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The appropriate assessment of threat and safety is important for decision‐making but might be altered in old age due to neurobiological changes. The literature on threat and safety processing in older adults is sparse and it is unclear how healthy ageing affects the brain's functional networks associated with affective processing. We measured skin conductance responses as an indicator of sympathetic arousal and used functional magnetic resonance imaging and independent component analysis to compare young and older adults' functional connectivity in the default mode (DMN) and salience networks (SN) during a threat conditioning and extinction task. While our results provided evidence for differential threat processing in both groups, they also showed that functional connectivity within the SN – but not the DMN – was weaker during threat processing in older compared to young adults. This reduction of within‐network connectivity was accompanied by an age‐related decrease in low frequency spectral power in the SN and a reduction in inter‐network connectivity between the SN and DMN during threat and safety processing. Similarly, we found that skin conductance responses were generally lower in older compared to young adults. Our results are the first to demonstrate age‐related changes in brain activation during aversive conditioning and suggest that the ability to adaptively filter affective information is reduced in older adults., We measured skin conductance responses as an indicator of sympathetic arousal and used functional magnetic resonance imaging and independent component analysis to compare young and older adults’ functional connectivity in the default mode (DMN) and salience networks (SN) during a threat conditioning and extinction task. While our results provided evidence for differential threat processing in both groups, they also showed that functional connectivity within the SN – but not the DMN – was weaker during threat processing in older compared to young adults. Our results are the first to demonstrate age‐related changes in brain activation during aversive conditioning and suggest that the ability to adaptively filter affective information is reduced in older adults.

Background/objectives Obesity affects more than forty percent of adults over the age of sixty. Aberrant eating styles such as disinhibition have been associated with the engagement of brain networks underlying executive functioning, attentional control, and interoception. However, these effects have been exclusively studied in young samples overlooking those most at risk of obesity related harm. Methods Here we assessed associations between resting-state functional connectivity and disinhibited eating (using the Three Factor Eating Questionnaire) in twenty-one younger (aged 19–34 years, BMI range: 18–31) and twenty older (aged 60–73 years, BMI range: 19–32) adults matched for BMI. The Alternative Healthy Eating Index was used to quantify diet quality. Results Older, compared to younger, individuals reported lower levels of disinhibited eating, consumed a healthier diet, and had weaker connectivity in the frontoparietal (FPN) and default mode (DMN) networks. In addition, associations between functional connectivity and eating behaviour differed between the two age groups. In older adults, disinhibited eating was associated with weaker connectivity in the FPN and DMN––effects that were absent in the younger sample. Importantly, these effects could not be explained by differences in habitual diet. Conclusions These findings point to a change in interoceptive signalling as part of the ageing process, which may contribute to behavioural changes in energy intake, and highlight the importance of studying this under researched population.

Epilepsy surgery is the best therapeutic option for patients with drug-resistant focal epilepsy. During presurgical investigation, interictal spikes can provide important information on eligibility, lateralisation and localisation of the surgical target. However, their relationship to epileptogenic tissue is variable. Interictal spikes with concurrent high-frequency oscillations (HFOs) have been postulated to reflect epileptogenic tissue more reliably. Here, we studied the voltage distribution of scalp-recorded spikes with and without concurrent HFO and identified their respective haemodynamic correlates using simultaneous electroencephalography and functional Magnetic Resonance Imaging (EEG-fMRI).The scalp topography of spikes with and without concurrent HFOs were assessed in 31 consecutive patients with focal drug-resistant epilepsy who showed interictal spikes during presurgical evaluation. Simultaneous EEG-fMRI was then used in 17 patients with spikes and concurrent HFOs. Haemodynamic changes were obtained from the spatial correlation between the patient-specific voltage map of each spike population and the intra-scanner EEG. The haemodynamic response of spikes with and without HFOs were compared in terms of their spatial similarity, strength, the distance between activation peaks and concordance with interictal localisation.Twenty-five patients showed spikes with and without concurrent HFOs. Among patients with both types of spikes, most spikes were not associated with HFOs (p 0.0001, Mann-Whitney test). Twenty of the 25 patients showed an average of 8 ± 6 (standard deviation) electrodes with significant voltage differences (p = 0.025, permutation test corrected for multiple comparisons) on scalp electrodes within and distant to the spike field. Comparing the haemodynamic response between both spike populations, we found no significant differences in the peak strength (p = 0.71, Mann-Whitney test), spatial distribution (p = 0.113, One-sample Wilcoxon test) and distance between activation peaks (p = 0.5, One-sample Wilcoxon test), with all peaks being co-localised in the same lobe.Our data showed that spikes with and without HFOs have different scalp voltage distributions. However, when assessing the haemodynamic changes of each spike type, we found that both elicit similar haemodynamic changes and share high spatial similarity suggesting that the epileptic networks of spikes with and without HFOs have the same underlying neural substrate.

Age-related decline in motor function is associated with over-activation of the sensorimotor circuitry. Using a multimodal MEG-fMRI paradigm, we investigated whether this neural over-recruitment in old age would be related to changes in movement-related beta desynchronization (MRBD), a correlate of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), and whether it would characterize compensatory recruitment or a reduction in neural specialization (dedifferentiation). We used MEG to assess age-related changes in beta band oscillations in primary motor cortices, fMRI to localize age-related changes in brain activity, and the Finger Configuration Task to measure task performance during overt and covert motor processing: motor execution (ME) and motor imagery (MI). The results are threefold: first, showing age-related neuroplasticity during ME of older adults, compared to young adults, as evidenced by increased MRBD in motor cortices and over-recruitment of sensorimotor areas; second, showing similar age-related neuroplastic changes during MI; and finally, showing signs of dedifferentiation during ME in older adults whose performance negatively correlated with connectivity to bilateral primary motor cortex. Together, these findings demonstrate that elevated MRBD levels, reflecting greater GABAergic inhibitory activity, and over-activation of the sensorimotor network during ME may not be compensatory, but rather might reflect an age-related decline of the quality of the underlying neural signal.

Purpose Quantitative susceptibility mapping is a technique to estimate the magnetic property of tissue with particularly high sensitivity at ultra-high field. However, a key challenge at ultra-high field is the combination of phase data acquired using phased array receive coils. Several methods for combining phase data have been proposed, but the influence of coil combination choices on susceptibility quantitation has not been studied systematically. Methods We combined phase data using COMPOSER (COMbining Phase data using a Short Echo-time Reference scan) and a reference-free channel-by-channel method. We investigated the effect of the chosen combination method on susceptibility results in a group of 28 participants at 7 Tesla. Results Our results show that reference scans can bias susceptibility values. Although the proposed reference-free channel-by-channel method cannot remove transmit field phase, it shows comparable results to the COMPOSER method in which a high-resolution ultrashort echo-time reference scan was used. Conclusions We conclude that ultrashort echo-time reference scans reduce quantitation bias and remove the transmit field phase when using COMPOSER to combine phase data, and not combining the phase data before susceptibility processing avoids this bias, resulting in comparable results. Magn Reson Med 79:97–107, 2018. © 2017 InternationalSociety for Magnetic Resonance in Medicine.

Logopenic progressive aphasia (LPA) is a neurodegenerative disorder characterised by profound naming and sentence repetition disturbances, attributable to disproportionately left-sided temporo-parietal atrophy. Accumulating evidence suggests, in addition to language impairments, the presence of stark verbal and nonverbal episodic memory dysfunction in LPA. The neurocognitive bases of such impairments, however, remain to be clarified. Here, we characterised episodic memory disruption and its corresponding grey and white matter correlates in the LPA syndrome. Nineteen LPA patients were contrasted with 23 matched typical Alzheimer's disease (AD) patients and 31 healthy Controls on standardized verbal and nonverbal episodic delayed recall measures. Participants further underwent structural magnetic resonance and diffusion-weighted imaging. Significant verbal memory deficits were evident in both patient groups, with LPA patients performing at an intermediate level to AD and Controls. For nonverbal memory, however, LPA performance was indistinguishable from that of AD, with both groups displaying marked impairments relative to Controls. Whole-brain voxel-based morphometry analyses revealed significant left temporo-parietal and left hippocampal atrophy in the LPA group. Covariate analyses showed that verbal and nonverbal amnesia in LPA correlated with grey matter integrity of bilateral frontoparietal and left medial temporal lobe regions. Notably, the common regions underpinning verbal and nonverbal memory dysfunction in LPA were the left orbitofrontal cortex and bilateral angular gyri in the inferior parietal cortex. The bilateral angular gyri, along with prefrontal and hippocampal regions further emerged as disease-general correlates of verbal and nonverbal memory performance. Alterations in mean diffusivity in structural connections between the left angular gyrus and medial temporal lobes were further associated with verbal memory performance in all participants. Our findings reveal, for the first time, the presence of pervasive memory impairments in LPA mediated by degeneration of a distributed prefrontal-hippocampal-parietal network, and disrupted parieto-hippocampal structural connectivity.

The processes that characterize the neural development of long-term memory (LTM) are largely unknown. In young adults, the degree of activation of a single large-scale memory network corresponds to the level of contextual detail involved; thus, differentiating between autobiographical, episodic, and semantic retrieval. In contrast to young adults, children and adolescents retrieve fewer contextual details, suggesting that they might not yet engage the entire memory circuitry and that this brain recruitment might lack the characteristic contextual differentiation found in adults. Twenty-one children (10-12 years of age), 20 adolescents (14-16 years of age), and 22 young adults (20-35 years of age) were assessed on a previously validated LTM retrieval task, while their brain activity was measured with functional magnetic resonance imaging. The results demonstrate that children, adolescents, and adults recruit a left-lateralized subset of the large-scale memory network, comprising semantic and language processing regions, with neither developmental group showing evidence of contextual differentiation within this network. Additionally, children and adolescents recruited occipital and parietal regions during all memory recall conditions, in contrast to adults who engaged the entire large-scale memory network, as described previously. Finally, a significant covariance between age and brain activation indicates that the reliance on occipital and parietal regions during memory retrieval decreases with age. These results suggest that both children and adolescents rely on semantic processing to retrieve long-term memories, which, we argue, may restrict the integration of contextual detail required for complex episodic and autobiographical memory retrieval.

Healthy aging is accompanied by neurobiological changes that affect the brain's functional organization and the individual's cognitive abilities. The aim of this study was to investigate the effect of global age-related differences in the cortical white and gray matter on neural activity in three key large-scale networks. We used functional-structural covariance network analysis to assess resting state activity in the default mode network (DMN), the fronto-parietal network (FPN), and the salience network (SN) of young and older adults. We further related this functional activity to measures of cortical thickness and volume derived from structural MRI, as well as to measures of white matter integrity (fractional anisotropy [FA], mean diffusivity [MD], and radial diffusivity [RD]) derived from diffusion-weighted imaging. First, our results show that, in the direct comparison of resting state activity, young but not older adults reliably engage the SN and FPN in addition to the DMN, suggesting that older adults recruit these networks less consistently. Second, our results demonstrate that age-related decline in white matter integrity and gray matter volume is associated with activity in prefrontal nodes of the SN and FPN, possibly reflecting compensatory mechanisms. We suggest that age-related differences in gray and white matter properties differentially affect the ability of the brain to engage and coordinate large-scale functional networks that are central to efficient cognitive functioning.

The controlled semantic cognition framework proposes that the ventral anterior temporal lobes (vATL) in the left and right hemisphere function as an integrated hub region supporting transmodal semantic representations. The clinical evidence for the transmodal function of vATL is largely based on studies of semantic dementia patients with severe anomia, who also show impaired performance on nonverbal tasks that involve the retrieval of knowledge about objects and their prototypical use, such as the production of tool use pantomimes. Yet, evidence from patients with apraxia and functional neuroimaging studies in healthy adults does not implicate vATL in pantomime production. We, therefore, compared semantic retrieval of object-action associations for overt verb and pantomime production from picture and word stimuli. Our results show that, independent of stimulus modality, the retrieval of object-action associations for verb, but not pantomime, production is related to activity in bilateral vATL. Bilateral vATL activation was also observed for meaningless verbal responses that did not require the retrieval of object-action associations. Taken together, our results suggest that bilateral vATL is not engaged in the retrieval of object-action associations per se, but rather supports semantic representations that are functionally specialized for language. These findings have implications for the semantic cognition framework and our understanding of the dependence of conceptual knowledge on language.

ObjectiveMinimum deformation averaging (MDA) procedures exploit the information contained in inter-individual variations to generate high-resolution, high-contrast models through iterative model building. However, MDA models built from different image contrasts reside in disparate spaces and their complementary information cannot be utilized easily. The aim of this work was to develop an algorithm for the non-linear alignment of two MDA models with different contrasts to create a high-resolution in vivo model of the human hippocampus with a spatial resolution of 300 μm.MethodsA Turbo Spin Echo MDA model covering the hippocampus was contrast matched to a whole-brain MP2RAGE MDA model and aligned using cross-correlation and non-linear transformation. The contrast matching algorithm followed a global voxel location-based approach to estimate the relationship between intensity values of the two models. The performance of the algorithm was evaluated by comparing it to a non-linear registration obtained using mutual information without contrast matching. The complimentary information from both contrasts was then utilized in an automated hippocampal subfield segmentation pipeline.ResultsThe contrast of the Turbo Spin Echo MDA model could successfully be matched to the MP2RAGE MDA model. Registration using cross correlation provided more accurate alignment of the models compared to a mutual information based approach. The segmentation using ASHS resulted in hippocampal subfield delineations that resembled the tissue boundaries observed in the Turbo Spin Echo MDA model.ConclusionThe developed contrast matching algorithm facilitated the creation of a high-resolution multi-modal in vivo MDA model of the human hippocampus. This model can be used to improve algorithms for hippocampal subfield segmentation and could potentially support the early detection of neurodegenerative diseases.

Co-speech gestures constitute a unique form of multimodal communication because here the hand movements are temporally synchronized and semantically integrated with speech. Recent neuroimaging studies indicate that the perception of co-speech gestures might engage a core set of frontal, temporal, and parietal areas. However, no study has compared the neural processes during perception of different types of co-speech gestures, such as beat, deictic, iconic, and metaphoric co-speech gestures. The purpose of this study was to review the existing literature on the neural correlates of co-speech gesture perception and to test whether different types of co-speech gestures elicit a common pattern of brain activity in the listener. To this purpose, we conducted a meta-analysis of neuroimaging studies, which used different types of co-speech gestures to investigate the perception of multimodal (co-speech gestures) in contrast to unimodal (speech or gestures) stimuli. The results show that co-speech gesture perception consistently engages temporal regions related to auditory and movement perception as well as frontal-parietal regions associated with action understanding. The results of this study suggest that brain regions involved in multisensory processing and action understanding constitute the general core of co-speech gesture perception.

Co-speech gestures have been shown to interact with working memory (WM). However, no study has investigated whether there are individual differences in the effect of gestures on WM. Combining a novel gesture/no-gesture task and an operation span task, we examined the differences in WM accuracy between individuals who gestured and individuals who did not gesture in relation to their WM capacity. Our results showed individual differences in the gesture effect on WM. Specifically, only individuals with low WM capacity showed a reduced WM accuracy when they did not gesture. Individuals with low WM capacity who did gesture, as well as high-capacity individuals (irrespective of whether they gestured or not), did not show the effect. Our findings show that the interaction between co-speech gestures and WM is affected by an individual's WM load.

In social interactions, individuals who are slower at differentiating between facial expressions signalling direct and indirect threat might be at a serious disadvantage. However, the neurobiological underpinnings of individual differences in face processing are not yet fully understood. The aim of this study was to use multimodal neuroimaging to investigate how the speed of emotion recognition is related to the structural and functional connectivity underlying the differentiation of direct and indirect threat displays. Our results demonstrate that individuals, who are faster at discriminating angry faces, engaged areas of the extended emotional system more strongly than individuals with slower reaction times, showed higher white matter integrity in the inferior longitudinal fasciculus (ILF), as well as stronger functional connectivity with the right amygdala. In contrast, individuals, who were faster at discriminating fearful faces, engaged visual-attentional regions outside of the face processing network more strongly than individuals with slower reaction times, showed higher white matter integrity in the ILF, as well as reduced functional connectivity with the right amygdala. Our findings suggest that the high survival value of rapid and appropriate responses to threat has defined but separate neurobiological correlates for angry and fearful facial expressions.

Safety learning describes the ability to learn that certain cues predict the absence of a dangerous or threatening event. Although incidental observations of activity within the default mode network (DMN) during the processing of safety cues have been reported previously, there is as yet no evidence demonstrating that the DMN plays a functional rather than a corollary role in safety learning. Using functional magnetic resonance imaging and a Pavlovian fear conditioning and extinction paradigm, we investigated the neural correlates of danger and safety learning. Our results provide evidence for a functional role of the DMN by showing that (i) the DMN is activated by safety but not danger cues, (ii) the DMN is anti‐correlated with a fear‐processing network, and (iii) DMN activation increases with safety learning. Based on our results, we formulate a novel proposal, arguing that activity within the DMN supports the contextualization of safety memories, constrains the generalization of fear, and supports adaptive fear learning. Our findings have important implications for our understanding of affective and stress disorders, which are characterized by aberrant DMN activity, as they suggest that therapies targeting the DMN through mindfulness practice or brain stimulation might help prevent pathological over‐generalization of fear associations. Hum Brain Mapp 38:1082–1091, 2017. © 2016 Wiley Periodicals, Inc.

The consequences of losing the ability to move a limb are traumatic. One approach that examines the impact of pathological limb nonuse on the brain involves temporary immobilization of a healthy limb. Here, we investigated immobilization-induced plasticity in the motor imagery (MI) circuitry during hand immobilization. We assessed these changes with a multimodal paradigm, using functional magnetic resonance imaging (fMRI) to measure neural activation, magnetoencephalography (MEG) to track neuronal oscillatory dynamics, and transcranial magnetic stimulation (TMS) to assess corticospinal excitability. fMRI results show a significant decrease in neural activation for MI of the constrained hand, localized to sensorimotor areas contralateral to the immobilized hand. MEG results show a significant decrease in beta desynchronization and faster resynchronization in sensorimotor areas contralateral to the immobilized hand. TMS results show a significant increase in resting motor threshold in motor cortex contralateral to the constrained hand, suggesting a decrease in corticospinal excitability in the projections to the constrained hand. These results demonstrate a direct and rapid effect of immobilization on MI processes of the constrained hand, suggesting that limb nonuse may not only affect motor execution, as evidenced by previous studies, but also MI. These findings have important implications for the effectiveness of therapeutic approaches that use MI as a rehabilitation tool to ameliorate the negative effects of limb nonuse.

The perception of co-speech gestures, i.e., hand movements that co-occur with speech, has been investigated by several studies. The results show that the perception of co-speech gestures engages a core set of frontal, temporal, and parietal areas. However, no study has yet investigated the neural processes underlying the production of co-speech gestures. Specifically, it remains an open question whether Broca’s area is central to the coordination of speech and gestures as has been suggested previously. The objective of this study was to use functional magnetic resonance imaging to (i) investigate the regional activations underlying overt production of speech, gestures, and co-speech gestures, and (ii) examine functional connectivity with Broca’s area. We hypothesized that co-speech gesture production would activate frontal, temporal, and parietal regions that are similar to areas previously found during co-speech gesture perception and that both speech and gesture as well as co-speech gesture production would engage a neural network connected to Broca’s area. Whole-brain analysis confirmed our hypothesis and showed that co-speech gesturing did engage brain areas that form part of networks known to subserve language and gesture. Functional connectivity analysis further revealed a functional network connected to Broca’s area that is common to speech, gesture, and co-speech gesture production. This network consists of brain areas that play essential roles in motor control, suggesting that the coordination of speech and gesture is mediated by a shared motor control network. Our findings thus lend support to the idea that speech can influence co-speech gesture production on a motoric level.

The relations among structural integrity, functional connectivity (FC), and cognitive performance in the aging brain are still understudied. Here, we used multimodal and multivariate approaches to specifically examine age-related changes in task-related FC, gray-matter volumetrics, white-matter integrity, and performance. Our results are two-fold, showing (i) age-related differences in FC of the working memory network and (ii) age-related recruitment of a compensatory network associated with better accuracy on the task. Increased connectivity in the compensatory network correlates positively with preserved white-matter integrity in bilateral frontoparietal tracks and with larger gray-matter volume of right inferior parietal lobule. These findings demonstrate the importance of structural integrity and FC in working memory performance associated with healthy aging.

The temporal scale of neuroplasticity following acute alterations in brain structure due to neurosurgical intervention is still under debate. We conducted a longitudinal study with the objective of investigating the postoperative changes in a patient who underwent cerebrovascular surgery and who subsequently lost proprioception in the fingers of her right hand. The results show increased activation in contralesional somatosensory areas, additional recruitment of premotor and posterior parietal areas, and changes in functional connectivity with left postcentral gyrus. These findings demonstrate long-term modifications of cortical organization and as such have important implications for treatment strategies for patients with brain injury.

The study of the production of co-speech gestures (CSGs), i.e., meaningful hand movements that often accompany speech during everyday discourse, provides an important opportunity to investigate the integration of language, action, and memory because of the semantic overlap between gesture movements and speech content. Behavioral studies of CSGs and speech suggest that they have a common base in memory and predict that overt production of both speech and CSGs would be preceded by neural activity related to memory processes. However, to date the neural correlates and timing of CSG production are still largely unknown. In the current study, we addressed these questions with magnetoencephalography and a semantic association paradigm in which participants overtly produced speech or gesture responses that were either meaningfully related to a stimulus or not. Using spectral and beamforming analyses to investigate the neural activity preceding the responses, we found a desynchronization in the beta band (15–25 Hz), which originated 900 ms prior to the onset of speech and was localized to motor and somatosensory regions in the cortex and cerebellum, as well as right inferior frontal gyrus. Beta desynchronization is often seen as an indicator of motor processing and thus reflects motor activity related to the hand movements that gestures add to speech. Furthermore, our results show oscillations in the high gamma band (50–90 Hz), which originated 400 ms prior to speech onset and were localized to the left medial temporal lobe. High gamma oscillations have previously been found to be involved in memory processes and we thus interpret them to be related to contextual association of semantic information in memory. The results of our study show that high gamma oscillations in medial temporal cortex play an important role in the binding of information in human memory during speech and CSG production.

Representations are internal models of the environment that can provide guidance to a behaving agent, even in the absence of sensory information. It is not clear how representations are developed and whether or not they are necessary or even essential for intelligent behavior. We argue here that the ability to represent relevant features of the environment is the expected consequence of an adaptive process, give a formal definition of representation based on information theory, and quantify it with a measure R. To measure how R changes over time, we evolve two types of networks---an artificial neural network and a network of hidden Markov gates---to solve a categorization task using a genetic algorithm. We find that the capacity to represent increases during evolutionary adaptation, and that agents form representations of their environment during their lifetime. This ability allows the agents to act on sensorial inputs in the context of their acquired representations and enables complex and context-dependent behavior. We examine which concepts (features of the environment) our networks are representing, how the representations are logically encoded in the networks, and how they form as an agent behaves to solve a task. We conclude that R should be able to quantify the representations within any cognitive system, and should be predictive of an agent's long-term adaptive success., Comment: 36 pages, 10 figures, one Table