Temporal precedence of emotion over attention modulations in the lateral amygdala: Intracranial ERP evidence from a patient with temporal lobe epilepsy

Previous fMRI studies have reported mixed evidence for the influence of selective attention on amygdala responses to emotional stimuli, with some studies showing "automatic" emotional effects to threat-related stimuli without attention (or even without awareness), but other studies showing a gating of amygdala activity by selective attention with no response to unattended stimuli. We recorded intracranial local field potentials from the intact left lateral amygdala in a human patient prior to surgery for epilepsy and tested, with a millisecond time resolution, for neural responses to fearful faces appearing at either task-relevant or task-irrelevant locations. Our results revealed an early emotional effect in the amygdala arising prior to, and independently of, attentional modulation. However, at a later latency, we found a significant modulation of the differential emotional response when attention was directed toward or away from fearful faces. These results suggest separate influences of emotion and attention on amygdala activation and may help reconcile previous discrepancies concerning the relative responsiveness of the human amygdala to emotional and attentional factors

Inferior frontal oscillations reveal visuo-motor matching for actions and speech: evidence from human intracranial recordings.

The neural correspondence between the systems responsible for the execution and recognition of actions has been suggested both in humans and non-human primates. Apart from being a key region of this visuo-motor observation-execution matching (OEM) system, the human inferior frontal gyrus (IFG) is also important for speech production. The functional overlap of visuo-motor OEM and speech, together with the phylogenetic history of the IFG as a motor area, has led to the idea that speech function has evolved from pre-existing motor systems and to the hypothesis that an OEM system may exist also for speech. However, visuo-motor OEM and speech OEM have never been compared directly. We used electrocorticography to analyze oscillations recorded from intracranial electrodes in human fronto-parieto-temporal cortex during visuo-motor (executing or visually observing an action) and speech OEM tasks (verbally describing an action using the first or third person pronoun). The results show that neural activity related to visuo-motor OEM is widespread in the frontal, parietal, and temporal regions. Speech OEM also elicited widespread responses partly overlapping with visuo-motor OEM sites (bilaterally), including frontal, parietal, and temporal regions. Interestingly a more focal region, the inferior frontal gyrus (bilaterally), showed both visuo-motor OEM and speech OEM properties independent of orolingual speech-unrelated movements. Building on the methodological advantages in human invasive electrocorticography, the present findings provide highly precise spatial and temporal information to support the existence of a modality-independent action representation system in the human brain that is shared between systems for performing, interpreting and describing actions

Seizure onset zone localization from ictal high-density EEG in five patients

Rationale Because epilepsy is a network disease, localization of the exact seizure onset zone (SOZ) is difficult because the epileptic activity can spread to other regions within milliseconds. Functional connectivity metrics quantify how the activity in different brain regions is interrelated. In the past, it has been shown that functional connectivity analysis of ictal intracranial EEG (icEEG) recordings can help with SOZ localization in patients with focal epilepsy (van Mierlo et al., 2014). However, it would be of high clinical value to be able to localize the SOZ based on non-invasive ictal EEG recordings to optimize the icEEG implantation scheme or to avoid invasive monitoring and improve surgical outcome. In this work, we propose an approach to localize the SOZ based on non-invasive ictal high-density EEG (hd-EEG) recordings. Methods We considered retrospective ictal epochs of 2.4 s up to 10 s recorded with hd-EEG (256 electrodes) in five patients who were rendered seizure free after surgery. From the 256 electrodes, the facial electrodes were removed, resulting in a subset of 204 electrodes. A 28-channel subset was constructed to mimic a low-density (ld) electrode setup used in clinical practice. EEG source imaging (ESI) was performed in the CARTOOL software using an individual head model (LSMAC) to calculate the forward model (Brunet et al., 2011). We considered sources uniformly distributed in the brain with a spacing of 5 mm. LORETA (Pascal-Marqui et al., 1994) was used as inverse solution method. In each cluster of activity, we determined a central source based on the criterion that there was no higher power in its neighborhood. The time-varying connectivity pattern between the time series of these sources was calculated using Granger causality (van Mierlo et al., 2013). This was done in the frequency band containing the fundamental seizure frequency, 3-30Hz. The outdegree of each selected dipole was determined as the sum over time of all outgoing connections. Around the dipole with the highest outdegree, we determined a region of dipoles that had a power that was at least 90% of the power of the center dipole. This region was then considered as the SOZ. Results We were able to successfully localize the driver in the resected zone for all patients based on ESI followed by connectivity analysis of the hd-EEG (mean localization error (LE) = 0 mm). If we chose the cluster with the highest power as driver, the mean LE was 59.69 mm. For the ld-EEG, ESI followed by connectivity analysis resulted in a mean LE of 23.30 mm and when selecting the cluster with the highest power as driver, the mean LE was 31.21 mm. Conclusions ESI in combination with connectivity analysis can successfully localize the SOZ in non-invasive ictal hd-EEG recordings and greatly outperforms localization based on power. For ld-EEG recordings, the localization error remains significant but still outperforms localization based on power. This could have important clinical relevance for the presurgical evaluation in focal epilepsy

Organisation of cross-sector collaboration and its influence on crisis management effectiveness among pharmaceutical supply chain stakeholders during the COVID-19 pandemic

Objectives: To investigate the organisation of cross-sector collaboration and how it influenced crisis management effectiveness among pharmaceutical supply chain stakeholders in Finland during the COVID-19 pandemic. Study design: Qualitative semi-structured interview study. Methods: Purposeful selection was used to obtain the study sample consisting of leaders and specialists from the pharmaceutical industry and wholesalers (n = 9), community pharmacy owners (n = 9), hospital pharmacy heads (n = 6), government agency directors and officials (n = 5) and advocacy organisation representatives (n = 2). Inductive content analysis was performed to examine the data from the semi-structured individual (n = 29) and paired (n = 2) interviews in March–May 2021. Results: A new conceptual model was developed to describe the organisation of collaborative crisis management. Without a predefined crisis management organisation, cross-sector collaboration was organised based on previous collaboration structures, channels and relationships and through the establishment of issue-specific groups by government agencies as per legal mandates. Crisis dynamics and related issues guided the group formation and meeting frequency. Advocacy organisations and government agencies acted in bridging role between stakeholders. Shared knowledge among pharmaceutical supply chain stakeholders enabled anticipation and preparedness during crisis; shared resources fostered maintenance of core functions; and shared problem-solving facilitated cross-sectoral solutions. Conclusion: This was the first study exploring cross-sector collaboration among pharmaceutical supply chain stakeholders during a crisis. Sharing knowledge, resources and problem-solving increased the crisis management effectiveness. The study presented a new illustration of organising for collaborative crisis management and added knowledge about private-third sector collaboration and issue-specific groups to the cross-sector collaboration and crisis management literature

Decoding sequence learning from single-trial intracranial EEG in humans.

We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG) after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM) that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep) in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT) using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep) or a later consolidated phase (day 2, after sleep), whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence). Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition) at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes

Errors recruit both cognitive and emotional monitoring systems: Simultaneous intracranial recordings in the dorsal anterior cingulate gyrus and amygdala combined with fMRI

We studied error monitoring in a human patient with unique implantation of depth electrodes in both the left dorsal cingulate gyrus and medial temporal lobe prior to surgery. The patient performed a speeded go/nogo task and made a substantial number of commission errors (false alarms). As predicted, intracranial Local Field Potentials (iLFPs) in dorsal anterior cingulate indexed the detection of errors, showing an early differential activity around motor execution for false alarms, relative to correct responses (either hits or correct inhibitions). More surprisingly, we found that the left amygdala also participated to error monitoring (although no emotional stimuli were used), but with a very different neurophysiological profile as compared with the dorsal cingulate cortex. Amygdala iLFPs showed a precise and reproducible temporal unfolding, characterized by an early monophasic response for correct hits around motor execution, which was delayed by approximately 300ms for errors (even though actual RTs were almost identical in these two conditions). Moreover, time-frequency analyses demonstrated a reliable and transient coupling in the theta band around motor execution between these two distant regions. Additional fMRI investigation in the same patient confirmed a differential involvement of the dorsal cingulate cortex vs. amygdala in error monitoring during this go/nogo task. Finally, these intracranial results for the left amygdala were replicated in a second patient with intracranial electrodes in the right amygdala. Altogether, these results suggest that the amygdala may register the motivational significance of motor actions on a trial-by-trial basis, while the dorsal anterior cingulate cortex may provide signals concerning failures of cognitive control and behavioral adjustment. More generally, these data shed new light on neural mechanisms underlying self-monitoring by showing that even "simple" motor actions recruit not only executive cognitive processes (in dorsal cingulate) but also affective processes (in amygdala)

Temporal lobe epilepsy and postural orthostatic tachycardia syndrome (POTS)

We describe a 20-year-old woman suffering from right temporal epilepsy, behavioral disorder, and a complaint of paroxysmal palpitations accompanied by anxiety. Detailed cardiac evaluation revealed that the palpitations were due to episodes of marked sinus tachycardia secondary to a concomitant postural orthostatic tachycardia syndrome (POTS) and not of psychogenic origin as initially thought. Treatment with a beta-blocker resulted in the disappearance of palpitations and the associated anxiety. This is the first report of the coexistence of partial epilepsy and POTS. The recognition of such a syndrome in epileptic patients is important in order to offer appropriate therapy

Direction-specific motion blindness induced by focal stimulation of human extrastriate cortex

Motion blindness (MB) or akinetopsia is the selective disturbance of visual motion perception while other features of the visual scene such as colour and shape are normally perceived. Chronic and transient forms of MB are characterized by a global deficit of direction discrimination (pandirectional), which is generally assumed to result from damage to, or interference with, the motion complex MT+/V5. However, the most characteristic feature of primate MT-neurons is not their motion specificity, but their preference for one direction of motion (direction specificity). Here, we report that focal electrical stimulation in the human posterior temporal lobe selectively impaired the perception of motion in one direction while the perception of motion in other directions was completely normal (unidirectional MB). In addition, the direction of MB was found to depend on the brain area stimulated. It is argued that direction specificity for visual motion is not only represented at the single neuron level, but also in much larger cortical units

Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients

Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission-computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (<32 channels) and a template head model. This study demonstrated the validity and clinical utility of electric source imaging in a large prospective study. Given the low cost and high flexibility of electroencephalographic systems even with high channel counts, we conclude that electric source imaging is a highly valuable tool in pre-surgical epilepsy evaluatio