Automated emotion classification in the early stages of cortical processing: An MEG study.

PURPOSE: Here we aimed to automatically classify human emotion earlier than is typically attempted. There is increasing evidence that the human brain differentiates emotional categories within 100-300 ms after stimulus onset. Therefore, here we evaluate the possibility of automatically classifying human emotions within the first 300 ms after the stimulus and identify the time-interval of the highest classification performance. METHODS: To address this issue, MEG signals of 17 healthy volunteers were recorded in response to three different picture stimuli (pleasant, unpleasant, and neutral pictures). Six Linear Discriminant Analysis (LDA) classifiers were used based on two binary comparisons (pleasant versus neutral and unpleasant versus neutral) and three different time-intervals (100-150 ms, 150-200 ms, and 200-300 ms post-stimulus). The selection of the feature subsets was performed by Genetic Algorithm and LDA. RESULTS: We demonstrated significant classification performances in both comparisons. The best classification performance was achieved with a median AUC of 0.83 (95 %- CI [0.71; 0.87]) classifying brain responses evoked by unpleasant and neutral stimuli within 100-150 ms, which is at least 850 ms earlier than attempted by other studies. CONCLUSION: Our results indicate that using the proposed algorithm, brain emotional responses can be significantly classified at very early stages of cortical processing (within 300 ms). Moreover, our results suggest that emotional processing in the human brain occurs within the first 100-150 ms.

The Temporal and Spatial Dynamics of Cortical Emotion Processing in Different Brain Frequencies as Assessed Using the Cluster-Based Permutation Test: An MEG Study.

The processing of emotions in the human brain is an extremely complex process that extends across a large number of brain areas and various temporal processing steps. In the case of magnetoencephalography (MEG) data, various frequency bands also contribute differently. Therefore, in most studies, the analysis of emotional processing has to be limited to specific sub-aspects. Here, we demonstrated that these problems can be overcome by using a nonparametric statistical test called the cluster-based permutation test (CBPT). To the best of our knowledge, our study is the first to apply the CBPT to MEG data of brain responses to emotional stimuli. For this purpose, different emotionally impacting (pleasant and unpleasant) and neutral pictures were presented to 17 healthy subjects. The CBPT was applied to the power spectra of five brain frequencies, comparing responses to emotional versus neutral stimuli over entire MEG channels and time intervals within 1500 ms post-stimulus. Our results showed significant clusters in different frequency bands, and agreed well with many previous emotion studies. However, the use of the CBPT allowed us to easily include large numbers of MEG channels, wide frequency, and long time-ranges in one study, which is a more reliable alternative to other studies that consider only specific sub-aspects.

Abnormal Emotional Processing and Emotional Experience in Patients with Peripheral Facial Nerve Paralysis: An MEG Study.

Abnormal emotional reactions of the brain in patients with facial nerve paralysis have not yet been reported. This study aims to investigate this issue by applying a machine-learning algorithm that discriminates brain emotional activities that belong either to patients with facial nerve paralysis or to healthy controls. Beyond this, we assess an emotion rating task to determine whether there are differences in their experience of emotions. MEG signals of 17 healthy controls and 16 patients with facial nerve paralysis were recorded in response to picture stimuli in three different emotional categories (pleasant, unpleasant, and neutral). The selected machine learning technique in this study was the logistic regression with LASSO regularization. We demonstrated significant classification performances in all three emotional categories. The best classification performance was achieved considering features based on event-related fields in response to the pleasant category, with an accuracy of 0.79 (95% CI (0.70, 0.82)). We also found that patients with facial nerve paralysis rated pleasant stimuli significantly more positively than healthy controls. Our results indicate that the inability to express facial expressions due to peripheral motor paralysis of the face might cause abnormal brain emotional processing and experience of particular emotions.

Attention modulates topology and dynamics of auditory sensory gating.

This work challenges the widely accepted model of sensory gating as a preattention inhibitory process by investigating whether attention directed at the second tone (S2) within a paired-click paradigm could affect gating at the cortical level. We utilized magnetoencephalography, magnetic resonance imaging and spatio-temporal source localization to compare the cortical dynamics underlying gating responses across two conditions (passive and attention) in 19 healthy subjects. Source localization results reaffirmed the existence of a fast processing pathway between the prefrontal cortex (PFC) and bilateral superior temporal gyri (STG) that underlies the auditory gating process. STG source dynamics comprised two gating sub-components, Mb1 and Mb2, both of which showed significant gating suppression (>51%). The attention directed to the S2 tone changed the gating network topology by switching the prefrontal generator from a dorsolateral location, which was active in the passive condition (18/19), to a medial location, active in the attention condition (19/19). Enhanced responses to the attended stimulus caused a significant reduction in gating suppression in both STG gating components (>50%). Our results demonstrate that attention not only modulates sensory gating dynamics, but also exerts topological rerouting of information processing within the PFC. The present data, suggesting that the cortical levels of early sensory processing are subject to top-down influences, change the current view of gating as a purely automatic bottom-up process.

Impact of transcranial direct current stimulation on structural plasticity of the somatosensory system.

While there is a growing body of evidence regarding the behavioral and neurofunctional changes in response to the longitudinal delivery of transcranial direct current stimulation (tDCS), there is limited evidence regarding its structural effects. Therefore, the present study was intended to investigate the effect of repeatedly applied anodal tDCS over the primary somatosensory cortex on the gray matter (GM) and white matter (WM) compartment of the brain. Structural tDCS effects were, moreover, related to effects evidenced by functional imaging and behavioral assessment. tDCS was applied over the course of 5 days in 25 subjects with concomitant assessment of tactile acuity of the right and left index finger as well as imaging at baseline, after the last delivery of tDCS and at follow-up 4 weeks thereafter. Irrespective of the stimulation condition (anodal vs. sham), voxel-based morphometry revealed a behaviorally relevant decrease of GM in the precuneus co-localized with a functional change of its activity. Moreover, there was a decrease in GM of the bilateral lingual gyrus and the right cerebellum. Diffusion tensor imaging analysis showed an increase of fractional anisotropy exclusively in the tDCSanodal condition in the left frontal cortex affecting the final stretch of a somatosensory decision making network comprising the middle and superior frontal gyrus as well as regions adjacent to the genu of the corpus callosum. Thus, this is the first study in humans to identify structural plasticity in the GM compartment and tDCS-specific changes in the WM compartment in response to somatosensory learning.

The Use of Ostrich Eggs for In Ovo Research: Making Preclinical Imaging Research Affordable and Available.

In ovo studies are a valuable option in preclinical research, but imaging studies are severely limited by the costs of dedicated equipment needed for small-sized eggs. We sought to verify the feasibility of using larger, ostrich, eggs (Struthio camelus) for imaging on the PET/CT scanners used for routine clinical investigations. Methods: Ostrich eggs were incubated until shortly before hatching, prepared for intravitelline venous injection of contrast medium or radiotracer, and imaged using native CT, contrast-enhanced CT, and PET/CT. Any technical adaptations that were needed to improve the outcome were noted. Results: Of the 34 eggs initially incubated, 12 became fully available for imaging of embryonal development. In ovo imaging with conventional PET/CT not only was feasible but also provided images of good quality, including on dynamic PET imaging. Conclusion: In ovo imaging with ostrich eggs and routine clinical scanners may allow broader application of this field of preclinical research, obviating costly dedicated equipment and reducing the number of animals needed for classic animal research. Further experiments are warranted to refine this novel approach, especially to reduce motion artifacts and improve monitoring of viability.

Impact of transcranial direct current stimulation on somatosensory transfer learning: When the secondary somatosensory cortex comes into play.

Transfer learning is an immanent feature of perceptual learning. Yet, despite the increasingly widespread application of transcranial direct current stimulation (tDCS) to study learning, transfer effects in response to tDCS have not been studied. Therefore, the present study investigated the transfer of tactile acuity evoked by repeatedly applied anodal tDCS over the left primary somatosensory cortex (S1) over the course of five days from the dominant (right) to the non-dominant (left) index finger (IF). There was a complete transfer of improvement of the right IF to its contralateral homologue by follow-up four weeks later. Changes in tactile acuity of the left IF in the tDCSanodal condition were accompanied by a significant longitudinal change in functional connectivity between the left S1 and the right secondary somatosensory cortex (S2) assessed at day five of tDCS delivery and four week later. Moreover, we observed a close link between tactile acuity and (changes of) functional connectivity of the right S2 in the tDCSanodal condition identifying the S2 as neural correlate to mediate the transfer of tDCS effects in the somatosensory domain. These findings provide unprecedented evidence of transfer effects evoked by tDCS, implicate the S2 in somatosensory transfer learning and provide evidence in support of models of perceptual learning allocating learning to the reweighting of connections between different levels of processing.

The Influence of Eye Closure on Somatosensory Discrimination: A Trade-off Between Simple Perception and Discrimination.

We often close our eyes to improve perception. Recent results have shown a decrease of perception thresholds accompanied by an increase in somatosensory activity after eye closure. However, does somatosensory spatial discrimination also benefit from eye closure? We previously showed that spatial discrimination is accompanied by a reduction of somatosensory activity. Using magnetoencephalography, we analyzed the magnitude of primary somatosensory (somatosensory P50m) and primary auditory activity (auditory P50m) during a one-back discrimination task in 21 healthy volunteers. In complete darkness, participants were requested to pay attention to either the somatosensory or auditory stimulation and asked to open or close their eyes every 6.5 min. Somatosensory P50m was reduced during a task requiring the distinguishing of stimulus location changes at the distal phalanges of different fingers. The somatosensory P50m was further reduced and detection performance was higher during eyes open. A similar reduction was found for the auditory P50m during a task requiring the distinguishing of changing tones. The function of eye closure is more than controlling visual input. It might be advantageous for perception because it is an effective way to reduce interference from other modalities, but disadvantageous for spatial discrimination because it requires at least one top-down processing stage.

Dermatomal Organization of SI Leg Representation in Humans: Revising the Somatosensory Homunculus.

Penfield and Rasmussen's homunculus is the valid map of the neural body representation of nearly each textbook of biology, physiology, and neuroscience. The somatosensory homunculus places the foot representation on the mesial surface of the postcentral gyrus followed by the representations of the lower leg and the thigh in superio-lateral direction. However, this strong homuncular organization contradicts the "dermatomal" organization of spinal nerves. We used somatosensory-evoked magnetic fields and source analysis to study the leg's neural representation in the primary somatosensory cortex (SI). We show that the representation of the back of the thigh is located inferior to the foot's representation in SI whereas the front of the thigh is located laterally to the foot's representation. This observation indicates that the localization of the leg in SI rather follows the dermatomal organization of spinal nerves than the typical map of neighboring body parts as depicted in Penfield and Rasmussen's illustration of the somatosensory homunculus.

The loss of neural synchrony in the post septic brain.

OBJECTIVE: Survivors of sepsis often develop long-term neuropsychological malfunctions, which can be reversible to a certain extent. The following study aimed to investigate whether this recovery is due to a loss in neural synchrony by regarding the response to a given frequency. METHODS: Magnetoencephalography measurements were conducted in 36 survivors of severe sepsis and septic shock three times within a time range of 12months after discharge from intensive care unit. We analyzed steady state visual evoked responses using a set of familiar vs. unfamiliar pictures. RESULTS: Sepsis survivors exhibit oscillatory deficits in terms of an impaired response to periodic visual stimulation. Oscillatory deficits and neuropsychological impairments obtained by the DemTect questionnaire were strongly linked. Impaired responses were equally found during the presentation of familiar and unfamiliar stimuli. Compared to familiar stimuli however, the response to unfamiliar stimuli was significantly lower in the follow up but not in the post-acute stage. CONCLUSIONS: We assume that the processing of unfamiliar pictures requires a higher amount of networking. In case of a disrupted network, complex networking might not be maintained. SIGNIFICANCE: Results indicate that neural synchrony might be restored to a certain level while more complex networking remains impaired.

Behavioural and neurofunctional impact of transcranial direct current stimulation on somatosensory learning.

We investigated the effect of repeated delivery of anodal transcranial direct current stimulation (tDCS) on somatosensory performance and long-term learning. Over the course of five days, tDCS was applied to the primary somatosensory cortex (S1) by means of neuronavigation employing magnetencephalography (MEG). Compared to its sham application, tDCS promoted tactile learning by reducing the two-point discrimination threshold assessed by the grating orientation task (GOT) primarily by affecting intersessional changes in performance. These results were accompanied by alterations in the neurofunctional organization of the brain, as revealed by functional magnetic resonance imaging conducted prior to the study, at the fifth day of tDCS delivery and four weeks after the last application of tDCS. A decrease in activation at the primary site of anodal tDCS delivery in the left S1 along retention of superior tactile acuity was observed at follow-up four weeks after the application of tDCS. Thus, we demonstrate long-term effects that repeated tDCS imposes on somatosensory functioning. This is the first study to provide insight into the mode of operation of tDCS on the brain's response to long-term perceptual learning, adding an important piece of evidence from the domain of non-invasive brain stimulation to show that functional changes detectable by fMRI in primary sensory cortices participate in perceptual learning.

The Processing of Somatosensory Information Shifts from an Early Parallel into a Serial Processing Mode: A Combined fMRI/MEG Study.

The question regarding whether somatosensory inputs are processed in parallel or in series has not been clearly answered. Several studies that have applied dynamic causal modeling (DCM) to fMRI data have arrived at seemingly divergent conclusions. However, these divergent results could be explained by the hypothesis that the processing route of somatosensory information changes with time. Specifically, we suggest that somatosensory stimuli are processed in parallel only during the early stage, whereas the processing is later dominated by serial processing. This hypothesis was revisited in the present study based on fMRI analyses of tactile stimuli and the application of DCM to magnetoencephalographic (MEG) data collected during sustained (260 ms) tactile stimulation. Bayesian model comparisons were used to infer the processing stream. We demonstrated that the favored processing stream changes over time. We found that the neural activity elicited in the first 100 ms following somatosensory stimuli is best explained by models that support a parallel processing route, whereas a serial processing route is subsequently favored. These results suggest that the secondary somatosensory area (SII) receives information regarding a new stimulus in parallel with the primary somatosensory area (SI), whereas later processing in the SII is dominated by the preprocessed input from the SI.

Slowed peak resting frequency and MEG overactivation in survivors of severe sepsis and septic shock.

OBJECTIVE: Survivors of severe sepsis and septic shock suffer from residual severe cognitive impairments, which persist even years after intensive care unit (ICU) discharge. As the awareness of long-term consequences gradually grows, research has focused on cognitive impairments via questionnaires, but only few have focused on structural or electrophysiological features, such as the peak resting frequency, which is commonly seen as a hallmark of brain function. METHODS: We aimed to analyze the long-term progression of the peak resting activity in terms of frequency and power in sepsis survivors. Healthy individuals with no history of ICU stay served as controls. Data were collected three times (shortly, 6 and 12 months after ICU discharge) in sepsis survivors and three times in controls. Participants also underwent behavioral neuropsychological assessment. RESULTS: Sepsis survivors exhibited significantly higher spectral power of the dominant peak, which was shifted towards lower frequencies. Within one year, resting frequency increased to the level of controls, but power did not decrease. We observed a close correlation between resting frequency and mental status. CONCLUSIONS: Results support the assumption of a causal relationship between brain oscillations and behavioral performance. SIGNIFICANCE: We suggest that the postseptic frequency shift is due to abnormal thalamocortical dynamics.

Modality-independent reduction mechanisms of primary sensory evoked fields in a one-back task.

Attentional modulation of early, primary sensory components is still a topic of debate, as studies have produced conflicting results concerning the existence of a modulation within the primary somatosensory cortex and its direction. We previously showed that attention to tactile stimuli in a stream with visual stimuli leads to a reduction of primary somatosensory components when discrimination of different stimulus locations is requested. The question arises whether this effect is universal and independent from the distracting or attended modality. To test this, we compared the magnitude of primary somatosensory evoked fields (somatosensory P50m) in a one-back task after tactile finger stimulation during attention to tactile stimuli vs. auditory distraction in 28 volunteers. In comparison to acoustic distraction, we found a significantly decreased primary somatosensory activity when attending to tactile stimuli. Strikingly, similar results were produced within the auditory modality: when attention was focused on acoustic targets, primary auditory (auditory P50m) fields were lower as compared to the situation when attention was directed to the tactile stimulation. Our results clearly indicate that the type of task, independent from the modality, is actually the crucial factor for the direction of modulation of early sensory components by attention. Therefore, our finding of reduced primary sensory components in a discrimination task represents a universal effect independent from the distracting or attended modality.

Parallel processing of somatosensory information: Evidence from dynamic causal modeling of MEG data.

The advent of methods to investigate network dynamics has led to discussion of whether somatosensory inputs are processed in serial or in parallel. Both hypotheses are supported by DCM analyses of fMRI studies. In the present study, we revisited this controversy using DCM on magnetoencephalographic (MEG) data during somatosensory stimulation. Bayesian model comparison was used to allow for direct inference on the processing stream. Additionally we varied the duration of the time-window of analyzed data after the somatosensory stimulus. This approach allowed us to explore time dependent changes in the processing stream of somatosensory information and to evaluate the consistency of results. We found that models favoring a parallel processing route best describe neural activities elicited by somatosensory stimuli. This result was consistent for different time-windows. Although it is assumed that the majority of somatosensory information is delivered to the SI, the current results indicate that at least a small part of somatosensory information is delivered in parallel to the SII. These findings emphasize the importance of data analysis with high temporal resolution.

Thalamocortical impulse propagation and information transfer in EEG and MEG.

Measures of functional connectivity and information transfer between the thalamus and the cortex can provide detailed insight into brain function. Employing magnetoencephalography and electrical median nerve stimulation, it has been recently proposed that impulse propagation along the thalamocortical fiber tract can be described by a single moving dipole source. Other studies, however, using electroencephalography observed dipole clustering in the thalamus and the cortex. To assess the source of these conflicting results, we simultaneously recorded somatosensory evoked potentials and fields in 12 healthy volunteers. Using a single dipole model for the time interval of 10 to 30 milliseconds after stimulus onset, we found continuous thalamocortical dipole movement in 10 volunteers and dipole clustering in the precortical near thalamic and cortical regions in 2 volunteers. Thus, independent of the recording method, both clustering and movement can be observed. The degree of temporal overlap between the precortical near thalamic and the cortical activity distinguished the volunteers exhibiting clustering and those exhibiting movement. In a subsequent simulation study, we could show that both dipole clustering and dipole movement can occur, depending on the temporal overlap of the precortical and cortical activities. In conclusion, we propose a two-dipole model to better account for precortical and cortical activity and information transfer.

Cortical reorganization after macroreplantation at the upper extremity: a magnetoencephalographic study.

With the development of microsurgical techniques, replantation has become a feasible alternative to stump treatment after the amputation of an extremity. It is known that amputation often induces phantom limb pain and cortical reorganization within the corresponding somatosensory areas. However, whether replantation reduces the risk of comparable persisting pain phenomena as well as reorganization of the primary somatosensory cortex is still widely unknown. Therefore, the present study aimed to investigate the potential development of persistent pain and cortical reorganization of the hand and lip areas within the sensory cortex by means of magnetoencephalographic dipole analyses after replantation of a traumatically amputated upper limb proximal to the radiocarpal joint. Cortical reorganization was investigated in 13 patients with limb replantation using air puff stimulation of the phalanges of both thumbs and both corners of the lower lip. Displacement of the centre of gravity of lip and thumb representations and increased cortical activity were found in the limb and face areas of the primary somatosensory cortex contralateral to the replanted arm when compared to the ipsilateral hemisphere. Thus, cortical reorganization in the primary somatosensory cortex also occurs after replantation of the upper extremity. Patients' reports of pain in the replanted body part were negatively correlated with the amount of cortical reorganization, i.e. the more pain the patients reported, the less reorganization of the subjects' hand representation within the primary somatosensory cortex was observed. Longitudinal studies in patients after macroreplantation are necessary to assess whether the observed reorganization in the primary somatosensory cortex is a result of changes within the representation of the replanted arm and/or neighbouring representations and to assess the relationship between the development of persistent pain and reorganization.

Magnetic source localization of early visual mismatch response.

Previous studies have reported a visual analogue of the auditory mismatch negativity (MMN) response that is based on sensory memory. The neural generators and attention dependence of the visual MMN (vMMN) still remain unclear. We used magnetoencephalography (MEG) and spatio-temporal source localization to determine the generators of the sensory-memory-based vMMN response to non-attended deviants. Ten participants were asked to discriminate between odd and even digits presented at the center of the visual field while grating patterns with different spatial frequencies were presented outside the focus of attention. vMMN was calculated as the difference between MEG responses to infrequent gratings in oddball blocks and the same gratings in equiprobable blocks. The peak latency of the vMMN response was between 100 and 160 ms. The neuromagnetic sources of the vMMN localized in the occipital cortex differed from the sources evoked by the equiprobable gratings and were stimulus-dependent. Our results suggest the existence of separate neural systems for pre-attentive memory-based detection of visual change and provide new evidence that the vMMN is feature-specific.

Impaired evoked and resting-state brain oscillations in patients with liver cirrhosis as revealed by magnetoencephalography.

A number of studies suggest that the clinical manifestation of neurological deficits in hepatic encephalopathy results from pathologically synchronized neuronal oscillations and altered oscillatory coupling. In the present study spontaneous and evoked oscillatory brain activities were analyzed jointly with established behavioral measures of altered visual oscillatory processing. Critical flicker and fusion frequencies (CFF, FUF) were measured in 25 patients diagnosed with liver cirrhosis and 30 healthy controls. Magnetoencephalography (MEG) data were collected at rest and during a visual task employing repetitive stimulation. Resting MEG and evoked fields were analyzed. CFF and FUF were found to be reduced in patients, providing behavioral evidence for deficits in visual oscillatory processing. These alterations were found to be related to resting brain activity in patients, namely that the lower the dominant MEG frequency at rest, the lower the CFF and FUF. An analysis of evoked fields at sensor level indicated that in comparison to normal controls, patients were not able to dynamically adapt to flickering visual stimulation. Evoked activity was also analyzed based on independent components (ICs) derived by independent component analysis. The similarity between the shape of each IC and an artificial sine function representing the stimulation frequency was tested via magnitude squared coherence. In controls, we observed a small number of components that correlated strongly with the sine function and a high number of ICs that did not correlate with the sine function. Interestingly, patient data were characterized by a high number of moderately correlating components. Taken together, these results indicate a fundamental divergence of the cerebral resonance activity in cirrhotic patients.

Fetal development of complex autonomic control evaluated from multiscale heart rate patterns.

Development of the fetal autonomic nervous system's integrative capacity in relation to gestational age and emerging behavioral pattern is reflected in fetal heart rate patterns. Conventional indices of vagal and sympathetic rhythms cannot sufficiently reflect their complex interrelationship. Universal behavioral indices of developing complex systems may provide additional information regarding the maturating complex autonomic control. We investigated fetal magnetocardiographic recordings undertaken at 10-min intervals in active (n = 248) and quiet (n = 111) states between 22 and 39 wk gestational age. Standard deviation of heartbeat intervals, skewness, contribution of particular rhythms to the total power, and multiscale entropy were analyzed. The multiscale entropy methodology was validated for 10-min data sets. Age dependence was analyzed by linear regression. In the quiet state, contribution of sympathovagal rhythms and their complexity over a range of corresponding short scales increased with rising age, and skewness shifted from negative to positive values. In the active state, age dependencies were weaker. Skewness as the strongest parameter shifted in the same direction. Fluctuation amplitude and the complexity of scales associated with sympathovagal rhythms increased. We conclude that in the quiet state, stable complex organized rhythms develop. In the active state, however, increasing behavioral variability due to multiple internal coordinations, such as movement-related heart rate accelerations, and external influences develop. Hence, the state-selective assessment in association with developmental indices used herein may substantially improve evaluation of maturation age and early detection and interpretation of developmental problems in prenatal diagnosis.