How to make calibration less painful-A proposition for an automatic, reliable and time-efficient procedure.

In behavioral and neurophysiological pain studies, multiple types of calibration methods are used to quantify the individual pain sensation stimuli. Often, studies lack a detailed calibration procedure description, data linearity, and quality quantification and omit required control for sex pain differences. This hampers study repetition and interexperimental comparisons. Moreover, typical calibration procedures require a high number of stimulations, which may cause discomfort and stimuli habituation among participants. To overcome those shortcomings, we present an automatic calibration procedure with a novel stimuli estimation method for intraepidermal stimulation. We provide an in-depth data analysis of the collected self-reports from 70 healthy volunteers (37 males) and propose a method based on a dynamic truncated linear regression model (tLRM). We compare its estimates for the sensation (t) and pain (T) thresholds and mid-pain stimulation (MP), with those calculated using traditional estimation methods and standard linear regression models. Compared to the other methods, tLRM exhibits higher R2 and requires 36% fewer stimuli applications and has significantly higher t intensity and lower T and MP intensities. Regarding sex differences, t and T were found to be lower for females compared to males, regardless of the estimation method. The proposed tLRM method quantifies the calibration procedure quality, minimizes its duration and invasiveness, and provides validation of linearity between stimuli intensity and subjective scores, making it an enabling technique for further studies. Moreover, our results highlight the importance of control for sex in pain studies.

Amygdala and cortical gamma-band responses to emotional faces are modulated by attention to valence.

The amygdala might support an attentional bias for emotional faces. However, whether and how selective attention toward a specific valence modulates this bias is not fully understood. Likewise, it is unclear whether amygdala and cortical signals respond to emotion and attention in a similar way. We recorded gamma-band activity (GBA, > 30 Hz) intracranially in the amygdalae of 11 patients with epilepsy and collected scalp recordings from 19 healthy participants. We presented angry, neutral, and happy faces randomly, and we denoted one valence as the target. Participants detected happy targets most quickly and accurately. In the amygdala, during attention to negative faces, low gamma-band activity (LGBA, < 90 Hz) increased for angry compared with happy faces from 160 ms. From 220 ms onward, amygdala high gamma-band activity (HGBA, > 90 Hz) was higher for angry and neutral faces than for happy ones. Monitoring neutral faces increased amygdala HGBA for emotions compared with neutral faces from 40 ms. Expressions were not differentiated in GBA while monitoring positive faces. On the scalp, only threat monitoring resulted in expression differentiation. Here, posterior LGBA was increased selectively for angry targets from 60 ms. The data show that GBA differentiation of emotional expressions is modulated by attention to valence: Top-down-controlled threat vigilance coordinates widespread GBA in favor of angry faces. Stimulus-driven emotion differentiation in amygdala GBA occurs during a neutral attentional focus. These findings align with a multi-pathway model of emotion processing and specify the role of GBA in this process.

Mu-Suppression Neurofeedback Training Targeting the Mirror Neuron System: A Pilot Study.

Neurofeedback training (NFT) is a promising adjuvant intervention method. The desynchronization of mu rhythm (8-13 Hz) in the electroencephalogram (EEG) over centro-parietal areas is known as a valid indicator of mirror neuron system (MNS) activation, which has been associated with social skills. Still, the effect of neurofeedback training on the MNS requires to be well investigated. The present study examined the possible impact of NFT with a mu suppression training protocol encompassing 15 NFT sessions (45 min each) on 16 healthy neurotypical participants. In separate pre- and post-training sessions, 64-channel EEG was recorded while participants (1) observed videos with various types of movements (including complex goal-directed hand movements and social interaction scenes) and (2) performed the "Reading the Mind in the Eyes Test" (RMET). EEG source reconstruction analysis revealed statistically significant mu suppression during hand movement observation across MNS-attributed fronto-parietal areas after NFT. The frequency analysis showed no significant mu suppression after NFT, despite the fact that numerical mu suppression appeared to be visible in a majority of participants during goal-directed hand movement observation. At the behavioral level, RMET accuracy scores did not suggest an effect of NFT on the ability to interpret subtle emotional expressions, although RMET response times were reduced after NFT. In conclusion, the present study exhibited preliminary and partial evidence that mu suppression NFT can induce mu suppression in MNS-attributed areas. More powerful experimental designs and longer training may be necessary to induce substantial and consistent mu suppression, particularly while observing social scenarios.

Ultrafast Cortical Gain Adaptation in the Human Brain by Trial-To-Trial Changes of Associative Strength in Fear Learning.

In fear conditioning, more efficient sensory processing of a stimulus (the conditioned stimulus, CS) that has acquired motivational relevance by being paired with an aversive event (the unconditioned stimulus, US) has been associated with increased cortical gain in early sensory brain areas (Miskovic and Keil, 2012). Further, this sensory gain modulation related to short-term plasticity changes occurs independently of aware cognitive anticipation of the aversive US, pointing toward implicit learning mechanisms (Moratti and Keil, 2009). However, it is unknown how quickly the implicit learning of CS-US associations results in the adaptation of cortical gain. Here, using steady-state visually evoked fields derived from human Magnetoencephalography (MEG) recordings in two experiments (N = 33, 17 females and 16 males), we show that stimulus-driven neuromagnetic oscillatory activity increases and decreases quickly as a function of associative strength within three or four trials, as predicted by a computationally implemented Rescorla-Wagner model with the highest learning rate. These ultrafast cortical gain adaptations are restricted to early visual cortex using a delay fear conditioning procedure. Short interval (500 ms) trace conditioning resulted in the same ultrafast activity modulations by associative strength, but in a complex occipito-parieto-temporo-frontal network. Granger causal analysis revealed that reverberating top-down and bottom-up influences between anterior and posterior brain regions during trace conditioning characterized this network. Critically, in both delay and trace conditioning, ultrafast cortical gain modulations as a function of associative strength occurred independently of conscious US anticipation.SIGNIFICANCE STATEMENT In ever-changing environments, learned associations between a cue and an aversive consequence must change under new stimulus-consequence contingencies to be adaptive. What predicts potential dangers now might be meaningless in the next situation. Predictive cues are prioritized, as reflected by increased sensory cortex activity for these cues. However, this modulation also must adapt to altered stimulus-consequence contingencies. Here, we show that human visual cortex activity can be modulated quickly according to ultrafast contingency changes within a few learning trials. This finding extends to frontal brain regions when the cue and the aversive event are separated in time. Critically, this ultrafast updating process occurs orthogonally to aware aversive outcome anticipation and therefore relies on unconscious implicit learning mechanisms.

Thalamocortical interactions underlying visual fear conditioning in humans.

Despite a strong focus on the role of the amygdala in fear conditioning, recent works point to a more distributed network supporting fear conditioning. We aimed to elucidate interactions between subcortical and cortical regions in fear conditioning in humans. To do this, we used two fearful faces as conditioned stimuli (CS) and an electrical stimulation at the left hand, paired with one of the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically modulated leading to "entrainment" of brain oscillations at a predefined modulation frequency. Steady-state responses (SSR) were recorded by MEG. In addition to occipital regions, spectral analysis of SSR revealed increased power during fear conditioning particularly for thalamus and cerebellum contralateral to the upcoming US. Using thalamus and amygdala as seed-regions, directed functional connectivity was calculated to capture the modulation of interactions that underlie fear conditioning. Importantly, this analysis showed that the thalamus drives the fusiform area during fear conditioning, while amygdala captures the more general effect of fearful faces perception. This study confirms ideas from the animal literature, and demonstrates for the first time the central role of the thalamus in fear conditioning in humans.

Changes on the Modulation of the Startle Reflex in Alcohol-Dependent Patients after 12 Weeks of a Cognitive-Behavioral Intervention.

AIMS: Little is known about changes in the modulation of the startle reflex when patients go through an alcohol-dependence treatment in an outpatient facility. In the current study, the affective modulation of the cue-related startle reflex has been used to evaluate changes in the emotional processing of alcohol-related stimuli that occurred after a standard cognitive-behavioral intervention, and to assess the outcome of this intervention. We hypothesized a 'normalization' of the startle inhibition for the alcohol-related cues during the period of treatment. We also assumed that higher startle inhibition at baseline elicited by alcohol cues would predict the relapse on alcohol consumption during treatment. PARTICIPANTS: A total of 98 alcohol-dependent subjects were included who fulfilled DSM-IV criteria for alcohol dependence. A control group of 72 subjects was selected to match demographic characteristics. MEASUREMENTS: All patients received a standard cognitive-behavioral therapy once a week throughout the study period. FINDINGS: Results show that the startle response differed significantly after 12 weeks of treatment for alcohol-related, neutral and aversive stimuli between alcohol-dependent patients and controls. Low startle responses at baseline to alcohol cues predicted relapse. CONCLUSIONS: These results may indicate that the startle reflex is referred to enduring and permanent processes of cue reactivity, and that the emotional processing of alcohol-associated cues assessed with the affect-modulated startle reflex is less altered by interventions attempting to influence explicit cognitions. Furthermore, lower values of the baseline startle reflex elicited by alcohol-associated stimuli were associated with higher probability of relapse on alcohol use.

Distinct patterns of spatial attentional modulation of steady-state visual evoked magnetic fields (SSVEFs) in subdivisions of the human early visual cortex.

In recent years, steady-state visual evoked potentials (SSVEPs) became an increasingly valuable tool to investigate neural dynamics of competitive attentional interactions and brain-computer interfaces. This is due to their good signal-to-noise ratio, allowing for single-trial analysis, and their ongoing oscillating nature that enables to analyze temporal dynamics of facilitation and suppression. Given the popularity of SSVEPs, it is surprising that only a few studies looked at the cortical sources of these responses. This is in particular the case when searching for studies that assessed the cortical sources of attentional SSVEP amplitude modulations. To address this issue, we used a typical spatial attention task and recorded neuromagnetic fields (MEG) while presenting frequency-tagged stimuli in the left and right visual fields, respectively. Importantly, we controlled for attentional deployment in a baseline period before the shifting cue. Subjects either attended to a central fixation cross or to two peripheral stimuli simultaneously. Results clearly showed that signal sources and attention effects were restricted to the early visual cortex: V1, V2, hMT+, precuneus, occipital-parietal, and inferior-temporal cortex. When subjects attended to central fixation first, shifting attention to one of the peripheral stimuli resulted in a significant activation increase for the to-be-attended stimulus with no activation decrease for the to-be-ignored stimulus in hMT+ and inferio-temporal cortex, but significant SSVEF decreases from V1 to occipito-parietal cortex. When attention was first deployed to both rings, shifting attention away from one ring basically resulted in a significant activation decrease in all areas for the then-to-be-ignored stimulus.

Early prefrontal activation as a mechanism to prevent forgetting in the context of interference.

OBJECTIVE: Recent research has focused on interference resolution deficits as the main cause of short-term memory decreases in aging. To determine whether activation of brain compensatory mechanisms occur during the encoding process in older people. Moreover, two different levels of interference (distraction and interruption) were presented during the maintenance period to examine how they modulate brain activity profiles. DESIGN: A delayed match-to-sample task with two experimental conditions: distraction and interruption. PARTICIPANTS: Twenty-seven young adults from Complutense University of Madrid and 20 healthy older adults from Complutense Elderly University of Madrid. MEASUREMENTS: Magnetoencephalography scans were recorded during the execution of a working memory interference task. Brain activity sources from younger and older adults during the encoding stage were compared in each condition using minimum norm estimation analyses. RESULTS: The elderly showed enhancement of prefrontal activity during early latencies of the encoding process in both conditions. In the distraction condition, enhanced activity was located in left ventrolateral prefrontal regions, whereas in the interruption condition, enhanced activity was observed in the right ventral prefrontal areas and anterior cingulate cortex. CONCLUSION: Increased recruitment of prefrontal regions in the elderly might be related to the processing depth of information, encoding of new information and semantic associations that are successfully recalled, and with interference resolution and preparatory control when the level of interference becomes higher. These prefrontal modulations during early latencies might reflect a higher top-down control of the encoding process in normal aging to prevent forgetting.

Pavlovian conditioning-induced hallucinations reduce MMN amplitudes for duration but not frequency deviants.

The mismatch negativity (MMN) is an evoked potential that indexes auditory regularity violations. Since the 90's, a reduced amplitude of this brain activity in patients with schizophrenia has been consistently reported. Recently, this alteration has been related to the presence of auditory hallucinations (AHs) rather than the schizophrenia diagnostic per se. However, making this attribution is rather problematic due to the high heterogeneity of symptoms in schizophrenia. In an attempt to isolate the AHs influence on the MMN amplitude from other cofounding variables, we artificially induced AHs in a non-clinical population by Pavlovian conditioning. Before and after conditioning, volunteers (N = 31) participated in an oddball paradigm that elicited an MMN. Two different types of deviants were presented: a frequency and a duration deviant, as the MMN alteration seems to be especially present in schizophrenia with the latter type of deviant. Hence, this pre-post design allowed us to compare whether experiencing conditioning-induced AHs exert any influence on MMN amplitudes. Our results show that duration-deviant related MMN reductions significantly correlate with the number of AHs experienced. Moreover, we found a significant correlation between AHs proneness (measured with the Launay-Slade Hallucination Extended Scale) and the number of AHs experienced during the paradigm. In sum, our study shows that AHs can be conditioned and exert similar effects on MMN modulation in healthy participants as has been reported for patients with schizophrenia. Thus, conditioning paradigms offer the possibility to study the association between hallucinations and MMN reductions without the confounding variables present in schizophrenia patients.

Prefrontal-occipitoparietal coupling underlies late latency human neuronal responses to emotion.

Enhanced late positive potentials (LPPs) evoked by highly arousing unpleasant and pleasant stimuli have been consistently observed in event-related potential experiments in humans. Although the psychological factors modulating the LPP have been studied in detail, the neurobiological underpinnings of this response remain poorly understood. Current models suggest that the LPP is a product of both an automatic facilitation of perceptual activity, as well as postperceptual processing under cognitive control. Here we applied magnetoencephalography (MEG) and beamformer analysis combined with Granger causality measures to provide a mechanistic account for LPP generation that reconciles these two models. We demonstrate that the magnetic homolog of the LPP, mLPP, is localized within bilateral occipitoparietal and right prefrontal cortex. Critically, directed functional connectivity analysis between these brain regions, indexed by Granger causality, demonstrates stronger bidirectional influences between frontal and occipitoparietal cortex for high arousing emotional relative to low arousing neutral pictures. Thus, both bottom-up and top-down accounts of the late latency response to emotion derived from psychological studies can be explained by a reciprocal codependency between activity in prefrontal and occipitoparietal cortex.

Conditioned up and down modulations of short latency gamma band oscillations in visual cortex during fear learning in humans.

Over the course of evolution, the human brain has been shaped to prioritize cues that signal potential danger. Thereby, the brain does not only favor species-specific prepared stimulus sets such as snakes or spiders but can learn associations between new cues and aversive outcomes. One important mechanism to achieve this is associated with learning induced plasticity changes in sensory cortex that optimizes the representation of motivationally relevant sensory stimuli. Animal studies have shown that the modulation of gamma band oscillations predicts plasticity changes in sensory cortices by shifting neurons' responses to fear relevant features as acquired by Pavlovian fear conditioning. Here, we report conditioned gamma band modulations in humans during fear conditioning of orthogonally oriented sine gratings representing fear relevant and irrelevant conditioned cues. Thereby, pairing of a sine grating with an aversive loud noise not only increased short latency (during the first 180 ms) evoked visual gamma band responses, but was also accompanied by strong gamma power reductions for the fear irrelevant control grating. The current findings will be discussed in the light of recent neurobiological models of plasticity changes in sensory cortices and classic learning models such as the Rescorla-Wagner framework.

Emotion and attention in face processing: Complementary evidence from surface event-related potentials and intracranial amygdala recordings.

Face processing is biased by emotional and voluntarily directed attention, both of which modulate processing in distributed cortical areas. The amygdala is assumed to contribute to an attentional bias for emotional faces, although its interaction with directed attention awaits further clarification. Here, we studied the interaction of emotion and attention during face processing via scalp EEG potentials of healthy participants and intracranial EEG (iEEG) recordings of the right amygdala in one patient. Three randomized blocks consisting of angry, neutral, and happy facial expressions were presented, and one expression was denoted as the target category in each block. Happy targets were detected fastest and most accurately both in the group study and by the iEEG patient. Occipital scalp potentials revealed emotion differentiation for happy faces in the early posterior negativity (EPN) around 300 ms after stimulus onset regardless of the target condition. A similar response to happy faces occurred in the amygdala only for happy targets. On the scalp, a late positive potential (LPP, around 600 ms) enhancement for targets occurred for all target conditions alike. A simultaneous late signal in the amygdala was largest for emotional targets. No late signal enhancements were found for neutral targets in the amygdala. Cortical modulations, by contrast, showed both attention-independent effects of emotion and emotion-independent effects of attention. These results demonstrate an attention-dependence of amygdala activity during the processing of facial expressions and partly independent cortical mechanisms.

Aversive memory formation in humans involves an amygdala-hippocampus phase code.

Memory for aversive events is central to survival but can become maladaptive in psychiatric disorders. Memory enhancement for emotional events is thought to depend on amygdala modulation of hippocampal activity. However, the neural dynamics of amygdala-hippocampal communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, here we show that successful emotional memory encoding depends on the amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to a time period that enables lagged coherence between amygdala and downstream hippocampal gamma. These results reveal a mechanism whereby amygdala theta phase coordinates transient amygdala -hippocampal gamma coherence to facilitate aversive memory encoding. Pacing of lagged gamma coherence via amygdala theta phase may represent a general mechanism through which the amygdala relays emotional content to distant brain regions to modulate other aspects of cognition, such as attention and decision-making.

Threat imminence modulates neural gain in attention and motor relevant brain circuits in humans.

Different levels of threat imminence elicit distinct computational strategies reflecting how the organism interacts with its environment in order to guarantee survival. Thereby, parasympathetically driven orienting and inhibition of on-going behavior in post-encounter situations and defense reactions in circa-strike conditions associated with sympathetically driven action preparation are typically observed across species. Here, we show that healthy humans are characterized by markedly variable individual orienting or defense response tendencies as indexed by differential heart rate (HR) changes during the passive viewing of unpleasant pictures. Critically, these HR response tendencies predict neural gain modulations in cortical attention and preparatory motor circuits as measured by neuromagnetic steady-state visual evoked fields (ssVEFs) and induced beta-band (19-30 Hz) desynchronization, respectively. Decelerative HR orienting responses were associated with increased ssVEF power in the parietal cortex and reduced beta-band desynchronization in pre-motor and motor areas. However, accelerative HR defense response tendencies covaried with reduced ssVEF power in the parietal cortex and lower beta-band desynchronization in cortical motor circuits. These results show that neural gain in attention- and motor-relevant brain areas is modulated by HR indexed threat imminence during the passive viewing of unpleasant pictures. The observed mutual ssVEF and beta-band power modulations in attention and motor brain circuits support the idea of two prevalent response tendencies characterized by orienting and motor inhibition or reduced stimulus processing and action initiation tendencies at different perceived threat imminence levels.

A Model of the Early Visual System Based on Parallel Spike-Sequence Detection, Showing Orientation Selectivity.

Since the first half of the twentieth century, numerous studies have been conducted on how the visual cortex encodes basic image features. One of the hallmarks of basic feature extraction is the phenomenon of orientation selectivity, of which the underlying neuronal-level computational mechanisms remain partially unclear despite being intensively investigated. In this work we present a reduced visual system model (RVSM) of the first level of scene analysis, involving the retina, the lateral geniculate nucleus and the primary visual cortex (V1), showing orientation selectivity. The detection core of the RVSM is the neuromorphic spike-decoding structure MNSD, which is able to learn and recognize parallel spike sequences and considerably resembles the neuronal microcircuits of V1 in both topology and operation. This structure is equipped with plasticity of intrinsic excitability to embed recent findings about V1 operation. The RVSM, which embeds 81 groups of MNSD arranged in 4 oriented columns, is tested using sets of rotated Gabor patches as input. Finally, synthetic visual evoked activity generated by the RVSM is compared with real neurophysiological signal from V1 area: (1) postsynaptic activity of human subjects obtained by magnetoencephalography and (2) spiking activity of macaques obtained by multi-tetrode arrays. The system is implemented using the NEST simulator. The results attest to a good level of resemblance between the model response and real neurophysiological recordings. As the RVSM is available online, and the model parameters can be customized by the user, we propose it as a tool to elucidate the computational mechanisms underlying orientation selectivity.

Oscillatory activity in prefrontal and posterior regions during implicit letter-location binding.

Many cognitive abilities involve the integration of information from different modalities, a process referred to as "binding." It remains less clear, however, whether the creation of bound representations occurs in an involuntary manner, and whether the links between the constituent features of an object are symmetrical. We used magnetoencephalography to investigate whether oscillatory brain activity related to binding processes would be observed in conditions in which participants maintain one feature only (involuntary binding); and whether this activity varies as a function of the feature attended to by participants (binding asymmetry). Participants performed two probe recognition tasks that were identical in terms of their perceptual characteristics and only differed with respect to the instructions given (to memorize either consonants or locations). MEG data were reconstructed using a current source distribution estimation in the classical frequency bands. We observed implicit verbal-spatial binding only when participants successfully maintained the identity of consonants, which was associated with a selective increase in oscillatory activity over prefrontal regions in all frequency bands during the first half of the retention period and accompanied by increased activity in posterior brain regions. The increase in oscillatory activity in prefrontal areas was only observed during the verbal task, which suggests that this activity might be signaling neural processes specifically involved in cross-code binding. Current results are in agreement with proposals suggesting that the prefrontal cortex function as a "pointer" which indexes the features that belong together within an object.

Not what you expect: experience but not expectancy predicts conditioned responses in human visual and supplementary cortex.

When paired with aversive events, visual conditioned stimuli (CS) provoke increased activations in visual cortex. It is unclear however whether these changes reflect cognitive processes such as expectancy of the aversive unconditioned stimulus (US), or implicit associative learning of the contingencies outside awareness. Here, we used the "gambler's fallacy" phenomenon to parametrically and inversely manipulate the expectancy of an US and the number of conditioning trials: Increasing the number of CS-US pairings was associated with participants expecting the US to be less likely and vice versa. Magnetocortical activity evoked by the CS in occipital and supplementary motor areas was linearly related to the associative strength (number of CS-US pairings), but decreased as a function of expectancy. These results suggest that the cortical facilitation of fear cue processing is determined by associative strength and previous exposure to learning contingencies rather than by the cognitive anticipation for the US.

Temporal dynamics of amygdala response to emotion- and action-relevance.

It has been proposed that the human amygdala may not only encode the emotional value of sensory events, but more generally mediate the appraisal of their relevance for the individual's goals, including relevance for action or task-based needs. However, emotional and non-emotional/action-relevance might drive amygdala activity through distinct neural signals, and the relative timing of both kinds of responses remains undetermined. Here, we recorded intracranial event-related potentials from nine amygdalae of patients undergoing epilepsy surgery, while they performed variants of a Go/NoGo task with faces and abstract shapes, where emotion- and action-relevance were orthogonally manipulated. Our results revealed early amygdala responses to emotion facial expressions starting ~ 130 ms after stimulus-onset. Importantly, the amygdala responded to action-relevance not only with face stimuli but also with abstract shapes (squares), and these relevance effects consistently occurred in later time-windows (starting ~ 220 ms) for both faces and squares. A similar dissociation was observed in gamma activity. Furthermore, whereas emotional responses habituated over time, the action-relevance effect increased during the course of the experiment, suggesting progressive learning based on the task needs. Our results support the hypothesis that the human amygdala mediates a broader relevance appraisal function, with the processing of emotion-relevance preceding temporally that of action-relevance.

Propofol-induced deep sedation reduces emotional episodic memory reconsolidation in humans.

The adjustment of maladaptive thoughts and behaviors associated with emotional memories is central to treating psychiatric disorders. Recent research, predominantly with laboratory animals, indicates that memories can become temporarily sensitive to modification following reactivation, before undergoing reconsolidation. A method to selectively impair reconsolidation of specific emotional or traumatic memories in humans could translate to an effective treatment for conditions such as posttraumatic stress disorder. We tested whether deep sedation could impair emotional memory reconsolidation in 50 human participants. Administering the intravenous anesthetic propofol following memory reactivation disrupted memory for the reactivated, but not for a non-reactivated, slideshow story. Propofol impaired memory for the reactivated story after 24 hours, but not immediately after propofol recovery. Critically, memory impairment occurred selectively for the emotionally negative phase of the reactivated story. One dose of propofol following memory reactivation selectively impaired subsequent emotional episodic memory retrieval in a time-dependent manner, consistent with reconsolidation impairment.

Human amygdala response to unisensory and multisensory emotion input: No evidence for superadditivity from intracranial recordings.

The amygdala is crucially implicated in processing emotional information from various sensory modalities. However, there is dearth of knowledge concerning the integration and relative time-course of its responses across different channels, i.e., for auditory, visual, and audiovisual input. Functional neuroimaging data in humans point to a possible role of this region in the multimodal integration of emotional signals, but direct evidence for anatomical and temporal overlap of unisensory and multisensory-evoked responses in amygdala is still lacking. We recorded event-related potentials (ERPs) and oscillatory activity from 9 amygdalae using intracranial electroencephalography (iEEG) in patients prior to epilepsy surgery, and compared electrophysiological responses to fearful, happy, or neutral stimuli presented either in voices alone, faces alone, or voices and faces simultaneously delivered. Results showed differential amygdala responses to fearful stimuli, in comparison to neutral, reaching significance 100-200 ms post-onset for auditory, visual and audiovisual stimuli. At later latencies, ∼400 ms post-onset, amygdala response to audiovisual information was also amplified in comparison to auditory or visual stimuli alone. Importantly, however, we found no evidence for either super- or subadditivity effects in any of the bimodal responses. These results suggest, first, that emotion processing in amygdala occurs at globally similar early stages of perceptual processing for auditory, visual, and audiovisual inputs; second, that overall larger responses to multisensory information occur at later stages only; and third, that the underlying mechanisms of this multisensory gain may reflect a purely additive response to concomitant visual and auditory inputs. Our findings provide novel insights on emotion processing across the sensory pathways, and their convergence within the limbic system.