Common and distinct patterns underlying different linguistic tasks: multivariate disconnectome symptom mapping in poststroke patients.

Numerous studies have been devoted to neural mechanisms of a variety of linguistic tasks (e.g. speech comprehension and production). To date, however, whether and how the neural patterns underlying different linguistic tasks are similar or differ remains elusive. In this study, we compared the neural patterns underlying 3 linguistic tasks mainly concerning speech comprehension and production. To address this, multivariate regression approaches with lesion/disconnection symptom mapping were applied to data from 216 stroke patients with damage to the left hemisphere. The results showed that lesion/disconnection patterns could predict both poststroke scores of speech comprehension and production tasks; these patterns exhibited shared regions on the temporal pole of the left hemisphere as well as unique regions contributing to the prediction for each domain. Lower scores in speech comprehension tasks were associated with lesions/abnormalities in the superior temporal gyrus and middle temporal gyrus, while lower scores in speech production tasks were associated with lesions/abnormalities in the left inferior parietal lobe and frontal lobe. These results suggested an important role of the ventral and dorsal stream pathways in speech comprehension and production (i.e. supporting the dual stream model) and highlighted the applicability of the novel multivariate disconnectome-based symptom mapping in cognitive neuroscience research.

Type III and IV deformation twins in minerals and metals.

SignificanceHistorically, two types of twins (I and II) have been categorized for twinning in minerals and metals. When analyzed by the topological model, a crystallographic construction used to define the defect structure of interfaces, triclinic and some other low-symmetry crystals do not fall into either category and instead form two new twinning types, namely, III and IV. Aside from accurately describing twin structures, these concepts are important for understanding the deformation of minerals such as plagioclase and for deriving constitutive models for the deformation.

In Situ TEM Tracking of Disconnection Motion and Atomic Cooperative Reorientation in the Oriented Attachment of Pt Nanoparticles.

The oriented attachment (OA) of nanoparticles (NPs) is an important crystal growth mechanism in many materials. However, a comprehensive understanding of the atomic-scale alignment and attachment processes is still lacking. We conducted in situ atomic resolution studies using high-resolution transmission electron microscopy to reveal how two Pt NPs coalesce into a single particle via OA, which involves the formation of atomic-scale links and a grain boundary (GB) between the NPs, as well as GB migration. Density functional theory calculations showed that the system energy changes as a function of the number of disconnections during the coalescence process. Additionally, the formation and annihilation processes of disconnection are always accompanied by the cooperative reorientation motion of atoms. These results further elucidate the growth mechanism of OA at the atomic scale, providing microscopic insights into OA dynamics and a framework for the development of processing strategies for nanocrystalline materials.

Role of Piriform Cortex and Its Afferent Projections in Relapse to Fentanyl Seeking after Food Choice-Induced Voluntary Abstinence.

We previously demonstrated a role of piriform cortex (Pir) in relapse to fentanyl seeking after food choice-induced voluntary abstinence. Here, we used this model to further study the role of Pir and its afferent projections in fentanyl relapse. We trained male and female rats to self-administer palatable food pellets for 6 d (6 h/day) and fentanyl (2.5 µg/kg/infusion, i.v.) for 12 d (6 h/day). We assessed relapse to fentanyl seeking after 12 voluntary abstinence sessions, achieved through a discrete choice procedure between fentanyl and palatable food (20 trials/session). We determined projection-specific activation of Pir afferents during fentanyl relapse with Fos plus the retrograde tracer cholera toxin B (injected into Pir). Fentanyl relapse was associated with increased Fos expression in anterior insular cortex (AI) and prelimbic cortex (PL) neurons projecting to Pir. We next used an anatomical disconnection procedure to determine the causal role of these two projections (AI→Pir and PL→Pir) in fentanyl relapse. Contralateral but not ipsilateral disconnection of AI→Pir projections decreased fentanyl relapse but not reacquisition of fentanyl self-administration. In contrast, contralateral but not ipsilateral disconnection of PL→Pir projections modestly decreased reacquisition but not relapse. Fluorescence-activated cell sorting and quantitative PCR data showed molecular changes within Pir Fos-expressing neurons associated with fentanyl relapse. Finally, we found minimal or no sex differences in fentanyl self-administration, fentanyl versus food choice, and fentanyl relapse. Our results indicate that AI→Pir and PL→Pir projections play dissociable roles in nonreinforced relapse to fentanyl seeking versus reacquisition of fentanyl self-administration after food choice-induced voluntary abstinence.SIGNIFICANCE STATEMENT We previously showed a role of Pir in fentanyl relapse after food choice-induced voluntary abstinence in rats, a procedure mimicking human abstinence or a significant reduction in drug self-administration because of the availability of alternative nondrug rewards. Here, we aimed to further characterize the role of Pir in fentanyl relapse by investigating the role of Pir afferent projections and analyzing molecular changes in relapse-activated Pir neurons. We identified dissociable roles of two Pir afferent projections (AI→Pir and PL→Pir) in relapse to fentanyl seeking versus reacquisition of fentanyl self-administration after voluntary abstinence. We also characterized molecular changes within Pir Fos-expressing neurons associated with fentanyl relapse.

Distributed associations among white matter hyperintensities and structural brain networks with fluid cognition in healthy aging.

White matter hyperintensities (WMHs) are associated with age-related cognitive impairment and increased risk of Alzheimer's disease. However, the manner by which WMHs contribute to cognitive impairment is unclear. Using a combination of predictive modeling and network neuroscience, we investigated the relationship between structural white matter connectivity and age, fluid cognition, and WMHs in 68 healthy adults (18-78 years). Consistent with previous work, WMHs were increased in older adults and exhibited a strong negative association with fluid cognition. Extending previous work, using predictive modeling, we demonstrated that age, WMHs, and fluid cognition were jointly associated with widespread alterations in structural connectivity. Subcortical-cortical connections between the thalamus/basal ganglia and frontal and parietal regions of the default mode and frontoparietal networks were most prominent. At the network level, both age and WMHs were negatively associated with network density and communicability, and positively associated with modularity. Spatially, WMHs were most prominent in arterial zones served by the middle cerebral artery and associated lenticulostriate branches that supply subcortical regions. Finally, WMHs overlapped with all major white matter tracts, most prominently in tracts that facilitate subcortical-cortical communication and are implicated in fluid cognition, including the anterior thalamic-radiations and forceps minor. Finally, results of mediation analyses suggest that whole-brain WMH load influences age-related decline in fluid cognition. Thus, across multiple levels of analysis, we showed that WMHs were increased in older adults and associated with altered structural white matter connectivity and network topology involving subcortical-cortical pathways critical for fluid cognition.

Topographic mapping of the sensorimotor qualities of empathic reactivity: A psychophysiological study in people with spinal cord injuries.

The experience of empathy for pain is underpinned by sensorimotor and affective dimensions which, although interconnected, are at least in part behaviorally and neurally distinct. Spinal cord injuries (SCI) induce a massive, below-lesion level, sensorimotor body-brain disconnection. This condition may make it possible to test whether sensorimotor deprivation alters specific dimensions of empathic reactivity to observed pain. To explore this issue, we asked SCI people with paraplegia and healthy controls to observe videos of painful or neutral stimuli administered to a hand (intact) or a foot (deafferented). The stimuli were displayed by means of a virtual reality set-up and seen from a first person (1PP) or third person (3PP) visual perspective. A number of measures were recorded ranging from explicit behaviors like explicit verbal reports on the videos, to implicit measures of muscular activity (like EMG from the corrugator and zygomatic muscles that may represent a proxy of sensorimotor empathy) and of autonomic reactivity (like the electrodermal response and Respiratory Sinus Arrhythmia that may represent a general proxy of affective empathy). While no across group differences in explicit verbal reports about the pain stimuli were found, SCI people exhibited reduced facial muscle reactivity to the stimuli applied to the foot (but not the hand) seen from the 1PP. Tellingly, the corrugator activity correlated with SCI participants' neuropathic pain. There were no across group differences in autonomic reactivity suggesting that SCI lesions may affect sensorimotor dimensions connected to empathy for pain.

Thalamocortical disconnection involved in pusher syndrome.

The presence of both isolated thalamic and isolated cortical lesions have been reported in the context of pusher syndrome-a disorder characterized by a disturbed perception of one's own upright body posture, following unilateral left- or right-sided stroke. In recent times, indirect quantification of functional and structural disconnection increases the knowledge derived from focal brain lesions by inferring subsequent brain network damage from the respective lesion. We applied both measures to a sample of 124 stroke patients to investigate brain disconnection in pusher syndrome. Our results suggest a hub-like function of the posterior and lateral portions of the thalamus in the perception of one's own postural upright. Lesion network symptom mapping investigating functional disconnection indicated cortical diaschisis in cerebellar, frontal, parietal and temporal areas in patients with thalamic lesions suffering from pusher syndrome, but there was no evidence for functional diaschisis in pusher patients with cortical stroke and no evidence for the convergence of thalamic and cortical lesions onto a common functional network. Structural disconnection mapping identified posterior thalamic disconnection to temporal, pre-, post- and paracentral regions. Fibre tracking between the thalamic and cortical pusher lesion hotspots indicated that in cortical lesions of patients with pusher syndrome, it is disconnectivity to the posterior thalamus caused by accompanying white matter damage, rather than the direct cortical lesions themselves, that lead to the emergence of pusher syndrome. Our analyses thus offer the first evidence for a direct thalamo-cortical (or cortico-thalamic) interconnection and, more importantly, shed light on the location of the respective thalamo-cortical disconnections. Pusher syndrome seems to be a consequence of direct damage or of disconnection of the posterior thalamus.

Thalamostriatal disconnection underpins long-term seizure freedom in frontal lobe epilepsy surgery.

Around 50% of patients undergoing frontal lobe surgery for focal drug-resistant epilepsy become seizure free post-operatively; however, only about 30% of patients remain seizure free in the long-term. Early seizure recurrence is likely to be caused by partial resection of the epileptogenic lesion, whilst delayed seizure recurrence can occur even if the epileptogenic lesion has been completely excised. This suggests a coexistent epileptogenic network facilitating ictogenesis in close or distant dormant epileptic foci. As thalamic and striatal dysregulation can support epileptogenesis and disconnection of cortico-thalamostriatal pathways through hemispherotomy or neuromodulation can improve seizure outcome regardless of focality, we hypothesize that projections from the striatum and the thalamus to the cortex may contribute to this common epileptogenic network. To this end, we retrospectively reviewed a series of 47 consecutive individuals who underwent surgery for drug-resistant frontal lobe epilepsy. We performed voxel-based and tractography disconnectome analyses to investigate shared patterns of disconnection associated with long-term seizure freedom. Seizure freedom after 3 and 5 years was independently associated with disconnection of the anterior thalamic radiation and anterior cortico-striatal projections. This was also confirmed in a subgroup of 29 patients with complete resections, suggesting these pathways may play a critical role in supporting the development of novel epileptic networks. Our study indicates that network dysfunction in frontal lobe epilepsy may extend beyond the resection and putative epileptogenic zone. This may be critical in the pathogenesis of delayed seizure recurrence as thalamic and striatal networks may promote epileptogenesis and disconnection may underpin long-term seizure freedom.

Evaluation of putative signatures of consciousness using specific definitions of responsiveness, connectedness, and consciousness.

BACKGROUND: Understanding the neural correlates of consciousness has important ramifications for the theoretical understanding of consciousness and for clinical anaesthesia. A major limitation of prior studies is the use of responsiveness as an index of consciousness. We identified a collection of measures derived from unresponsive subjects and more specifically their association with consciousness (any subjective experience) or connectedness (specific experience of environmental stimuli). METHODS: Using published data generated through the UNderstanding Consciousness Connectedness and Intra-Operative Unresponsiveness Study (NCT03284307), we evaluated 10 previously published resting-state EEG-based measures that were derived using unresponsiveness as a proxy for unconsciousness. Measures were tested across dexmedetomidine and propofol sedation and natural sleep. These markers represent the complexity, connectivity, cross-frequency coupling, graph theory, and power spectrum measures. RESULTS: Although many of the proposed markers were associated with consciousness per se (reported subjective experience), none were specific to consciousness alone; rather, each was also associated with connectedness (i.e. awareness of the environment). In addition, multiple markers showed no association with consciousness and were associated only with connectedness. Of the markers tested, loss of normalised-symbolic transfer entropy (front to back) was associated with connectedness across all three experimental conditions, whereas the transition from disconnected consciousness to unconsciousness was associated with significant decreases in permutation entropy and spectral exponent (P<0.05 for all conditions). CONCLUSIONS: None of the proposed EEG-based neural correlates of unresponsiveness corresponded solely to consciousness, highlighting the need for a more conservative use of the term (un)consciousness when assessing unresponsive participants. CLINICAL TRIAL REGISTRATION: NCT03284307.

A fronto-insular-parietal network for the sense of body ownership.

Neuropsychological disturbances in the sense of limb ownership provide unique opportunities to study the neurocognitive basis of body ownership. Previous small sample studies that showed discrete cortical lesions cannot explain why multisensory, affective, and cognitive manipulations alter disownership symptoms. We tested the novel hypothesis that disturbances in the sense of limb ownership would be associated not only with discrete cortical lesions but also with disconnections of white-matter tracts supporting specific functional networks. We drew on an advanced lesion-analysis and Bayesian statistics approach in 49 right-hemisphere patients (23 with and 26 without limb disownership). Our results reveal that disturbances in the sense of ownership are associated with lesions in the supramarginal gyrus and disconnections of a fronto-insular-parietal network, involving the frontal-insular and frontal inferior longitudinal tracts, confirming previous disconnection hypotheses. Together with previous behavioral and neuroanatomical results, these findings lead us to propose that the sense of body ownership involves the convergence of bottom-up, multisensory integration, and top-down monitoring of sensory salience based on contextual demands.

Endoscopic callosotomy as a minimally invasive approach to treat paediatric refractory epilepsy: case series.

BACKGROUND: Endoscopic callosotomy has emerged as a promising and minimally invasive technique for the treatment of refractory epilepsy. This paper aims to review the clinical outcomes and advancements associated with endoscopic callosotomy as a therapeutic option. MATERIALS AND METHODS: This study includes 14 Paediatric patients diagnosed and managed at Al-azhar university hospitals. Those 14 patients were studied over 2 years. All patients underwent a corpus callosotomy using the bimanual endoscopic technique. RESULTS: Endoscopic anterior corpus callosotomy was done in 13 patients while one case underwent endoscopic complete callosotomy. The most frequent complication was transient disconnection syndrome followed by transient Urinary incontinence and one case had minor CSF leak. As regard seizure freedom outcome (Engel's Outcome Scale): 4 cases (28.6%) became seizure free (Engle class I), 5 cases (35.7%) with Engle class II, 1 case (7.1%) with Engle class III and 4 cases (28.6%) classify as Engle class IV. CONCLUSION: As a minimally invasive technique with a favorable impact on cognitive function, less complications and a significant reduction in seizure frequency and severity in the majority of paediatric patients, endoscopic corpus callosotomy offeres substantial benefits in managing refractory epilepsy in paediatric.

Combined sewer overflow mitigation through SUDS - A review on modelling practices, scenario elaboration, and related performances.

Hydrologic-hydraulic modelling of urban catchment is an asset for land managers to simulate Sustainable Urban Drainage Systems (SUDS) implementation to fulfil combined sewer overflow (CSO) regulations. This review aims to assess the current practices in modelling SUDS scenarios at large scale for CSO mitigation encompassing every stage of the modelling process from the choice of the equation to the validation of the initial state of the urban system, right through to the elaboration, modelling, and selection of SUDS scenarios to evaluate their performance on CSO. Through a quantitative and qualitative analysis of 50 published studies, we found a diversity of choices when modelling the status quo of the urban system. Authors generally do not explain the modelling processes of slow components (deep infiltration, groundwater infiltration) and interconnexion between SUDS and the sewer system. In addition, only a few authors explain how CSO structures are modelled. Furthermore, the modelling of SUDS implementation at catchment scale is highlighted in the 50 studies retrieved with three different approaches going from simplified to detailed. SUDS modelling choices seem to be consistent with the objectives: studies focusing on dealing with several objectives at the time typically opt for a complex system configuration that includes the surface processes, network, CSO, SUDS, and often the soil and/or groundwater components. Conversely, authors who have selected a basic configuration generally aim to address a single, straightforward question (e.g., which type of SUDS). However, elaboration and selection of scenarios for CSO mitigation is mainly based on local constraints, which does not allow hydrological performance to be directly optimised. In conclusion, to improve current practices in modelling SUDS scenarios at large scale for CSO mitigation, authors suggest to: (i) improve clear practices of CSO modelling, calibration and validation at the urban catchment scale, (ii) develop methods to optimize the performance of scenarios for CSO mitigation using hydrological drivers, and (iii) improve parsimonious and user-friendly models to simulate SUDS scenarios in a context of data scarcity.

Alexia without agraphia: from infarctions to malignancies.

Alexia without agraphia is a neurological syndrome characterised by an acquired inability to read with a preserved ability to write. It is caused by the combined effect of two lesions: in the splenium of the corpus callosum and in the occipital lobe of the dominant hemisphere. Splenial lesions disconnect the language areas in the temporal and parietal lobes of the dominant hemisphere from the visual areas in the occipital cortex of the contralateral side, while lesions in the dominant occipital lobe cause homonymous hemianopia. We describe two patients with lesions affecting the splenium and dominant occipital lobe, with different causes. Together, these cases highlight the importance of performing a thorough language evaluation in patients presenting with homonymous visual field deficits, as otherwise, clinicians may overlook impairments in writing (agraphia) or reading (alexia).

Bayesian lesion-deficit inference with Bayes factor mapping: Key advantages, limitations, and a toolbox.

Statistical lesion-symptom mapping is largely dominated by frequentist approaches with null hypothesis significance testing. They are popular for mapping functional brain anatomy but are accompanied by some challenges and limitations. The typical analysis design and the structure of clinical lesion data are linked to the multiple comparison problem, an association problem, limitations to statistical power, and a lack of insights into evidence for the null hypothesis. Bayesian lesion deficit inference (BLDI) could be an improvement as it collects evidence for the null hypothesis, i.e. the absence of effects, and does not accumulate α-errors with repeated testing. We implemented BLDI by Bayes factor mapping with Bayesian t-tests and general linear models and evaluated its performance in comparison to frequentist lesion-symptom mapping with a permutation-based family-wise error correction. We mapped the voxel-wise neural correlates of simulated deficits in an in-silico-study with 300 stroke patients, and the voxel-wise and disconnection-wise neural correlates of phonemic verbal fluency and constructive ability in 137 stroke patients. Both the performance of frequentist and Bayesian lesion-deficit inference varied largely across analyses. In general, BLDI could find areas with evidence for the null hypothesis and was statistically more liberal in providing evidence for the alternative hypothesis, i.e. the identification of lesion-deficit associations. BLDI performed better in situations in which the frequentist method is typically strongly limited, for example with on average small lesions and in situations with low power, where BLDI also provided unprecedented transparency in terms of the informative value of the data. On the other hand, BLDI suffered more from the association problem, which led to a pronounced overshoot of lesion-deficit associations in analyses with high statistical power. We further implemented a new approach to lesion size control, adaptive lesion size control, that, in many situations, was able to counter the limitations imposed by the association problem, and increased true evidence both for the null and the alternative hypothesis. In summary, our results suggest that BLDI is a valuable addition to the method portfolio of lesion-deficit inference with some specific and exclusive advantages: it deals better with smaller lesions and low statistical power (i.e. small samples and effect sizes) and identifies regions with absent lesion-deficit associations. However, it is not superior to established frequentist approaches in all respects and therefore not to be seen as a general replacement. To make Bayesian lesion-deficit inference widely accessible, we published an R toolkit for the analysis of voxel-wise and disconnection-wise data.

The central role of the left inferior longitudinal fasciculus in the face-name retrieval network.

Unsuccessful retrieval of proper names (PNs) is commonly observed in patients suffering from neurological conditions such as stroke or epilepsy. While a large body of works has suggested that PN retrieval relies on a cortical network centered on the left anterior temporal lobe (ATL), much less is known about the white matter connections underpinning this process. Sparse studies provided evidence for a possible role of the uncinate fasciculus, but the inferior longitudinal fasciculus (ILF) might also contribute, since it mainly projects into the ATL, interconnects it with the posterior lexical interface and is engaged in common name (CN) retrieval. To ascertain this hypothesis, we assessed 58 patients having undergone a neurosurgery for a left low-grade glioma by means of a famous face naming (FFN) task. The behavioural data were processed following a multilevel lesion approach, including location-based analyses, voxel-based lesion-symptom mapping (VLSM) and disconnection-symptom mapping. Different statistical models were generated to control for sociodemographic data, familiarity, biographical knowledge and control cognitive performances (i.e., semantic and episodic memory and CN retrieval). Overall, VLSM analyses indicated that damage to the mid-to-anterior part of the ventro-basal temporal cortex was especially associated with PN retrieval deficits. As expected, tract-oriented analyses showed that the left ILF was the most strongly associated pathway. Our results provide evidence for the pivotal role of the ILF in the PN retrieval network. This novel finding paves the way for a better understanding of the pathophysiological bases underlying PN retrieval difficulties in the various neurological conditions marked by white matter abnormalities.

The contextual fear conditioning consolidation depends on the functional interaction of the dorsal subiculum and basolateral amygdala in rats.

Fear conditioning tasks enable us to explore the neural basis of adaptative and maladaptive behaviors related to aversive memories. Recently, we provided the first evidence of the dorsal subiculum (DSub) involvement in contextual fear conditioning (CFC) consolidation by showing that the post-training bilateral NMDA (N-methyl-D-aspartate) receptor blockade in DSub impaired the performance of animals in the test session. As the memory consolidation process depends on the coordinated engagement of different brain regions, and the DSub share reciprocal projections with the basolateral amygdala (BLA), which is also involved in CFC, it is possible that the functional interaction between these sites can be relevant for the consolidation of this task. In this sense, the present study aimed to explore the effects of the functional disconnection of the DSub and BLA in the CFC consolidation after NMDA post-training blockade. In addition, to verify if the observed effects were due to spatial representation processes mediated by the DSub, we employed a hippocampal-independent procedure: tone fear conditioning (TFC). Results showed that the functional disconnection of these regions by post-training NMDA blockade impaired CFC consolidation, whereas there was no impairment in TFC. Altogether, the present data suggest that the DSub and BLA would functionally interact through NMDA-related synaptic plasticity to support CFC consolidation probably due to DSub-related spatial processing showing that the TFC consolidation was not disrupted. This work contributes to filling a gap of studies exploring the DSub involvement in fear conditioning by providing a broad framework of the subicular-amygdaloid connection functionality.

Corpus callosum damage to account for cognitive, affective, and social-cognitive dysfunctions in multiple sclerosis: A model of callosal disconnection syndrome?

The corpus callosum (CC) is the major commissure interconnecting the two hemispheres and is particularly affected in multiple sclerosis (MS). In the present review, we aimed to investigate the role played by callosal damages in the pathogenesis of MS-related dysfunctions and examine whether a model of callosal disconnection syndrome is a valid model for MS. For this purpose, we will first review structural and functional evidence of callosal pathology in MS. Second, we will account for the potential role of CC abnormalities in MS-related dysfunctions. Finally, we will report data concurring with a "multiple disconnection hypothesis" that has been proposed to explain those dysfunctions, and we will examine evidence pointing toward MS as a "callosal disconnection syndrome." We will end by discussing the contribution of this interpretation to the understanding of MS and MS-related deficits.

Hemispherotomy in children: A retrospective analysis of 152 surgeries at a single center and predictors for long-term seizure outcome.

OBJECTIVE: Completeness as a predictor of seizure freedom is broadly accepted in epilepsy surgery. We focused on the requirements for a complete hemispherotomy and hypothesized that the disconnection of the insula contributes to a favorable postoperative seizure outcome. We analyzed surgical and nonsurgical predictors influencing long-term seizure outcome before and after a modification of our hemispherotomy technique. METHODS: We retrospectively studied surgical procedures, electroclinical parameters, magnetic resonance imaging (MRI) results, and follow-up data in all children who had undergone hemispherotomy between 2001 and 2018 at our institution. We used logistic regression models to analyze the influence of different factors on seizure outcome. RESULTS: A total of 152 patients were eligible for seizure outcome analysis only. Of these, 140 cases had complete follow-up data for ≥24 months and provide the basis for the following results. The median age at surgery was 4.3 years (range = .3-17.9 years). Complete disconnection (including the insular tissue) was achieved in 63.6% (89/140). At 2-year follow-up, seizure freedom (Engel class IA) was observed in 34.8% (8/23) with incomplete insular disconnection, whereas this was achieved in 88.8% (79/89) with complete surgical disconnection (p < .001, odds ratio [OR] = 10.41). In the latter group (n = 89), a potentially epileptogenic contralateral MRI lesion was the strongest predictor for postoperative seizure recurrence (OR = 22.20). SIGNIFICANCE: Complete surgical disconnection is the most important predictor of seizure freedom following hemispherotomy and requires disconnection of the insular tissue at the basal ganglia level. Even if the hemispherotomy is performed surgically completely, a potentially epileptogenic contralateral lesion on preoperative MRI significantly reduces the chances of postoperative seizure freedom.

Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection.

BACKGROUND: Sensory disconnection is a key feature of sleep and anaesthesia. We have proposed that predictive coding offers a framework for understanding the mechanisms of disconnection. Low doses of ketamine that do not induce disconnection should thus diminish predictive coding, but not abolish it. METHODS: Ketamine was administered to 14 participants up to a blood concentration of 0.3 µg ml-1 Participants were played a series of tones comprising a roving oddball sequence while electroencephalography evoked response potentials were recorded. We fit a Bayesian observer model to the tone sequence, correlating neural activity with the prediction errors generated by the model using linear mixed effects models and cluster-based statistics. RESULTS: Ketamine modulated prediction errors associated with the transition of one tone to the next (transitional probability), but not how often tones changed (environmental volatility), of the system. Transitional probability was reduced when blood concentrations of ketamine were increased to 0.2-0.3 µg ml-1 (96-208 ms, P=0.003); however, correlates of prediction error were still evident in the electroencephalogram (124-168 ms, P=0.003). Prediction errors related to environmental volatility were associated with electroencephalographic activity before ketamine (224-284 ms, P=0.028) and during 0.2-0.3 µg ml-1 ketamine (108-248 ms, P=0.003). At this subanaesthetic dose, ketamine did not exert a dose-dependent modulation of prediction error. CONCLUSIONS: Subanaesthetic dosing of ketamine reduced correlates of predictive coding but did not eliminate them. Future studies should evaluate whether states of sensory disconnection, including anaesthetic doses of ketamine, are associated with a complete absence of predictive coding responses. CLINICAL TRIAL REGISTRATION: NCT03284307.

Breathe-squeeze: pharmacodynamics of a stimulus-free behavioural paradigm to track conscious states during sedation☆.

BACKGROUND: Conscious states are typically inferred through responses to auditory tasks and noxious stimulation. We report the use of a stimulus-free behavioural paradigm to track state transitions in responsiveness during dexmedetomidine sedation. We hypothesised that estimated dexmedetomidine effect-site (Ce) concentrations would be higher at loss of responsiveness (LOR) compared with return of responsiveness (ROR), and both would be lower than comparable studies that used stimulus-based assessments. METHODS: Closed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine data were analysed for secondary analysis. Fourteen healthy volunteers were asked to perform the breathe-squeeze task of gripping a dynamometer when inspiring and releasing it when expiring. LOR was defined as five inspirations without accompanied squeezes; ROR was defined as the return of five inspirations accompanied by squeezes. Brain states were monitored using 64-channel EEG. Dexmedetomidine was administered as a target-controlled infusion, with Ce estimated from a pharmacokinetic model. RESULTS: Counter to our hypothesis, mean estimated dexmedetomidine Ce was lower at LOR (0.92 ng ml-1; 95% confidence interval: 0.69-1.15) than at ROR (1.43 ng ml-1; 95% confidence interval: 1.27-1.58) (paired t-test; P=0.002). LOR was characterised by progressively increasing fronto-occipital EEG power in the 0.5-8 Hz band and loss of occipital alpha (8-12 Hz) and global beta (16-30 Hz) power. These EEG changes reverted at ROR. CONCLUSIONS: The breathe-squeeze task can effectively track changes in responsiveness during sedation without external stimuli and might be more sensitive to state changes than stimulus-based tasks. It should be considered when perturbation of brain states is undesirable. CLINICAL TRIAL REGISTRATION: NCT04206059.