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Biomedical subjects

J R Madsen

Publications and source records attributed to J R Madsen.

At least 19 recordsLinked to original sources
PubMed2003

Reset of human neocortical oscillations during a working memory task.

Both amplitude and phase of rhythmic slow-wave electroencephalographic activity are physiological correlates of learning and memory in rodents. In humans, oscillatory amplitude has been shown to correlate with memory; however, the role of oscillatory phase in human memory is unknown. We recorded intracranial electroencephalogram from human cortical and hippocampal areas while subjects performed a short-term recognition memory task. On each trial, a series of four list items was presented followed by a memory probe. We found agreement across trials of the phase of oscillations in the 7- to 16-Hz range after randomly timed stimulus events, evidence that these events either caused a phase shift in the underlying oscillation or initiated a new oscillation. Phase locking in this frequency range was not generally associated with increased poststimulus power, suggesting that stimulus events reset the phase of ongoing oscillations. Different stimulus classes selectively modulated this phase reset effect, with topographically distinct sets of recording sites exhibiting preferential reset to either probe items or to list items. These findings implicate the reset of brain oscillations in human working memory.

Brain Injuries↗
PubMed2001

[Irritable colon].

Irritable bowel syndrome is a chronic, relapsing functional bowel disorder of unknown aetiology. Methods of studying intestinal motor function, nociception, and interactions of the central nervous system and enteric nervous system are not applicable for clinical use. The diagnosis is therefore made on the symptoms, but it is necessary to exclude relevant organic disease. Establishment of the diagnosis, information about the disorder, elimination of foods and other factors that provoke the symptoms, and a change in life-style are sufficient in most cases. Treatment is hampered by the lack of effective treatment and the psychological aspects. The therapeutic gain of drug administration is modest and the rate of response to placebo is high. Fibre supplementation, magnesium oxide or cisapride may be tried for constipation, diphenoxylate or loperamide for diarrhoea, and low dose tricyclic antidepressants or serotonin reuptake blockers for severe pain. The introduction of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists seems promising.

Colonic Diseases, Functional↗
PubMed2001

Gating of human theta oscillations by a working memory task.

Electrode grids on the cortical surface of epileptic patients provide a unique opportunity to observe brain activity with high temporal-spatial resolution and high signal-to-noise ratio during a cognitive task. Previous work showed that large-amplitude theta frequency oscillations occurred intermittently during a maze navigation task, but it was unclear whether theta related to the spatial or working memory components of the task. To determine whether theta occurs during a nonspatial task, we made recordings while subjects performed the Sternberg working memory task. Our results show event-related theta and reveal a new phenomenon, the cognitive "gating" of a brain oscillation: at many cortical sites, the amplitude of theta oscillations increased dramatically at the start of the trial, continued through all phases of the trial, including the delay period, and decreased sharply at the end. Gating could be seen in individual trials and varying the duration of the trial systematically varied the period of gating. These results suggest that theta oscillations could have an important role in organizing multi-item working memory.

Adolescent↗
PubMed2001

Gentle dorsal root retraction and dissection can cause areflexia: implications for intraoperative monitoring during "selective" partial dorsal rhizotomy.

During partial dorsal rhizotomy (PDR), intraoperative dorsal rootlet stimulation often evokes nonreflex, rather than reflex, motor responses that are due to costimulation of adjacent ventral roots. Intraoperative areflexia typically predicts that motor responses evoked by dorsal rootlet stimulation are nonreflexive. The cause of areflexia during PDR is in part due to anesthesia, but other mechanisms are likely to play a role as well. In this study of three consecutive patients undergoing lumbosacral neurosurgery, soleus H-reflexes evoked by tibial nerve stimulation at the popliteal fossa were found to suddenly decline in amplitude following retraction and gentle dissection of the S-1 dorsal root. In one areflexic patient, dorsal rootlet stimulation proximal to the main site of dissection evoked soleus H-reflexes, although they could not be evoked by tibial nerve stimulation. We conclude that the gentle retraction and dissection of dorsal rootlets that occurs during PDR can induce conduction block of reflex afferents. High-intensity dorsal rootlet stimulation distal to the site of conduction block may then evoke not reflex responses, but rather nonreflex motor responses, due to the costimulation of adjacent ventral roots.

Cerebral Palsy↗
PubMed2001

Vagus nerve stimulation in pediatric epilepsy: a review.

Therapeutic options for intractable epilepsy include new and investigational antiepileptic drugs, ketogenic diet, epilepsy surgery, and, now, vagus nerve stimulation, which is approved by the U.S. Food and Drug Administration for the treatment of refractory partial seizures in adolescents and adults. The exact mechanisms of action are unknown. Although the use of vagus nerve stimulation in children has increased, including those younger than 12 years of age or those with generalized epilepsy, there has been no large controlled pediatric study to date. The identification of favorable prognostic indicators, especially in children, would be useful. Preliminary results suggest that children with Lennox-Gastaut syndrome may have a favorable response, with improvement in both seizure control and global evaluation scores. Improved global evaluation scores have occurred even without an associated improvement in seizure control.

Adolescent↗
PubMed2001

Theta returns.

Recent physiological studies have implicated theta - a high-amplitude 4-8 Hz oscillation that is prominent in rat hippocampus during locomotion, orienting and other voluntary behaviors - in synaptic plasticity, information coding and the function of working memory. Intracranial recordings from human cortex have revealed evidence of high-amplitude theta oscillations throughout the brain, including the neocortex. Although its specific role is largely unknown, the observation of human theta has begun to reveal an intriguing connection between brain oscillations and cognitive processes.

Animals↗
PubMed2001

Distinct patterns of brain oscillations underlie two basic parameters of human maze learning.

We examine how oscillations in the intracranial electroencephalogram (iEEG) relate to human maze learning. Theta- band activity (4-12 Hz in rodents; 4-8 Hz in humans) plays a significant role in memory function in rodents and in humans. Recording intracranially in humans, we have reported task-related, theta-band rhythmic activity in the raw trace during virtual maze learning and during a nonspatial working memory task. Here we analyze oscillations during virtual maze learning across a much broader range of frequencies and analyze their relationship to two task variables relevant to learning. We describe a new algorithm for detecting oscillatory episodes that takes advantage of the high signal-to-noise ratio and high temporal resolution of the iEEG. Accounting for the background power spectrum of the iEEG, the algorithm allows us to directly compare levels of oscillatory activity across frequencies within the 2- to 45-Hz band. We report that while episodes of oscillatory activity are found at various frequencies, most of the rhythmic activity during virtual maze learning occurs within the theta band. Theta oscillations are more prevalent when the task is made more difficult (manipulation of maze length). However, these oscillations do not tend to covary significantly with decision time, a good index of encoding and retrieval operations. In contrast, lower- and higher-frequency oscillations do covary with this variable. These results suggest that while human cortically recorded theta might play a role in encoding, the overall levels of theta oscillations tell us little about the immediate demands on encoding or retrieval. Finally, different patterns of oscillations may reflect distinct underlying aspects of memory function.

Adolescent↗
PubMed2001

Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study.

This six-center, retrospective study evaluated the effectiveness, tolerability, and safety of vagus nerve stimulation in children. Data were available for 125 patients at baseline, 95 patients at 3 months, 56 patients at 6 months, and 12 patients at 12 months. The typical patient, aged 12 years, had onset of seizures at age 2 years and had tried nine anticonvulsants before implantation. Collected data included preimplant history, seizures, implant, device settings, quality of life, and adverse events. Average seizure reduction was 36.1% at 3 months and 44.7% at 6 months. Common adverse events included voice alteration and coughing during stimulation. Rare adverse events, unique to this age group, included increased drooling and increased hyperactivity. Quality of life improved in alertness, verbal communication, school performance, clustering of seizures, and postictal periods. We concluded that vagus nerve stimulation is an effective treatment for medically refractory epilepsy in children.

Adolescent↗
PubMed2000

[Chronic inflammatory bowel disease--pathogenic concepts and therapeutic perspectives].

Chronic inflammatory bowel disease (IBD) is considered to be a consequence of inappropriate upregulation of immune reactions evoked by the colonic microflora. Abnormalities observed in IBD may be explained, at least in part, by an unfavourable balance between pro- and anti-inflammatory cytokines. Conventional drug treatment of IBD may soon be replaced by more selective inhibitors that act centrally in the inflammatory process. Immunoneutralisation with chimeric anti-tumour necrosis factor-alpha (TNF alpha) antibodies reduces treatment refractory IBD, including fistular Chrons' disease, but recombinant human TNF alpha-receptor fusion proteins may be equally effective with potentially fewer side effects. This view also applies to chimeric antibodies directed against cytokines or adhesion molecules. Potentially more promising are antisense oligonucleotides and matrix-metalloproteinase inhibitors. Whether sustained remission can be achieved probably depends on successful unravelling of the aetiology of IBD.

Antibodies↗
PubMed2000

Pathophysiology, prevention, and potential treatment of neural tube defects.

Neural tube defects (NTD) remain a major cause of morbidity in spite of the reduction in liveborn incidence with periconceptional folic acid. However, the etiology remains unknown. This article reviews studies that address causation and potential treatment of NTD in humans and in animal models that resemble aspects of the common human NTD. Studies of nutritional markers of vitamin B12 and folic acid support a defect in homocysteine metabolism; a thermolabile variant of methylene tetrahydrofolate reductase, an enzyme that remethylates homocysteine to methionine, correlates with a risk of NTD in some human populations. Numerous mouse mutant models of NTD exist, attesting to the ease of disruption of neurulation, and a genetic basis for this malformation. Of these models, the curly tail mouse mutant most closely resembles the common human NTD. Folic acid does not prevent NTD in this model; however inositol supplementation does result in a significant reduction in incidence. Recent advances in fetal surgery, and evidence from mechanically created myelomeningocele in large animals amenable to surgical intervention suggest that the handicaps associated with myelomeningocele and associated Chiari Type II malformation may be prevented by in utero NTD closure. Success will depend on preservation of neurological tissue until such intervention is possible. Further research in animal models at the genetic and cellular levels, together with technological surgical advances, provide hope that prevention of more NTD and the associated handicaps may be possible. MRDD Research Reviews 6:6-14, 2000.

Animals↗
PubMed2000

The effect of propofol on intraoperative electrocorticography and cortical stimulation during awake craniotomies in children.

Propofol has been proposed as a sedative agent during awake craniotomies. However, there are reports of propofol suppressing spontaneous epileptiform electrocorticography (ECoG) activity during seizure surgery, while others describe propofol-induced epileptiform activity. The purpose of this study was to determine if propofol interferes with ECoG and direct cortical stimulation during awake craniotomies in children. Children scheduled for awake craniotomies for resection of epileptic foci or tumours were studied. An intravenous bolus of 1-2 mg.kg-1 followed by infusion of 100-200 microgram.kg-1.min-1 of propofol was administered to induce unconsciousness. Fentanyl (0.5 microgram.kg-1) was administered incrementally to provide analgesia. After the cortex was exposed, the propofol infusion was stopped and the patient permitted to awaken. Cortical electrodes were applied. ECoG was recorded continuously on a Grass polygraph. Motor, sensory, language, and memory testing were done throughout the procedure. The cortex was stimulated with a hand-held electrode using sequential increases in voltage to map the relevant speech and motor areas. We studied 12 children (aged 11-15 years) with intractable seizures. The raw ECoG did not reveal any prolonged beta-waves associated with propofol effect. Electroencephalogram spikes due to spontaneous activity or cortical stimulation were easily detected. Cognitive, memory and speech testing was also successful. We conclude that propofol did not interfere with intraoperative ECoG during awake craniotomies. Using this technique, we were able to fully assess motor, sensory, cognitive, speech and memory function and simultaneously avoid routine airway manipulation.

Adolescent↗
PubMed2000

The living shunt: a tissue engineering approach in the treatment of hydrocephalus.

Tissue engineering is the use of cultured cells seeded into biodegradable polymers to create custom designed, living implantable devices. As a first approach to the use of this technique in the treatment of hydrocephalus, we have prepared chondrocyte-seeded polyglycolic acid (PGA) tubes coated with polylactic glycolic acid (PGLA), implanted initially with thin silastic stents removed four weeks after shunt insertion. The use of bovine xenograft cells in athymic (nude) rats resulted in more efficient seeding with chondrocytes, stiffer tube walls, and better patency. When implanted in 6-week-old rats made hydrocephalic by cisternal injection of kaolin at 4 weeks of age, six of eight 'living shunts' remained patent to radio-opaque contrast injection at two weeks after stent removal. At four weeks after stent removal, all four of the shunts had occluded at the ventricular end, three of the four apparently due to growth of the animal. We conclude that polymer type, cell type, and cell density will require considerable optimization, but a working tissue engineered shunt is feasible and may one day address some problems of interactions of living tissue and inert polymer.

Animals↗
PubMed2000

Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial.

Intrathecal baclofen infusion has demonstrated effectiveness in decreasing spasticity of spinal origin. Oral antispasticity medication is minimally effective or not well tolerated in cerebral palsy. This study assessed the effectiveness of intrathecal baclofen in reducing spasticity in cerebral palsy. Candidates were screened by randomized, double-blind, intrathecal injections of baclofen and placebo. Responders were defined as those who experienced an average reduction of 1.0 in the lower extremities on the Ashworth Scale for spasticity. Responders received intrathecal baclofen via the SynchroMed System and were followed for up to 43 months. Fifty-one patients completed screening and 44 entered open-label trials. Lower-extremity spasticity decreased from an average baseline score of 3.64 to 1.90 at 39 months. A decrease in upper extremity spasticity was evidenced over the same study period. Forty-two patients reported adverse events. Most common reports were hypotonia, seizures (no new onset), somnolence, and nausea or vomiting. Fifty-nine percent of the patients experienced procedural or system-related events. Spasticity in patients with cerebral palsy can be treated effectively by continuous intrathecal baclofen. Adverse events, although common, were manageable.

Adolescent↗
PubMed1999

Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury.

The purine nucleoside inosine has been shown to induce axon outgrowth from primary neurons in culture through a direct intracellular mechanism. For this study, we investigated the effects of inosine in vivo by examining whether it would stimulate axon growth after a unilateral transection of the corticospinal tract. Inosine applied with a minipump to the rat sensorimotor cortex stimulated intact pyramidal cells to undergo extensive sprouting of their axons into the denervated spinal cord white matter and adjacent neuropil. Axon growth was visualized by anterograde tracing with biotinylated dextran amine and by immunohistochemistry with antibodies to GAP-43. Thus, inosine, a naturally occurring metabolite without known side effects, might help to restore essential circuitry after injury to the central nervous system.

Animals↗
PubMed1999

Human theta oscillations exhibit task dependence during virtual maze navigation.

Theta oscillations (electroencephalographic activity with a frequency of 4-8 Hz) have long been implicated in spatial navigation in rodents; however, the role of theta oscillators in human spatial navigation has not been explored. Here we describe subdural recordings from epileptic patients learning to navigate computer-generated mazes. Visual inspection of the raw intracranial signal revealed striking episodes of high-amplitude slow-wave oscillations at a number of areas of the cortex, including temporal cortex. Spectral analysis showed that these oscillations were in the theta band. These episodes of theta activity, which typically last several cycles, are dependent on task characteristics. Theta oscillations occur more frequently in more complex mazes; they are also more frequent during recall trials than during learning trials.

Adolescent↗
PubMed1999

Central nervous system abnormalities assessed with prenatal magnetic resonance imaging.

OBJECTIVE: To determine the frequency at which magnetic resonance imaging (MRI) provides additional information in fetuses with suspected central nervous system (CNS) abnormalities on ultrasound. METHODS: Between May 1, 1996, and March 26, 1999, 83 women with 90 fetuses (including seven sets of live twins) had 91 ultrasonographic and MRI examinations of the fetal CNS. Eight women were studied twice, one for two different indications. If referrals came from outside our institution, a confirmatory sonogram was obtained. Indications for examination were ventriculomegaly (n = 25), suspected neural tube defect (n = 16), arachnoid cyst (n = 12), large cisterna magna (n = 11), and miscellaneous indications (n = 20). RESULTS: Magnetic resonance imaging findings led to changed diagnoses in 26 (40%) of 66 fetuses with abnormal confirmatory sonograms. Magnetic resonance imaging findings not found by ultrasound included partial or complete agenesis of the corpus callosum (n = 11), porencephaly (n = 6), hemorrhage (n = 5), tethered cord (n = 3), cortical gyral abnormality (n = 2), cortical cleft (n = 2), midbrain abnormality (n = 2), and partial or complete agenesis of the septi pellucidi (n = 3), as well as holoprosencephaly, cerebellar hypoplasia, subependymal and cortical tubers, vascular malformation, and vermian cysts (one case each). Abnormalities better delineated by MRI than ultrasound included three cephaloceles, a dural arteriovenous malformation, one distal sacral neural tube defect, and the mass effect of three arachnoid cysts. That information was used to alter patient counseling and at times management. CONCLUSION: When a CNS anomaly is detected by sonography or suspected on ultrasound, MRI findings might lead to altered diagnosis and patient counseling.

Central Nervous System↗