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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.

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.

Highlights • The irritative zone differs on Electrical Source Imaging (ESI) and EEG-fMRI. • Findings differ in functional connectivity and show low temporal correlation. • ESI and EEG-fMRI reveal distinct aspects of the irritative zone. • The differences may reflect differences in temporal resolution of the techniques., Summary Objective The irritative zone - the area generating epileptic spikes - can be studied non-invasively during the interictal period using Electrical Source Imaging (ESI) and simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI). Although the techniques yield results which may overlap spatially, differences in spatial localization of the irritative zone within the same patient are consistently observed. To investigate this discrepancy, we used Blood Oxygenation Level Dependent (BOLD) functional connectivity measures to examine the underlying relationship between ESI and EEG-fMRI findings. Methods Fifteen patients (age 20–54), who underwent presurgical epilepsy investigation, were scanned using a single-session resting-state EEG-fMRI protocol. Structural MRI was used to obtain the electrode localisation of a high-density 64-channel EEG cap. Electrical generators of interictal epileptiform discharges were obtained using a distributed local autoregressive average (LAURA) algorithm as implemented in Cartool EEG software. BOLD activations were obtained using both spike-related and voltage-map EEG-fMRI analysis. The global maxima of each method were used to investigate the temporal relationship of BOLD time courses and to assess the spatial similarity using the Dice similarity index between functional connectivity maps. Results ESI, voltage-map and spike-related EEG-fMRI methods identified peaks in 15 (100%), 13 (67%) and 8 (53%) of the 15 patients, respectively. For all methods, maxima were localised within the same lobe, but differed in sub-lobar localisation, with a median distance of 22.8 mm between the highest peak for each method. The functional connectivity analysis showed that the temporal correlation between maxima only explained 38% of the variance between the time course of the BOLD response at the maxima. The mean Dice similarity index between seed-voxel functional connectivity maps showed poor spatial agreement. Significance Non-invasive methods for the localisation of the irritative zone have distinct spatial and temporal sensitivity to different aspects of the local cortical network involved in the generation of interictal epileptiform discharges.

Neuroimaging studies have shown that the neural mechanisms of motor imagery (MI) overlap substantially with the mechanisms of motor execution (ME). Surprisingly, however, the role of several regions of the motor circuitry in MI remains controversial, a variability that may be due to differences in neuroimaging techniques, MI training, instruction types, or tasks used to evoke MI. The objectives of this study were twofold: (i) to design a novel task that reliably invokes MI, provides a reliable behavioral measure of MI performance, and is transferable across imaging modalities; and (ii) to measure the common and differential activations for MI and ME with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). We present a task in which it is difficult to give accurate responses without the use of either motor execution or motor imagery. The behavioral results demonstrate that participants performed similarly on the task when they imagined vs. executed movements and this performance did not change over time. The fMRI results show a spatial overlap of MI and ME in a number of motor and premotor areas, sensory cortices, cerebellum, inferior frontal gyrus, and ventrolateral thalamus. MI uniquely engaged bilateral occipital areas, left parahippocampus, and other temporal and frontal areas, whereas ME yielded unique activity in motor and sensory areas, cerebellum, precuneus, and putamen. The MEG results show a robust event-related beta band desynchronization in the proximity of primary motor and premotor cortices during both ME and MI. Together, these results further elucidate the neural circuitry of MI and show that our task robustly and reliably invokes motor imagery, and thus may prove useful for interrogating the functional status of the motor circuitry in patients with motor disorders.

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 high evolutionary value of learning when to respond to threats or when to inhibit previously learned associations after changing threat contingencies is reflected in dedicated networks in the animal and human brain. Recent evidence further suggests that adaptive learning may be dependent on the dynamic interaction of meta-stable functional brain networks. However, it is still unclear which functional brain networks compete with each other to facilitate associative learning and how changes in threat contingencies affect this competition. The aim of this study was to assess the dynamic competition between large-scale networks related to associative learning in the human brain by combining a repeated differential conditioning and extinction paradigm with independent component analysis of functional magnetic resonance imaging data. The results (i) identify three task-related networks involved in initial and sustained conditioning as well as extinction, and demonstrate that (ii) the two main networks that underlie sustained conditioning and extinction are anti-correlated with each other and (iii) the dynamic competition between these two networks is modulated in response to changes in associative contingencies. These findings provide novel evidence for the view that dynamic competition between large-scale functional networks differentiates fear conditioning from extinction learning in the healthy brain and suggest that dysfunctional network dynamics might contribute to learning-related neuropsychiatric disorders.

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 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.