Search

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 amount 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.

BackgroundIn neurophysiological pain studies, multiple types of calibration methods are used to quantify the individual pain sensation stimuli that have different modalities. However, such studies often lack calibration procedure implementation, have a vague protocol description, do not provide data quality quantification, or even omit required control for gender pain differences. All this hampers not only study repetition but also interexperimental comparisons. Moreover, typical calibration procedures are long and require a high number of stimulations which may cause participants’ discomfort and stimuli habituation.MethodTo overcome those shortcomings, we present an automatic staircase pain calibration method for A-delta-specific electrical stimulation adjusted to the magnetoencephalography environment. We provide an in-depth data analysis of the collected self-reports from seventy 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, as well as for the mid-pain stimulation (MP), with those calculated using a traditional threshold method and standard linear regression models.ResultsCompared to the other threshold methods, tLRM exhibits higher R2and requires 36% fewer stimuli application and has significantly highertand lowerTandMPintensities. Regarding sex differences, both lowertandTwere found for females compared to males, regardless of the calibration method.ConclusionsThe proposed tLRM method quantifies the quality of the calibration procedure, minimizes its duration and invasiveness, as well as 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 gender in pain studies.SummaryThe purpose of this study was to shorten and automatize the calibration method which is an enabling technique for realizing neurophysiological studies on pain. The proposed method is based on a dynamic truncated linear regression model and was shown to require 36% fewer stimuli application compared to the traditional staircase method. Furthermore, the calibration was adjusted to A-delta specific intraepidermal electrical stimulation, quantifies the quality of the resulting calibration parameters and provides a validation of linearity between stimuli intensity and subjective scores. The results also highlight the importance of control for participant gender in studies where different types of stimulation are used to induce pain sensation.

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.

The capacity-limited human brain is constantly confronted with a huge amount of sensory information. Selective attention is needed for biasing neural processing towards relevant information and consequently allows meaningful interaction with the environment. Activity in the alpha-band has been proposed to be related to top-down modulation of neural inhibition and could thus represent a viable candidate to control the priority of stimulus processing. It is, however, unknown whether modulations in the alpha-band directly relate to changes in the sensory gain control of the early visual cortex. Here, we used a spatial cueing paradigm while simultaneously measuring ongoing alpha-band oscillations and steady-state visual evoked potentials (SSVEPs) as a marker of continuous early sensory processing in the human visual cortex. Thereby, the effects of spatial attention for both of these signals and their potential interactions were assessed. As expected, spatial attention modulated both alpha-band and SSVEP responses. However, their modulations were independent of each other and the corresponding activity profiles differed across task demands. Thus, our results challenge the view that modulations of alpha-band activity represent a mechanism that directly alters or controls sensory gain. The potential role of alpha-band oscillations beyond sensory processing will be discussed in light of the present results.

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.

The hippocampus is implicated in novelty detection, thought to be important for regulating entry of information into long-term memory. Whether electrophysiological responses to novelty differ along the human hippocampal long axis is currently unknown. By recording from electrodes implanted longitudinally in the hippocampus of epilepsy patients, here we show a gradual increase of theta frequency oscillatory power from anterior to posterior in response to unexpected stimuli, superimposed on novelty responses common to all long axis portions. Intracranial event-related potentials (iERPs) were larger for unexpected vs. expected stimuli and demonstrated a polarity inversion between the hippocampal head (HH) and body (HB). We observed stronger theta coherence between HH and hippocampal tail (HT) than between HB and HT, similarly for expected and unexpected stimuli. This was accompanied by theta and alpha traveling waves with surprisingly variable direction of travel characterized by a ∼180° phase lag between hippocampal poles. Interestingly, this phase lag showed a pronounced phase offset between anterior and middle (HH-HB) hippocampal portions coinciding anatomically with a drop in theta coherence and the novelty iERP polarity inversion. Our findings indicate common response properties along the hippocampal long axis to unexpected stimuli, as well as a multifaceted, non-uniform engagement along the long axis for novelty processing.

Memory for aversive events is central to survival, but can also become maladaptive in psychiatric disorders. Emotional memory relies on the amygdala and hippocampus, but the neural dynamics of their communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, we show that in response to emotionally aversive, but not neutral, visual stimuli, the amygdala transmits unidirectional influence on the hippocampus through theta oscillations. Critically, successful emotional memory encoding depends on the precise 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 ∼25-45 milliseconds, a time period that enables lagged coherence between amygdala and downstream hippocampal gamma activity. These results reveal a mechanism whereby amygdala theta phase coordinates transient coherence between amygdala and hippocampal gamma activity to facilitate the encoding of aversive memories in humans.

Simple Summary A computational model of primates’ early visual processing, showing orientation selectivity, is presented. The system importantly integrates two key elements: (1) a neuromorphic spike-decoding structure that considerably resembles the circuitry between layers IV and II/III of the primary visual cortex, both in topology and operation; (2) the plasticity of intrinsic excitability, to embed recent findings about the operation of the same area. The model is proposed as a tool for the analysis and reproduction of the orientation selectivity phenomenon, whose underlying neuronal-level computational mechanisms are today the subject of intense scrutiny. In response to rotated Gabor patches the model is able to exhibit realistic orientation tuning curves and to reproduce responses similar to those found in neurophysiological recordings from the primary visual cortex obtained under the same task, considering different stages of the network. This demonstrates its aptness to capture the mechanisms underlying the evoked response in the primary visual cortex. Our tool is available online, and can be expanded to other experiments using a dedicated software library developed by the authors, to elucidate the computational mechanisms underlying orientation selectivity. Abstract 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.

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 specie-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 cholinergic driven plasticity changes in sensory cortices shifting neurons’ responses to fear relevant features as acquired by Pavlovian fear conditioning. Here, we report conditioned excitatory and inhibitory gamma band modulations in humans during fear conditioning of orthogonally oriented sinus gratings representing fear relevant and irrelevant conditioned cues, respectively. Thereby, pairing of a sinus 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 cholinergic driven plasticity changes in sensory cortices and classic learning models such as the Rescorla-Wagner framework.

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.

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.

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.

Administering the anesthetic propofol after a brief reminder reduces retrieval of established emotional memory 24 hours later., 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.

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.

Cannabis-induced psychotic disorder (CIPD) refers to psychotic symptoms that arise in the context of cannabis intoxication. Prepulse inhibition (PPI) deficits have been extensively identified in schizophrenia and in cannabis abusers. We aimed to characterize PPI in CIPD patients. We used a sample of 48 CIPD patients, 54 schizophrenia patients and cannabis abuse (SCHZ), 44 cannabis dependents (CD), and 44 controls. CIPD, SCHZ and CD were abstinent of cannabis consumption for 9 months. Participants were assessed with PPI at 30, 60, and 120 ms. At 30 ms, CIPD showed lower PPI levels than controls, and SCHZ obtained worse functioning than controls and CD. At 60 ms, only SCHZ exhibited worse PPI percentages (of object) than controls. Finally, at 120 ms, CIPD showed higher PPI levels than SCHZ, and SCHZ obtained lower percentages than controls. We found that CIPD and SCHZ patients showed deficits at the most pre-attentional levels, whereas CIPD patients performed better than SCHZ at higher attentional levels. These results suggest that CIPD constitutes a different group of patients than that of SCHZ. Deficits in PPI functioning at 30 ms could be a useful psychophysiological measure to detect CIPD patients, who are frequently confused with cannabis abusers whose symptoms may mimic that of schizophrenia.

A fast, subcortical pathway to the amygdala is thought to have evolved to enable rapid detection of threat. This pathway's existence is fundamental for understanding nonconscious emotional responses, but has been challenged as a result of a lack of evidence for short-latency fear-related responses in primate amygdala, including humans. We recorded human intracranial electrophysiological data and found fast amygdala responses, beginning 74-ms post-stimulus onset, to fearful, but not neutral or happy, facial expressions. These responses had considerably shorter latency than fear responses that we observed in visual cortex. Notably, fast amygdala responses were limited to low spatial frequency components of fearful faces, as predicted by magnocellular inputs to amygdala. Furthermore, fast amygdala responses were not evoked by photographs of arousing scenes, which is indicative of selective early reactivity to socially relevant visual information conveyed by fearful faces. These data therefore support the existence of a phylogenetically old subcortical pathway providing fast, but coarse, threat-related signals to human amygdala.

Depression is a psychiatric disorder with high prevalence in Mental Health Centers and in the general population. In recent decades there has been a growing interest in applying models of emotion and motivation to the study of affective disorders. Two of the most relevant models in this field have investigated the relationship between depression and positive and negative affects and also the association between emotional functioning and cortical brain asymmetries in subjects with depression.

Depression has been associated with low emotional arousal. Highly arousing emotional stimuli engage the cortical circuits related to the allocation of attention towards these stimuli. Thus, it has been hypothesized that depression could be characterized by a deficit in these brain circuits. This brief review summarizes how attention and emotion are interconnected and suggests that common brain mechanisms underlie the link between emotion and attention. Finally, the results from depression research are presented that show that low emotional arousal in depression could arise from a deficit in brain circuits related to attention.

Depression has been associated with low emotional arousal. Highly arousing emotional stimuli engage the cortical circuits related to the allocation of attention towards these stimuli. Thus, it has been hypothesized that depression could be characterized by a deficit in these brain circuits. This brief review summarizes how attention and emotion are interconnected and suggests that common brain mechanisms underlie the link between emotion and attention. Finally, the results from depression research are presented that show that low emotional arousal in depression could arise from a deficit in brain circuits related to attention.

Schizophrenia patients (SZ) show early visual processing deficits in many, but not all, tasks. These deficits may be associated with dysregulation of intrinsic oscillatory activity that compromises signal-to-noise in the SZ brain. This question was studied using visual steady-state stimulation and post-steady-state presentation of transient visual stimuli. SZ had higher intrinsic oscillatory activity at the steady-state stimulation frequency (12.5 Hz) and at the 6.25 Hz subharmonic, showed a significant decrease in visual steady-state magnitude over 2 s of stimulation, and were unable to promptly terminate the steady-state response following stimulation offset. If adjustment for levels of intrinsic brain activity were made, however, it would have appeared that SZ had activity of similar magnitude as healthy subjects following steady-state stimulus termination, indicating that such adjustments could substantially alter theoretical interpretations. Visual evoked potential abnormalities (N1/P2 amplitudes) present among SZ at the initiation of steady-state stimulation were less apparent in the 750 ms immediately following steady-state stimulation offset. Higher intrinsic oscillatory brain activity may be a fundamental characteristic of SZ that merits further evaluation for understanding this disorder's neuropathological correlates and associated symptomatology.

In order to explore the relationships of fronto-limbic dysfunction with the clinical features of borderline personality disorder (BPD), the authors investigated brain electrophysiological activity in BPD patients following stimulation with emotionally arousing images.Seventeen non-medicated patients with borderline personality disorder were studied with magneto-encephalography. Regional cortical activities were obtained by minimum norm estimate (MNE) of steady-state visual evoked fields (ssVEFs). Linear regression models were conducted to explore clinical correlates of brain activity.Although no interaction group × picture category × brain region was found, a significant interaction group × brain region appeared for orbito-frontal cortex (OFC). BPD patients showed significantly reduced magnetocortical activity in left OFC across all picture categories (F = 26.4; p.05; F = 31.4). Left OFC activity was inversely correlated with depression score in the BDI (r: -0.48, p0.05), with score in the Cornell Dysthymia rating scale (r: -0.52, p0.05) and with the number of criteria met for depressive personality disorder (r: -0.44, p0.05). Left orbitofrontal activity was also inversely correlated with the global score in the GAF (r-0.63, p0.01). No correlations were found between OFC activity and impulsivity or global severity of BPD symptoms.Abnormal functioning at orbitofrontal areas in BPD could be related to the presence of affective symptomatology and is associated with greater functional deterioration of patients.

The ability to react rapidly and efficiently to adverse stimuli is crucial for survival. Neuroscience and behavioral studies have converged to show that visual information associated with aversive content is processed quickly and accurately and is associated with rapid amplification of the neural responses. In particular, unpleasant visual information has repeatedly been shown to evoke increased cortical activity during early visual processing between 60 and 120 milliseconds following the onset of a stimulus. However, the nature of these early responses is not well understood. Using neutral versus unpleasant colored pictures, the current report examines the time course of short-term changes in the human visual cortex when a subject is repeatedly exposed to simple grating stimuli in a classical conditioning paradigm. We analyzed changes in amplitude and synchrony of large-scale oscillatory activity across two days of testing, which included baseline measurements, 2 conditioning sessions, and a final extinction session. We found a gradual increase in amplitude and synchrony of very early cortical oscillations in the 20–35 Hz range across conditioning sessions, specifically for conditioned stimuli predicting aversive visual events. This increase for conditioned stimuli affected stimulus-locked cortical oscillations at a latency of around 60–90 ms and disappeared during extinction. Our findings suggest that reorganization of neural connectivity on the level of the visual cortex acts to optimize early perception of specific features indicative of emotional relevance.

It is not clear whether enhanced cortical processing of reinforced stimuli as reported by neuroimaging studies is due to expectancy of an aversive event alone or to activation of the fear system. The present study investigated cortical and autonomic responses of aware participants using an instructed fear conditioning design. Steady-state visual evoked fields (ssVEF) and heart rate change were recorded to assess sensory processing and activation of the fear system by reinforced (CS+) and nonreinforced stimuli (CS - ). Participants who showed heart rate acceleration demonstrated increased ssVEFs in visual and parietal cortex during CS+ in acquisition trials. Heart rate decelerators did not show enhanced cortical activation with respect to the CS+. Participants in both groups reported awareness of CS- US contingencies. Awareness of stimulus contingency in fear conditioning seems not to be sufficient to elicit enhanced visual cortical processing. Descriptors: Fear conditioning, Fear system, MEG, Heart rate, Steady-state visual evoked field potentials, Awareness

Background Structural and Electroencephalography (EEG) abnormalities in right temporoparietal cortex have been associated with family history of depression (FH). Here we investigate if functional abnormalities in this area, indexed by attenuated responses to emotionally arousing stimuli, are also family-history-dependent. Methods Neuromagnetic activity for emotional and neutral complex scenes was recorded by Magnetoencephalography (MEG) in 20 depressed patients without, 8 depressed patients with FH, and 15 healthy controls. Emotion-sensitive neuronal steady state responses were cortical source localized and tested for group-by-emotion interactions. Results The group-by-emotion interaction (F(4, 80)=4.4, p=0.004) was explained by a significant modulation of right temporoparietal cortex activity by emotional arousal in controls and patients without FH. This effect was reduced in FH positive patients. The difference between patient groups remained when clinical variables such as symptom severity were accounted for. Limitations All patients were medicated, but differences between patient groups remained after accounting for medication dosage. Further, the sample size was limited, but data-driven resampling statistics showed the robustness of our effects. Finally, the sample consists of female patients only and we cannot generalize our results to male samples. Conclusions Patients with FH show impaired recruitment of attention-relevant cortical circuitry by emotional stimuli. The neuroanatomical locus of this effect accords with previous reports on structural abnormalities and electrophysiological deficits at rest in individuals with FH. Our results speak to the relevance of right temporoparietal dysfunction in emotional information processing as a potential endophenotype for depression with FH.

Previous research has demonstrated optimized processing of motivationally significant stimuli early in perception. In the present study, the time course and underlying mechanisms for such fast differentiation are of interest. We investigated the involvement of the primary visual cortex in affective evaluation of conditioned stimuli (CSs). In order to elicit learning within the visual system we chose affective pictures as unconditioned stimuli and used laterally presented gratings as CSs. Using high-density electroencephalography, we demonstrated modulation of the C1 visual event-related component for threat-related stimuli versus neutral stimuli, which increased with continuing acquisition of affective meaning. The differentiation between aversive and neutral visual stimuli occurred as early as 65--90 ms after stimulus onset and suggested involvement of the primary visual areas in affective evaluation. As an underlying mechanism, we discuss short-term reorganization in visual cortex, enabling sensory amplification of specific visual features that are related to motivationally relevant information.

Allocation of processing resources to emotional picture stimuli was examined using steady-state visual evoked brain potentials (ssVEPs). Participants viewed a set of 60 colored affective pictures from the International Affective Picture System, presented in a flickering mode at 10 Hz in order to elicit ssVEPs. Phase and amplitude of the 10-Hz ssVEP were examined for six picture categories: threat and mutilation (unpleasant), families and erotica (pleasant), and household objects and persons (neutral). Self-reported affective arousal and hedonic valence of the picture stimuli were assessed by means of subjective ratings. Viewing affectively arousing (unpleasant and pleasant) pictures was associated with enhanced ssVEP amplitude at parieto-occipital recording sites, as compared with neutral stimuli. Phase information suggested increased coactivation of right occipitotemporal and frontotemporal sources during processing of affectively arousing stimuli. These findings are consistent with reentrant modulation of early visual processing by distributed networks including subcortical and neocortical structures according to a stimulus's motivational relevance.

It is known that patients with schizophrenia show a deficiency in the prepulse inhibition reflex (PPI). These patients display abnormalities in autonomic nervous system and hypothalamic–pituitary–adrenal function and may have an altered sensitivity to stress. To date, no studies have been carried out to determine the effect of acute stress on the PPI. We investigated whether there was a differential response in reactivity to acute stress caused by the socially evaluated cold-pressor test (SECPT) in a sample of 58 chronic male patients with schizophrenia and 28 healthy control subjects. PPI, salivary cortisol and heart rate (HR) were measured. The patients were evaluated in two sessions (with and without the SECPT) 72 h apart and basal measurements were carried out and 30 min post-startle probe. We found an increase in salivary cortisol levels and the HR with SECPT condition in both groups and a significantly lower PPI% in patients with schizophrenia. The most relevant findings of this study are that the impairment of the PPI is increased by stress. Stress-induced increase in cortisol in both groups, mainly in healthy control group which allows us to hypothesize that at least such deterioration may be due to the hypercortisolemia caused by the SECPT.

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.

To perceive a coherent environment, incomplete or overlapping visual forms must be integrated into meaningful coherent percepts, a process referred to as “Gestalt” formation or perceptual completion. Increasing evidence suggests that this process engages oscillatory neuronal activity in a distributed neuronal assembly. A separate line of evidence suggests that Gestalt formation requires top-down feedback from higher order brain regions to early visual cortex. Here we combine magnetoencephalography (MEG) and effective connectivity analysis in the frequency domain to specifically address the effective coupling between sources of oscillatory brain activity during Gestalt formation. We demonstrate that perceptual completion of two-tone “Mooney” faces induces increased gamma frequency band power (55–71Hz) in human early visual, fusiform and parietal cortices. Within this distributed neuronal assembly fusiform and parietal gamma oscillators are coupled by forward and backward connectivity during Mooney face perception, indicating reciprocal influences of gamma activity between these higher order visual brain regions. Critically, gamma band oscillations in early visual cortex are modulated by top-down feedback connectivity from both fusiform and parietal cortices. Thus, we provide a mechanistic account of Gestalt perception in which gamma oscillations in feature sensitive and spatial attention-relevant brain regions reciprocally drive one another and convey global stimulus aspects to local processing units at low levels of the sensory hierarchy by top-down feedback. Our data therefore support the notion of inverse hierarchical processing within the visual system underlying awareness of coherent percepts.

Background: Schizophrenic patients exhibit more activityin the electroencephalographic delta and theta frequencyrange than do control subjects. Using magnetic sourceimaging (MSI) our study aimed to explore this phenomenonin the magnetoencephalogram (MEG), the distributionof its sources, and associations between symptomprofiles and sources of low-frequency activity in the brain.Methods: Whole-head MEG recordings were obtainedfrom 28 schizophrenic patients and 20 healthy controlsubjects during a resting condition. The generators of thefocal magnetic slow waves were located employing asingle moving dipole model. Distributed or multiple deltaand theta sources were captured by the minimum normestimate.Results: Both localization procedures showed slow waveactivity to be enhanced in schizophrenic patients comparedwith control subjects. Focal slow wave activitydiffered most between groups in frontotemporal and inposterior regions. Slow wave activity was associated withsymptom characteristics in that positive symptoms variedwith frontal delta and theta activity.Conclusions: Results indicate that activity in low-frequencybands in schizophrenic patients exceeds the activityof control subjects in distinct areas, and that this focalclustering of neuromagnetic slow waves may be related to psychopathologic characteristics.

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.

In the study of addiction, attentional bias refers to the observation that substance-related cues tend to capture the attention of experienced substance users. Attentional bias is a cognitive intermediate in the conditioned association between drug-related cues, craving, and relapse. Numerous studies have documented the existence of attentional bias for cues associated with substances. By contrast, few studies have investigated attentional bias in individuals with pathological gambling (PG) or problematic gambling. In this study, we sought to assess attentional bias at the level of maintenance of attention in a sample of pathological gamblers. Twenty-three pathological gamblers and 21 healthy volunteers performed the Visual Probe Task to compare attentional bias with gambling-related cues between individuals with PG and healthy volunteers. The measured of attentional bias was based on their reaction times (RTs) to probes replacing neutral and gambling-related cues (images). Second, we examined the correlation between PG severity and degree of attentional bias among individuals with PG. Results show that pathological gamblers, but not healthy volunteers, had attentional bias for gambling-related cues with exposure times that assess maintenance of attention. There was no correlation between PG severity and degree of attentional bias. Theoretical and clinical implications of these results are discussed.

New diagnostic criteria for Alzheimer's disease (AD) stress the role of in vivo biomarkers. Neurophysiological markers are usually not considered as such criteria, although theoretical and practical reasons would justify them. In order to assess the value of neurophysiology as an AD biomarker, whole-head magnetoencephalographic (MEG) resting state recordings were obtained from 35 AD patients, 23 mild cognitive impairment (MCI) patients, and 24 healthy controls. The AD group was further split into two groups differing in severity according to the GDS/FAST criteria. A Minimum Norm Estimation procedure was utilized to estimate the cortical origin of slow brain oscillatory activity in the delta band (2–4 Hz). Eight regions of interest (ROIs) discriminated between AD patients and controls. Delta current density (DCD) in all ROIs showed a significant negative correlation with cognitive status (p < 0.001). DCD values in posterior parietal, occipital, prerolandic, and precuneus cortices distinguished reliably between MCI patients, AD patients with different severity scores, and controls. Importantly, an increase of DCD in right parietal cortex and precuneus indexed the transition from MCI to mild dementia and from mild to more severe dementia. MEG delta mapping might be a serious candidate for a “neural degeneration” marker of AD reflecting dysfunctional synaptic transmission. More importantly, the localization of DCD values is in line with functional imaging markers of AD. However, MEG delta mapping is a totally non-invasive technique that directly measures neural activity. We propose that individuals with enhanced DCD in posterior parietal and precuneus cortices are at risk of progression to full dementia.

It is well established that aesthetic appreciation is related with activity in several different brain regions. The identification of the neural correlates of beauty or liking ratings has been the focus of most prior studies. Not much attention has been directed towards the fact that humans are surrounded by objects that lead them to experience aesthetic indifference or leave them with a negative aesthetic impression. Here we explore the neural substrate of such experiences. Given the neuroimaging techniques that have been used, little is known about the temporal features of such brain activity. By means of magnetoencephalography we registered the moment at which brain activity differed while participants viewed images they considered to be beautiful or not. Results show that the first differential activity appears between 300 and 400 ms after stimulus onset. During this period activity in right lateral orbitofrontal cortex (lOFC) was greater while participants rated visual stimuli as not beautiful than when they rated them as beautiful. We argue that this activity is associated with an initial negative aesthetic impression formation, driven by the relative hedonic value of stimuli regarded as not beautiful. Additionally, our results contribute to the understanding of the nature of the functional roles of the lOFC.

An increasing number of neuroimaging studies are concerned with the identification of interactions or statistical dependencies between brain areas. Dependencies between the activities of different brain regions can be quantified with functional connectivity measures such as the cross-correlation coefficient. An important factor limiting the accuracy of such measures is the amount of empirical data available. For event-related protocols, the amount of data also affects the temporal resolution of the analysis. We use analytical expressions to calculate the amount of empirical data needed to establish whether a certain level of dependency is significant when the time series are autocorrelated, as is the case for biological signals. These analytical results are then contrasted with estimates from simulations based on real data recorded with magnetoencephalography during a resting-state paradigm and during the presentation of visual stimuli. Results indicate that, for broadband signals, 50–100s of data is required to detect a true underlying cross-correlations coefficient of 0.05. This corresponds to a resolution of a few hundred milliseconds for typical event-related recordings. The required time window increases for narrow band signals as frequency decreases. For instance, approximately 3 times as much data is necessary for signals in the alpha band. Important implications can be derived for the design and interpretation of experiments to characterize weak interactions, which are potentially important for brain processing.

One of the current issues of debate in the study of mild cognitive impairment (MCI) is deviations of oscillatory brain responses from normal brain states and its dynamics. This work aims to characterize the differences of power in brain oscillations during the execution of a recognition memory task in MCI subjects in comparison with elderly controls. Magnetoencephalographic (MEG) signals were recorded during a continuous recognition memory task performance. Oscillatory brain activity during the recognition phase of the task was analyzed by wavelet transform in the source space by means of minimum norm algorithm. Both groups obtained a 77% hit ratio. In comparison with healthy controls, MCI subjects showed increased theta (p < 0.001), lower beta reduction (p < 0.001) and decreased alpha and gamma power (p < 0.002 and p < 0.001 respectively) in frontal, temporal and parietal areas during early and late latencies. Our results point towards a dual pattern of activity (increase and decrease) which is indicative of MCI and specific to certain time windows, frequency bands and brain regions. These results could represent two neurophysiological sides of MCI. Characterizing these opposing processes may contribute to the understanding of the disorder.

It has been reported that mild cognitive impairment (MCI) patients, when compared with controls, show increased activity in different brain regions within the ventral pathway during memory tasks. A key question is whether this profile of increased activity could be useful to predict which patients will develop dementia. Herein, we present profiles of brain magnetic activity during a memory task recorded with magnetoencephalography from MCI patients (N = 10), Alzheimer's disease (AD) patients (N = 10), and healthy volunteers (N = 17). After 2½ years of follow-up, five of the MCI patients developed AD. Patients who progressed to AD (PMCI) showed higher activity than those who remained stable (SMCI), AD patients and controls. This increased activity in PMCI patients involves regions within the ventral and dorsal pathways. In contrast, SMCI patients showed higher activation than controls only along the ventral pathway. This increase in both the ventral and dorsal pathways in PMCI patients may reflect a compensatory mechanism for the loss in efficiency in memory networks, which would be absent in AD patients as they showed lower activity levels than the rest of the groups.