmasking frames. Positive judgments of surprised faces were uniquely accompanied by slower response times and strong, late activation in the CO network. These results support the initial negativity hypothesis, which posits that the default response to ambiguity is negative and positive judgments are associated with a more effortful controlled process, and additionally suggest that this controlled process is mediated by the CO network. Moreover, ambiguous trials were characterized by a second CO response at the end of the trial, firmly placing CO function late in the decision-making process.

Explicit and Implicit Emotion Processing in the Cerebellum: A Meta-analysis and Systematic Review.

The cerebellum's role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for affective disruptions following cerebellar damage. To improve the characterization of emotion processing and investigate how attention allocation impacts this processing, we conducted a meta-analysis on task activation foci using GingerALE software. Eighty human neuroimaging studies of emotion including 2761 participants identified through Web of Science and ProQuest databases were analyzed collectively and then divided into two categories based on the focus of attention during the task: explicit or implicit emotion processing. The results examining the explicit emotion tasks identified clusters within the posterior cerebellar hemispheres (bilateral lobule VI/Crus I/II), the vermis, and left lobule V/VI that were likely to be activated across studies, while implicit tasks activated clusters including bilateral lobules VI/Crus I/II, right Crus II/lobule VIII, anterior lobule VI, and lobules I-IV/V. A direct comparison between these categories revealed five overlapping clusters in right lobules VI/Crus I/Crus II and left lobules V/VI/Crus I of the cerebellum common to both the explicit and implicit task contrasts. There were also three clusters activated significantly more for explicit emotion tasks compared to implicit tasks (right lobule VI, left lobule VI/vermis), and one cluster activated more for implicit than explicit tasks (left lobule VI). These findings support previous studies indicating affective processing activates both the lateral hemispheric lobules and the vermis of the cerebellum. The common and distinct activation of posterior cerebellar regions by tasks with explicit and implicit attention demonstrates the supportive role of this structure in recognizing, appraising, and reacting to emotional stimuli.

Affective flexibility as a developmental building block of cognitive reappraisal: An fMRI study.

Cognitive reappraisal is a form of emotion regulation that involves reinterpreting the meaning of a stimulus, often to downregulate one's negative affect. Reappraisal typically recruits distributed regions of prefrontal and parietal cortex to generate new appraisals and downregulate the emotional response in the amygdala. In the current study, we compared reappraisal ability in an fMRI task with affective flexibility in a sample of children and adolescents (ages 6-17, N = 76). Affective flexibility was defined as variability in valence interpretations of ambiguous (surprised) facial expressions from a second behavioral task. Results demonstrated that age and affective flexibility predicted reappraisal ability, with an interaction indicating that flexibility in children (but not adolescents) supports reappraisal success. Using a region of interest-based analysis of participants' BOLD time courses, we also found dissociable reappraisal-related brain mechanisms that support reappraisal success and affective flexibility. Specifically, late increases in middle prefrontal cortex activity supported reappraisal success and late decreases in amygdala activity supported flexibility. Together, these results suggest that our novel measure of affective flexibility - the ability to see multiple interpretations of an ambiguous emotional cue - may represent part of the developmental building blocks of cognitive reappraisal ability.

Task-irrelevant emotional faces impact BOLD responses more for prosaccades than antisaccades in a mixed saccade fMRI task.

Cognitive control allows individuals to flexibly and efficiently perform tasks by attending to relevant stimuli while inhibiting distraction from irrelevant stimuli. The antisaccade task assesses cognitive control by requiring participants to inhibit a prepotent glance towards a peripheral stimulus and generate an eye movement to the mirror image location. This task can be administered with various contextual manipulations to investigate how factors such as trial timing or emotional content interact with cognitive control. In the current study, 26 healthy adults completed a mixed antisaccade and prosaccade fMRI task that included task irrelevant emotional faces and gap/overlap timing. The results showed typical antisaccade and gap behavioral effects with greater BOLD activation in frontal and parietal brain regions for antisaccade and overlap trials. Conversely, there were no differences in behavior based on the emotion of the task irrelevant face, but trials with neutral faces had greater activation in widespread visual regions than trials with angry faces, particularly for prosaccade and overlap trials. Together, these effects suggest that a high level of cognitive control and inhibition was required throughout the task, minimizing the impact of the face presentation on saccade behavior, but leading to increased attention to the neutral faces on overlap prosaccade trials when both the task cue (look towards) and emotion stimulus (neutral, non-threatening) facilitated disinhibition of visual processing.

Reward-Based Learning and Emotional Habit Formation in the Cerebellum.

There is growing evidence of the cerebellum's contribution to emotion processing from neuroimaging studies of healthy function and clinical studies of cerebellar patients. As demonstrated initially in the motor domain, one of the cerebellum's functions is to construct internal models of an individual's state and make predictions about how future behaviors will impact that state. By utilizing widespread connections with neocortex and subcortical regions such as the basal ganglia, the cerebellum can monitor and modulate precisely timed patterns of events using prediction and reward-based error feedback in a diverse range of tasks including auditory emotion prosody recognition. In coordination with a broader affective network, the cerebellum helps to select and refine emotional responses that are the most rewarded in a particular context, strengthening neural activity in relevant regions to form a representational chunk. This chunked set of affective stimuli, cognitive evaluations, and physiological responses subsequently can be enacted as a unitary response (i.e., an emotional habit) more quickly and with less attentional control than for a novel stimulus or goal-oriented action. Such emotional habits can allow for efficient, automatic, stimulus-triggered responses while maintaining the flexibility to adapt output when prediction errors signal a renewed need for cerebellar modification of cortical activity, or, conversely, may lead to behavioral or mood disorders when habitual responses persist despite negative consequences.

Motor symptom asymmetry predicts non-motor outcome and quality of life following STN DBS in Parkinson's disease.

Risk factors for long-term non-motor symptoms and quality of life following subthalamic nucleus deep brain stimulation (STN DBS) have not yet been fully identified. In the present study, we investigated the impact of motor symptom asymmetry in Parkinson's disease. Data were extracted for 52 patients with Parkinson's disease (half with predominantly left-sided motor symptoms and half with predominantly right-sided ones) who underwent bilateral STN and a matched healthy control group. Performances for cognitive tests, apathy and depression symptoms, as well as quality-of-life questionnaires at 12 months post-DBS were compared with a pre-DBS baseline. Results indicated a deterioration in cognitive performance post-DBS in patients with predominantly left-sided motor symptoms. Performances of patients with predominantly right-sided motor symptoms were maintained, except for a verbal executive task. These differential effects had an impact on patients' quality of life. The results highlight the existence of two distinct cognitive profiles of Parkinson's disease, depending on motor symptom asymmetry. This asymmetry is a potential risk factor for non-motor adverse effects following STN DBS.

Reappraisal-related downregulation of amygdala BOLD activation occurs only during the late trial window.

During cognitive reappraisal, an individual reinterprets the meaning of an emotional stimulus to regulate the intensity of their emotional response. Prefrontal cortex activity has been found to support reappraisal and is putatively thought to downregulate the amygdala response to these stimuli. The timing of these regulation-related responses during the course of a trial, however, remains poorly understood. In the current fMRI study, participants were instructed to view or reappraise negative images and then rate how negative they felt following each image. The hemodynamic response function was estimated in 11 regions of interest for the entire time course of the trial including image viewing and rating. Notably, within the amygdala there was no evidence of downregulation in the early (picture viewing) window of the trial, only in the late (rating) window, which also correlated with a behavioral measure of reappraisal success. With respect to the prefrontal regions, some (e.g., inferior frontal gyrus) showed reappraisal-related activation in the early window, whereas others (e.g., middle frontal gyrus) showed increased activation primarily in the late window. These results highlight the temporal dynamics of different brain regions during emotion regulation and suggest that the amygdala response to negative images need not be immediately dampened to achieve successful cognitive reappraisal.

A novel computerized assessment of manual spatial exploration in unilateral spatial neglect.

Unilateral spatial neglect is a neuropsychological syndrome commonly observed after stroke and defined by the inability to attend or respond to contralesional stimuli. Typically, symptoms are assessed using clinical tests that rely upon visual/perceptual abilities. However, neglect may affect high-level representations controlling attention in other modalities as well. Here we developed a novel manual exploration test using a touch screen computer to quantify spatial search behaviour without visual input. Twelve chronic stroke patients with left neglect and 27 patients without neglect (based on clinical tests) completed our task. Four of the 12 "neglect" patients exhibited clear signs of neglect on our task as compared to "non-neglect" patients and healthy controls, and six other patients (from both groups) also demonstrated signs of neglect compared to healthy controls only. While some patients made asymmetrical responses on only one task, generally, patients with the strongest neglect performed poorly on multiple tasks. This suggests that representations associated with different modalities may be affected separately, but that severe forms of neglect are more likely related to damage in a common underlying representation. Our manual exploration task is easy to administer and can be added to standard neglect screenings to better measure symptom severity.

An atypical case of congenital lobar emphysema in an adult, non-smoker patient presenting with pneumothorax.

Congenital lobar emphysema (CLE) is a developmental anomaly of the lower respiratory tract characterized by hyperinflation of one or more pulmonary lobes in the absence of extrinsic bronchial obstruction. We present a case of a 24-year-old male, nonsmoker who presented with shortness of breath and severe left sided chest pain. A chest x-ray was significant for a very large left-sided pneumothorax and chest CT showed lobar emphysematous changes. Video assisted thoracoscopic surgery (VATS) and lobectomy was subsequently performed after persistence of pneumothorax despite chest tube insertion and conservative management. Surgical pathology of resected specimen showed chronic emphysematous changes with patchy chronic organizing pneumonitis. Histology showed advanced emphysematous changes of pulmonary parenchyma consistent with congenital lobar emphysema. This finding combined with features seen on computed tomography of the chest led to the diagnosis of congenital lobar emphysema. This case demonstrated that CLE can be a cause of tension pneumothorax in adults in rare cases.

Real-time fMRI and EEG neurofeedback: A perspective on applications for the rehabilitation of spatial neglect.

Spatial neglect is a neuropsychological syndrome characterized by a failure to orient, perceive, and act toward the contralesional side of the space after brain injury. Neglect is one of the most frequent and disabling neuropsychological syndromes following right-hemisphere damage, often persisting in the chronic phase and responsible for a poor functional outcome at hospital discharge. Different rehabilitation approaches have been proposed over the past 60 years, with a variable degree of effectiveness. In this point-of-view article, we describe a new rehabilitation technique for spatial neglect that directly targets brain activity and pathological physiological processes: namely, neurofeedback (NFB) with real-time brain imaging methodologies. In recent proof-of-principle studies, we have demonstrated the potential of this rehabilitation technique. Using real-time functional MRI (rt-fMRI) NFB in chronic neglect, we demonstrated that patients are able to upregulate their right visual cortex activity, a response that is otherwise reduced due to losses in top-down attentional signals. Using real-time electroencephalography NFB in patients with acute or chronic condition, we showed successful regulation with partial restoration of brain rhythm dynamics over the damaged hemisphere. Both approaches were followed by mild, but encouraging, improvement in neglect symptoms. NFB techniques, by training endogenous top-down modulation of attentional control on sensory processing, might induce sustained changes at both the neural and behavioral levels, while being non-invasive and safe. However, more properly powered clinical studies with control groups and longer follow-up are needed to fully establish the effectiveness of the techniques, identify the most suitable candidates, and determine how the techniques can be optimized or combined in the context of rehabilitation.

Basal ganglia and cerebellum contributions to vocal emotion processing as revealed by high-resolution fMRI.

Until recently, brain networks underlying emotional voice prosody decoding and processing were focused on modulations in primary and secondary auditory, ventral frontal and prefrontal cortices, and the amygdala. Growing interest for a specific role of the basal ganglia and cerebellum was recently brought into the spotlight. In the present study, we aimed at characterizing the role of such subcortical brain regions in vocal emotion processing, at the level of both brain activation and functional and effective connectivity, using high resolution functional magnetic resonance imaging. Variance explained by low-level acoustic parameters (fundamental frequency, voice energy) was also modelled. Wholebrain data revealed expected contributions of the temporal and frontal cortices, basal ganglia and cerebellum to vocal emotion processing, while functional connectivity analyses highlighted correlations between basal ganglia and cerebellum, especially for angry voices. Seed-to-seed and seed-to-voxel effective connectivity revealed direct connections within the basal ganglia-especially between the putamen and external globus pallidus-and between the subthalamic nucleus and the cerebellum. Our results speak in favour of crucial contributions of the basal ganglia, especially the putamen, external globus pallidus and subthalamic nucleus, and several cerebellar lobules and nuclei for an efficient decoding of and response to vocal emotions.

Subthalamic nucleus oscillations during vocal emotion processing are dependent of the motor asymmetry of Parkinson's disease.

The subthalamic nucleus (STN) is involved in different aspects of emotional processes and more specifically in emotional prosody recognition. Recent studies on the behavioral effects of deep brain stimulation (DBS) in patients with Parkinson's disease (PD) have uncovered an asymmetry in vocal emotion decoding in PD, with left-onset PD patients showing deficits for the processing of happy voices. Whether and how PD asymmetry affects STN electrophysiological responses to emotional prosody, however, remains unknown. In the current study, local field potential activity was recorded from eight left- and six right-lateralized motor-onset PD patients (LOPD/ROPD) undergoing DBS electrodes implantation, while they listened to angry, happy and neutral voices. Time-frequency decomposition revealed that theta (2-6 Hz), alpha (6-12 Hz) and gamma (60-150 Hz) band responses to emotion were mostly bilateral with a differential pattern of response according to patient's sides-of onset. Conversely, beta-band (12-20 Hz and 20-30 Hz) emotional responses were mostly lateralized in the left STN for both patient groups. Furthermore, STN theta, alpha and gamma band responses to happiness were either absent (theta band) or reduced (alpha and gamma band) in the most affected STN hemisphere (contralateral to the side-of onset), while a late low-beta band left STN happiness-specific response was present in ROPD patients and did not occur in LOPD patients. Altogether, in this study, we demonstrate a complex pattern of oscillatory activity in the human STN in response to emotional voices and reveal a crucial influence of disease laterality on STN low-frequency oscillatory activity.

Exact design of complex amplitude holograms for producing arbitrary scalar fields.

Typical methods to holographically encode arbitrary wavefronts assume the hologram medium only applies either phase shifts or amplitude attenuation to the wavefront. In many cases, phase cannot be introduced to the wavefront without also affecting the amplitude. Here we show how to encode an arbitrary wavefront into an off-axis transmission hologram that returns the exact desired arbitrary wavefunction in a diffracted beam for phase-only, amplitude-only, or mixed phase and amplitude holograms with any periodic groove profile. We apply this to design thin holograms for electrons in a TEM, but our results are generally applicable to light and X-ray optics. We employ a phase reconstruction from a series of focal plane images to qualitatively show the accuracy of this method to impart the expected amplitude and phase to a specific diffraction order.

The basal ganglia and the cerebellum in human emotion.

The basal ganglia (BG) and the cerebellum historically have been relegated to a functional role in producing or modulating motor output. Recent research, however, has emphasized the importance of these subcortical structures in multiple functional domains, including affective processes such as emotion recognition, subjective feeling elicitation and reward valuation. The pathways through the thalamus that connect the BG and cerebellum directly to each other and with extensive regions of the cortex provide a structural basis for their combined influence on limbic function. By regulating cortical oscillations to guide learning and strengthening rewarded behaviors or thought patterns to achieve a desired goal state, these regions can shape the way an individual processes emotional stimuli. This review will discuss the basic structure and function of the BG and cerebellum and propose an updated view of their functional role in human affective processing.

Rightward exogenous attentional shifts impair perceptual memory of spatial locations in patients with left unilateral spatial neglect.

Spatial remapping implies the updating and maintaining of the spatial position of objects in successive visual images across time, despite their displacement on the retina due to eye movements. In the parietal cortex, the representation of spatial locations appears to be partly centered on gaze direction, and thus modulated by current eye-gaze position. It has been suggested that short-term memory for spatial locations across delays might be impaired in right brain-injured patients with left spatial neglect, but more so after rightward than leftward gaze shifts - an asymmetry attributed to a loss of spatial representations normally transferred from left to right hemisphere during remapping. Because several studies point to a strong link between attentional and oculomotor circuits in the brain, we hypothesized that similar remapping effects might result from attentional displacements without overt eye movements. We tested this hypothesis in right-brain damaged patients with and without left neglect in a visuo-spatial memory task. As predicted, neglect patients showed a selective deficit in location memory following an exogenous attentional shift caused by a brief flash in the periphery of their right (but not left) visual field. We conclude that an attentional displacement without eye movements is sufficient to remap spatial representations across hemifields, and that this process is impaired in neglect patients when a location has to be transferred to the neglected/left side relative to current gaze or attention focus. More generally, these results support the notion of neural overlap between oculomotor and attentional mechanisms, and confirm a role for impaired remapping in the neglect syndrome, wherein spatial representations of contralesional locations may fail to be maintained during active attentional behavior.

Differential parietal activations for spatial remapping and saccadic control in a visual memory task.

Remapping is a process that updates visual information in internal spatial representations across eye movements, allowing for stable perception of the environment. Previous work has demonstrated visual remapping activity in parietal cortex during saccades, but it remains unclear whether remapping is triggered by overt saccades only (or by attentional shifts also), and whether it engages parietal areas only (or other cortical areas). Here, we used fMRI to investigate spatial remapping during two visuospatial memory tasks requiring either overt (accompanied by a saccade) or covert (with central fixation) attention shifts to peripheral distracters. Participants had to remember the position and color of a lateralized dot during a saccade or attention shift, requiring them to update the dot position in memory, and then indicate if a second dot matched the first. Differential activation patterns were observed within parietal cortex as a function of the different visual, motor, and interhemispheric remapping demands in the saccade task, presumably mediating the maintenance of spatial position in perceptual and motor maps. Remapping engaged parietal areas adjacent to, but not overlapping with, those activated by saccade execution, while it did not engage the frontal eye fields, pointing to distinct neural substrates for ocular motor and spatial updating processes. No differential activation related to remapping was found during the covert attention shift task, suggesting that this condition did not necessitate the same remapping as the saccade condition. Overall these results further elucidate the mechanisms of spatial remapping in human parietal cortex and their relationship with attention processing and ocular motor behavior, with implications for understanding visuospatial attention deficits in hemispatial neglect.

Regularized aggregation of statistical parametric maps.

Combining statistical parametric maps (SPM) from individual subjects is the goal in some types of group-level analyses of functional magnetic resonance imaging data. Brain maps are usually combined using a simple average across subjects, making them susceptible to subjects with outlying values. Furthermore, t tests are prone to false positives and false negatives when outlying values are observed. We propose a regularized unsupervised aggregation method for SPMs to find an optimal weight for aggregation, which aids in detecting and mitigating the effect of outlying subjects. We also present a bootstrap-based weighted t test using the optimal weights to construct an activation map robust to outlying subjects. We validate the performance of the proposed aggregation method and test using simulated and real data examples. Results show that the regularized aggregation approach can effectively detect outlying subjects, lower their weights, and produce robust SPMs.

A critical review of the role of impaired spatial remapping processes in spatial neglect.

Objective: Unilateral spatial neglect is a multi-faceted syndrome that arises from brain lesions, typically in the right hemisphere, and is characterized by the failure to attend or respond to stimuli in contralesional space. Here, we expand on the proposal that one deficit contributing to the diverse symptoms in neglect involves spatial remapping processes. Spatial remapping is required to maintain a stable visual representation despite frequent eye movements that change the retinal image. Neglect patients' lesions may disrupt the transfer of this representation across saccades, resulting in the loss of spatial information in working memory or even awareness of an object's presence. Method: In this review, we will characterize the neglect syndrome and its anatomical origins, describe spatial remapping in healthy individuals, then focus on how impairments of remapping and spatial working memory could contribute to some reported neglect symptoms. Finally, we will discuss the effectiveness of a rehabilitation method known as prism adaptation for alleviating visual spatial symptoms in neglect patients in relation to spatial remapping performance. Conclusions: The heterogeneity of spatial neglect makes it difficult to pinpoint a single underlying dysfunction or causal lesion. Given the number of brain regions that may be damaged across neglect patients, it is likely that many different processes contribute to the manifested attentional symptoms. In this review, we highlight the role of spatial remapping mechanisms subserved by posterior parietal cortex as one of the underlying deficits leading to visual spatial neglect.

Microstructural differences in visual white matter tracts in people with aniridia.

Aniridia is a panocular disorder characterized chiefly by iris hypoplasia. Most cases result from mutations of the PAX6 gene, which is important in both eye and brain development. In addition to ocular alterations, differences in global brain volume and functional connectivity have been reported in humans with aniridia. Understanding neural alterations in aniridia may require examination of possible differences in white matter structure, as few studies have assessed white matter in this population. The current study utilized diffusion-weighted imaging to assess white matter structure in 11 people with aniridia and 11 healthy comparison participants, matched for sex and age. A map of the local connectome was calculated to compare quantitative anisotropy (QA), an index of white matter tract density, in all white matter voxels, revealing subcomponents of white matter tracts with differing QA between people with aniridia and healthy comparisons. The analysis indicated that QA was lower for people with aniridia in portions of bilateral optic tract [t(20)=-4.23, P=0.001, d=-1.80], bilateral optic radiation [t(20)=-4.06, P=0.001, d=-1.73], forceps major [t(20)=-3.65, P=0.002, d=-1.55], bilateral superior longitudinal fasciculus [left: t(20)=-3.15, P=0.005, d=-1.34; right, t(20)=-4.28, P<0.001, d=-1.83], and right posterior corona radiata [t(20)=-3.19, P=0.006, d=-1.36]. These differences demonstrate that white matter structure is altered in people with aniridia in both visual tracts and associated posterior visual pathways.