Altered static and dynamic cerebellar-cerebral functional connectivity in acute pontine infarction.

This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.

Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.

Deciphering the functional role of insular cortex stratification in trigeminal neuropathic pain.

Trigeminal neuropathic pain (TNP) is a major concern in both dentistry and medicine. The progression from normal to chronic TNP through activation of the insular cortex (IC) is thought to involve several neuroplastic changes in multiple brain regions, resulting in distorted pain perception and associated comorbidities. While the functional changes in the insula are recognized contributors to TNP, the intricate mechanisms underlying the involvement of the insula in TNP processing remain subjects of ongoing investigation. Here, we have overviewed the most recent advancements regarding the functional role of IC in regulating TNP alongside insights into the IC's connectivity with other brain regions implicated in trigeminal pain pathways. In addition, the review examines diverse modulation strategies that target the different parts of the IC, thereby suggesting novel diagnostic and therapeutic management of chronic TNP in the future.

An exploration of neural predictors of treatment compliance in cognitive-behavioral group therapy for hoarding disorder.

A persistent and influential barrier to effective cognitive-behavioral therapy (CBT) for patients with hoarding disorder (HD) is treatment retention and compliance. Recent research has suggested that HD patients have abnormal brain activity identified by functional magnetic resonance (fMRI) in regions often engaged for executive functioning (e.g., right superior frontal gyrus, anterior insula, and anterior cingulate), which raises questions about whether these abnormalities could relate to patients' ability to attend, understand, and engage in HD treatment. We examined data from 74 HD-diagnosed adults who completed fMRI-measured brain activity during a discarding task designed to elicit symptom-related brain dysfunction, exploring which regions' activity might predict treatment compliance variables, including treatment engagement (within-session compliance), homework completion (between-session compliance), and treatment attendance. Brain activity that was significantly related to within- and between-session compliance was found largely in insula, parietal, and premotor areas. No brain regions were associated with treatment attendance. The results add to findings from prior research that have found prefrontal, cingulate, and insula activity abnormalities in HD by suggesting that some aspects of HD brain dysfunction might play a role in preventing the engagement needed for therapeutic benefit.

Role of the medial agranular cortex in unilateral spatial neglect.

Unilateral spatial neglect (USN) results from impaired attentional networks and can affect various sensory modalities, such as visual and somatosensory. The rodent medial agranular cortex (AGm), located in the medial part of the forebrain from rostral to caudal direction, is considered a region associated with spatial attention. The AGm selectively receives multisensory input with the rostral AGm receiving somatosensory input and caudal part receiving visual input. Our previous study showed slower recovery from neglect with anterior AGm lesion using the somatosensory neglect assessment. Conversely, the functional differences in spatial attention across the entire AGm locations (anterior, intermediate, and posterior parts) are unknown. Here, we investigated the relationship between the severity of neglect and various locations across the entire AGm in a mouse stroke model using a newly developed program-based analysis method that does not require human intervention. Among various positions of the lesions, the recovery from USN during recovery periods (postoperative day; POD 10-18) tended to be slower in cases with more rostral lesions in the AGm (r = - 0.302; p = 0.028). Moreover, the total number of arm entries and maximum moving speed did not significantly differ between before and after AGm infarction. According to these results, the anterior lesions may slowly recover from USN-like behavior, and there may be a weak association between the AGm infarct site and recovery rate. In addition, all unilateral focal infarctions in the AGm induced USN-like behavior without motor deficits.

Simultaneous EEG-fMRI Investigation of Rhythm-Dependent Thalamo-Cortical Circuits Alteration in Schizophrenia.

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls ([Formula: see text]). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater ([Formula: see text]), and the degree of coupling was negatively correlated with the duration of disease ([Formula: see text], [Formula: see text]). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia.

Auditory Encoding of Natural Speech at Subcortical and Cortical Levels Is Not Indicative of Cognitive Decline.

More and more patients worldwide are diagnosed with dementia, which emphasizes the urgent need for early detection markers. In this study, we built on the auditory hypersensitivity theory of a previous study-which postulated that responses to auditory input in the subcortex as well as cortex are enhanced in cognitive decline-and examined auditory encoding of natural continuous speech at both neural levels for its indicative potential for cognitive decline. We recruited study participants aged 60 years and older, who were divided into two groups based on the Montreal Cognitive Assessment, one group with low scores (n = 19, participants with signs of cognitive decline) and a control group (n = 25). Participants completed an audiometric assessment and then we recorded their electroencephalography while they listened to an audiobook and click sounds. We derived temporal response functions and evoked potentials from the data and examined response amplitudes for their potential to predict cognitive decline, controlling for hearing ability and age. Contrary to our expectations, no evidence of auditory hypersensitivity was observed in participants with signs of cognitive decline; response amplitudes were comparable in both cognitive groups. Moreover, the combination of response amplitudes showed no predictive value for cognitive decline. These results challenge the proposed hypothesis and emphasize the need for further research to identify reliable auditory markers for the early detection of cognitive decline.

A dynamic computational model of the parallel circuit on the basal ganglia-cortex associated with Parkinson's disease dementia.

The cognitive impairment will gradually appear over time in Parkinson's patients, which is closely related to the basal ganglia-cortex network. This network contains two parallel circuits mediated by putamen and caudate nucleus, respectively. Based on the biophysical mean-field model, we construct a dynamic computational model of the parallel circuit in the basal ganglia-cortex network associated with Parkinson's disease dementia. The simulated results show that the decrease of power ratio in the prefrontal cortex is mainly caused by dopamine depletion in the caudate nucleus and is less related to that in the putamen, which indicates Parkinson's disease dementia may be caused by a lesion of the caudate nucleus rather than putamen. Furthermore, the underlying dynamic mechanism behind the decrease of power ratio is investigated by bifurcation analysis, which demonstrates that the decrease of power ratio is due to the change of brain discharge pattern from the limit cycle mode to the point attractor mode. More importantly, the spatiotemporal course of dopamine depletion in Parkinson's disease patients is well simulated, which states that with the loss of dopaminergic neurons projecting to the striatum, motor dysfunction of Parkinson's disease is first observed, whereas cognitive impairment occurs after a period of onset of motor dysfunction. These results are helpful to understand the pathogenesis of cognitive impairment and provide insights into the treatment of Parkinson's disease dementia.

Alterations in gamma frequency oscillations correlate with cortical tau deposition in Alzheimer's disease.

We assessed the relationship of gamma oscillations with tau deposition in Alzheimer's disease (AD) and other cognitive diseases, as both are altered during the disease course and relate to neurodegeneration. We retrospectively analyzed data from 7 AD, tau positive patients and 9 tau negative patients, who underwent cerebral amyloid PET and tau PET, and EEG within 12 months. Relative gamma power was higher in tau positive (AD) patients than in tau negative patients (p < .05). In tau positive AD patients, tau burden was associated with a linear increase in gamma power (p < .05), while no association was present in the tau negative group nor with amyloid-ß burden in either group. Thus, increase in the gamma power might represent a novel biomarker for tau driven neurodegeneration.

Functional gradients reveal cortical hierarchy changes in multiple sclerosis.

Functional gradient (FG) analysis represents an increasingly popular methodological perspective for investigating brain hierarchical organization but whether and how network hierarchy changes concomitant with functional connectivity alterations in multiple sclerosis (MS) has remained elusive. Here, we analyzed FG components to uncover possible alterations in cortical hierarchy using resting-state functional MRI (rs-fMRI) data acquired in 122 MS patients and 97 healthy control (HC) subjects. Cortical hierarchy was assessed by deriving regional FG scores from rs-fMRI connectivity matrices using a functional parcellation of the cerebral cortex. The FG analysis identified a primary (visual-to-sensorimotor) and a secondary (sensory-to-transmodal) component. Results showed a significant alteration in cortical hierarchy as indexed by regional changes in FG scores in MS patients within the sensorimotor network and a compression (i.e., a reduced standard deviation across all cortical parcels) of the sensory-transmodal gradient axis, suggesting disrupted segregation between sensory and cognitive processing. Moreover, FG scores within limbic and default mode networks were significantly correlated ( ρ = 0.30 $$ \rho =0.30 $$ , p < .005 after Bonferroni correction for both) with the symbol digit modality test (SDMT) score, a measure of information processing speed commonly used in MS neuropsychological assessments. Finally, leveraging supervised machine learning, we tested the predictive value of network-level FG features, highlighting the prominent role of the FG scores within the default mode network in the accurate prediction of SDMT scores in MS patients (average mean absolute error of 1.22 ± 0.07 points on a hold-out set of 24 patients). Our work provides a comprehensive evaluation of FG alterations in MS, shedding light on the hierarchical organization of the MS brain and suggesting that FG connectivity analysis can be regarded as a valuable approach in rs-fMRI studies across different MS populations.

Mice harboring the T316N variant in the GABAAR γ2 subunit exhibit sleep-related hypermotor epilepsy phenotypes and hypersynchronization in the thalamocortical pathway.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy syndrome characterized by seizures that predominantly occur during sleep. The pathogenesis of these seizures remains unclear. We previously detected rare variants in GABRG2, which encodes the γ2 subunit of γ-aminobutyric acid type A receptor (GABAAR), in patients with SHE and demonstrated that these variants impaired GABAAR function in vitro. However, the mechanisms by which GABRG2 variants contribute to seizure attacks during sleep remain unclear. METHODS: In this study, we designed a knock-in (KI) mouse expressing the mouse Gabrg2 T316N variant, corresponding to human GABRG2 T317N variant, using CRISPR/Cas9. Continuous video-electroencephalogram monitoring and in vivo multichannel electrophysiological recordings were performed to explore seizure susceptibility to pentylenetetrazol (PTZ), alterations in the sleep-wake cycle, spontaneous seizure patterns, and synchronized activity in the motor thalamic nuclei (MoTN) and secondary motor cortex (M2). Circadian variations in the expression of total, membrane-bound, and synaptic GABAAR subunits were also investigated. RESULTS: No obvious changes in gross morphology were detected in Gabrg2T316N/+ mice compared to their wild-type (Gabrg2+/+) littermates. Gabrg2T316N/+ mice share key phenotypes with patients, including sleep fragmentation and spontaneous seizures during sleep. Gabrg2T316N/+ mice showed increased susceptibility to PTZ-induced seizures and higher mortality after seizures. Synchronization of the local field potentials between the MoTN and M2 was abnormally enhanced in Gabrg2T316N/+ mice during light phase, when sleep dominates, accompanied by increased local activities in the MoTN and M2. Interestingly, in Gabrg2+/+ mice, GABAAR γ2 subunits showed a circadian increase on the neuronal membrane and synaptosomes in the transition from dark phase to light phase, which was absent in Gabrg2T316N/+ mice. CONCLUSION: We generated a new SHE mouse model and provided in vivo evidence that rare variants of GABRG2 contribute to seizure attacks during sleep in SHE.

Hippocampus, amygdala, and insula activation in response to romantic relationship dissolution stimuli: A case-case-control fMRI study on emerging adult students.

BACKGROUND: Romantic relationship dissolutions (RRDs) are associated with posttraumatic stress symptoms (PTSS). Functional magnetic resonance imaging in RRD studies indicate overlapping neural activation similar to posttraumatic stress disorder. These studies combine real and hypothetical rejection, and lack contextual information and control and/or comparison groups exposed to non-RRD or DSM-5 defined traumatic events. AIM: We investigated blood oxygen level dependent (BOLD) activation in the hippocampus, amygdala, and insula of participants with RRDs compared with other traumatic or non-trauma stressors. METHODS: Emerging adults (mean age = 21.54 years; female = 74.7 %) who experienced an RRD (n = 36), DSM-5 defined trauma (physical and/or sexual assault: n = 15), or a non-RRD or DSM-5 stressor (n = 28) completed PTSS, depression, childhood trauma, lifetime trauma exposure, and attachment measures. We used a general and customised version of the International Affective Picture System to investigate responses to index-trauma-related stimuli. We used mixed linear models to assess between-group differences, and ANOVAs and Spearman's correlations to analyse factors associated with BOLD activation. RESULTS: BOLD activity increased between index-trauma stimuli as compared to neutral stimuli in the hippocampus and amygdala, with no significant difference between the DSM-5 Trauma and RRD groups. Childhood adversity, sexual orientation, and attachment style were associated with BOLD activation changes. Breakup characteristics (e.g., initiator status) were associated with increased BOLD activation in the hippocampus and amygdala, in the RRD group. CONCLUSION: RRDs should be considered as potentially traumatic events. Breakup characteristics are risk factors for experiencing RRDs as traumatic. LIMITATION: Future studies should consider more diverse representation across sex, ethnicity, and sexual orientation.

Multi-timescale neuromodulation strategy for closed-loop deep brain stimulation in Parkinson's disease.

Objective.Beta triggered closed-loop deep brain stimulation (DBS) shows great potential for improving the efficacy while reducing side effect for Parkinson's disease. However, there remain great challenges due to the dynamics and stochasticity of neural activities. In this study, we aimed to tune the amplitude of beta oscillations with different time scales taking into account influence of inherent variations in the basal ganglia-thalamus-cortical circuit.Approach. A dynamic basal ganglia-thalamus-cortical mean-field model was established to emulate the medication rhythm. Then, a dynamic target model was designed to embody the multi-timescale dynamic of beta power with milliseconds, seconds and minutes. Moreover, we proposed a closed-loop DBS strategy based on a proportional-integral-differential (PID) controller with the dynamic control target. In addition, the bounds of stimulation amplitude increments and different parameters of the dynamic target were considered to meet the clinical constraints. The performance of the proposed closed-loop strategy, including beta power modulation accuracy, mean stimulation amplitude, and stimulation variation were calculated to determine the PID parameters and evaluate neuromodulation performance in the computational dynamic mean-field model.Main results. The Results show that the dynamic basal ganglia-thalamus-cortical mean-field model simulated the medication rhythm with the fasted and the slowest rate. The dynamic control target reflected the temporal variation in beta power from milliseconds to minutes. With the proposed closed-loop strategy, the beta power tracked the dynamic target with a smoother stimulation sequence compared with closed-loop DBS with the constant target. Furthermore, the beta power could be modulated to track the control target under different long-term targets, modulation strengths, and bounds of the stimulation increment.Significance. This work provides a new method of closed-loop DBS for multi-timescale beta power modulation with clinical constraints.

Two are better than one: Differences in cortical EEG patterns during auditory and visual verbal working memory processing between Unilateral and Bilateral Cochlear Implanted children.

Despite the proven effectiveness of cochlear implant (CI) in the hearing restoration of deaf or hard-of-hearing (DHH) children, to date, extreme variability in verbal working memory (VWM) abilities is observed in both unilateral and bilateral CI user children (CIs). Although clinical experience has long observed deficits in this fundamental executive function in CIs, the cause to date is still unknown. Here, we have set out to investigate differences in brain functioning regarding the impact of monaural and binaural listening in CIs compared with normal hearing (NH) peers during a three-level difficulty n-back task undertaken in two sensory modalities (auditory and visual). The objective of this pioneering study was to identify electroencephalographic (EEG) marker pattern differences in visual and auditory VWM performances in CIs compared to NH peers and possible differences between unilateral cochlear implant (UCI) and bilateral cochlear implant (BCI) users. The main results revealed differences in theta and gamma EEG bands. Compared with hearing controls and BCIs, UCIs showed hypoactivation of theta in the frontal area during the most complex condition of the auditory task and a correlation of the same activation with VWM performance. Hypoactivation in theta was also observed, again for UCIs, in the left hemisphere when compared to BCIs and in the gamma band in UCIs compared to both BCIs and NHs. For the latter two, a correlation was found between left hemispheric gamma oscillation and performance in the audio task. These findings, discussed in the light of recent research, suggest that unilateral CI is deficient in supporting auditory VWM in DHH. At the same time, bilateral CI would allow the DHH child to approach the VWM benchmark for NH children. The present study suggests the possible effectiveness of EEG in supporting, through a targeted approach, the diagnosis and rehabilitation of VWM in DHH children.

Localized alterations in cortical thickness and sulcal depth of the cingulo-opercular network in relation to lower reading fluency skills in children with dyslexia.

The traditional models of reading development describe how language processing and word decoding contribute to reading comprehension and how impairments in word decoding, a defining feature of dyslexia, affect reading comprehension outcomes. However, these models do not include word and sentence reading (contextual reading) fluency, both of which engage executive functions, with notably decreased performance in children with dyslexia. In the current study, we compared cortical thickness and sulcal depth (CT/SD) in the cingulo-opercular (CO) executive functions brain network in children with dyslexia and typical readers and examined associations with word vs. contextual reading fluency. Overall, CT was lower in insular regions and higher in parietal and caudal anterior cingulate cortex regions in children with dyslexia. Children with dyslexia showed positive correlations between word reading fluency and CT/SD in insular regions, whereas no significant correlations were observed in typical readers. For sentence reading fluency, negative correlations with CT/SD were found in insular regions in children with dyslexia, while positive correlations with SD were found in insular regions in typical readers. These results demonstrate the differential relations between word and sentence reading fluency and anatomical circuitry supporting executive functions in children with dyslexia vs. typical readers. It also suggests that word and sentence reading fluency, relate to morphology of executive function-related regions in children with dyslexia, whereas in typical readers, only sentence reading fluency relates to morphology of executive function regions. The results also highlight the role of the insula within the CO network in reading fluency. Here we suggest that word and sentence reading fluency are distinct components of reading that should each be included in the Simple View of Reading traditional model.

Insula-cortico-subcortical networks predict interoceptive awareness and stress resilience.

BACKGROUND: Interoception, the neural sensing of visceral signals, and interoceptive awareness (IA), the conscious perception of interoception, are crucial for life survival functions and mental health. Resilience, the capacity to overcome adversity, has been associated with reduced interoceptive disturbances. Here, we sought evidence for our Insula Modular Active Control (IMAC) model that suggest that the insula, a brain region specialized in the processing of interoceptive information, realizes IA and contributes to resilience and mental health via cortico-subcortical connections. METHODS: 64 healthy participants (32 females; ages 18-34 years) answered questionnaires that assess IA and resilience. Mental health was evaluated with the Beck Depression Inventory II that assesses depressive mood. Participants also underwent a 15 minute resting-state functional resonance imaging session. Pearson correlations and mediation analyses were used to investigate the relationship between IA and resilience and their contributions to depressive mood. We then performed insula seed-based functional connectivity analyzes to identify insula networks involved in IA, resilience and depressive mood. RESULTS: We first demonstrated that resilience mediates the relationship between IA and depressive mood. Second, shared and distinct intra-insula, insula-cortical and insula-subcortical networks were associated with IA, resilience and also predicted the degree of experienced depressive mood. Third, while resilience was associated with stronger insula-precuneus, insula-cerebellum and insula-prefrontal networks, IA was linked with stronger intra-insula, insula-striatum and insula-motor networks. CONCLUSIONS: Our findings help understand the roles of insula-cortico-subcortical networks in IA and resilience. These results also highlight the potential use of insula networks as biomarkers for depression prediction.

Multiscale neuro-inspired models for interpretation of EEG signals in patients with epilepsy.

OBJECTIVE: The aim is to gain insight into the pathophysiological mechanisms underlying interictal epileptiform discharges observed in electroencephalographic (EEG) and stereo-EEG (SEEG, depth electrodes) recordings performed during pre-surgical evaluation of patients with drug-resistant epilepsy. METHODS: We developed novel neuro-inspired computational models of the human cerebral cortex at three different levels of description: i) microscale (detailed neuron models), ii) mesoscale (neuronal mass models) and iii) macroscale (whole brain models). Although conceptually different, micro- and mesoscale models share some similar features, such as the typology of neurons (pyramidal cells and three types of interneurons), their spatial arrangement in cortical layers, and their synaptic connectivity (excitatory and inhibitory). The whole brain model consists of a large-scale network of interconnected neuronal masses, with connectivity based on the human connectome. RESULTS: For these three levels of description, the fine-tuning of free parameters and the quantitative comparison with real data allowed us to reproduce interictal epileptiform discharges with a high degree of fidelity and to formulate hypotheses about the cell- and network-related mechanisms underlying the generation of fast ripples and SEEG-recorded epileptic spikes and spike-waves. CONCLUSIONS: The proposed models provide valuable insights into the pathophysiological mechanisms underlying the generation of epileptic events. The knowledge gained from these models effectively complements the clinical analysis of SEEG data collected during the evaluation of patients with epilepsy. SIGNIFICANCE: These models are likely to play a key role in the mechanistic interpretation of epileptiform activity.

Cortico-cortical evoked potentials of language tracts in minimally invasive glioma surgery guided by Penfield stimulation.

OBJECTIVE: We investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and asleep surgery, as well as those stimulated from the functional Broca area and recorded from the functional Wernicke area (BtW), and vice versa (WtB). We also analyzed CCEP properties according to tumor location, histopathology, and aphasia. METHODS: We included 20 patients who underwent minimally invasive surgery in an asleep-awake-asleep setting. Strip electrode placement was guided by classical Penfield stimulation of positive language sites and fiber tracking of the arcuate fascicle. CCEPs were elicited with alternating monophasic single pulses of 1.1 Hz frequency and recorded as averaged signals. Intraoperatively, there was no post-processing of the signal. RESULTS: Ninety-seven CCEPs from 19 patients were analyzed. There was no significant difference in CCEP properties when comparing awake versus asleep, nor BtW versus WtB. CCEP amplitude and latency were affected by tumor location and histopathology. CCEP features after tumor resection correlated with short- and long-term postoperative aphasia. CONCLUSION: CCEP recordings are feasible during minimally invasive surgery. CCEPs might be surrogate markers for altered connectivity of the language tracts. SIGNIFICANCE: This study may guide the incorporation of CCEPs into intraoperative neurophysiological monitoring.