Contralateral Cerebral Cortex Research Articles

Cerebral Ischemia Increases the Distribution and Residence Time of 6-Hydroxykynurenic Acid in the Ischemic Cerebral Cortex of Mice

Background 6-hydroxykynurenic acid (6-HKA), isolated from Ginkgo biloba leaves, has demonstrated neurorestorative properties against cerebral ischemia in middle cerebral artery occlusion (MCAO) mice models. However, our previous studies showed that 6-HKA was difficult to penetrate the blood brain barrier (BBB) to exert its pharmacological effects in rats. Therefore, this study aims to investigate the pharmacokinetics and cerebral cortex distribution of 6-HKA in MCAO mice, to determine whether the ability of 6-HKA to cross the BBB is contingent upon barrier integrity. Methods This study established and validated the ultra-performance liquid chromatography tandem mass spectrometric (UPLC-MS/MS) methods for the quantification of 6-HKA in mouse plasma and brain, and investigated the pharmacokinetics and cerebral cortex distribution of 6-HKA in MCAO mice and sham-operated mice. Results This study demonstrates that the mean residence time (MRT0−t) of 6-HKA in the MCAO group was significantly prolonged compared to the sham-operated group, and there was a higher distribution of 6-HKA in the ischemic cerebral cortex than in the contralateral normal cerebral cortex. Conclusion This study illustrated that in MCAO mice, the prolonged MRT0−t of 6-HKA and the increased permeability of BBB made the accumulation of 6-HKA in the ischemic cerebral cortex, thereby enabling 6-HKA to exert neurorestorative effects.

Development and characterization of a non-human primate model of disseminated synucleinopathy.

The presence of a widespread cortical synucleinopathy is the main neuropathological hallmark underlying clinical entities such as Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). There currently is a pressing need for the development of non-human primate (NHPs) models of PDD and DLB to further overcome existing limitations in drug discovery. Here we took advantage of a retrogradely-spreading adeno-associated viral vector serotype 9 coding for the alpha-synuclein A53T mutated gene (AAV9-SynA53T) to induce a widespread synucleinopathy of cortical and subcortical territories innervating the putamen. Four weeks post-AAV deliveries animals were sacrificed and a comprehensive biodistribution study was conducted, comprising the quantification of neurons expressing alpha-synuclein, rostrocaudal distribution and their specific location. Intraputaminal deliveries of AAV9-SynA53T lead to a disseminated synucleinopathy throughout ipsi- and contralateral cerebral cortices, together with transduced neurons located in the ipsilateral caudal intralaminar nuclei and in the substantia nigra pars compacta (leading to thalamostriatal and nigrostriatal projections, respectively). Cortical afferent systems were found to be the main contributors to putaminal afferents (superior frontal and precentral gyri in particular). Obtained data extends current models of synucleinopathies in NHPs, providing a reproducible platform enabling the adequate implementation of end-stage preclinical screening of new drugs targeting alpha-synuclein.

Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

The utility of arterial spin labelled perfusion-weighted magnetic resonance imaging in measuring the vascularity of high grade gliomas – A prospective study

BackgroundDynamic susceptibility contrast (DSC) perfusion weighted imaging (PWI) currently remains the gold standard technique for measuring cerebral perfusion in glioma diagnosis and surveillance. Arterial spin labelling (ASL) PWI is a non-invasive alternative that does not require gadolinium contrast administration, although it is yet to be applied in widespread clinical practice. This study aims to assess the utility of measuring signal intensity in ASL PWI in predicting glioma vascularity by measuring maximal tumour signal intensity in patients based on pre-operative imaging and comparing this to maximal vessel density on histopathology. MethodsPseudocontinuous ASL (pCASL) and DSC images were acquired pre-operatively in 21 patients with high grade gliomas. The maximal signal intensity within the gliomas over a region of interest of 100 mm2 was measured and also normalised to the contralateral cerebral cortex (nTBF-C), and cerebellum (nTBF-Cb). Maximal vessel density per 1 mm2 was determined on histopathology using CD31 and CD34 immunostaining on all participants. ResultsUsing ASL, statistically significant correlation was observed between maximal signal intensity (p < 0.05) and nTBF-C (p < 0.05) to maximal vessel density based on histopathology. Although a positive trend was also observed nTBF-Cb, this did not reach statistical significance. Using DSC, no statistically significant correlation was found between signal intensity, nTBF-C and nTBF-Cb. There was no correlation between maximal signal intensity between ASL and DSC. Average vessel density did not correlate with age, sex, previous treatment, or IDH status. ConclusionsASL PWI imaging is a reliable marker of evaluating the vascularity of high grade gliomas and may be used as an adjunct to DSC PWI.

NI-2 DUAL-ISOTOPE 123I-IMP/201TL SPECT FOR THE DIFFERENTIAL DIAGNOSIS OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA AND GLIOBLASTOMA

Abstract Background Preoperative differential diagnosis between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is important because these tumors require different surgical strategies. This study investigated the usefulness of dual isotope, iodine-123-labeled N-isopropyl-p-iodoamphetamine (123I-IMP) and thallium-201 chloride single photon emission computed tomography (201Tl SPECT) for the differential diagnosis. Methods Sixteen PCNSL patients and 20 GBM patients who underwent dual isotope imaging, 123I-IMP and 201Tl SPECT, are included. Early and delayed SPECT images were obtained after 30 minutes and 4 hours, respectively. Tumor to normal (T/N) ratio was calculated from the ratio of maximum tracer counts in the lesion to the mean counts in the contralateral cerebral cortex. The mean and minimum apparent diffusion coefficient values (ADCmean and ADCmin, respectively) on magnetic resonance imaging were also analyzed for comparison of diagnostic accuracy. Results Delayed phase 123I-IMP SPECT was the most useful imaging examination for the differentiation between PCNSL and GBM compared with early phase 123I-IMP SPECT, early and delayed phase 201Tl SPECT, ADCmean and ADCmin. However, the median T/N ratios of PCNSL and GBM were 1.29 and 0.84, respectively, in the delayed phase 123I-IMP SPECT, and the tumor detection was inadequate. On the other hand, the median T/N ratios of PCNSL and GBM were 3.23 and 2.34, respectively, in the delayed phase 201Tl SPECT, with excellent tumor detection. Thirty-five of 36 patients (97.2%) showed a tracer retention rate of 201Tl SPECT 0.7 or higher, which indicates malignant property of brain tumors. Conclusion Delayed phase 123I-IMP SPECT could differentiate between PCNSL and GBM with high accuracy, but T/N ratio was low and tumor detection was poor. 201Tl SPECT was useful for estimation of the localization and the malignant property of the tumors. The combination of these isotopes was useful for the diagnosis of PCNSL and GBM.

Usefulness of dual isotope 123I-IMP and 201Tl SPECT for the diagnosis of primary central nervous system lymphoma and glioblastoma.

Preoperative differential diagnosis between primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is important because these tumors require different surgical strategies. This study investigated the usefulness of dual isotope, iodine-123-labeled N-isopropyl-p-iodo-amphetamine (123I-IMP) and thallium-201 chloride single-photon emission computed tomography (201Tl SPECT) for the differential diagnosis. Twenty-five PCNSL patients and 27 GBM patients who underwent dual isotope imaging, 123I-IMP and 201Tl SPECT, are included. Tumor-to-normal (T/N) ratio was calculated from the ratio of maximum tracer counts in the lesion to the mean counts in the contralateral cerebral cortex. The mean and minimum apparent diffusion coefficient values (ADCmean and ADCmin, respectively) on magnetic resonance imaging were also analyzed. Delayed phase 123I-IMP SPECT was the most useful imaging examination for the differentiation between PCNSL and GBM compared with early phase 123I-IMP SPECT, early and delayed phase 201Tl SPECT, ADCmean, and ADCmin. However, the median T/N ratios of PCNSL and GBM were 1.32 and 0.83, respectively, in the delayed phase 123I-IMP SPECT. On the other hand, the median T/N ratios of PCNSL and GBM were 3.10 and 2.34, respectively, in the delayed phase 201Tl SPECT, with excellent tumor detection. Delayed phase 123I-IMP SPECT could differentiate between PCNSL and GBM with high accuracy, but T/N ratio was low and tumor detection was poor. 201Tl SPECT was useful for estimation of the malignancy and localization of the tumors with high T/N ratio. Dual isotope 123I-IMP and 201Tl SPECT was useful for the preoperative diagnosis of PCNSL and GBM.

Effects of 1 Hz Low Frequency Repetitive Transcranial Magnetic Stimulation with Neuromuscular Electrical Stimulation Applied to Contralateral Cerebral Cortex on Muscle Activity, Muscle Tone and Upper Limb Motor Function in Stroke Patients

This study was to investigate effects of NMES with 1 Hz low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) applied to unaffected cerebral cortex on muscle activities, tone, and motor function of upper limb (UL) in stroke patients. 16 patients were randomly divided into two groups, and experimental group (EG) was subjected to 1 Hz LF-rTMS and neuromuscular electrical stimulation (NMES). In control group (CG), Facilitation of hand intrinsic muscles and NMES were performed. It was evaluated using electromyography (EEG), MyotonePRO, and Fugl-Meyer assessment (FMA). As a result, there were significant differences on EMG of the anterior deltoid, triceps brachii (TB), MyotonePRO, and FMA in the EG. CG showed a significant difference in EMG of TB. Between groups, there was a significant difference in the biceps brachii and TB. It’s thought that 1 Hz LF-rTMS and NMES can have a positive effect to improve muscle activity and UL in stroke patients.

Effect of electroacupuncture of Taichong (LR3) on somatosensory evoked cortical potentials in healthy volunteers

To explore the excitatory effect of the sensory cortex through somatic electroacupuncture (EA) stimulation at Taichong (LR3). Ten healthy volunteer men ranging in age from 20 to 50 years were enrolled in this study. EA (2 Hz, a tolerable strength) was applied to the left LR3. Before and after EA, the somatosensory evoked potential (SEP) from the Cz' area of the scalp was recorded by electrical stimulation of the bilateral dorsal penile nerves and the indentation behind the medial malleolus of the foot, termed as the pudendal SEP (PSEP) and lower extremity SEP (LSEP), respectively. The amplitude of the left LSEP induced by stimulation of the left medial malleolus was significantly increased after EA (P < 0.05), but there were no significant changes in the latency of LSEP and PSEP, and the amplitude of right LSEP evoked by stimulation of the left medial malleolus, and that of the PSEP. EA at LR3 increases the excitability of the contralateral cerebral sensory cortex (lower extremity area), but has no effect on the adjacent sensory cortex (genital area).

BFGF-CRS Elicits Endogenous Neurogenesis and Functional Recovery&amp;nbsp;In Adult Mice After Brain Injury

The regenerative potential of endogenous neural stem cells (NSCs) in the adult mammalian brain is considered as a possible source of neural repair. However, adult neurogenesis after traumatic brain injury (TBI), especially in the sensorimotor cortex of the brain, is unknown. Here, we reported that a controlled release system, bFGF-sodium hyaluronate collagen scaffolds (bFGF-CRS), implanted into the injured area after traumatic brain injury, could effectively activate endogenous NSCs to proliferate and migrate to the injured area. Immunofluorescence results reveal that these actived NSCs differentiate into new naive neurons, mature neurons and reconstruct cortical layers I-VI. Neurocircuit tracing results show that newborn neurons reconstruct neural circuits with the contralateral cerebral cortex and ipsilateral thalamus VL in the injured area, partially restore CST neural circuits, and finally improve the function of sensorimotor behavior in the horizontal and vertical plane of the right forelimb. In addition, transplantation of bFGF-CRS promoted Nestin+ SVZ cells to proliferate and migrate to the injured area, and could differentiate into neurons, which were involved in repairing brain injury. Our study showed that bFGF-CRS broadened the strategy for treating neurological disorders such as traumatic brain injury by recruiting endogenous NSCs for neural repair.

Brain-derived neurotrophic factor and its related enzymes and receptors play important roles after hypoxic-ischemic brain damage.

Brain-derived neurotrophic factor (BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The mRNA expression levels of BDNF and its processing enzymes and receptors (Furin, matrix metallopeptidase 9, tissue-type plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury; however, the expression levels of these mRNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia (approval No. U12-18) on July 30, 2018.

Differentiating Radiation-Induced Necrosis from Tumor Progression After Stereotactic Radiosurgery for Brain Metastases, Using Evaluation of Blood Flow with Arterial Spin Labeling (ASL): The Importance of Setting a Baseline.

This study evaluated the usefulness of arterial spin labeling (ASL) for assessment of tumor blood flow (TBF) and cerebral blood flow (CBF) before Gamma Knife surgery (GKS) for intracranial metastases, in order to analyze the variability of perfusion characteristics at baseline and to reveal how these data may impact differentiation of radiation-induced effects from tumor progression during follow-up. Radiological data from 87 patients with intracranial metastases of solid cancers, who underwent TBF/CBF analysis by means of ASL at the Hawaii Advanced Imaging Institute between 2015 and 2018 both before and after GKS, were reviewed retrospectively. Only cases with a largest tumor diameter of ≥10 mm were included in the study cohort (N=53). In comparison with CBF in the healthy contralateral cerebral cortex, TBF before GKS was greater in 32 cases (60%), lesser in 7cases (13%), and equivalent in 14cases (27%). There was significant variability in TBF both within and between histologically different groups of tumors. Since, at baseline, approximately 40% of intracranial metastases have TBF that is lesser or equivalent to CBF, increased blood flow in the contrast-enhancing lesion after GKS may have insufficient sensitivity for identification of tumor progression. Availability of baseline TBF data may significantly facilitate differential diagnosis in such cases.

An Enriched Environment Enhances Angiogenesis Surrounding the Cingulum in Ischaemic Stroke Rats

An enriched environment (EE) has been demonstrated to improve functional recovery in animal models of ischaemic stroke through enhancing vascular endothelial growth factor- (VEGF-) mediated neuroprotection accompanied by angiogenesis in the ischaemic hemisphere. Whether EEs also promote VEGF-mediated neuroprotection and angiogenesis in the contralateral hemisphere remains unclear. Here, we explored the effect of EEs on VEGF expression and angiogenesis within the contralateral cerebral cortex in a rat middle cerebral artery occlusion/reperfusion (MCAO/r) model. We assessed the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), VEGF, and endothelial nitric oxide synthase (eNOS) in the whole contralateral cerebral cortex using Western blotting assay but did not find an increase in the expression of CD31, VEGF, or eNOS in MCAO/r rats housed in EEs, which suggested that EEs did not enhance the overall expression of VEGF and eNOS or angiogenesis in the entire contralateral cortex. We further analysed the local effect of EEs by immunohistochemistry and found that in and around the bilateral cingulum in MCAO/r rats housed in EEs, haematopoietic progenitor cell antigen- (CD34-) positive endothelial progenitor cells were significantly increased compared with those of rats housed in standard cages (SCs). Further experiments showed that EEs increased neuronal VEGF expression surrounding the cingulum in MCAO/r rats and robustly upregulated eNOS expression. These results revealed that EEs enhanced angiogenesis, VEGF expression, and activation of the VEGF-eNOS pathway in and/or around the cingulum in MCAO/r rats, which were involved in the functional recovery of MCAO/r rats.

Blood CT pefusion analysis of cerebral gray matter and white matter in supply region of chronic cerebral artery occlusion

Objective To study the different ischemic characteristics of cerebral gray matter and deep white matter in patients with chronic cerebral artery severe stenosis or occlusion. Methods A retrospective study was conducted on 30 patients with chronic unilateral cerebral artery severe stenosis or occlusion from April 2014 to April 2018 in our hospital. Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time of peak time (TTP) and time to delay(TTD) of cerebral cortex gray matter and deep white matter in the blood supply area of the responsible artery (the affected side) and the contralateral hemisphere (the healthy side) were measured. Statistical analysis of the perfusion parameters of cerebral cortex gray matter and deep white matter in the affected side and contralateral side were performed using SPSS13.0 software package. T test was used for variance homogeneity, and t′ test was used for variance discrepancy, and P<0.05 was statistically significant. Results The average values of CBF and CBV of the ipsilateral and contralateral cerebral cortex were increased than those of ipsilateral and contralateral cerebral deep white matter respectively(P<0.01). MTT, TTP and TTD of the ipsilateral and contralateral cerebral cortex were decreased than that of ipsilateral and contralateral cerebral deep white matter (P<0.01); CBF of ipsilateral cerebral cortex and CBV of ipsilateral cerebral deep white matter were not different from those of the contralateral cerebral cortex and deep white matter respectively, but CBF of ipsilateral cerebral deep white matter is decreased than that of the contralateral deep white matter (P<0.01). CBV of ipsilateral cerebral cortex is increased than that of the contralateral cerebral cortex (P<0.01). MTT, TTP and TTD of ipsilateral cerebral cortex and deep white matter were increased than those of contralateral cerebral cortex and deep white matter respectively(P<0.01). Conclusion Deep cerebral white matter perfusion decreased more significantly than cortical gray matter in the supply region of chronic cerebral artery severe stenosis or occlusion. CT perfusion imaging can quantify the degree of chronic cerebral ischemia and can provide quantitative diagnostic information for clinical treatment and efficacy evaluation. Key words: Cerebral arteries; Tomography, X-ray computed; Stenosis; Occlusion

Characterization of cerebral cortical endocannabinoid levels in a rat inguinal surgery model using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

The brain endocannabinoid system is believed to play significant roles in anti-nociception, fear response, anxiety, and stress. This study investigated the effects of rat inguinal surgery on the levels of endocannabinoids in the cerebral cortex. The aim of this study was to investigate the effects of acute post-surgical pain on the levels of endocannabinoids in the cerebral cortex. Quantitation of endocannabinoids in the rat cerebral cortex was performed by liquid chromatography-tandem mass spectrometry. There was no significant difference in the cerebral cortical levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) between the sham and surgery experimental groups. However, there were lateralized differences in the levels of these endocannabinoids between the right and left cerebral cortices irrespective of the two groups. The concentrations of AEA and 2-AG were significantly higher in the right cerebral cortex compared to the contralateral cerebral cortex. Acute post-surgical pain did not induce significant alterations in the cerebral cortical levels of endocannabinoids in this study, but the phenomenon of lateralization of the cerebral cortical AEA and 2-AG levels was observed; this latter finding may be related to the role played by endocannabinoids in fear conditioning.

Measurement of Projections Between Dentate Nucleus and Contralateral Frontal Cortex in Human Brain Via Diffusion Tensor Tractography.

We propose a probabilistic fiber-tracking scheme to reconstruct the fiber tracts between the dentate nucleus (DN) in the cerebellum and the entire contralateral cerebral frontal cortex in the human brain. We assessed diffusion tensor imaging (DTI) data from 39 healthy controls. The connection fibers between the DN and contralateral frontal cortex of all subjects were successfully reconstructed and studied. We demonstrated that multi-fiber probabilistic models must be used to resolve the challenge of crossing fibers. We also demonstrated that the entire pathway can be reconstructed without using any synaptic regions of interest along the path and that the reconstructed tracts connected the ipsilateral superior cerebellar peduncle, contralateral red nucleus, and ventral lateral and ventral anterior nuclei of thalamus in the path traveling to the contralateral frontal cortex. The fibers in the pathway projected into all areas of the contralateral frontal cortex but were predominantly located in the primary motor and premotor areas. A large portion of fibers terminated in the prefrontal cortex, which included dorsolateral prefrontal areas, anterior prefrontal areas, and the Broca language area. Our findings provide robust, reproducible, and direct DTI-based evidence that the DN through the efferent cerebellar pathway has considerable contribution to high-level executive functions of the human brain.

Involvement of miR-34a and p53 protein of cerebral cortex in electroacpuncture analgesia in mice with neuropathic pain

To explore the involvement of miR-34a in cerebral cortex mediated anti-hyperalgesic effect of electroacupuncture (EA) in mice with neuropathic pain induced by chronic constriction injury (CCI) of sciatic nerve, so as to reveal its mechanisms underlying improvement of neuropathic pain. A total of 75 male C57BL/6 mice were equally randomized into 3 groups: sham, CCI model and CCI+EA (n=25 in each group). Mice of the sham group received simple separation of the right sciatic nerve without ligation. The CCI model was established by liagation of the right sciatic nerve. EA (2 Hz /15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36) and "Sanyinjiao" (SP9) for 30 min, once every other day. The mechanical and thermal pain threshold of the bilateral hind-paws was detected at the 3rd, 5th and 7th day after modeling, and the expression of miR-34a of bilateral cerebral cortex tissues and that of p53 protein of the left cerebral cortex were determined by using quantitive real time PCR and Western blot, respectively. The mechnical paw withdrawal frequency were significantly higher and the thermal paw withdrawal latencies (PWLs) were significantly shorter at the affected hind-limb (rather than at the healthy hind limb) on day 3, 5 and 7 in the CCI model group than those in the sham group (P<0.05), and considerably reversed at the affected hind-limb (rather than at the healthy hind limb) in the EA group than in the CCI model group (P<0.05), suggesting an analgesic effect of EA intervention. After modeling, the expression levels of miR-34a and p53 on day 3, 5 and 7 were significantly up-regulated in the left cerebral cortex tissue (rather than in the right cerebral cortex) of the CCI model group in comparison with the sham group (P<0.05). After EA intervention, the up-regulated expression levels of miR-34a and p53 in the left cerebral cortex tissue (rather than in the right cerebral cortex) were obviously suppressed in the EA group relevant to the CCI model group (P<0.05). EA stimulation of ST36 and SP9 can down-regulate the expression of miR-34a and p53 in the contra-lateral cerebral cortex tissue of the CCI mice, which may contribute to its anti-hyperalgesic effect.

Mortality with brainstem seizures from focal 4-aminopyridine-induced recurrent hippocampal seizures.

Sudden unexplained death in epilepsy is the leading cause of death in young adult epilepsy patients, typically occurring during the early postictal period, presumably resulting from brainstem and cardiorespiratory dysfunction. We hypothesized that ictal discharges in the brainstem disrupt the cardiorespiratory network, causing mortality. To study this hypothesis, we chose an animal model comprising focal unilateral hippocampal injection of 4-aminopyridine (4-AP), which produced focal recurrent hippocampal seizures with secondary generalization in awake, behaving rats. We studied ictal and interictal intracranial electrographic activity (iEEG) in 23 rats implanted with a custom electrode array into the hippocampus, the contralateral cortex, and brainstem. The hippocampal electrodes contained a cannula to administer the potassium channel blocker and convulsant (4-AP). iEEG was recorded continuously before, during, and after seizures induced by 4-AP infusion into the hippocampus. The control group (n = 5) was monitored for 2-3 months, and the weekly baseline iEEG recordings showed long-term stability. The low-dose group (1 μL 4-AP, 40 mm, n = 5) exhibited local electrographic seizures without spread to the contralateral cerebral cortex or brainstem. The high-dose group (5 μL 4-AP, 40 mm, n = 3) had several hippocampal electrographic seizures, which spread contralaterally and triggered brainstem discharges within 40 min, and were associated with violent motor seizures followed by dyspnea and respiratory arrest, with cortical and hippocampal iEEG flattening. The group that received high-dose 4-AP without brainstem implantation (n = 5) had similar seizure-related respiratory difficulties. Finally, five rats that received high-dose 4-AP without EEG recording also developed violent motor seizures with postictal respiratory arrest. Following visualized respiratory arrest in groups III, IV, and V, manual respiratory resuscitation was successful in five of 13 animals. These studies show that hippocampal seizure activity can spread or trigger brainstem epileptiform discharges that may cause mortality, possibly mediated by respiratory network dysfunction.

Transcranial magnetic stimulation for monitoring the rehabilitation of upper-extremity function after stroke

Objective To evaluate the effect of the transcranial magnetic stimulation on upper-extremity function rehabilitation and changes in the excitability of cerebral cortex, and to evaluate from the viewpoint of electrophysiology the prognosis so as to guide the rehabilitation treatment of patients after stroke. Methods Forty-six patients in the early stage after a stroke were given TMS examinations of the ipsilateral brain region. Those with the motor evoked potentials (MEPs) amplitudes lower than 50 μV were classified into a motion-induced experimental negative group (the negative group), while those whose MEP amplitude reached 50 μV or more were classified as movement-induced positive (the positive group). Both groups were given the same treatment. Before and after 2, 4 and 8 weeks of treatment the Fugl-Meyer movement function rating scale was used to assess their bilateral upper limb movement function. TMS technology was used to detect any change in the resting motor threshold (RMT) and the amplitude (Amp) of MEPs in the motor cortex. The incubation period of the cortex (CL) and the central motor conduction time (CMCT) in the contralateral motor cerebral cortex were also observed. Results After 4 weeks of treatment, the average score of the positive group on Fugl-Meyer upper movement function rating scale reached (54.99±2.76), significantly higher than before treatment and significantly higher than the negative group's average (P 0.05). After the treatment the CL and CMCT had shortened significantly in the negative group compared to before the treatment (P 0.05). Conclusions The excitability of the contralateral motor cortex changes after a stroke. TMS can be used to characterize the MEP to monitor and predict recovery. This should help clinicians prepare more scientific rehabilitation plans. Key words: Transcranial magnetic stimulation; Stroke; Upper limb movement function; Cortical excitability

The Cerebellum and Neurodevelopmental Disorders.

Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior.

Corticopontocerebellar Connectivity Disruption in Congenital Hemiplegia

Background. Crossed cerebellar diaschisis is the disruption of functional connectivity between cerebrum and cerebellum after hemispheric unilateral brain lesions. In adults and to a lesser extent in children, crossed cerebellar diaschisis has been largely investigated by functional connectivity and demonstrated to influence paretic hand function. Objective. We aim to demonstrate a disruption in structural corticopontocerebellar (CPC) connectivity in children with congenital brain lesions and examine its correlation with paretic hand motor function. Methods. Thirty-six children (Manual Ability Classification System: I, n = 21; II, n = 15) with unilateral brain lesions and 18 controls were analyzed in a case-control study, and diffusion magnetic resonance imaging data were acquired at 3T. High angular resolution diffusion imaging probabilistic tractography was employed for the region of interest–based reconstruction of CPC tracts. To identify statistical differences in structural cerebrocerebellar connectivity between case and control groups, an asymmetry index based on the number of streamlines of CPC tracts was used. In the case group, the correlation between asymmetry index and hand function measures was also determined. Results. Projections through the middle cerebellar peduncle to the contralateral cerebral cortex showed greater asymmetry in children with congenital unilateral brain lesion compared to controls (P = .03), thus indicating a disruption of structural cerebrocerebellar connectivity. The degree of asymmetry index showed a correlation (P < .03; r = −0.31) with impaired hand abilities in bimanual tasks. Conclusions. Disruption of structural cerebrocerebellar connectivity is present in patients with congenital unilateral brain injury and might be related to impaired hand function in bimanual skills, with potential implication in tailoring early intervention strategies.