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Background: Cortico-cortical evoked potentials (CCEPs) are a common tool for probing effective connectivity in intracranial human electrophysiology. As with all human electrophysiology data, CCEP data are highly susceptible to noise. To address noise, filters and re-referencing are often applied to CCEP data, but different processing strategies are used from study to study., New Method: We systematically compare how common average re-referencing and filtering CCEP data impacts quantification., Results: We show that common average re-referencing and filters, particularly filters that cut out more frequencies, can significantly impact the quantification of CCEP magnitude and morphology. We identify that high cutoff high pass filters (> 0.5 Hz), low cutoff low pass filters (< 200 Hz), and common average re-referencing impact quantification across subjects. However, we also demonstrate that the presence of noise may impact CCEP quantification, and preprocessing is necessary to mitigate this. We show that filtering is more effective than re-referencing or averaging across trials for reducing most common types of noise., Comparison With Existing Methods: These results suggest that existing CCEP processing methods must be applied with care to maximize noise reduction and minimize changes to the data. We do not test every available processing strategy; rather we demonstrate that processing can influence the results of CCEP studies. We emphasize the importance of reporting all processing methods, particularly re-referencing methods., Conclusions: We propose a general framework for choosing an appropriate processing pipeline for CCEP data, taking into consideration the noise levels of a specific dataset. We suggest that minimal gentle filtering is preferable., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Because hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels modulate the excitability of cortical and hippocampal principal neurons, these channels play a key role in the hyperexcitability that occurs during the development of epilepsy after a brain insult, or epileptogenesis. In epileptic rats generated by pilocarpine-induced status epilepticus, HCN channel activity is downregulated by two main mechanisms: a hyperpolarizing shift in gating and a decrease in amplitude of the current mediated by HCN channels, I h . Because these mechanisms are modulated by various phosphorylation signaling pathways, we hypothesized that phosphorylation changes occur at individual HCN channel amino acid residues (phosphosites) during epileptogenesis. We collected CA1 hippocampal tissue from male Sprague Dawley rats made epileptic by pilocarpine-induced status epilepticus, and age-matched naïve controls. We also included resected human brain tissue containing epileptogenic zones (EZs) where seizures arise for comparison to our chronically epileptic rats. After enrichment for HCN1 and HCN2 isoforms by immunoprecipitation and trypsin in-gel digestion, the samples were analyzed by mass spectrometry. We identified numerous phosphosites from HCN1 and HCN2 channels, representing a novel survey of phosphorylation sites within HCN channels. We found high levels of HCN channel phosphosite homology between humans and rats. We also identified a novel HCN1 channel phosphosite S791, which underwent significantly increased phosphorylation during the chronic epilepsy stage. Heterologous expression of a phosphomimetic mutant, S791D, replicated a hyperpolarizing shift in I h gating seen in neurons from chronically epileptic rats. These results show that HCN1 channel phosphorylation is altered in epilepsy and may be of pathogenic importance., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Often diagnosed at birth or in early childhood, mitochondrial disease presents with a variety of clinical symptoms, particularly in organs and tissues that require high energetic demand such as brain, heart, liver, and skeletal muscles. In a group of pediatric patients identified as having complex I or I/III deficits on muscle biopsy but with white matter tissue appearing qualitatively normal for age, we hypothesized that quantitative DTI analyses might unmask disturbance in microstructural integrity., Materials and Methods: In a retrospective study, DTI and structural MR brain imaging data from 10 pediatric patients with confirmed mitochondrial disease and 10 clinical control subjects were matched for age, sex, scanning parameters, and date of examination. Paired TBSS was performed to evaluate differences in FA, MD, and the separate diffusion direction terms (λr and λa)., Results: In patients with mitochondrial disease, significant widespread reductions in FA values were shown in white matter tracts. Mean diffusivity values were significantly increased in patients, having a sparser distribution of affected regions compared with FA. Separate diffusion maps showed significant increase in λr and no significant changes in λa., Conclusions: Despite qualitatively normal-appearing white matter tissues, patients with complex I or I/III deficiency have widespread microstructural changes measurable with quantitative DTI.

Nested oscillation occurs when the amplitude of a faster rhythm is coupled to the phase of a slower rhythm. It has been proposed to underlie the discrete nature of perception and the capacity of working memory and is a phenomenon observable in human brain imaging data. This paper compares three published methods for detecting nested oscillation and a fourth method proposed in this paper. These are: (i) the modulation index, (ii) the phase-locking value (PLV), (iii) the envelope-to-signal correlation (ESC) and (iv) a general linear model (GLM) measure derived from ESC. We applied the methods to electrocorticographic (ECoG) data recorded during a working-memory task and to data from a simulated hippocampal interneuron network. Further simulations were then made to address the dependence of each measure on signal to noise level, coupling phase, epoch length, sample rate, signal nonstationarity, and multi-phasic coupling. Our overall conclusion is that the GLM measure is the best all-round approach for detecting nested oscillation.

We report the case of a patient with frontal lobe epilepsy in whom the Wada test failed to lateralize representation of language (fluent speech was observed after amobarbital injection on both the right and left side). Functional magnetic resonance imaging (fMRI) during a lexical processing task revealed an atypical organization of language represented by an interhemispheric dissociation of language regions with a right frontal dominance and a left temporal dominance. Consistent with the fMRI results, the patient's ability to name pictures was not reliably impaired by electrocortical stimulation (ECS) of left frontal cortex. The findings from Wada, fMRI, and ECS were confirmed by a lack of language impairment after left frontal lobectomy for seizures. This case illustrates that fMRI can precisely map cortical language networks in epileptic patients and that fMRI may be used to help interpret laterality results provided by the Wada procedure.

Chiari I malformation is a well-described entity characterized by hindbrain herniation through the foramen magnum. Although the exact origin of congenital Chiari I malformation is unknown, it appears to be caused by a mismatch between the volume of the posterior fossa neural elements and the posterior fossa cranial content. Several theories have been proposed to describe the resultant pathophysiology of this mismatch. It is clear, however, that abnormal cerebrospinal fluid flow and velocity play a role in the symptoms and signs associated with this disorder. The authors will review the pathophysiology, clinical presentation, and treatment options for patients with Chiari I malformation.

In fMRI studies of language processing, it would be extremely useful to obtain high-quality images during tasks requiring spoken output. Recent studies have suggested that this may be possible, particularly if event-related fMRI methods are used. This study assesses the feasibility of acquiring interpretable images during speech by applying event-related methods to visual word stem completion, a task that has been studied extensively. On each trial, a different three-letter word stem (e.g., COU) was presented visually and subjects were required to generate a word beginning with that stem (e.g., COUSIN). In covert runs, subjects were instructed to say the word once to themselves, without moving their lips. In overt runs, subjects were instructed to say the word once aloud. Ten subjects were scanned during six overt runs and six covert runs at three presentation rates. Data were analyzed using an implementation of the general linear model making no assumptions about response shape. Images were relatively free of artifacts, and regions demonstrating task-related activation were similar to those reported in previous imaging studies. Regions active during overt task performance were similar to those active during covert task performance, with the addition of several regions commonly associated with motor aspects of speech production. Consistent with other studies, magnitude of activation was greater in the overt condition than in the covert condition, and there was a modest decrease in magnitude at the fastest presentation rate. Together, these results help to validate the use of event-related fMRI during tasks that require spoken output. Press

In 2 cases of infants with the Chiari II malformation, a prepontine cyst presented in association with the hindbrain abnormalities characteristic of the Chiari II syndrome. Both infants presented with bulbar dysfunction and had poor outcome despite decompression of the cerebellar tonsillar herniation and drainage of the prepontine cysts. No such association between prepontine lesions and Chiari II has been described previously., (Copyright 2000 S. Karger AG, Basel)

Using functional MRI we compared the patterns of activation in an effortful word retrieval task (stem completion) performed both silently and aloud. The silent and overt conditions showed expected differences in activation magnitude in regions such as primary motor cortex. Some regions, such as frontal operculum and dorsolateral frontal cortex, showed similar activation magnitude across conditions. Thalamus was more active on the left in both conditions and showed a symmetric drop in activity in the silent compared with the overt condition. Putamen was also more active in the overt condition and showed a larger decrease in activity on the right than on the left in the silent compared with the overt condition. Thus it appears that silent and overt performance of this task engage the thalamus and putamen in different ways., (Copyright 2000 Academic Press.)

Lesions involving the sagittal sinus typically present as masses compressing the sinus externally. The authors describe two cases of lesions entirely within the lumen of the sagittal sinus. In one of the cases, syncope was the presenting symptom and surgical resection of the cyst was performed. An entirely intraluminal cyst, consistent with a dural cyst, was resected, followed by reconstruction of the sinus and resolution of symptoms. Entirely intraluminal lesions of the sagittal sinus have rarely been reported as incidental findings. This represents the first report of symptomatic occlusion of a venous sinus by an intraluminal cyst.

Functional magnetic resonance imaging (fMRI) was used to compare directly episodic encoding and retrieval. During encoding, subjects studied visually presented words and reported via keypress whether each word represented a pleasant or unpleasant concept (intentional, deep encoding). During the retrieval phase, subjects indicated (via keypress) whether visually presented words had previously been studied. No reliable differences were found during the recognition phase for words that had been previously studied and those that had not been studied. Areas preferentially active during encoding (relative to retrieval) included left superior frontal cortex, medial frontal cortex, left superior temporal cortex, posterior cingulate, left parahippocampal gyrus, and left inferior frontal gyrus. Regions more active in retrieval than encoding included bilateral inferior parietal cortex, bilateral precuneus, right frontal polar cortex, right dorsolateral prefrontal cortex, and right inferior frontal/insular cortex.

Functional imaging of a language task using positron emission tomography was performed as part of the preoperative assessment of a patient with a left supplementary motor area (SMA) tumor. Positron emission tomography scans were obtained during language tasks (verb generation and word reading of visually presented nouns) that normally lead to increased blood flow in the SMA relative to a control condition (visual fixation). In the patient, the normal SMA response was an order of magnitude larger in the region of the tumor. Other regions, such as left inferior frontal cortex and right cerebellum, showed equivalent activation in the patient and normal subjects. Histopathologic study revealed an anaplastic astrocytoma. Thus, this exaggerated vascular response to local neuronal activation occurred in the setting of a proliferation of glial cells. This is consistent with models of coupling of regional CBF and neuronal activity that implicate glia as the mediator between neurons and vasculature. The concept that tumoral disruption of normal vascular responses could, in some cases, potentially enhance rather than dampen the response is proposed.

Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD-fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word-stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient-refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated.

Functional magnetic resonance imaging (fMRI) techniques, such as echo-planar imaging, can permit rapid, sensitive, whole-brain measurements of local blood flow-induced MR signal changes seen during cognitive paradigms. Changes in blood oxygenation due to mismatch of flow and oxygen metabolism cause dynamic variations in microscopic susceptibility effects, leading to the blood oxygenation level-dependent (BOLD) signal measured by fMRI techniques. A related static macroscopic susceptibility effect is known to cause artifacts that attenuate the MR signal, leading to "blind spots" in some regions of brain adjacent to bone and air sinuses. The anatomical location, spatial extent, and magnitude of signal loss artifact are quantitated for a common whole-brain fMRI technique. Resting gradient-echo EPI studies were obtained in four healthy volunteers. Signal loss was primarily localized to inferior frontal regions (medial orbital gyri and gyrus rectus) and to inferior lateral temporal lobe (including part of fusiform gyrus) bilaterally. Increased echo time (TE) uniformly produced larger artifacts. The orientation of acquired slices and choice of phase-encoding direction influenced the location, shape, and extent of the artifacts. Regions of the brain with severe artifact may have attenuated activation signal, with potential implications for the design and interpretation of fMRI studies targeting activations in these areas., (Copyright 1997 Academic Press.)

Objective and Importance: Foramen magnum encroachment has been cited as a potential cause for the premature demise of patients afflicted with craniometaphyseal dysplasia (CMD). To our knowledge, the association of Chiari malformation and syringomyelia with CMD has not been previously reported. We describe our evaluation and surgical treatment of a patient presenting with CMD, foramen magnum stenosis, Chiari I malformation, and syringomyelia., Clinical Presentation: A 15-year-old female patient with CMD presented with severe headaches and progressive myelopathy. Evaluation by computed tomography and magnetic resonance imaging revealed mild ventriculomegaly, cervicomedullary compression secondary to Chiari I malformation and foramen magnum stenosis, and C3-T10 syringomyelia., Intervention: Foramen magnum decompression was performed via suboccipital craniectomy, C1-C2 laminectomy, and dural augmentation. Dysplastic bone was revealed to be extremely thick and mineralized. Removal required lengthy and extensive drilling. The postoperative course was complicated by prolonged intubation secondary to airway obstruction and a perforated duodenal ulcer. Airway obstruction was attributed to severe nasopharyngeal bony dysplasia and soft tissue edema. The use of steroids in the treatment of airway edema and delayed enteral feeding was thought to contribute to ulcer development. Nevertheless, neurological symptoms improved dramatically., Conclusion: Foramen magnum decompression can be used to treat life-threatening cervicomedullary compression in patients with CMD. However, caution should be used because surgical intervention may be associated with a higher incidence of complications because of lengthy procedures and the spectrum of craniofacial impairments in patients with CMD.

Functional brain imaging studies of memory and attention with positron emission tomography and functional magnetic resonance imaging demonstrate involvement of specific regions of the normal human brain. Possible anatomical substrates for different types of memory have been identified. Different aspects of attention mechanisms, such as modulation of early visual areas, shifts of attention, and selection of response, also appear to involve specific anatomic regions revealed by imaging. Many of these studies show activation in regions clinically considered to be "silent" regions.

This 52-year-old woman developed crystal deposition disease involving the cervical vertebrae. She presented with symptomatic spinal cord compression secondary to extensive calcified lesions in the posterior elements of the cervical spine. Surgical decompression with posterior fusion was performed. Histological examination showed hardened deposits of calcium carbonate involving the soft tissue, and dissolution of the vertebral bone trabeculae. There was no inflammatory response to these deposits. One year postoperatively the patient developed severe pulmonary disease associated with the collagen-vascular disorder, scleroderma (calcinosis, Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia [CREST] syndrome). Calcium carbonate deposition disease represents an unusual clinical entity that is possibly associated with scleroderma or other collagen-vascular diseases, and it is distinct from ligamentum flavum calcification, calcium pyrophosphate deposition disease, and hydroxyapatite deposition disease.

The authors investigated the efficacy of anal sphincter electromyography (EMG) in identifying the lower sacral roots during selective dorsal rhizotomy. In nine children undergoing selective dorsal rhizotomy for cerebral palsy (CP) spasticity, direct electrical stimulation of the L1-S5 dorsal and ventral roots was performed while monitoring EMG responses from the anal sphincter and lower-extremity muscles. Anal sphincter activation was seen with stimulation of lumbosacral roots at many levels. Stimulation of dorsal and ventral roots gave anal sphincter EMG responses in 100% of the dorsal and ventral roots from L-4 and caudally. Only at the L-1 level did a minority of nerve roots have anal sphincter response to stimulation. Patterns of extremity muscle and sphincter activation specific to the S3-5 roots, namely anal sphincter activation without activation of other muscle groups, were found in only five (22%) of 23 roots stimulated. The pattern of stimulation responses in the majority of S3-5 roots indicated that the pathophysiology of lower-extremity spasticity in CP may involve the anal sphincter and does not spare the lower sacral roots. Thus, this study indicates that electrophysiological mapping alone, without anatomical identification, cannot be used to identify the lower sacral roots during selective dorsal rhizotomy for CP spasticity, and it proposes a model for investigation of associated bowel and bladder symptoms.

Objective: Intrinsic brain tumors can arise within regions of the cortex that are essential to language, motor, and somatosensory functions. Although it is commonly thought that such tumors can be safely resected, as long as the resection is limited to grossly abnormal cortex, functional mapping of the cerebral cortex during tumor resection does not support this contention., Methods: We report our experience with 14 patients (9 men, 5 women; median age, 43 yr) with intrinsic brain tumors of varying degrees of malignancy (four glioblastomas multiforme, four anaplastic astrocytomas, two anaplastic oligodendrogliomas, one anaplastic mixed glioma, three gangliogliomas). Cortical mapping was performed either intraoperatively (n = 11) or extraoperatively via intracranial electrodes (n = 3)., Results: Tumors were found to grossly invade functioning cortices (frontal lobe language cortex, four tumors; temporal lobe language cortex, five tumors; motor cortex, four tumors; somatosensory cortex, one tumor). The gross invasion of functional cortex by tumor limited safe resection in all patients. Three patients experienced transient postoperative deficits caused by the proximity of the resection to functional cortex. One patient suffered a delayed postoperative hemorrhage, with resultant persistent motor aphasia., Conclusion: Intrinsic brain tumors grow by infiltration of normal brain. Consequently, brain that appears to be abnormal may remain functional, thus precluding safe tumor resection.

Findings of intraoperative rolandic cortex mapping during awake craniotomy for a tumor in a patient with a contralateral upper-extremity amputation are presented. This patient sustained a traumatic amputation at the mid-humerus 24 years previously. Initially he had experienced rare painless phantom limb sensations but none in the past 10 years. Functional mapping during an awake craniotomy was performed to maximize safe tumor resection. Typical temporal and frontal speech areas were identified; motor representation of face and jaw extended more superiorly than sensory representation. Shoulder movements were evoked more laterally than usual at the superior aspect of the craniotomy. A small region of precentral gyrus, between the jaw and shoulder representations, elicited no detectable effect when stimulated. Somatosensory mapping showed a similar topographical distribution of face and mouth cortex; however, posterior and inferior to the shoulder motor cortex, right arm and hand (phantom) sensations were evoked. Evidence suggests that significant motor reorganization occurs following an amputation, with expansion of neighboring homuncular representations without loss of somatosensory representation, despite a long period of time without any sensation referable to the amputated limb. Contrary to models of sensory cortex plasticity, the plasticity of the adult cortex may be system specific, with reorganization present in motor, but not in sensory, cortical systems.

Across three experiments, PET scans were obtained while subjects performed different word-stem completion and FIXATION control tasks designed to study the functional anatomy of memory retrieval. During each of three different word-stem completion scans, word-stem cues were visually presented in uppercase letters. The RECALL task required explicit retrieval of study words presented prior to the PET scan. The PRIMING task addressed the implicit effects of the prior study words without requiring intentional recall. The BASELINE task encouraged retrieval of information from a general knowledge store. Across experiments, the similarity between study words and word stems was manipulated by presenting prescan study words in either uppercase letters identical to the stems, in lowercase letters, or auditorily. The PRIMING task was not studied with auditory presentation. Many activations were consistent across experiments. The BASELINE task activated several regions in response to the reading and verbal-response demands of the task (visual, motor, and premotor cortices, cerebellum), as well as a left prefrontal region. The RECALL task additionally activated regions in anterior right prefrontal cortex. Bilateral occipitotemporal regions showed blood flow reductions during the PRIMING task as compared to the BASELINE task. Activation in the right hippocampal/parahippocampal region was observed only in one experiment, and no experiment showed activation in the left medial temporal lobe. These experiments suggest that areas of frontal cortex play a role in explicit recall and that an effect of priming may be to require less activation of perceptual regions for the processing of recently presented information.

Neuronal activity was recorded from 13 sites in right nondominant superior and middle temporal gyrus during matching of faces (FM), matching of complex figures (CM), labelling of facial emotional expression (FE) and object naming (N) in 11 patients undergoing craniotomy under local anaesthesia. These extracellular recordings were divided into 21 neuronal populations of one to a few cells, using amplitude window discriminators. Sixty-two percent of those populations showed statistically significant changes in activity during FM; 52% during FE; 38% during N and 38% during CM. Fifty-one percent of changes were in the first 1.3 s of each task and 33% in the next 1.3 s, when overt speech responses to the tasks occurred. Significant changes lasting throughout the 4 s allotted to each task were not seen. Functional correlates of some populations were derived from patterns of changes during FM and other tasks: four populations were related to 'matching', in that significant changes occurred with FM and CM. One of these populations, and six other populations were related to face perception, with significant change with FM and FE, confirming the presence in man of neuronal activity related to faces, as previously described from primate cortex. Six populations increased activity with overt speech; four of these showed greater increases when overt speech was in response to a visuospatial task compared with the lexical task.