The effect of negative arousal on declarative memory.

Arousing events influence retrieval success, with a number of studies supporting a context-dependent effect of arousal on episodic memory retrieval. An improvement in speed and accuracy of episodic memories is observed when negative arousal is attached to them. In contrast, enhancing effects of negative arousal have not been reported to improve semantic memory retrieval. Episodic and semantic memory are highly interactive and yet differ based on their embedded contextual content. Although differences in brain activity exist between episodic and semantic memory, the two types of memory retrieval are part of a common long-term memory system. Considering the shared processes between episodic and semantic memory, the objectives of the current study were twofold: i) to examine, employing a novel paradigm, whether performance on episodic and semantic memory retrieval would be influenced differently by varying levels of arousal, between negative and neutral valence; and ii) to explore the neural patterns underlying these processes. Forty-seven healthy young adults were recruited and completed the experiment in the MRI scanner. The results demonstrated a negative arousal effect on the brain circuitry subserving both memory conditions as well as on behavioural performance, as indicated by better accuracy and faster reaction times. The study provides an insight into the role of negative arousal in memory processes and contributes to our understanding of the interplay between cognitive and emotional factors in memory modulation. Our work also highlights the highly interactive nature of episodic and semantic memory, and emphasises the importance in understanding how negative arousal interacts with the contextual content of a memory, on a behavioural and neurofunctional level.

The effects of age bias on neural correlates of successful and unsuccessful response inhibition in younger and older adults.

Facilitating communication between generations has become increasingly important. However, individuals often demonstrate a preference for their own age group, which can impact social interactions, and such bias in young adults even extends to inhibitory control. To assess whether older adults also experience this phenomenon, a group of younger and older adults completed a Go/NoGo task incorporating young and old faces, while undergoing functional magnetic resonance imaging. Within the networks subserving successful and unsuccessful response inhibition, patterns of activity demonstrated distinct neural age bias effects in each age group. During successful inhibition, the older adult group demonstrated significantly increased activity to other-age faces, whereas unsuccessful inhibition in the younger group produced significantly enhanced activity to other-age faces. Consequently, the findings of the study confirm that neural responses to successful and unsuccessful inhibition can be contingent on the stimulus-specific attribute of age in both younger and older adults. These findings have important implications in regard to minimizing the emergence of negative consequences, such as ageism, as a result of related implicit biases.

Spikes with and without concurrent high-frequency oscillations: Topographic relationship and neural correlates using EEG-fMRI.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. SIGNIFICANCE: 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.

The effects of age-bias on neural correlates of successful and unsuccessful response inhibition.

Response inhibition is important for adherence to social norms, especially when norms conflict with biases based on one's social identity. While previous studies have shown that in-group bias generally modulates neural activity related to stimulus appraisal, it is unclear whether and how an in-group bias based on age affects neural information processing during response inhibition. To assess this potential influence, young adults completed a Go/NoGo task incorporating younger face (in-group) and older face (out-group) stimuli while undergoing functional magnetic resonance imaging (fMRI). Our results replicated previous findings by demonstrating higher accuracy in successful Go compared to NoGo trials, as well as the engagement of nodes of the response inhibition network during successful response inhibition, and brain regions comprising the salience network during unsuccessful response inhibition. Importantly, despite a lack of behavioural differences, our results showed that younger and older face stimuli modulated activity in the response inhibition and salience networks during successful and unsuccessful inhibition, respectively. Interestingly, these effects were not uniform across networks. During successful response inhibition, in-group stimuli increased activity in medial prefrontal cortex and temporo-parietal junction, whereas out-group stimuli more strongly engaged pre-supplemental motor area. During unsuccessful response inhibition, in-group stimuli increased activity in posterior insula, whereas out-group stimuli more strongly engaged angular gyrus and intraparietal sulcus. Consequently, the results infer the presence of an age-bias effect in the context of inhibitory control, which has substantial implications for future experimental design and may also provide the means of investigating the neural correlates of implicit beliefs that contribute to ageism.

Weaker connectivity in resting state networks is associated with disinhibited eating 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.

Rule-based generalization of threat without similarity.

Threat generalization to novel instances is central to adaptive behavior. Most previous work has investigated threat generalization based on the perceptual similarity between past and novel stimuli. Few studies have explored generalization based on abstract, non-perceptual relations despite their importance for cognitive flexibility. In order to measure such rule-based generalization of threat without perceptual similarity, we developed a novel paradigm that prevents perceptual features from gaining predictive value. Our results demonstrate that participants responded according to the correct abstract rule and used it to successfully generalize their anticipatory behavioral threat responses (expectancy ratings, sudomotor nerve activity, and heart rate responses). Our results further show that participants flexibly adapted their responses to an unsignaled mid-session contingency reversal. We interpret our results in the context of other rule-based generalization tasks and argue that variations of our paradigm make possible a wide range of investigations into the conceptual aspects of threat generalization.

Salience and default-mode network connectivity during threat and safety processing in older adults.

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.

Functional connectivity of the irritative zone identified by electrical source imaging, and EEG-correlated fMRI analyses.

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.

Motor neuroplasticity: A MEG-fMRI study of motor imagery and execution in healthy ageing.

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.

Understanding the neural basis of episodic amnesia in logopenic progressive aphasia: A multimodal neuroimaging study.

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.

Differentiation of functional networks during long-term memory retrieval in children and adolescents.

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.

Evidence for a functional specialization of ventral anterior temporal lobe for language.

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.

The challenge of bias-free coil combination for quantitative susceptibility mapping at ultra-high field.

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.

Adaptive contextualization: A new role for the default mode network in affective learning.

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.

Individual differences in structural and functional connectivity predict speed of emotion discrimination.

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.

Dynamic competition between large-scale functional networks differentiates fear conditioning and extinction in humans.

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.

Adaptive Motor Imagery: A Multimodal Study of Immobilization-Induced Brain Plasticity.

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 relation of structural integrity and task-related functional connectivity in the aging brain.

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.

Long-term plasticity in adult somatosensory cortex: functional reorganization after surgical removal of an arteriovenous malformation.

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.

High gamma oscillations in medial temporal lobe during overt production of speech and gestures.

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.