Global and Parallel Cortical Processing Based on Auditory Gamma Oscillatory Responses in Humans.

Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.

Deviance detection is the dominant component of auditory contextual processing in the lateral superior temporal gyrus: A human ECoG study.

Auditory contextual processing has been assumed to be based on a hierarchical structure consisting of the primary auditory cortex, superior temporal gyrus (STG), and frontal lobe. Recent invasive studies on mismatch negativity (MMN) have revealed functional segregation for auditory contextual processing such as neural adaptation in the primary auditory cortex and prediction in the frontal lobe. However, the role of the STG remains unclear. We obtained induced activity in the high gamma band as mismatch response (MMR), an electrocorticographic (ECoG) counterpart to scalp MMN, and the components of MMR by analyzing ECoG data from patients with refractory epilepsy in an auditory oddball task paradigm. We found that MMR localized mainly in the bilateral posterior STGs, and that deviance detection largely accounted for MMR. Furthermore, adaptation was identified in a limited number of electrodes on the superior temporal plane. Our findings reveal a mixed contribution of deviance detection and adaptation depending on location in the STG. Such spatial considerations could lead to further understanding of the pathophysiology of relevant psychiatric disorders.

Long-term outcome and neuroradiologic changes after multiple hippocampal transection combined with multiple subpial transection or lesionectomy for temporal lobe epilepsy.

OBJECTIVE: Multiple hippocampal transection (MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy (MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation. METHODS: Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy (mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit (LV). Three subgroups were evaluated as well: magnetic resonance imaging (MRI) negative (MN), hippocampal sclerosis (HS), and normal hippocampus with extrahippocampal lesion (NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume (HV), diffusion tensor parameters (DTP), and glucose utilization (GU) were determined from MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) studies performed before and >6 months after surgery. RESULTS: Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level. SIGNIFICANCE: The long-term outcome for complex partial seizures after MHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI.

Visualization of declamping procedure during carotid endarterectomy by ICG videoangiography.

BACKGROUND: ICG videoangiography (ICG-VAG) is widely used in neurovascular surgery. In carotid artery disease, it has been used to assess the extent of the plaque and to confirm the removal of the plaque and patency of the artery. We introduce a novel usage of the ICG-VAG to confirm the patency of the external carotid artery (ECA) and superior thyroid artery (STA), which should work as a drainage system of possible debris in the lumen. METHOD: Consecutive 27 patients with severe internal carotid artery stenosis were employed. Carotid endarterectomy (CEA) was done in the usual fashion. After suturing the arteriotomy, ICG was injected intravenously before reperfusion. Before declamping procedure, ICG-VAG mode was started. As the declamping procedure went on, the assistant judged whether the STA and the ECA were patent by watching the ICG flow on the monitor. After confirming the patency of the ECA-CCA system, the ICA was reperfused. RESULT: The back flow from the STA was not confirmed in two cases. The back flow from the ECA was confirmed in all 27 cases. In four cases, the ICG-VAG showed air bubbles in the lumen; these bubbles were washed away to the ECA or STA. CONCLUSION: Using ICG-VAG during the reperfusion procedure of CEA, the patency of the ECA and the STA can be confirmed. It may contribute to reduce embolic complication during reperfusion procedure.

[Surgical Treatment for Epilepsy: An Updated Summary of Treatment Modalities and Clinical Evidence].

The efficacy of surgical treatment for drug-resistant epilepsy has been proven based on accumulated evidence, such as several randomized controlled trials. There are emerging treatment modalities, including less invasive surgical techniques and neuromodulation devices, which have also been proven to benefit patients by improving seizure control. A recent methodological shift from subdural electrocorticography recordings to stereo-encephalography recordings for intracranialelectroencephalography (iEEG) monitoring has also positively impacted clinical decision-making. Although some of these newer modalities are yet to be implemented in Japan, this article provides updated evidence and a summary of the currently available options for surgical treatment of patients with drug-resistant epilepsy. We hope that this summary will widen the treatment opportunities for patients with this highly impactful disease.

Intraarterial encephalography from an acutely implanted aneurysm embolization device in awake humans.

OBJECTIVE: Endovascular electroencephalography (evEEG) uses the cerebrovascular system to record electrical activity from adjacent neural structures. The safety, feasibility, and efficacy of using the Woven EndoBridge Aneurysm Embolization System (WEB) for evEEG has not been investigated. METHODS: Seventeen participants undergoing awake WEB endovascular treatment of unruptured cerebral aneurysms were included. After WEB deployment and before detachment, its distal deployment wire was connected to an EEG receiver, and participants performed a decision-making task for 10 minutes. WEB and scalp recordings were captured. RESULTS: All patients underwent successful embolization and evEEG with no complications. Event-related potentials were detected on scalp EEG in 9/17 (53%) patients. Of these 9 patients, a task-related low-gamma (30-70 Hz) response on WEB channels was captured in 8/9 (89%) cases. In these 8 patients, the WEB was deployed in 2 middle cerebral arteries, 3 anterior communicating arteries, the terminal internal carotid artery, and 2 basilar tip aneurysms. Electrocardiogram artifact on WEB channels was present in 12/17 cases. CONCLUSIONS: The WEB implanted within cerebral aneurysms of awake patients is capable of capturing task-specific brain electrical activities. Future studies are warranted to establish the efficacy of and support for evEEG as a tool for brain recording, brain stimulation, and brain-machine interface applications.

Frequency-specific modulation of oscillatory activity in the rat auditory cortex by vagus nerve stimulation.

BACKGROUND: We previously found that vagus nerve stimulation (VNS) strengthened stimulus-evoked activity in the superficial layer of the sensory cortex but not in the deep layer, suggesting that VNS altered the balance between the feedforward (FF) and feedback (FB) pathways. Band-specific oscillatory activities in the cortex could serve as an index of the FF-FB balance, but whether VNS affects cortical oscillations along sensory pathways through neuromodulators remains unclear. HYPOTHESIS: VNS modulates the FF-FB balance through the cholinergic and noradrenergic systems, which modulate stimulus gain in the cortex. METHODS: We investigated the effects of VNS using electrocorticography in the auditory cortex of 34 Wistar rats under general anesthesia while presenting click stimuli. In the time-frequency analyses, the putative modulation of the FF and FB pathways was estimated using high- and low-frequency power. We assessed, using analysis of variance, how VNS modulates auditory-evoked activities and how the modulation changes with cholinergic and noradrenergic antagonists. RESULTS: VNS increased auditory cortical evoked potentials, consistent with results of our previous work. Furthermore, VNS increased auditory-evoked gamma and beta powers and decreased theta power. Local administration of cholinergic antagonists in the auditory cortex selectively disrupted the VNS-induced increase in gamma and beta power, while noradrenergic antagonists disrupted the decrease in theta power. CONCLUSIONS: VNS might strengthen the FF pathway through the cholinergic system and attenuate the FB pathway through the noradrenergic system in the auditory cortex. Cortical gain modulation through the VNS-induced neuromodulatory system provides new mechanistic insights into the effect of VNS on auditory processing.

[A case of a penetrating brain injury due to an explosion of a construction machine].

Penetrating brain injury caused by a high speed projectile is rather rare in Japan, known for its strict gun-control laws. We report a case of a 55-year-old male, who was transferred to our hospital with a foreign body in the brain due to penetrating head injury, which was caused by an explosion of a construction machine. Neurological examination demonstrated severe motor aphagia with no apparent motor paresis. The patient had a scalp laceration on his left forehead with exposed cerebral tissue and CSF leakage. Head CT scan and plain skull X-ray revealed a 20 mm×25 mm bolt which had penetrated due to the explosion of the machine. The anterior wall of the left frontal sinus was fractured resulting in dural laceration, and scattered bone fragments were seen along the trajectory of the bolt. Digital subtraction angiography showed no significant vascular injuries including superior sagittal sinus. We performed open surgery, and successfully removed the bolt along with the damaged frontal lobe. The patient had no infection or seizure after the surgery, and was transferred for further rehabilitation therapy. We performed a cosmetic cranioplasty six months later. Surgical debridement of the damaged cerebral tissue along the trajectory led to successful removal of the bolt with no further neurological deficit.

Focal Cortical Surface Cooling is a Novel and Safe Method for Intraoperative Functional Brain Mapping.

OBJECTIVE: Electric cortical stimulation (ECS) has been the gold standard for intraoperative functional mapping in neurosurgery, yet it carries the risk of induced seizures. We assess the safety of focal cortical cooling (CC) as a potential alternative to ECS. METHODS: We reviewed 40 patients (13 with tumor and 27 with mesial temporal lobe epilepsy) who underwent intraoperative CC at the University of Iowa Hospital and Clinics (CC group), of whom 38 underwent ECS preceding CC. Intraoperative and postoperative seizure incidence, postoperative neurologic deficits, and new postoperative radiographic findings were collected to assess CC safety. Fifty-five patients who underwent ECS mapping without CC (ECS-alone group) were reviewed as a control cohort. Another 25 patients who underwent anterior temporal lobectomy (ATL) without CC or ECS (no ECS/no CC-ATL group) were also reviewed to evaluate long-term effects of CC. RESULTS: Seventy-nine brain sites in the CC group were cooled, comprising inferior frontal gyrus (44%), precentral gyrus (39%), postcentral gyrus (6%), subcentral gyrus (4%), and superior temporal gyrus (6%). The incidence of intraoperative seizure(s) was 0% (CC group) and 3.6% (ECS-alone group). The incidence of seizure(s) within the first postoperative week did not significantly differ among CC (7.9%), ECS-alone (9.0%), and no ECS/no CC-ATL groups (12%). There was no significant difference in the incidence of postoperative radiographic change between CC (7.5%) and ECS-alone groups (5.5%). Long-term seizure outcome (Engel I+II) for mesial temporal epilepsy did not differ among CC (80%), ECS-alone (83.3%), and no ECS/no CC-ATL groups (83.3%). CONCLUSIONS: CC when used as an intraoperative mapping technique is safe and may complement ECS.

Vagus nerve stimulation (VNS)-induced layer-specific modulation of evoked responses in the sensory cortex of rats.

Neuromodulation achieved by vagus nerve stimulation (VNS) induces various neuropsychiatric effects whose underlying mechanisms of action remain poorly understood. Innervation of neuromodulators and a microcircuit structure in the cerebral cortex informed the hypothesis that VNS exerts layer-specific modulation in the sensory cortex and alters the balance between feedforward and feedback pathways. To test this hypothesis, we characterized laminar profiles of auditory-evoked potentials (AEPs) in the primary auditory cortex (A1) of anesthetized rats with an array of microelectrodes and investigated the effects of VNS on AEPs and stimulus specific adaptation (SSA). VNS predominantly increased the amplitudes of AEPs in superficial layers, but this effect diminished with depth. In addition, VNS exerted a stronger modulation of the neural responses to repeated stimuli than to deviant stimuli, resulting in decreased SSA across all layers of the A1. These results may provide new insights that the VNS-induced neuropsychiatric effects may be attributable to a sensory gain mechanism: VNS strengthens the ascending input in the sensory cortex and creates an imbalance in the strength of activities between superficial and deep cortical layers, where the feedfoward and feedback pathways predominantly originate, respectively.

Layer-specific representation of long-lasting sustained activity in the rat auditory cortex.

In the auditory system, distinct and reproducible transient activities responding to the onset of sound have long been the focus when characterizing the auditory cortex, i.e., tonotopic maps, subregions, and layer-specific representation. There is limited information on sustained activities because the rapid adaptation impairs reproducibility and the signal-to-noise ratio. We recently overcame this problem by focusing on neural synchrony and machine learning demonstrated that band-specific power and the phase locking value (PLV) represent sound information in a tonotopic and region-specific manner. Here, we attempted to reveal the layer-specific representation of sustained activities. A microelectrode array recorded sustained activities from layers 2/3, 4, and 5/6 of the rat auditory cortex. We characterized band-specific power and PLV patterns and applied sparse logistic regression (SLR) to discriminate (1) between the sound-induced and spontaneous activities and (2) five test frequencies from the sound-induced activities in each layer. SLR achieved the highest discrimination performance in high-gamma activities in layers 4 and 5/6, higher than in layer 2/3, indicating poor sound representation in layer 2/3. Moreover, the recording sites that contributed to the discrimination in layers 4 and 5/6 had a characteristic frequency similar to the test frequency and were often located in the belt area, indicating tonotopic and region-specific representation. These results indicate that information processing of sustained activities may depend on high-gamma oscillators, i.e., cortical inhibitory interneurons, and reflects layer-specific thalamocortical and corticocortical neural circuits in the auditory system, which may contribute to associative information processing beyond sound frequency in auditory perception.

Intraoperative Resuturing of Occluded Superficial Temporal Artery-Middle Cerebral Artery Anastomoses: Single-Center Retrospective Study.

BACKGROUND: In superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis, there is a certain risk of intraoperative acute occlusion of the bypass that can cause operative complications. OBJECTIVE: We sought to assess the efficacy of resuturing at the same site after intraoperative acute occlusion of the bypass. METHODS: In total, 129 STA-MCA anastomosis operations were performed on 125 patients at our institution. The electronic medical records of each patient were reviewed to gather information regarding intraoperative occlusion events, and the operative videos and postoperative radiologic images were also reviewed. RESULTS: Twelve intraoperative acute occlusions were identified. In each case, resuturing was performed after cutting all knots, flushing the thrombus, and trimming the edges of the STAs. In 11 cases, indocyanine green videoangiography and/or Doppler sonography revealed patency during the operation, which was confirmed by postoperative magnetic resonance angiography. None of the 12 cases exhibited high-signal intensities in the MCA area on diffusion-weighted images. CONCLUSION: If intraoperative acute occlusion of STA-MCA anastomosis occurs, reanastomosis at the site should be the first option.

Disconnection Surgery for Intractable Epilepsy with a Structural Abnormality in the Medial Posterior Cortex.

BACKGROUND: The lesionectomy is a general surgical procedure for treating focal epilepsy resulting from a structural abnormality, but a favorable outcome cannot be achieved in some patients, especially patients whose symptomatogenic zone is located in remote regions. Herein we propose the surgical disconnection of the seizure propagation pathway, which consists of short and long associating fibers linking the epileptogenic zone to the remote symptomatogenic zone, as an effective method of achieving favorable seizure outcomes in patients with posterior cortex epilepsy. METHODS: Three patients with intractable epilepsy showing a structural abnormality in the medial posterior cortex participated in this study. Their habitual seizures were complex partial seizures stemming from remote symptomatogenic zones. Seizure propagation-related fibers were assumed by non-invasive examination and semiology. RESULTS: Cingulum and superior/inferior longitudinal fasciculus were considered to form main seizure propagation pathway. Based on the preoperative assumption and the intraoperative intracranial electroencephalogram findings, a lesionectomy and corticectomy were performed for 2 patients while a clusterectomy and corticectomy were performed for the remaining patient. The resection area was extended in the direction of the association fibers to disconnect the remote symptomatogenic zone completely from the epileptogenic zone. Engel class I was achieved in all the patients. CONCLUSION: The current study suggested that assuming the presence of association fibers was an important factor for achieving a favorable outcome in the surgical treatment of posterior cortex epilepsy. Though further study is required, disconnection surgery is recommended as a treatment option for cases in which the epileptogenic zone is located in an eloquent area.

Decoding Speech With Integrated Hybrid Signals Recorded From the Human Ventral Motor Cortex.

Restoration of speech communication for locked-in patients by means of brain computer interfaces (BCIs) is currently an important area of active research. Among the neural signals obtained from intracranial recordings, single/multi-unit activity (SUA/MUA), local field potential (LFP), and electrocorticography (ECoG) are good candidates for an input signal for BCIs. However, the question of which signal or which combination of the three signal modalities is best suited for decoding speech production remains unverified. In order to record SUA, LFP, and ECoG simultaneously from a highly localized area of human ventral sensorimotor cortex (vSMC), we fabricated an electrode the size of which was 7 by 13 mm containing sparsely arranged microneedle and conventional macro contacts. We determined which signal modality is the most capable of decoding speech production, and tested if the combination of these signals could improve the decoding accuracy of spoken phonemes. Feature vectors were constructed from spike frequency obtained from SUAs and event-related spectral perturbation derived from ECoG and LFP signals, then input to the decoder. The results showed that the decoding accuracy for five spoken vowels was highest when features from multiple signals were combined and optimized for each subject, and reached 59% when averaged across all six subjects. This result suggests that multi-scale signals convey complementary information for speech articulation. The current study demonstrated that simultaneous recording of multi-scale neuronal activities could raise decoding accuracy even though the recording area is limited to a small portion of cortex, which is advantageous for future implementation of speech-assisting BCIs.

A Secure Approach to the Inferior Horn Using the Deep Medullary Vein as an Anatomic Guide.

BACKGROUND: Safe entry to the inferior horn is required for a selective approach to the medial temporal region. This can be challenging sometimes for inexperienced surgeons. Our objective was to verify the usefulness of the deep medullary vein (DMV) as an intraoperative landmark for safely entering the inferior horn during the transsylvian selective approach to the mesial temporal region. METHODS: Videos of 8 cases of transsylvian selective amygdalohippocampectomies performed at the University of Tokyo Hospital from 2013 to 2015 were reviewed. Consistency of the DMV and time required to open the inferior horn via the temporal stem through the inferior limiting sulcus were retrospectively evaluated. RESULTS: DMVs were identified in all cases; the average number identified was 2.5 ± 0.3 (mean ± SE). The inferior horn was opened without disorientation in all cases, with mean dissecting time of 7.0 minutes ± 1.1. No complications were caused by disorientation within the temporal stem white matter. CONCLUSIONS: Consideration of the venous system within the white matter and following the DMV could reduce the risk of disorientation and enable the surgeon to reach the inferior horn in a straightforward manner without accidental white matter damage.

Impact of volume-conducted potential in interpretation of cortico-cortical evoked potential: Detailed analysis of high-resolution electrocorticography using two mathematical approaches.

OBJECTIVE: Cortico-cortical evoked potential (CCEP) has been utilized to evaluate connectivity between cortices. However, previous reports have rarely referred to the impact of volume-conducted potential (VCP) which must be a confounding factor of large potential around the stimulation site. To address this issue, we challenged the null hypothesis that VCP accounts for the majority of the recorded potential, particularly around the stimulation site. METHODS: CCEP was recorded with high-density intracranial electrodes in 8 patients with intractable epilepsy. First, we performed regression analysis for describing the relationship between the distance and potential of each electrode. Second, we performed principal component analysis (PCA) to reveal the temporal features of recorded waveforms. RESULTS: The regression curve, declining by the inverse square of the distance, fitted tightly to the plots (R2: 0.878-0.991) with outliers. PCA suggested the responses around the stimulation site had the same temporal features. We also observed the continuous declination over the anatomical gap and the phase reversal phenomena around the stimulation site. CONCLUSIONS: These results were consistent with the null hypothesis. SIGNIFICANCE: This study highlighted the risk of misinterpreting CCEP mapping, and proposed mathematical removal of VCP, which could lead to more reliable mapping based on CCEP.

Effect of vagus nerve stimulation on neural adaptation in thalamo-cortical system in rats.

Vagus nerve stimulation (VNS) is a therapy on medically refractory epilepsy, and recently reported to improve cognitive function including learning and memory. The thalamo-cortical system may underlie such VNS-induced cognitive improvements. Thus, the present study targeted the auditory cortex and thalamus in rats, and investigated whether and how VNS modulates stimulus-specific adaptation (SSA) of the neural activity in these nuclei. A depth electrode array recorded auditory evoked potentials from the auditory thalamus and cortex under an oddball paradigm either with or without VNS. Consequently, VNS weakened SSA in the cortex, but did not affect that in the thalamus, indicating that VNS has neuromodulatory effects on the cortical inhibitory system and the thalamo-cortical projections, but not on the feedforward projections from the auditory periphery up to thalamus.