A cognitive brain-computer interface for patients with amyotrophic lateral sclerosis.

Brain-computer interfaces (BCIs) are often based on the control of sensorimotor processes, yet sensorimotor processes are impaired in patients suffering from amyotrophic lateral sclerosis (ALS). We devised a new paradigm that targets higher-level cognitive processes to transmit information from the user to the BCI. We instructed five ALS patients and twelve healthy subjects to either activate self-referential memories or to focus on a process without mnemonic content while recording a high-density electroencephalogram (EEG). Both tasks are designed to modulate activity in the default mode network (DMN) without involving sensorimotor pathways. We find that the two tasks can be distinguished after only one experimental session from the average of the combined bandpower modulations in the theta- (4-7Hz) and alpha-range (8-13Hz), with an average accuracy of 62.5% and 60.8% for healthy subjects and ALS patients, respectively. The spatial weights of the decoding algorithm show a preference for the parietal area, consistent with modulation of neural activity in primary nodes of the DMN.

BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation.

UNLABELLED: Direct vagus nerve stimulation (VNS) has proved to be an effective treatment for seizure disorder and major depression. However, since this invasive technique implies surgery, with its side-effects and relatively high financial costs, a non-invasive method to stimulate vagal afferences would be a great step forward. We studied effects of non-invasive electrical stimulation of the nerves in the left outer auditory canal in healthy subjects (n = 22), aiming to activate vagal afferences transcutaneously (t-VNS). Short-term changes in brain activation and subjective well-being induced by t-VNS were investigated by functional magnetic resonance imaging (fMRI) and psychometric assessment using the Adjective Mood Scale (AMS), a self-rating scale for current subjective feeling. Stimulation of the ear lobe served as a sham control. fMRI showed that robust t-VNS induced BOLD-signal decreases in limbic brain areas, including the amygdala, hippocampus, parahippocampal gyrus and the middle and superior temporal gyrus. Increased activation was seen in the insula, precentral gyrus and the thalamus. Psychometric assessment revealed significant improvement of well-being after t-VNS. Ear lobe stimulation as a sham control intervention did not show similar effects in either fMRI or psychometric assessment. No significant effects on heart rate, blood pressure or peripheral microcirculation could be detected during the stimulation procedure. CONCLUSIONS: Our study shows the feasibility and beneficial effects of transcutaneous nerve stimulation in the left auditory canal of healthy subjects. Brain activation patterns clearly share features with changes observed during invasive vagus nerve stimulation.

Cerebral representation of the anorectum using functional magnetic resonance imaging.

BACKGROUND: Anorectal continence depends not only on the organs of continence but also on cerebral control. There are relatively few data regarding cerebral processing of anorectal continence. METHODS: Thirteen healthy subjects underwent rectal distension to cause urge increasing to discomfort during functional magnetic resonance imaging (fMRI). In addition, a painful heat stimulus was applied to the skin of the anterior abdominal wall in the dermatome corresponding to the rectum. Voluntary contraction of the anal sphincter was also performed. Subjective rating of stimulus intensity was recorded. Evaluation of the data used a general linear model with Brain Voyager(trade mark). RESULTS: Subjective sensation of discomfort increased during repeated rectal distension and caused activation in the anterior cingulate gyrus, insula, thalamus and secondary somatosensory cortex seen on fMRI. Perception of rectal urge and discomfort activated the same cerebral regions with differing intensity. Application of a painful thermal stimulus in the corresponding dermatome showed a modification of the response. Voluntary contraction of the anal sphincter led to activation of the motor cortex and increased activity in the supplementary motor cortex and the insula. CONCLUSION: Cerebral representation of the anorectum as mapped by fMRI is intricate and reflects the complexity of the continence mechanism.

An examination of the treatment of iron-dosed waste activated sludge by anaerobic digestion.

Anaerobic digestion is an important sludge treatment process enabling stabilisation of the organic fraction of sewage sludge prior to land application. Any practice which might retard the anaerobic digestion process will jeopardize the stability of the resulting digested sludge. This paper reports on an investigation into the relative digestibility of iron-dosed waste activated sludge (WAS) from a sewage treatment works (STW) with chemical phosphorus removal (CPR), in comparison to WAS from a works without phosphorus removal. Two laboratory scale anaerobic digesters (51) were fed initially with non iron-dosed WAS (Works M) at a solids retention time of 19 days. After 2 months the iron-dosed CPR sludge (Works R) was introduced into the second digester, resulting in a 32% decrease in biogas production and an increase in the methane content of the biogas from an average of 74% to 81%. Pre-treatment of the CPR sludge with sodium sulphide and shear, both alone and in combination, caused the gas production to deteriorate further. Pre-acidification and pre-treatment with EDTA did result in an enhanced gas production but it was still not comparable with that of the digester being fed with non-iron-dosed sludge. The daily gas production was found to be linearly related to the amount of bound iron in the sludge.

Effect of topical capsaicin on the cutaneous reactions and itching to histamine in atopic eczema compared to healthy skin.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is thought to produce analgesic and possibly also antipruritic effects when applied topically. Capsaicin 0.05% was applied three times daily over a 5-day period to the same infrascapular region. The effects of the pretreatment upon the pruritogenic and wheal and flare reactions to subsequent histamine iontophoresis (20 mC) were evaluated on the following day. The antipruritic effects of the pretreatment were compared with the effects of placebo pretreatment and no pretreatment. Wheal and flare areas were evaluated planimetrically. Itch or pain were rated every minute over a 24-min period. The areas of alloknesis, i.e. the induction of perifocal itch sensation by usually nonitching (e.g. mechanical) stimuli, were also evaluated. In control subjects, but not in atopic eczema (AE) patients, capsaicin pretreatment significantly reduced the flare area. Compared with control subjects, AE patients showed a lack of alloknesis or significantly smaller areas of alloknesis in pretreated and nonpretreated skin. In control subjects, capsaicin pretreatment significantly reduced itch sensations compared with nonpretreated skin, whereas in AE patients no differences were seen. Itch sensations in capsaicin-pretreated skin were significantly lower in control subjects than in AE patients. We conclude that capsaicin does effectively suppress histamine-induced itching in healthy skin but has less effect in AE. The diminished itch sensations and the absence of alloknesis in atopic individuals indicate that histamine is not the key factor in itching in AE.

Role of gender and vascular endothelium in rat aorta response to 17 beta-estradiol.

Estrogen supplementation in postmenopausal women offers significant cardiovascular protection. The mechanism for this benefit is unclear but may be due to an interaction of estrogen with the blood vessel wall (vascular smooth muscle and endothelium). We examined the response of weight-matched female and male endothelium-intact and -denuded aortae to 17 beta-estradiol, its interaction with noradrenaline, and the effect of N-nitro-L-arginine. Estradiol produced relaxation responses that were significantly greater in female endothelium-intact preparations. This response was sensitive to N-nitro-L-arginine, while the response to 17 beta-estradiol in male endothelum-intact and both female and male endothelum-denuded preparations was resistant. Estradiol also inhibited contractions to noradrenaline, which was more pronounced in the female endothelium-intact aortic rings. These data imply that estradiol interacts preferentially with the female vascular endothelium, but there exists an endothelium-independent process that can also be activated in the male aorta. Further studies are warranted to elucidate these differential mechanisms.

[Optimization of the Barron ligature treatment of 2nd and 3rd-degree hemorrhoids using a therapeutic troika]. / Optimierung der Barron-Ligaturbehandlung von Hämorrhoiden zweiten und dritten Grades durch therapeutische Troika.

Due to the fact that the intensity of haemorrhoidal complaints may rapidly change, also numerous therapeutic approaches of minor effectiveness are considered a helpful remedy. However, the advantage of the Barron-ligature is not seriously doubted. By placing it correctly at the insensitive distal rectum, haemorrhoidal operations are only necessary in very advanced stages. Can the Barron ligature be optimized even more? Three patient groups consisting of 120 patients with 2nd degree haemorrhoids who were simultaneously treated by anal dilation using an appropriate lubricant for the anal dilator, were compared with each other in a randomized, open, placebo-controlled study conducted in two centres. In these groups treatment consisted of: rubber-band ligature alone rubber-band ligature and anal dilator and Kamillosan ointment rubber-band ligature and anal dilator and vaseline The observation period comprised six weeks. Every two weeks a check was made. Assessment criteria were: light-red haemorrhage, itching, oozing, sensation of incomplete evacuation, nodal prolapse and slight staining after defecation The pressure ratios of the closing apparatus were investigated at the beginning and end of the study. The group who had been treated with rubber-band ligature, anal dilator and Kamillosan ointment showed the best results. By simultaneously applying the rubber-band ligature, anal dilator and Kamillosan ointment as a lubricant, significantly better results could be obtained. The findings are based on a former retrospective study carried out in 500 patients with 2nd degree haemorrhoids. In this study by applying the anal dilator and Kamillosan ointment, the number of treatments could significantly be reduced from 5.95 to 4.2 and the number of necessary ligatures from 3.8 to 2.76 which, also from the economic point of view, was favourable.

Limitation of sensitization to injured parts of receptive fields in human skin C-nociceptors.

Unmyelinated cutaneous mechano-heat fibers (CMH) in the peroneal nerve of healthy human volunteers were studied by means of a "marking" technique which allows stable recordings from identified single units over extended periods. Mechanoreceptive field sizes were 105 +/- 13 mm2 in 25 units. These large receptive fields indicate extensive terminal branching of C fibers in the skin of foot and lower leg. Sensitization of CMHs was tested by assessment of thresholds for mechanical (von Frey hair) and heat stimuli before and after topical application of mustard oil (allyl isothiocyanate) and capsaicin (8-methyl-N-vanillyl-6-noneamide). While in a group of 14 CMHs the entire receptive field was treated with these irritant substances, in another group of 11 CMH units only parts of the receptive field were treated to check for signs of spreading sensitization through axon collaterals. Mustard oil application did not change mechanical thresholds, regardless of whether parts of or complete receptive fields were treated. However, mean heat thresholds dropped by 5.6 degrees C to 36.5 +/- 1.5 degrees C in completely treated receptive fields and by 5.7 degrees C to 37.3 +/- 3.4 degrees C in treated parts of receptive fields ("primary sensitization"). In contrast, heat thresholds in the nontreated parts did not change significantly (42.1 +/- 3.4 degrees C vs 41.2 +/- 3.9 degrees C), i.e. "secondary sensitization" to heat was lacking. The absence of primary sensitization to probing with von Frey hairs indicates that sensitization of insensitive C fibers and recruitment of insensitive axon collaterals may be more important for mechanical hyperalgesia than sensitization of conventional CMH units-apart from the contribution of central mechanisms. The lack of spread of sensitization to untreated parts of the receptive fields o CMHs ("secondary sensitization") indicates that this fiber group is probably not involved in any form of secondary hyperalgesia to heating.

Inflammatory models of cutaneous hyperalgesia are sensitive to effects of ibuprofen in man.

A new experimental procedure was developed to quantify the analgesic actions of non-steroidal anti-inflammatory drugs (NSAIDs) in healthy human subjects. In order to mimic the clinical situation, the drug was 'therapeutically' administered 1 day after induction of inflammation by freezing a small skin area. The procedure was easily tolerated and led to a marked hyperalgesia without ongoing pain which was tested using mechanical impact stimulation and magnitude estimation. For comparison, we used a previously established model of repeated noxious pinching of an interdigital skin web which induces a hyperalgesia to pressure (rated via visual analogue scale), and topical application of capsaicin which leads to quantifiable flare and allodynia responses. The effects of a cumulative drug regime of ibuprofen in 2 different doses (3 x 400 mg and 3 x 800 mg at 2-h intervals) were tested versus placebo using a double-blind cross-over design with 24 volunteers of either gender. Ibuprofen caused a significant suppression of the hyperalgesia to repeated pinching and of the hyperalgesia to impact stimulation following freeze trauma. In contrast, there was no effect on the areas of flare and allodynia induced by capsaicin application and on the impact evoked sensations from untreated skin. The two dosages of ibuprofen, however, appeared to be equally effective in a way that suggests a plateauing of the antihyperalgesic effect. The two models in which hyperalgesia is affected by ibuprofen, i.e., repeated pinching and impact stimulation after freeze trauma, seem to provide comparable sensitivity. The freeze model may in the future have the advantage to allow for a better temporal resolution of the drug's action profile.

Novel classes of responsive and unresponsive C nociceptors in human skin.

One hundred ninety-four cutaneous C-fibers were recorded from the human peroneal nerve; 118 units were found by mechanical stimuli and 76 units were detected by electrical stimulation through a surface electrode. Needle electrodes were then inserted for electrical intradermal stimulation in the innervation territory of the units. Afferent and efferent sympathetic C-fibers were identified by slowing of conduction velocity after activation either by physical or chemical skin stimuli, or by arousal maneuvers eliciting sympathetic reflexes. In addition to mechano-heat-responsive C units (CMH) also found in previous studies, we here report on novel classes of C nociceptors in human skin, namely, units responding only to mechanical stimuli (CM), units responding only to heating (CH), and units that were insensitive to mechanical and heating stimuli and also to sympathetic provocation tests (CMiHi). With the electrical search technique we found 45% CMH, 13% CM, 6% CH, 24% CMiHi, and 12% sympathetic units. Excitation by topically applied mustard oil occurred in 58% of CMH units, and in one-third of CM and CMiHi units, respectively. Some CM, CH, and CMiHi units were sensitized to heating and/or to mechanical stimuli after topical application of mustard oil or capsaicin. These units then acquired responsiveness to a stimulus modality to which they previously were insensitive. Such recruitment of previously silent nociceptors implies spatial summation to the nociceptive barrage at central levels, and may contribute both to primary hyperalgesia to heat and pressure after chemical irritation, and to secondary hyperalgesia as a consequence of central sensitization.

Discharge patterns of human C-fibers induced by itching and burning stimuli.

1. The aim of this investigation was to study the peripheral neural mechanisms of the C-fiber-mediated modalities of burning pain and itch by the use of microneurography of human unmyelinated afferents. 2. Sixteen stable recordings of single C-fibers and 6 multiunit recordings were obtained from the superficial radial nerves of volunteers. All units were excited by stimulating their receptive fields with von Frey bristles (range 10-600 mN), and all but four units were also driven by radiant heat stimulation. 3. Histamine was iontophoretically applied to the receptive fields of these units for 20 or 30 s and was found to provoke itching sensations lasting several minutes, together with wheal and flare responses. Subsequently a solution containing 20 or 30% mustard oil was applied to the receptive field of the respective unit, which provoked a sensation of burning pain. 4. One-half of the units were excited by histamine, and the median discharge rates derived from interspike intervals ranged from approximately 0.1 to 0.8 Hz. Mustard oil-induced activity was observed in all histamine-sensitive units and also in three single units and in one multiunit recording that revealed no histamine response. Median interval-derived discharge rates ranged from 0.2 to 1.2 Hz. 5. Analysis of the interspike interval distribution and of the autocorrelation function derived from the chemically induced discharges of single units provided no evidence for an encoding of itch and burning pain in different discharge patterns of units responding to histamine and to mustard oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of plain and Gd-DTPA-enhanced MR-imaging in children.

40 children and adolescents (aged 1-16 years) were examined by MRI at 1.0 T. Gd-DTPA was given intravenously at a dose of 0.1 mmol/kg body weight. In all cases T1-weighted SE sequences were used to demonstrate contrast enhancement. No adverse effects were seen. 30 patients had one or more lesions; in 20 patients contrast enhancement was seen. In 4 cases lesions were not observed by plain MRI and could only be detected after Gd-DTPA. In addition, contrast enhancement provided additional information about the differentiation of lesion from edema or necrosis in 13 patients. Normal brain matter did not show any changes in signal intensity. However, an age-dependent signal increase was found in the normal vertebral bone marrow in all children. Gd-DTPA should be used as a supplementary examination whenever a tumor or an infectious disease of the CNS is suspected and plain MRI is normal, or when origin and extent of a lesion cannot be adequately defined with plain MRI.

Prostacyclin and cerebral vessel relaxation.

The authors have studied the ability of prostacyclin to reverse contractions of human basilar arteries in vitro that were induced by a wide range of substances implicated in the etiology of cerebral arterial spasm. Prostacyclin (10(-10) to 10(-6)M) caused a dose-related reversal of contractions induced by 5-hydroxytryptamine, noradrenaline, angiotensin II, prostaglandin (PG)F2 alpha, and U-46619 (a thromboxane-A2 mimetic). These agents were tested at concentrations or volumes that produced almost maximum or maximum responses and those that produced approximately 50% of the maximum response. Contractions induced by maximum concentrations of angiotensin II and U-46619 were least affected by prostacyclin. In addition, contractions induced by thromboxane-A2 generated from guinea-pig lung were reversed in a dose-dependent fashion by prostacyclin. This ability of prostacyclin to physiologically antagonize contractions of the human basilar artery in vitro induced by high concentrations of various spasmogenic agents suggests that such a potent vasodilator agent or more stable analogue may be of value in the treatment of such disorders as cerebral arterial spasm following subarachnoid hemorrhage.