Nobuhiro Mikuni

Intraoperative dorsal language network mapping by using single‐pulse electrical stimulation

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico‐cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language‐dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High‐frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single‐pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high‐frequency ES of the white matter produced naming impairment, this “eloquent” subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico‐ and subcortico‐cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network. Hum Brain Mapp 35:4345–4361, 2014.

Function of the nucleus accumbens in motor control during recovery after spinal cord injury

Motivation helps reverse neuronal damage Motivation plays a fundamental role in mediating recovery after neurological injuries. Sawada et al. evaluated the potential contribution of the nucleus accumbens, a brain motivation center, to movement control after spinal cord injury in monkeys. The activity of the nucleus accumbens during the early phase after injury was important for the recovery of motor performance. Science, this issue p. 98 Blockade of a motivation center in the brain impairs recovery from spinal cord lesions in monkeys. Motivation facilitates recovery after neuronal damage, but its mechanism is elusive. It is generally thought that the nucleus accumbens (NAc) regulates motivation-driven effort but is not involved in the direct control of movement. Using causality analysis, we identified the flow of activity from the NAc to the sensorimotor cortex (SMC) during the recovery of dexterous finger movements after spinal cord injury at the cervical level in macaque monkeys. Furthermore, reversible pharmacological inactivation of the NAc during the early recovery period diminished high-frequency oscillatory activity in the SMC, which was accompanied by a transient deficit of amelioration in finger dexterity obtained by rehabilitation. These results demonstrate that during recovery after spinal damage, the NAc up-regulates the high-frequency activity of the SMC and is directly involved in the control of finger movements.

Chloroquine potentiates temozolomide cytotoxicity by inhibiting mitochondrial autophagy in glioma cells

Mitochondrial autophagy eliminates damaged mitochondria and decreases reactive oxygen species (ROS). The autophagy inhibitor chloroquine (CQ) potentiates temozolomide (TMZ) cytotoxicity in glioma cells, but it is not known whether CQ does this by inhibiting mitochondrial autophagy. The effects of CQ and TMZ on MitoSOX Red fluorescence, a mitochondrial ROS indicator, and cell death were examined in rat C6 glioma cells. Mitochondrial autophagy was monitored by the colocalization of MitoTracker Red fluorescence and EGFP-LC3 dots. Mitochondrial content was measured by MitoTracker Green fluorescence and immunoblotting for a mitochondrial protein. Finally, CQ’s effects on tumor cells derived from a glioblastoma patient and human U87-MG glioblastoma cells were assessed. TMZ (100–1,000xa0μM) alone did not affect mitochondrial ROS or cell death in C6 cells, but when administered with CQ (10xa0μM), it increased mitochondrial ROS and cell death. Antioxidants significantly suppressed the CQ-augmented cell death in TMZ-treated cells, indicating that mitochondrial ROS were involved in this cell death. TMZ treatment reduced MitoTracker Green fluorescence and mitochondrial protein levels, and these effects were inhibited by CQ. TMZ also increased the colocalization of EGFP-LC3 dots with mitochondria, and CQ enhanced this effect. CQ potentiated TMZ-induced cytotoxicity in patient-derived glioblastoma cells as well as human U87-MG glioblastoma cells. These results suggest that CQ increases cellular ROS and augments TMZ cytotoxicity in glioma cells by inhibiting mitochondrial autophagy.

Intracranially recorded ictal direct current shifts may precede high frequency oscillations in human epilepsy.

OBJECTIVEnWe assessed the temporal-spatial characteristics of ictal direct current (DC) shifts (or infraslow activity) and high frequency oscillations (HFOs) in 16 patients with intractable focal epilepsy.nnnMETHODSnThe underlying etiology consisted of cortical dysplasia, glioma, hippocampal sclerosis, and low-grade neuroepithelial tumor in nine, four, two, and one patients, respectively. The median number of analyzed seizure events was 8.0 per patient (range: 2-10). Chronic electrocorticographic recording was performed with (1) a band-pass filter of 0.016-600Hz (or 0.016-300Hz) and a sampling rate of 2000Hz (or 1000Hz).nnnRESULTSnIctal DC shifts and a sustained form of ictal HFOs were observed in 75.0% and 50.0% of the patients, and 71.3% and 46.3% of the analyzed seizures. Visual assessment revealed that the onset of ictal DC shifts preceded that of ictal HFOs with statistical significance in 5/7 patients. The spatial extent of ictal DC shifts or HFOs was smaller than that of the conventionally defined seizure onset zone in 9/12 patients.nnnCONCLUSIONnBoth ictal DC shifts and HFOs might represent the core of tissue generating seizures.nnnSIGNIFICANCEnThe early occurrence of ictal DC shifts warrants further studies to determine the role of glia (possibly mediating ictal DC shifts) in seizure generation.

Neural correlates of mirth and laughter: A direct electrical cortical stimulation study

Laughter consists of both motor and emotional aspects. The emotional component, known as mirth, is usually associated with the motor component, namely, bilateral facial movements. Previous electrical cortical stimulation (ES) studies revealed that mirth was associated with the basal temporal cortex, inferior frontal cortex, and medial frontal cortex. Functional neuroimaging implicated a role for the left inferior frontal and bilateral temporal cortices in humor processing. However, the neural origins and pathways linking mirth with facial movements are still unclear. We hereby report two cases with temporal lobe epilepsy undergoing subdural electrode implantation in whom ES of the left basal temporal cortex elicited both mirth and laughter-related facial muscle movements. In one case with normal hippocampus, high-frequency ES consistently caused contralateral facial movement, followed by bilateral facial movements with mirth. In contrast, in another case with hippocampal sclerosis (HS), ES elicited only mirth at low intensity and short duration, and eventually laughter at higher intensity and longer duration. In both cases, the basal temporal language area (BTLA) was located within or adjacent to the cortex where ES produced mirth. In conclusion, the present direct ES study demonstrated that 1) mirth had a close relationship with language function, 2) intact mesial temporal structures were actively engaged in the beginning of facial movements associated with mirth, and 3) these emotion-related facial movements had contralateral dominance.

Diagnosis of Moyamoya Disease on Magnetic Resonance Imaging: Are Flow Voids in the Basal Ganglia an Essential Criterion for Definitive Diagnosis?

Flow voids in the basal ganglia cannot always be recognized on magnetic resonance imaging, even in patients with typical moyamoya disease. In this report, flow voids in the basal ganglia and cisternal flow voids of the sylvian valley were evaluated in patients with moyamoya disease, and their diagnostic value was verified. A total of 41 consecutive patients with moyamoya disease were included in this analysis. The number of flow voids in the basal ganglia and the sylvian valley were counted on each side by 3 observers. Then the numbers of flow voids were compared between the patients with moyamoya disease and controls. The patients with moyamoya disease had a significantly higher mean number of flow voids in the basal ganglia and the sylvian valley (P < .0001); however, the number of flow voids in the basal ganglia was 0 or 1 in 69 sides (28.0%) in patients with moyamoya disease. Comparative analysis using the area under the receiver operating curve indicated that the evaluation of flow voids in the sylvian valley was significantly superior method to that in the basal ganglia (P < .0001). The cutoff value for the number of cisternal flow voids in the sylvian valley for the diagnosis of moyamoya disease was 6. Based on these findings, we recommend a definitive diagnosis of moyamoya disease should include assessment for abnormal vessels around the terminal portions of the internal carotid arteries.

Arterial Spin-Labeling Magnetic Resonance Imaging After Revascularization of Moyamoya Disease

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is a technique for depicting cerebral perfusion without contrast medium. The purpose of this study was to determine whether ASL can be used to detect hyperperfusion after revascularization for moyamoya disease as effectively as N-isopropyl-[123I]β-iodoamphetamine ((123)I-IMP) single-photon emission computed tomography (SPECT). Fifteen consecutive patients with moyamoya disease were included in the study. All patients underwent surgical revascularization. Postoperatively, regional cerebral blood flow (rCBF) was measured by flow-sensitive alternating inversion recovery (FAIR) ASL and (123)I-IMP SPECT during the acute stage, and rCBF of the operative side was compared with the other side. The asymmetry ratio (AR) was then calculated from the rCBF as measured using each modality. The postoperative AR of ASL was moderately correlated with that of (123)I-IMP SPECT (y = 0.180x + 0.819; R = 0.80; P = .0003). In this series, 2 patients (13.3%) suffered symptomatic hyperperfusion after revascularization and accordingly exhibited increased AR of ASL. Our data indicate that early increases in rCBF in patients with hyperperfusion could be detected using FAIR ASL supplemental to (123)I-IMP SPECT after revascularization. Our data indicate that FAIR ASL is a convenient method for evaluating hyperperfusion that can be performed repeatedly without the use of contrast medium or radioisotopes.

Discrepancy Between Voluntary Movement and Motor-Evoked Potentials in Evaluation of Motor Function During Clipping of Anterior Circulation Aneurysms

BACKGROUNDnVarious modalities have been used to confirm the blood flow through parent arteries or surrounding perforating arteries during surgical aneurysm clipping, including motor-evoked potentials (MEPs), Doppler ultrasound, and indocyanine green videoangiography. Nonetheless, contralateral hemiparesis due to arterial blood flow insufficiency may arise because of false-positive or false-negative errors. By performing controlled intraoperative awakening during aneurysm clipping, we compared patients voluntary movements with simultaneous MEP.nnnMETHODSnFour patients with anterior choroidal artery aneurysms and one patient with a dorsal internal carotid artery aneurysm were included in this study. MEP and intraoperative voluntary movements under awake craniotomy were assessed simultaneously during and after the clipping procedure.nnnRESULTSnAneurysms were safely and successfully clipped in all patients, with no evidence of postoperative neurological deficits. Voluntary movements and MEP findings did not differ from the control state in three patients. In the other two patients, we observed a discrepancy between MEP amplitudes and voluntary movements. In one patient, deterioration and subsequent improvement in voluntary movements were preceded by MEP amplitude reduction during clipping. In the other patient, MEP amplitude did not change although voluntary movement deteriorated during temporary occlusion of the internal carotid artery.nnnCONCLUSIONSnIntraoperative neurological assessment during aneurysmal clipping under awake craniotomy is feasible and safe, and should be valuable for the assessment of ischemia, especially in the anterior choroidal artery. From a neurophysiologic viewpoint, MEP may be insufficiently sensitive for evaluating voluntary movement under ischemia.

Anterior temporal lobe white matter abnormal signal (ATLAS) as an indicator of seizure focus laterality in temporal lobe epilepsy: comparison of double inversion recovery, FLAIR and T2W MR imaging.

AbstractObjectivesTo investigate the diagnostic capability of anterior temporal lobe white matter abnormal signal (ATLAS) for determining seizure focus laterality in temporal lobe epilepsy (TLE) by comparing different MR sequences.MethodsThis prospective study was approved by the institutional review board and written informed consent was obtained. Three 3D sequences (double inversion recovery (DIR), fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging (T2WI)) and two 2D sequences (FLAIR and T2WI) were acquired at 3xa0T. Signal changes in the anterior temporal white matter of 21 normal volunteers were evaluated. ATLAS laterality was evaluated in 21 TLE patients. Agreement of independent evaluations by two neuroradiologists was assessed using κ statistics. Differences in concordance between ATLAS laterality and clinically defined seizure focus laterality were analysed using McNemar’s test with multiple comparisons.ResultsPre-amygdala high signals (PAHS) were detected in all volunteers only on 3D-DIR. Inter-evaluator agreement was moderate to almost perfect for each sequence. Correct diagnosis of seizure laterality was significantly more frequent on 3D-DIR than on any other sequences (Pu2009≤u20090.031 for each evaluator).ConclusionsThe most sensitive sequence for detecting ATLAS laterality was 3D-DIR. ATLAS laterality on 3D-DIR can be a good indicator for determining seizure focus localization in TLE.Key Points• Magnetic resonance imaging is widely used to investigate temporal lobe epilepsy.n • Numerous MR sequences can show anterior temporal lobe white matter abnormal signal.n • ATLAS on 3D-DIR can frequently indicate seizure focus laterality in TLE.n • 3D-DIR is more sensitive about ATLAS laterality than T2WI or FLAIR.

Bilateral cortical hyperactivity detected by fMRI associates with improved motor function following intravenous infusion of mesenchymal stem cells in a rat stroke model.

Intravenous transplantation of mesenchymal stem cells (MSCs) derived from bone marrow ameliorates functional deficits in rat cerebral infarction models. In this study, MSCs were intravenously administered 6h after right middle cerebral artery occlusion (MCAO) induction in rat. Functional MRI (fMRI) during electrical stimulation of the left forepaw and behavioral testing (treadmill stress test) were carried out at day 1, 4, 7, 14, 21, 28 and 42 following MCAO. In medium infused group (n=20) electrical stimulation of the left forepaw elicited a unilateral (right cortex) activated signal detected by fMRI in the infarcted somatosensory cortex. In the MSC infused animals two fMRI patterns were observed: unilateral (n=17) and bilateral (n=19) activation of sensorimotor cortex. In the MSC group both unilateral and bilateral cortical activated animals displayed significantly improved motor function compared to the medium infused group. However, the bilateral activated pattern in the MSC group showed the greatest functional recovery. Lesion volume as calculated from high intensity signals using T2WI was less in the MSC groups as compared to the medium group, but the lesion volume for the unilateral and bilateral signals in the MSC group was the same. These results suggest that the presence of a bilateral signal in sensorimotor cortex as detected by fMRI was more predictive of improved functional outcome than lesion volume alone.