Assessing the function of the fronto‐parietal attention network: Insights from resting‐state fMRI and the attentional network test

In the recent past, various intrinsic connectivity networks (ICN) have been identified in the resting brain. It has been hypothesized that the fronto‐parietal ICN is involved in attentional processes. Evidence for this claim stems from task‐related activation studies that show a joint activation of the implicated brain regions during tasks that require sustained attention. In this study, we used functional magnetic resonance imaging (fMRI) to demonstrate that functional connectivity within the fronto‐parietal network at rest directly relates to attention. We applied graph theory to functional connectivity data from multiple regions of interest and tested for associations with behavioral measures of attention as provided by the attentional network test (ANT), which we acquired in a separate session outside the MRI environment. We found robust statistical associations with centrality measures of global and local connectivity of nodes within the network with the alerting and executive control subfunctions of attention. The results provide further evidence for the functional significance of ICN and the hypothesized role of the fronto‐parietal attention network. Hum Brain Mapp 35:1700–1709, 2014. © 2013 Wiley Periodicals, Inc.     

Resting‐state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post‐surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting‐state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting‐state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left‐hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. Hum Brain Mapp, 36:288–303, 2015. © 2014 Wiley Periodicals, Inc.     

Characteristics of left and right scanning in schizophrenia patients using exploratory eye movements: comparison with healthy subjects

To characterize the left and right scanning function and the effect of affection in schizophrenia patients exploratory eye movements as biologic markers were recorded in 44 schizophrenia patients and 72 age-matched healthy controls. The total eye scanning length (TESL) and total number of gaze points (TNGP) in the left and right visual fields were calculated as subjects viewed neutral or affectively charged pictures. TESL of patients was shorter than that of controls when viewing pictures of smiling babies and open circles. TESL of patients was shorter for smiling faces than for crying babies, but TESL of controls was longer for smiling faces than for crying babies. Left TNGP for smiling faces and circles was lower in patients than in controls. In patients, left TNGP for crying babies was higher than for either smiling babies or circles. In controls, left TNGP for smiling babies was higher than crying babies. In patients, left TNGP for smiling babies and circles was smaller than the right TNGP. In controls, left TNGP was larger for smiling than for crying babies. When viewing smiling babies, both TESL and TNGP were negatively correlated with negative symptom scores in patients. Patients' eye movements in the left visual field were clearly different from controls', suggesting that visual cognitive function is impaired in schizophrenia patients. Exploratory eye movements are a useful marker of visual cognitive function, and are a useful tool to evaluate the influence of affection in schizophrenia patients.     

Empirical assessment of changing sample‐characteristics in task‐fMRI over two decades: An example from gustatory and food studies

Over the past two decades, functional neuroimaging has not only grown into a large field of research, but also substantially evolved. Here we provide a quantitative assessment of these presumed in sample composition and data analysis, using fMRI studies on food/taste research published between 1998 and 2019 as an exemplary case in which the scientific objectives themselves have remained largely stable. A systematic search for papers written in English was done using multiple databases and identified 426 original articles that were subsequently analyzed. The median sample size significantly increased from 11.5 to 35.5 while the ratio of male to female subjects remained stable. There were, however, more papers involving female subjects only, rather than male subjects only, since 2003. There was a decline in uncorrected results and statistical correction by false‐discovery rate. Reflecting a trend toward more conservative thresholding, the number of foci reported per paper did not change significantly and sample size (power) did not correlate with the number of reported foci. The median journal impact factor and the normalized number of citations (citations per year) of the papers, in turn, showed a significantly decreasing trend. Number of citations negatively correlated to sample size, publication year but positively correlated to journal impact factor, and was also influenced by statistical correction method. There was a decreasing trend in studies recruiting both left‐handed and right‐handed subjects. In summary, the present paper quantifies several large‐scale trends that have often been anecdotally discussed and reveals the changing nature of neuroimaging studies that may be considered when pursuing meta‐analytic approaches.     

Involvement of the dorsal and ventral attention networks in oddball stimulus processing: A meta‐analysis

The aim of this study was to provide the first, comprehensive meta‐analysis of the neuroimaging literature regarding greater neural responses to a deviant stimulus in a stream of repeated, standard stimuli, termed here oddball effects. The meta‐analysis of 75 independent studies included a comparison of auditory and visual oddball effects and task‐relevant and task‐irrelevant oddball effects. The results were interpreted with reference to the model in which a large‐scale dorsal frontoparietal network embodies a mechanism for orienting attention to the environment, whereas a large‐scale ventral frontoparietal network supports the detection of salient, environmental changes. The meta‐analysis yielded three main sets of findings. First, ventral network regions were strongly associated with oddball effects and largely common to auditory and visual modalities, indicating a supramodal “alerting” system. Most ventral network components were more strongly associated with task‐relevant than task‐irrelevant oddball effects, indicating a dynamic interplay of stimulus saliency and internal goals in stimulus‐driven engagement of the network. Second, the bilateral inferior frontal junction, an anterior core of the dorsal network, was strongly associated with oddball effects, suggesting a central role in top‐down attentional control. However, other dorsal network regions showed no or only modest association with oddball effects, likely reflecting active engagement during both oddball and standard stimulus processing. Finally, prominent oddball effects outside the two networks included the sensory cortex regions, likely reflecting attentive and preattentive modulation of early sensory activity, and subcortical regions involving the putamen, thalamus, and other areas, likely reflecting subcortical involvement in alerting responses. Hum Brain Mapp 35:2265–2284, 2014. © 2013 Wiley Periodicals, Inc .     

Alteration of the timing of self‐initiated but not reactive saccades by electrical stimulation in the supplementary eye field

Although we can generate movements whenever we feel like doing so, the way in which neuronal signals regulate the timing of self‐initiated movements remains elusive. There is evidence that the dorsomedial frontal cortex, including the supplementary eye field (SEF), is involved in the self‐triggering of movements. Because the gradual evolution of cortical activity over the dorsomedial frontal cortex is known to reflect the temporal prediction of an upcoming event, we postulated that the timing of self‐initiated movements is regulated by the time course of neuronal activity in the SEF. To test the causal role, we applied electrical microstimulation to the SEF when monkeys prepared for memory‐guided saccades. Stimulation delayed the initiation of saccades when animals were required to make saccades 1200 ± 300 ms following the cue (self‐timed task), but not when they generated memory‐guided saccades in response to the offset of the fixation point (conventional task). As well as the increment in median saccade latencies, stimulation at ～24% of sites also increased the occurrence of early erroneous saccades. Saccades facilitated by stimulation were always directed toward the cue, even when the cue was located away from the movement field. In contrast, stimulation to the frontal eye fields during saccade preparation exerted no effects in either task. These results suggest that the preparatory signals in the SEF may play a causal role in regulating the timing rather than the direction of self‐initiated saccades.     

Default mode network modifications in Fabry disease: A resting‐state fMRI study with structural correlations

Aim of the study was to evaluate the presence of Default Mode Network (DMN) modifications in Fabry Disease (FD), and their possible correlations with structural alterations and neuropsychological scores. Thirty‐two FD patients with a genetically confirmed diagnosis of classical FD (12 males, mean age 43.3 ± 12.2) were enrolled, along with 35 healthy controls (HC) of comparable age and sex (14 males, mean age 42.1 ± 14.5). Resting‐State fMRI data were analyzed using a seed‐based approach, with six different seeds sampling the main hubs of the DMN. Structural modifications were assessed by means of Voxel‐Based Morphometry (VBM) and Tract‐Based Spatial Statistics analyses. Between‐group differences and correlations with neuropsychological variables were probed voxelwise over the whole brain. Possible correlations between FC modifications and global measures of microstructural alteration were also tested in FD patients with a partial correlation analysis. In the FD group, clusters of increased functional connectivity involving both supratentorial and infratentorial regions emerged, partially correlated to the widespread white matter (WM) damage found in these patients. No gray matter volume differences were found at VBM between the two groups. The connectivity between right inferior frontal gyrus and precuneus was significantly correlated with the Corsi block‐tapping test results (p = .0001). Widespread DMN changes are present in FD patients that correlate with WM alterations and cognitive performance. Our results confirm the current view of a cerebral involvement in FD patients not simply associated to major cerebrovascular events, but also related to significant and diffuse microstructural and functional changes.     

The role of the right hemisphere in metaphor comprehension: A meta‐analysis of functional magnetic resonance imaging studies

The role of the right hemisphere (RH) in metaphor comprehension is still controversial. Numerous neuroimaging studies have found that conventionality, sentential context, and task demand can influence the involvement of the RH in metaphor processing. The current meta‐analysis used foci from 17 original functional magnetic resonance imaging studies to identify what factors modulate the involvement of the RH in metaphor processing. Activation likelihood estimation was used for quantification. We focused on the contrast of metaphorical meaning processing versus literal meaning processing and calculated the meta‐analysis effects when (1) metaphorical meaning is conventional, (2) metaphorical meaning is novel, (3) metaphorical and literal meaning are presented in words, (4) metaphorical and literal meaning are presented in sentential context, (5) task is valence judgment, and (6) task is semantic relatedness judgment. The results indicated that the RH only showed significant effects in metaphor processing when the metaphorical meaning is novel, when metaphorical meaning is presented in sentential context, and when the task is semantic relatedness judgment. The effects were located in right fronto‐temporal regions, including inferior frontal gyrus, middle frontal gyrus, insula, superior temporal gyrus, and middle temporal gyrus. These results suggest that conventionality, contextual complexity, and task demand can modulate the effect of figurativeness and influence the involvement of RH in metaphor comprehension. The main role of the RH in metaphor processing is related with activating broad semantic fields and integrating concepts that may have distant semantic relations, and hence provide support for the view that the RH is responsible for processing coarse semantic information in language comprehension. Hum Brain Mapp 35:107–122, 2014. © 2012 Wiley Periodicals, Inc.     

The neural control of bimanual movements in the elderly: Brain regions exhibiting age‐related increases in activity,frequency‐induced neural modulation,and task‐specific compensatory recruitment

Coordinated hand use is an essential component of many activities of daily living. Although previous studies have demonstrated age‐related behavioral deficits in bimanual tasks, studies that assessed the neural basis underlying such declines in function do not exist. In this fMRI study, 16 old and 16 young healthy adults performed bimanual movements varying in coordination complexity (i.e., in‐phase, antiphase) and movement frequency (i.e., 45, 60, 75, 90% of critical antiphase speed) demands. Difficulty was normalized on an individual subject basis leading to group performances (measured by phase accuracy/stability) that were matched for young and old subjects. Despite lower overall movement frequency, the old group “overactivated” brain areas compared with the young adults. These regions included the supplementary motor area, higher order feedback processing areas, and regions typically ascribed to cognitive functions (e.g., inferior parietal cortex/dorsolateral prefrontal cortex). Further, age‐related increases in activity in the supplementary motor area and left secondary somatosensory cortex showed positive correlations with coordinative ability in the more complex antiphase task, suggesting a compensation mechanism. Lastly, for both old and young subjects, similar modulation of neural activity was seen with increased movement frequency. Overall, these findings demonstrate for the first time that bimanual movements require greater neural resources for old adults in order to match the level of performance seen in younger subjects. Nevertheless, this increase in neural activity does not preclude frequency‐induced neural modulations as a function of increased task demand in the elderly. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Interests shape how adolescents pay attention: the interaction of motivation and top‐down attentional processes in biasing sensory activations to anticipated events

The voluntary allocation of attention to environmental inputs is a crucial mechanism of healthy cognitive functioning, and is probably influenced by an observer's level of interest in a stimulus. For example, an individual who is passionate about soccer but bored by botany will obviously be more attentive at a soccer match than an orchid show. The influence of monetary rewards on attention has been examined, but the impact of more common motivating factors (i.e. the level of interest in the materials under observation) remains unclear, especially during development. Here, stimulus sets were designed based on survey measures of the level of interest of adolescent participants in several item classes. High‐density electroencephalography was recorded during a cued spatial attention task in which stimuli of high or low interest were presented in separate blocks. The motivational impact on performance of a spatial attention task was assessed, along with event‐related potential measures of anticipatory top‐down attention. As predicted, performance was improved for the spatial target detection of high interest items. Further, the impact of motivation was observed in parieto‐occipital processes associated with anticipatory top‐down spatial attention. The anticipatory activity over these regions was also increased for high vs. low interest stimuli, irrespective of the direction of spatial attention. The results also showed stronger anticipatory attentional and motivational modulations over the right vs. left parieto‐occipital cortex. These data suggest that motivation enhances top‐down attentional processes, and can independently shape activations in sensory regions in anticipation of events. They also suggest that attentional functions across hemispheres may not fully mature until late adolescence.     

Alterations of the salience network in obesity: A resting‐state fMRI study

Obesity is a major health problem in modern societies. It has been related to abnormal functional organization of brain networks believed to process homeostatic (internal) and/or salience (external) information. This study used resting‐state functional magnetic resonance imaging analysis to delineate possible functional changes in brain networks related to obesity. A group of 18 healthy adult participants with obesity were compared with a group of 16 lean participants while performing a resting‐state task, with the data being evaluated by independent component analysis. Participants also completed a neuropsychological assessment. Results showed that the functional connectivity strength of the putamen nucleus in the salience network was increased in the obese group. We speculate that this abnormal activation may contribute to overeating through an imbalance between autonomic processing and reward processing of food stimuli. A correlation was also observed in obesity between activation of the putamen nucleus in the salience network and mental slowness, which is consistent with the notion that basal ganglia circuits modulate rapid processing of information. Hum Brain Mapp 34:2786–2797, 2013. © 2012 Wiley Periodicals, Inc.     

Subclinical cognitive decline in middle‐age is associated with reduced task‐induced deactivation of the brain's default mode network

Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task‐induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual‐motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging. Hum Brain Mapp 35:4488–4498, 2014. © 2014 Wiley Periodicals, Inc.     

The role of the dorsal anterior insula in sexual risk: Evidence from an erotic Go/NoGo task and real‐world risk‐taking

The insula plays an important role in response inhibition. Most relevant here, it has been proposed that the dorsal anterior insular cortex (dAIC) plays a central role in a salience network that is responsible for switching between the default mode network and the executive control network. However, the insula's role in sexually motivated response inhibition has not yet been studied. In this study, eighty‐five 18‐ to 30‐year‐old sexually active men who have sex with men (MSM) performed an erotic Go/NoGo task while in an MRI scanner. Participants' real‐world sexual risk‐taking (frequency of condomless anal intercourse over the past 90 days) was then correlated with their neural activity during the task. We found greater activity in bilateral anterior insular cortex (both dorsal and ventral) on contrasts with stronger motivational information (attractive naked male pictures versus pictures of clothed, middle‐aged females) and on contrasts requiring greater response inhibition (NoGo versus Go). We also found that activity in the right dAIC was negatively correlated with participants' real‐world sexual risk‐taking. Our results confirmed the involvement of the insular cortex in motivated response inhibition. Especially, the decreased right dAIC activity may reduce the likelihood that the executive control network will come online when individuals are faced with situations requiring inhibitory control and thus lead them to make more risky choices.     

Broadband neurophysiological abnormalities in the medial prefrontal region of the default‐mode network in adults with ADHD

Previous investigations of the default‐mode network (DMN) in persons with attention‐deficit/hyperactivity disorder (ADHD) have shown reduced functional connectivity between the anterior and posterior aspects. This finding was originally demonstrated in adults with ADHD, then in youth with ADHD, and has been tentatively linked to ultra low frequency oscillations within the DMN. The current study evaluates the specificity of DMN abnormalities to neuronal oscillations in the ultra low frequency range, and examines the regional specificity of these DMN aberrations in medicated and unmedicated adults with, and those without ADHD. An individually matched sample of adults with and without ADHD completed 6‐minute sessions of resting‐state magnetoencephalography (MEG). Participants with ADHD were known responders to stimulant medications and completed two sessions (predrug/postdrug). MEG data were coregistered to the participant's MRI, corrected for head motion, fitted to a regional‐level source model, and subjected to spectral analyses to extract neuronal population activity in regions of the DMN. The unmedicated adults with ADHD exhibited broadband deficits in medial prefrontal cortices (MPFC), but not other DMN regions compared to adults without ADHD. Unmedicated patients also showed abnormal cross‐frequency coupling in the gamma range between the MPFC and posterior cingulate areas, and disturbed balance within the DMN as activity in posterior regions was stronger than frontal regions at beta and lower frequencies, which dissipated at higher γ‐frequencies. Administration of pharmacotherapy significantly increased prefrontal alpha activity (8–14 Hz) in adults with ADHD, and decreased the cross‐frequency gamma coupling. These results indicate that neurophysiological aberrations in the DMN of patients with ADHD are not limited to ultra slow oscillations, and that they may be primarily attributable to abnormal broadband activity in the MPFC. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Functional centrality of amygdala,striatum and hypothalamus in a “small‐world” network underlying joy: An fMRI study with music

Current knowledge about small‐world networks underlying emotions is sparse, and confined to functional magnetic resonance imaging (fMRI) studies using resting‐state paradigms. This fMRI study applied Eigenvector Centrality Mapping (ECM) and functional connectivity analysis to reveal neural small‐world networks underlying joy and fear. Joy and fear were evoked using music, presented in 4‐min blocks. Results show that the superficial amygdala (SF), laterobasal amygdala (LB), striatum, and hypothalamus function as computational hubs during joy. Out of these computational hubs, the amygdala nuclei showed the highest centrality values. The SF showed functional connectivity during joy with the mediodorsal thalamus (MD) and nucleus accumbens (Nac), suggesting that SF, MD, and Nac modulate approach behavior in response to positive social signals such as joyful music. The striatum was functionally connected during joy with the LB, as well as with premotor cortex, areas 1 and 7a, hippocampus, insula and cingulate cortex, showing that sensorimotor, attentional, and emotional processes converge in the striatum during music perception. The hypothalamus showed functional connectivity during joy with hippocampus and MD, suggesting that hypothalamic endocrine activity is modulated by hippocampal and thalamic activity during sustained periods of music‐evoked emotion. Our study indicates high centrality of the amygdala nuclei groups within a functional network underlying joy, suggesting that these nuclei play a central role for the modulation of emotion‐specific activity within this network. Hum Brain Mapp 35:3485–3498, 2014. © 2013 Wiley Periodicals, Inc .     

Age‐related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice

Even in the absence of neurodegenerative diseases, progressing age often coincides with cognitive decline and morphological changes. However, longitudinal studies that directly link these two processes are missing. In this proof‐of‐concept study we therefore performed repeated within‐subject testing of healthy male R26R mice in a spatial learning task in combination with manganese‐enhanced volumetric MRI analyses at the ages of 8, 16, and 24 months. We grouped the mice into good and poor performers (n = 6, each), based on their spatial learning abilities at the age of 24 months. Using this stratification, we failed to detect a priori volume differences, but observed a significant decrease in total hippocampal volume over time for both groups. Interestingly, this volume decrease was specific for the dorsal hippocampus and significantly accelerated in poor performers between 16 and 24 months of age. This is the first time that individual changes in hippocampal volume were traced alongside cognitive performance within the same subjects over 1½ years. Our study points to a causal link between volume loss of the dorsal hippocampus and cognitive impairments. In addition, it suggests accelerated degenerative processes rather than a priori volume differences as determining trajectories of age‐related cognitive decline. Despite the relatively small sample sizes, the strong behavioral and moderate morphological alterations demonstrate the general feasibility of longitudinal studies of age‐related decline in cognition and hippocampus integrity. © 2016 Wiley Periodicals, Inc.     

Cortical network dysfunction in musicogenic epilepsy reflecting the role of snowballing emotional processes in seizure generation: an fMRI‐EEG study

Aim. Patients suffering from musicogenic epilepsy have focal seizures triggered by auditory stimuli. In some of these patients, the emotions associated with the music appear to play a role in the process triggering the seizure, however, the significance of these emotions and the brain regions involved are unclear. In order to shed some light on this, we conducted fMRI and EEG in a case of musicogenic epilepsy. Methods. In a 32‐year‐old male patient with seizures induced by a specific piece of Russian music, we performed video‐EEG monitoring as well as simultaneous fMRI and EEG registration. Results. Video‐EEG monitoring revealed a left temporo‐frontal epileptogenic focus. During fMRI‐EEG co‐registration, BOLD signal alterations were not only found in the epileptogenic focus but also in areas known for their role in the processing of emotions. Prior to a seizure in some of these areas, BOLD contrasts exponentially increased or decreased. Conclusion. These results suggest that in our case, dysfunction of the regulation processes of the musically‐induced emotions, and not the musical stimulus itself, led to the seizures.