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PubMed1992

Time-frequency representation of electrocorticograms in temporal lobe epilepsy.

Three time-frequency distributions are evaluated in terms of their efficacy in representing nonstationary electrocorticograms (ECoG's) in human temporal lobe epilepsy. The results of a new method, the exponential distribution, are compared with those of the spectrogram and the Wigner distribution. It is shown that the exponential distribution represents a considerable improvement over the spectrogram in terms of resolution and markedly reduces cross-terms present in the Wigner distribution. Exponential distribution representations of ECoG's from different stages of an epileptic record are developed as contour maps. These high-resolution representations offer a lucid display of temporal-spectral features of the rapidly varying signals that constitute ECoG's recorded in temporal lobe epilepsy.

Adult↗

PubMed2002

Quality estimation of subdurally recorded, event-related potentials based on signal-to-noise ratio.

Our goal is to develop a direct brain interface (DBI) that will provide communication and environmental control to persons who are "locked-in" (or nearly so) as a consequence of brainstem stroke, amyotrophic lateral sclerosis (ALS), or other etiologies. Previously we demonstrated that templates constructed from trigger averaged event-related potentials (ERPs) can be cross-correlated with ongoing electrocorticograms (ECoGs) to detect ERPs associated with the performance of simple motor actions. However, it was difficult to predict a priori which of many candidate ECoG recording site(s) could provide signals that would provide adequate motor action detection. We present here a measure of ERP quality based on an estimate of the signal to noise ratio (SNR) associated with the formation of an ERP template from the performance of consecutive voluntary actions. Detection-theory-based receiver operator characteristics (ROCs) and a database of ECoGs (6000+) recorded from the cortical surface of awake human subjects were used to assess the usefulness of the SNR technique. The SNR method was found to predict the detection efficacy of ERPs when characterized over a wide parameter range, with the majority of ROC curve areas greater than 90%. This method was compared with our previously developed quality measure (the peak-to-baseline ratio) and found to provide significantly better performance (ROC area differences from 4.4% to 13.7%). Thus, the SNR estimate of the ERP is a useful tool to predict the efficacy of ERP templates for cross-correlation-based detection and assist in the selection of viable ERP templates for DBI applications.

Adolescent↗

PubMed2006

Multi-center assessment of the Total Neuropathy Score for chemotherapy-induced peripheral neurotoxicity.

The aim of this multi-center study was to assess with reduced versions of the Total Neuropathy Score (TNS), the severity of chemotherapy-induced peripheral neurotoxicity (CIPN), and to compare the results with those obtained with common toxicity scales. An unselected population of 428 cancer patients was evaluated at 11 different centers using a composite (clinical + neurophysiological, TNSr) or clinical (TNSc) examination and with the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) 2.0 and Eastern Cooperative Oncology Group (ECOG) scores. A highly significant correlation was demonstrated between the TNSr and the NCI-CTC 2.0 and ECOG scores; but the TNSr evaluation was more accurate in view of the more extended score range. Also, the simpler and faster TNSc (based only on the clinical neurological examination) allowed to grade accurately CIPN and correlated with the common toxicity scores. The correlation tended to be closer when the sensory items were considered, but also the TNSr motor items, which were not specifically investigated in any other previous study, significantly correlated with the results of the common toxicity scales. In conclusion, this study suggests that the TNSr is a reliable tool for accurately grading and reporting CIPN, with the additional and so far unique support of a formal comparison with known and widely used common toxicity scales. The TNSc is a valid alternative if neurophysiological examination is not feasible. The longer time needed to calculate the TNSr and TNSc in comparison to the ECOG or the NCI-CTC 2.0 scales is offset by the more detailed knowledge of the CIPN characteristics.

Adolescent↗

PubMed2005

Gemcitabine and carboplatin in the treatment of locally advanced and metastatic non-small cell lung cancer.

OBJECTIVE: The aim of the study was to evaluate the response, survival advantage and toxicity profile of gemcitabine-carboplatin combination cytotoxic chemotherapy in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). METHODOLOGY: Patients who received gemcitabine-carboplatin combination chemotherapy over a 2.5-years period were analyzed. Carboplatin at a dose of 5 mg/mL/min (area under the concentration-time curve) was given on day 1 and gemcitabine (1000 mg/m(2)) on days 1 and 8, every 3 weeks. RESULTS: Of 49 chemotherapy-naive patients (median age, 62 years) who received this treatment, 57% were males, 12% had stage IIIa, 39% stage IIIb and 49% metastatic disease. The Eastern Cooperative Oncology Group (ECOG) performance status of 70% of the patients was 1 at the time of commencement of chemotherapy and 2 for the remaining 30% of patients. The overall response rate, based on 33 evaluable patients, was 27.3%. The response rate was not affected by age, stage of disease or performance status. The median survival was 9 months. Median survival among patients with an ECOG performance status of 1 was 11 months, as compared with 4 months for patients with an ECOG performance status of 2 (P < 0.001). Toxicity was generally well tolerated and there were no treatment-related deaths. CONCLUSIONS: Gemcitabine-carboplatin combination chemotherapy is an effective and well-tolerated cytotoxic regimen among Malaysian patients with advanced NSCLC. A performance status of 1 or less was associated with a better survival.

Adult↗

PubMed1970

Effects of nicotine and tobacco smoke on the electrical activity of the cerebral cortex and olfactory bulb.

1. Effects of nicotine, cigarette smoke and carbon monoxide have been compared in the cat encéphale isolé preparation, exhibiting a synchronized electrocorticogram (ECoG) and behavioural sleep.2. 2 ml samples of smoke, containing approximately 7 mug nicotine (approximately 2 mug nicotine/kg for a 3 kg cat), introduced into the lungs at 30 s intervals from a smoking simulator, caused desynchronization of the ECoG and behavioural arousal.3. Effects of smoke were matched in the same experiments by intravenous injections of nicotine, 2 mug/kg every 30 s.4. The use of specific nicotine antagonists, for example mecamylamine, and filters for removing nicotine, indicated the presence in smoke of other agents capable of exerting a pharmacological response.5. Cigarette smoke contains approximately 5.0% carbon monoxide. Introduced into the lungs of cats pretreated with mecamylamine (2 mg/kg), 2 ml samples of 5% carbon monoxide caused changes in the ECoG similar to those caused by smoke.6. Effects of nicotine or smoke were not modified by pretreatment with chlorpromazine (2.0-4.0 mg/kg). Atropine (0.3 mg/kg), however, prevented the cortical activation, but not the behavioural arousal.7. 2 ml samples of smoke applied to the nostrils caused the occurrence in the olfactory bulb of a discharge or burst of "induced" waves. This discharge was sometimes accompanied by a transient period of cortical activation.8. These studies demonstrate that in cats, nicotine is the principal pharmacological constituent of tobacco smoke as far as effects on the central nervous system are concerned, although other constituents of smoke may play a contributory role.

Animals↗

PubMed1987

Pediatric epilepsy surgery.

The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.

Brain↗

PubMedDate not supplied

Lipid peroxidation and glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and glucose-6-phosphate dehydrogenase activities in FeCl3-induced epileptogenic foci in the rat brain.

This study investigated the relationship between lipid peroxidation, subsequent activation of antioxidative enzymes, and development of iron-induced epilepsy in the rat. Epileptic foci were produced in rat cerebral cortex by intracortical injection of ferric chloride (FeCl3). The epileptic foci were identified by electrocorticography (ECoG). Epileptiform ECoG activity was shown to occur in the contralateral homotopic cerebral cortex as well. We measured levels of lipid peroxides and changes in the activities of the enzymes: superoxide dismutase (SOD), glutathione peroxidase (GP), glutathione reductase (GR), catalase (CA), and glucose-6-phosphate dehydrogenase (G6P) in the epileptogenic focus (both ipsilateral and contralateral) at days 3, 8, 15, and 23 after FeCl3 injection. Biochemical estimations were made in subcellular fractions, and changes in the ipsilateral site were compared with those in the contralateral site. The results of this study showed that large increases in lipid peroxidation were associated with development and buildup of the ECoG epileptiform discharges. Lipid peroxides increased in the ipsilateral focus by approximately 100% as compared with control. In the contralateral site, however, the increase in lipid peroxides was marginal only. The increase in lipid peroxidation was concomitant with development of the high level of epileptiform activity. The time course of changes in lipid peroxidation paralleled the time course of development and persistence of the epileptiform activity. Regarding changes in the enzyme activities accompanying development of iron epilepsy, the data showed that although SOD and G6P increased by approximately 60% and GR increased by approximately 40%, the increases in the enzyme GP and CA were much lower, less than 20%. Thus, comparatively less increase in CA and GP activities produces a deficiency of these two enzymes in the iron (ipsilateral) focus. Among the various biochemical disturbances that have been identified as involved in epileptogenesis, peroxidative injury resulting from lipid peroxidation in neural plasma membrane may be causally related to development of paroxysmal epileptiform activity in the iron focus. Since GP is an enzyme of major importance in detoxification of lipid peroxides in the brain, based on the results presented in this article, it appears reasonable to suggest that GP deficiency causes lipid peroxidation to increase tremendously during iron epileptogenesis.

Animals↗

PubMedDate not supplied

Electrocorticographic confirmation of focal positron emission tomographic abnormalities in children with intractable epilepsy.

The relationship between focal disturbances of glucose utilization demonstrated by positron emission tomography (PET) and electrophysiologic abnormalities defined by intraoperative electrocorticography (ECoG) was studied in eight children (aged 13 months to 12 years) who underwent cortical resection because of intractable seizures. None of the children had pure temporal lobe epilepsy. Computed tomography (CT) and/or magnetic resonance imaging (MRI) were normal in four of the eight children. The scalp electroencephalogram (EEG) showed lateralized interictal epileptiform abnormalities in all eight and lateralized ictal onset in five of eight. In seven children, interictal PET showed focal hypometabolism; the eighth child had focal, ictal hypermetabolism. ECoG at the time of surgery showed epileptiform spiking, slowing, and/or suppression of normal background activity that in every case corresponded to the focus on PET scan. The ECoG findings support the notion that in children with epilepsy focal metabolic abnormalities on PET correspond to electrophysiologically abnormal areas of cortex, which are presumably also the epileptogenic regions. Such areas can appear normal on anatomic imaging studies (CT and MRI). When ictal scalp EEG data are ambiguous or contradictory, PET provides a less invasive means than chronic grid or depth electrode recording for evaluating whether a localized epileptogenic area exists.

Cerebral Cortex↗

PubMedDate not supplied

Methohexital (Brevital) effect on electrocorticogram may be misleading.

Intravenous (i.v.) methohexital (MTH, Brevital) was found to have an effect on the intraoperative electrocorticogram (ECOG) of 63 patients who had temporal lobectomies performed under general anesthesia for intractable complex partial seizures. In the preresection ECOG, MTH increased the frequency of spikes in 78%, the area of cortical spiking in 30% and induced seemingly "new" spike foci in 43%. Similar although less dramatic changes occurred in the final (i.e., postresection) ECOG. Whether these changes induced by MTH, specifically the new spike foci, are significant was assessed by correlating surgical results with the presence of "residual spikes" (i.e., after all resections, not spontaneously occurring but activated by MTH). Surprisingly, nine patients with residual "MTH-spikes" did not have any postoperative seizures whereas two had some. This raises the question of whether MTH effects are significant overall. Caution is advised in the use of MTH in intraoperative assessment of interictal spike fields, especially when new spike foci are activated. Further study of the possibility of false activation, with a larger series, is advised.

Cerebral Cortex↗

PubMedDate not supplied

Rapid cessation of focally induced generalized seizures in rats through microinfusion of lidocaine hydrochloride into the focus.

An experimental animal model of complex partial seizures which become secondarily generalized is produced by microinfusion of the GABA antagonist bicuculline (BIC) into the deep prepiriform cortex (DPC) of rats. In the present study, we investigated the effects of microinfusion of the local anesthetic, lidocaine hydrochloride, directly into the BIC focus in the DPC and demonstrated that direct inactivation of the focus arrested a focal seizure that was in progress. A measure of the integrated amplitude of the electrocorticogram (ECoG) and behavioral seizure scores from unanesthetized and freely moving rats were used to address this question quantitatively. Microinfusion of 2% lidocaine hydrochloride into the BIC focus significantly reduced the integrated amplitude of the ECoG to levels that did not differ from baseline in either hemisphere (mean = 112% ipsilateral, 99% contralateral), whereas saline microinfusion had no effect (mean = 175% ipsilateral, 125% contralateral). Moreover, ECoG reductions after lidocaine were present as soon as the microinfusion was complete. Behaviorally, clonic seizure severity was assessed on a rating scale of 0-5. Lidocaine microinfusion significantly reduced the seizure scores to values not different from baseline during the first postinfusion measurement period (i.e., 30 s). Microinfusion of saline alone also significantly reduced behavioral seizure severity, although to a lesser degree and not as rapidly as lidocaine. This effect suggests the need for caution in interpretation and design of studies investigating the anticonvulsant effects of various pharmacologic agents when microinfusions are used.

Animals↗

PubMed1995

Effect of hypoxia/ischemia on bicuculline-induced seizures in immature rats: behavioral and electrocortical phenomena.

The relation between hypoxia/ischemia and subsequent alterations in seizure susceptibility in developing brain remains unclear. We assessed the behavioral and electrocorticographic (ECoG) effects of hypoxic/ischemic brain damage on bicuculline (BIC)-induced seizures in 7-day postnatal rats, and determined maturational changes in seizure susceptibility, behavior and ECoG activity. Rat pups were subjected to unilateral common carotid artery ligation, followed by exposure to 8% O2 at 37 degrees C for 2 h, an insult that produces brain damage in the cerebral hemisphere ipsilateral to carotid artery occlusion. The experimental group consisted of rat pups previously subjected to hypoxia/ischemia; control littermates received neither arterial ligation nor systemic hypoxia. Experimental animals received 4, 5, or 6 mg/kg BIC subcutaneously (s.c.) at 2 and 24 h, and at 3, 7, and 21 days of recovery from hypoxia/ischemia. Two animals at each interval of recovery, 1 each from the experimental and control groups, were used for ECoG monitoring. After BIC injection, animal behavior was observed for 2 h. Behaviors and seizures were classified in five categories based on severity, duration, and character: 1, mild irritability; 2, few clonic seizures and agitation; 3, few tonic-clonic seizures with swimming movements; 4, frequent tonic-clonic seizures with apneic episodes; 5, continuous tonic-clonic seizures and death. Rat pups previously subjected to hypoxia/ischemia had lesser seizure susceptibility than controls at 2-h recovery (p < 0.05) and greater susceptibility than controls at 24 h (p < 0.05). Tonic seizures were prominent at 2 and 24 h in both the experimental and control groups, whereas lesion-sided circling was prominent only in the hypoxic/ischemic rat pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Significance of spikes recorded on intraoperative electrocorticography in patients with brain tumor and epilepsy.

PURPOSE: Patients with medically intractable epilepsy due to brain tumors may undergo resective surgery for treatment of both the tumor and the epilepsy. In this instance, the extent of surgical resection is sometimes guided by spikes recorded on intraoperative electrocorticography (ECoG). Whether spikes recorded by electrocorticography imply active epileptogenicity has not been addressed adequately. METHODS: We performed preresection and postresection electrocorticography on 36 patients with brain tumor and seizures. There were 31 low-grade gliomas, 4 high grade gliomas, and 1 dysembryonic neuroepithelial tumor. Patients had resection of the tumor to normal tissue margins only. No additional surgery was performed, based on electrocorticography findings. Patients were divided into 2 groups: Group I (no seizures or rare seizures after resection) and Group II (recurrent seizures). Recorded spikes were analyzed for spike distribution and spike discharge rate. RESULTS: On preresection ECoG, 85% of patients in Group I and 88% of patients in Group II had spikes. In Group I, 70% of patients had spikes over the tumor bed, and 63% of patients had spikes in the surrounding tissue. In Group II, 55% of patients had spikes over the tumor bed and 89% of patients had spikes in the surrounding tissue. Spike distribution and discharge rate did not correlate with outcome. On postresection ECoG, 60% of patients in Group I and 67% of patients in Group II had residual spikes. In Group I, 46% of patients had spikes along the margin of resection and 26% of patients had extramarginal spikes. In Group II, 50% had spikes along the margin of resection and 67% of patients had extramarginal spikes. CONCLUSIONS: The difference in spike distribution in the extramarginal area between the 2 groups was not statistically significant, but showed a trend toward a relationship between postresection spikes and seizure recurrence.

Brain Neoplasms↗

PubMed2000

Do reactive post-resection "injury" spikes exist?

PURPOSE: New post-resection spikes on electrocorticography (ECoG) after lesionectomy in patients with seizures may represent residual epileptogenic tissue or presumed reactive injury spikes. We investigated the existence of post-resection injury spikes by eliminating the possibility of residual epileptogenic tissue. METHODS: Preresection and post-resection ECoG was performed on seven patients with an intra-axial neocortical tumor (glioblastoma multiforme or metastasis) and no history of seizures. All tumors were gross-totally resected. RESULTS: The mean age of the patients was 59 years. The tumor location was frontal in four patients, parietal in two, and temporal in one. Two patients had preresection spikes with an average rate of 68 spikes/min that disappeared after surgery. Two different patients had new post-resection spikes, with an average firing rate of 4 spikes/min, despite normal preresection ECoG. In one of these patients, the new spikes were superimposed over a burst suppression pattern. Neither patient developed seizures after surgery. CONCLUSIONS: Surgical irritation of the neocortex is sufficient to produce reactive post-resection epileptogenic discharges surrounding an intra-axial neocortical tumor even in the absence of preoperative seizures and spikes. Injury spikes fire at a slow rate and are not predictive of clinical seizures.

Adult↗

PubMedDate not supplied

Reactive oxygen species, antioxidant mechanisms and serum cytokine levels in cancer patients: impact of an antioxidant treatment.

OBJECTIVE: So far, it is not well established whether oxidative stress found in cancer patients results from an increased production of oxidants in the body or from a failure of physiological antioxidant systems. To further investigate this question we have assessed the blood levels of reactive oxygen species as a marker of free radicals producing oxidative stress and the most relevant of the physiological body enzymes counteracting reactive oxygen species, namely glutathione peroxidase and superoxide dismutase. Serum levels of proinflammatory cytokines and IL-2 were also investigated. All these parameters were studied in relation to the clinically most important index of disease progression, namely Performance Status (ECOG PS). We also tested the reducing ability of different antioxidant agents on reactive oxygen species levels by measuring the increase in glutathione peroxidase activity, and the reduction of serum levels of IL-6 and TNF. DESIGN, SETTING AND SUBJECTS: We carried out an open non randomized study on 28 advanced stage cancer patients (stage III, 10.7%, and stage IV, 89.3%) with tumours at different (8) sites: all were hospitalized in the Medical Oncology Dept, University of Cagliari Interventions. The patients were divided into 5 groups and a different antioxidant treatment was administered to each group. The selected antioxidants were: alpha lipoic acid 200 mg/day orally, N-acetylcysteine 1800 mg/day i.v. or carboxycysteine-lysine salt 2.7 g/day orally, amifostine 375 mg/day i.v., reduced glutathione 600 mg/day i.v., vitamin A 30000 IU/day orally plus vitamin E 70 mg/day orally plus Vitamin C 500 mg/day orally. The antioxidant treatment was administered for 10 consecutive days. RESULTS: Our results show that all but one of the antioxidants tested were effective in reducing reactive oxygen species levels and 2 of them (cysteine-containing compounds and amifostine) had the additional effect of increasing glutathione peroxidase activity. Comprehensively, the "antioxidant treatment" was found to have an effect both on reactive oxygen species levels and glutathione peroxidase activity. The antioxidant treatment also reduced serum levels of IL-6 and TNF. Patients in both ECOG PS 0-1 and ECOG PS 2-3 responded to antioxidant treatment.

Adult↗

PubMed1992

Altered sensitivity of alpha 2-adrenoceptors in the brain during aging in rats.

The soporific and cardiovascular responses to the injection of clonidine into the locus coeruleus and nucleus tractus solitarius, respectively, were studied in rats of different ages. Clonidine (0.09, 0.19, 0.28, and 0.56 nmol) microinfused into the LC of young rats induced dose-dependent behavioral and ECoG SWS with a significant increase in total voltage in the lower frequency bands. In contrast to young rats, clonidine (0.19 and 0.28 nmol) given into the LC did not affect the behavior and ECoG spectrum power in old rats. However, after higher doses of clonidine (0.56 and 1.2 nmol) a small, short-lasting period of behavioral and ECoG SWS was still evident. In 3-month-old rats clonidine (0.25, 0.5 and 1 micrograms) injected into the nucleus tractus solitarius in anesthetized rats produced a significant fall in blood pressure and a significant decrease in heart rate. In contrast, in 12-month-old rats the maximum fall in blood pressure and heart rate was significantly less than in young animals. In addition, in older rats (24-month old) clonidine at the same or larger doses given into the nucleus tractus solitarius did not produce any significant changes in the cardiovascular parameters studied. In conclusion, the present experiments provide evidence that during aging there is a progressive decrease in the soporific and cardiovascular responses to alpha 2-adrenoceptor stimulation in the locus coeruleus and nucleus tractus solitarius, respectively.

Aging↗

PubMed2000

Application of electrophysiological method to study interactions between ibogaine and cocaine.

The psychoactive indole alkaloid, ibogaine (IBO), has been investigated for over a decade concerning its reported anti-addictive properties for opioids as well as psychomotor stimulants. The mechanism for the anti-addictive action of IBO is still unclear. IBO interactions with opioid, NMDA, nicotinic, adrenergic, and serotonergic receptor sites have been suggested. The involvement of the dopaminergic system in IBO action is well documented. Increased or decreased levels of dopamine (DA) in specific brain regions following IBO pretreatment have been seen concomitantly with increased or decreased motor activity after subsequent amphetamine or cocaine administration. In this report, in vivo electrophysiological measures were monitored in awake adult male rats in order to investigate alterations of the electrocorticogram (ECoG) resulting from interactions between IBO and cocaine (COC). Rats were implanted bilaterally with bipolar ECoG electrodes. They were either injected with saline, COC alone (20 mg/kg, i.p.) or IBO (50 mg/kg, i.p.) and COC 1 hr later. The concentrations of DA, 5-HT, and their metabolites DOPAC, HVA, and 5-HIAA were assessed in the caudate nucleus in separate groups of saline-, COC-, and IBO/COC-treated rats. An alpha1 power increase was observed within 10 min after COC injection, which lasted for less than 20 min. A desynchronization over alpha2 and both beta power bands was observed throughout the recording. In IBO/COC-treated rats, a significant increase in delta, theta, and alpha1 power occurred within 20 min after COC injection (p <0.05). This effect lasted for up to an hour. DA levels significantly increased after COC only and decreased after IBO administration. A further decrease in levels of DA was observed in IBO/COC-treated rats. DA turnover increased significantly after IBO alone but was not observed after IBO/COC treatment. The alterations in ECoG and neurotransmitter levels suggest a decreased response to COC following IBO pretreatment.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Delayed synchronization of activity in cortex and subthalamic nucleus following cortical stimulation in the rat.

Oscillations may play a role in the functional organization of cortico-basal ganglia-thalamocortical circuits, and it is important to understand their underlying mechanisms. The cortex often drives basal ganglia (BG) activity, and particularly, oscillatory activity in the subthalamic nucleus (STN). However, the STN may also indirectly influence cortex. The aim of this study was to characterize the delayed (>200 ms) responses of STN neurons to synchronized cortical inputs, focusing on their relationship with oscillatory cortical activity. We recorded the short-latency and delayed responses of STN units and frontal electrocorticogram (ECoG) to cortical stimulation in anaesthetized rats. Similar to previous studies, stimulation of ipsilateral frontal cortex, but not temporal cortex, evoked a short-latency triphasic response, followed by a sustained reduction or pause in firing, in rostral STN units. Caudal STN units did not show the short-latency triphasic response but often displayed a prolonged firing reduction. Oscillations in STN unit activity and ECoG were common after this sustained firing reduction, particularly between 200 and 600 ms after frontal cortical stimulation. These delayed oscillations were significantly coherent in a broad frequency band of 5-30 Hz. Coherence with ECoG at 5-15 Hz was observed throughout STN, though coherence at 15-30 Hz was largely restricted to rostral STN. Furthermore, oscillatory responses at 5-30 Hz in rostral STN predominantly led those in cortex (mean latency of 29 ms) after frontal cortical stimulation. These findings suggest that STN neurons responding to corticosubthalamic inputs may provide a delayed input to cortex, via BG output nuclei, and thence, thalamocortical pathways.

Action Potentials↗

PubMed2026

Overall survival of immunotherapy versus standard of care in chemorefractory microsatellite stable metastatic colorectal cancer: a propensity score matched analysis of 708 patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC). However, selected patients with specific metastatic patterns may derive benefit. METHODS: Patients with chemorefractory pMMR/MSS mCRC treated with ICI-based regimens were retrospectively identified. A comparison cohort treated with trifluridine/tipiracil±bevacizumab, regorafenib, or fruquintinib as standard of care (SOC) was generated through 1:1 propensity score matching by age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), liver metastases (present/absent), and RAS/BRAF status. Overall survival (OS) was compared using Cox regression. RESULTS: A total of 354 patients treated with ICIs and 354 treated with SOC were matched. Median age was 55 years, 52% male, 32% ECOG PS 0, 30% right-sided, and 69% RAS mutated in both groups, while 61% and 60% had liver metastases, respectively. Median OS (mOS) was 10.8 months with ICIs and 9.0 months with SOC (HR 0.76, 95% CI 0.64 to 0.92, p=0.004). In patients without liver metastases, mOS was longer with ICIs than SOC (19.1 vs 13.2 months, HR 0.59, 95% CI 0.43 to 0.80, p<0.001), whereas outcomes were similar in patients with liver metastases (6.4 vs 6.5 months, p=0.303). In univariable analyses, age, sex, primary tumor site, and RAS/BRAF status were not associated with OS. Treatment with ICIs, absence of liver metastases, one prior line of therapy, less than three metastatic sites, and ECOG PS 0 were associated with the most favorable outcomes in univariable and multivariable models. CONCLUSIONS: In chemorefractory pMMR/MSS mCRC without liver metastases, ICI-based regimens yielded longer OS than SOC. Further investigation of ICIs in this patient population is warranted.

Humans↗