The spectrum of progressive multifocal leukoencephalopathy: a practical approach.

John Cunningham virus (JCV) infection of the central nervous system causes progressive multifocal leukoencephalopathy (PML) in patients with systemic immunosuppression. With the increased application of modern immunotherapy and biologics in various immune-mediated disorders, the PML risk spectrum has changed. Thus, new tools and strategies for risk assessment and stratification in drug-associated PML such as the JCV antibody indices have been introduced. Imaging studies have highlighted atypical presentations of cerebral JCV disease such as granule cell neuronopathy. Imaging markers have been developed to differentiate PML from new multiple sclerosis lesions and to facilitate the early identification of pre-clinical manifestations of PML and its immune reconstitution inflammatory syndrome. PML can be diagnosed either by brain biopsy or by clinical, radiographic and virological criteria. Experimental treatment options including immunization and modulation of interleukin-mediated immune response are emerging. PML should be considered in any patient with compromised systemic or central nervous system immune surveillance presenting with progressive neurological symptoms.

[Neuroenhancement]. / Neuroenhancement.

BACKGROUND: Cognitive enhancement or neuroenhancement describes the increase in cognitive performance in humans by means of psychotropic drugs or brain stimulation methods, such as transcranial magnetic stimulation (TMS). PROBLEM: This article discusses the potential of pharmacological cognitive enhancement with some of the most common drugs. METHODS: A selective literature search was performed taking into account the most important groups of substances (i.e. caffeine, nicotine, stimulants including modafinil, and acetylcholine esterase inhibitors) for which studies on the pharmacological elevation of cognitive performance in healthy subjects are available. RESULTS: The extent of the effects that can be pharmacologically achieved is essentially genetically determined. Some of the best-characterized polymorphisms are described here. Pharmacological enhancement of cognitive performance is currently possible with all of the compounds described here and caffeine and nicotine are used by millions of people without the explicit intention of most consumers of cognitive enhancement. DISCUSSION: Clinical neuroscientists are required to share their expertise to a greater extent in the social discourse on cognitive enhancement in the future in order to influence opinion-forming and decision-making processes.

Transcranial direct current stimulation of the right temporoparietal junction facilitates hippocampal spatial learning in Alzheimer's disease and mild cognitive impairment.

OBJECTIVE: Spatial memory deficits are an early symptom in Alzheimer's disease (AD), reflecting the neurodegenerative processes in the neuronal navigation network such as in hippocampal and parietal cortical areas. As no effective treatment options are available, neuromodulatory interventions are increasingly evaluated. Against this backdrop, we investigated the neuromodulatory effect of anodal transcranial direct current stimulation (tDCS) on hippocampal place learning in patients with AD or mild cognitive impairment (MCI). METHODS: In this randomized, double-blind, sham-controlled study with a cross-over design anodal tDCS of the right temporoparietal junction (2 mA for 20 min) was applied to 20 patients diagnosed with AD or MCI and in 22 healthy controls while they performed a virtual navigation paradigm testing hippocampal place learning. RESULTS: We show an improved recall performance of hippocampal place learning after anodal tDCS in the patient group compared to sham stimulation but not in the control group. CONCLUSIONS: These results suggest that tDCS can facilitate spatial memory consolidation via stimulating the parietal-hippocampal navigation network in AD and MCI patients. SIGNIFICANCE: Our findings suggest that tDCS of the temporoparietal junction may restore spatial navigation and memory deficits in patients with AD and MCI.

[Frontotemporal dementias]. / Frontotemporale Demenzen.

Frontotemporal dementias (FTD) account for only 5-7% of all dementia aetiologies. However, FTD is one common form of dementia in the presenile period with a symptom onset between an age of 45 and 65 years. FTD are clinically classified into a group of rare genetic variants, the behavioural variant, primary progressive aphasias and a variant including motor neuron symptoms (FTD-MNS). In recent years the pathobiological characteristics of some FTD variants was clarified, demonstrating a pathological accumulation of TAR-DNA binding protein 43 (TDP-43) as a common pathological substrate. The revised diagnostic criteria of the behavioural variant of the FTD require at least three of six clinically discriminating features (disinhibition, apathy, loss of sympathy, perseverative behaviours, hyperorality and dysexecutive neuropsychological profile). The primary progressive aphasias are classified in a nonfluent/agrammatic variant, a logopenic variant and a semantic variant according to clinical and imaging features. Movement disorders and more precisely a Parkinsonian syndrome can be part of the FTD spectrum. Some clinical features overlap the clinical diagnosis of a progressive supranuclear paralysis and the corticobasal ganglionic degeneration. A causal therapy does not exist and medical treatment is directed at the patient's key symptoms. Different agents such as serotonin reuptake inhibitors, tricyclic antidepressants, atypical neuroleptics, carbamazepine, valproate, lamotrigine and when indicated also acetylcholinesterase inhibitors are potentially helpful. All together, theses medical treatments have a low level of evidence. Non-pharmacological therapies such as physiotherapy, occupational therapy, speech therapy and disease-specific education of the patient and their relatives are important to ensure a safe residential environment and daily routine.

Deep brain stimulation of the posterior hypothalamic area in intractable short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT).

BACKGROUND: SUNCT (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing) is a rare syndrome characterized by the sudden onset of excruciating unilateral periorbital pain that is accompanied by conjunctival injection and lacrimation or further autonomic signs. Similar to patients with chronic cluster headache, Leone and Lyons showed a beneficial effect of deep brain stimulation of the posterior hypothalamic region in two patients with a chronic SUNCT. CASE: Here, we present the case of a man with a chronic SUNCT responding to deep brain stimulation of the posterior hypothalamic area. CONCLUSION: This case supports the idea of a central origin of SUNCT and shows that deep brain stimulation of the hypothalamic region can be effective in the treatment of the chronic form of this rare disorder.

Hypothalamic deep brain stimulation for cluster headache: experience from a new multicase series.

Deep brain stimulation (DBS) of the posterior hypothalamus was found to be effective in the treatment of drug-resistant chronic cluster headache. We report the results of a multicentre case series of six patients with chronic cluster headache in whom a DBS in the posterior hypothalamus was performed. Electrodes were implanted stereotactically in the ipsilateral posterior hypothalamus according to published coordinates 2 mm lateral, 3 mm posterior and 5 mm inferior referenced to the mid-AC-PC line. Microelectrode recordings at the target revealed single unit activity with a mean discharge rate of 17 Hz (range 13-35 Hz, n = 4). Out of six patients, four showed a profound decrease of their attack frequency and pain intensity on the visual analogue scale during the first 6 months. Of these, one patient was attack free for 6 months under neurostimulation before returning to the baseline which led to abortion of the DBS. Two patients had experienced only a marginal, non-significant decrease within the first weeks under neurostimulation before returning to their former attack frequency. After a mean follow-up of 17 months, three patients are almost completely attack free, whereas three patients can be considered as treatment failures. The stimulation was well tolerated and stimulation-related side-effects were not observed on long term. DBS of the posterior inferior hypothalamus is an effective therapeutic option in a subset of patients. Future controlled multicentre trials will need to confirm this open-label experience and should help to better define predictive factors for non-responders.

Selective affection of hippocampal CA-1 neurons in patients with transient global amnesia without long-term sequelae.

The aetiology, pathomechanisms and anatomical correlates of transient global amnesia (TGA) still remain obscure. Recently, focal MR-signal diffusion-weighted imaging (DWI) changes in the hippocampus have been described in patients with TGA, but the exact localization, long term outcome and pathophysiological nature of these lesions still remain unknown. The topography and time course of hippocampal DWI lesions in 41 TGA patients was studied using serial 3 T high-resolution MR-imaging and correlated to clinical and neuropsychometric results. Of these, 29 patients showed 36 DWI lesions with corresponding T(2) lesions in the hippocampus within a time window of 48 h after onset. Almost all lesions (94%; 34/36) were selectively found in the CA-1 sector (Sommer sector) of the hippocampal cornu ammonis. Most DWI lesions (8/10) were already detectable in the peri-acute phase <6 h after onset of symptoms. A follow-up study 4-6 months after the episode did not show evidence for residual structural sequelae of these lesions (n = 20/20). A venous MR angiography of the intracranial dural sinus showed an asymmetric venous drainage in 21/24 (88%) patients. In 11/16 (69%) patients with unilateral lesions, the asymmetry corresponded to the side of the DWI lesion. Significant episodic verbal memory deficits in the acute phase (n = 14/18) were associated with lesions of the dominant hemisphere while impairment of visuospatial memory was associated with lesions of the non-dominant hemisphere. Persistent neuropsychological sequelae were not detected 4-6 months after the episode (n = 16). This is the first prospective study combining high-resolution imaging and neuropsychometry analysing the detailed functional anatomy and outcome of hippocampal DWI/T(2) lesions in TGA supporting the view the TGA being a benign transient disorder. The TGA can be considered a model for a focal transient perturbation of memory circuits in the temporo-mesial region.

[Treatment of carotid artery aneurysms with covered stents]. / Aneurysmabehandlung der Arteria carotis interna mit gecoverten Stents.

PURPOSE: Evaluation of the use of covered stents in treating pseudoaneurysms of the cervical and intracranial/extradural carotid artery and determination of the periprocedural and short- to mid-term complication rate. MATERIALS AND METHODS: 8 patients with 9 spontaneous dissecting aneurysms of the cervical carotid artery--5 of which were symptomatic--plus one patient with ofthalmoplegia due to an aneurysm of the cavernous carotid artery were studied. While the latter was treated with a PTFE-covered balloon-mounted stainless steel stent (Jostent/Graftmaster), a self-expanding PTFE-covered Nitonol Stent (Symbiot) was used in all other cases. Intervention was performed with local anesthesia. Aspirin and Clopidogrel were both used as antiplatelet drugs. Clinical signs and symptoms and vascular imaging with DS, MR, CT angiography and ultrasound were recorded during patient follow-up, with a mean follow-up period of 14.6 months (4 - 30). RESULTS: We were able to treat 8 out of 10 aneurysms (80%) using covered stents. The aneurysms were immediately occluded and the associated stenoses of the parent vessel were eliminated. No clinically relevant complications occurred during the procedure or in the follow-up interval. In two cases, elongation of the carotid artery prevented the stent from being positioned over the aneurysm neck. These cases were shown to be stable with the use of antiplatelet drugs. CONCLUSION: Covered stents can be used in the treatment of pseudoaneurysms of the carotid artery as an alternative to long-term antithrombotic medication or surgery. In our study treatment was effective (80%) and free of complications in the short- and mid-term follow-up. Possible indications, technique and the use of imaging modalities for patient follow-up are discussed.

Inhibition of nociceptive dural input in the trigeminal nucleus caudalis by somatostatin receptor blockade in the posterior hypothalamus.

Somatostatin is a neuromodulator in the central nervous system and is involved in the regulation of metabolic and neuroendocrine functions. Recent experimental and clinical findings point to a role for somatostatin in the central processing of nociception. We studied the effects of somatostatin receptor modulation in the posterior hypothalamic area (PH) of the rat on dural nociceptive input. Somatostatin (10 microg/microl) and the somatostatin antagonist cyclo-somatostatin (50 microg/microl) were microinjected into the PH and the effects on responses of neurons in the trigeminal subnucleus caudalis studied. Injection of somatostatin (n=11) did not affect A- and C-fibre responses to dural electrical stimulation, nor was spontaneous activity altered (P>0.05). Injection of cyclo-somatostatin (n=10) into the PH reduced A-(-35.5+/-5.8%) and C-fibre (-43.1+/-7.5%) responses to dural stimulation and resulted in decreased spontaneous activity (-38.1+/-7.3%, P<0.05). Responses to facial thermal stimulation were decreased by 51.2+/-5.8% (n=5). Control injections had no significant effect (n=9). Blockade of somatostatin receptors in the PH has an anti-nociceptive effect on dural and facial input, probably mediated via GABAergic mechanisms. As somatostatin is also involved in hypothalamic regulation of metabolic, neuroendocrine and autonomic functions, somatostatin receptor mechanisms in the PH may play a role in the pathophysiology of primary headache disorders, such as migraine or cluster headache.

The hippocampus in aging and disease: From plasticity to vulnerability.

The hippocampus has a pivotal role in learning and in the formation and consolidation of memory and is critically involved in the regulation of emotion, fear, anxiety, and stress. Studies of the hippocampus have been central to the study of memory in humans and in recent years, the regional specialization and organization of hippocampal functions have been elucidated in experimental models and in human neurological and psychiatric diseases. The hippocampus has long been considered a classic model for the study of neuroplasticity as many examples of synaptic plasticity such as long-term potentiation and -depression have been identified and demonstrated in hippocampal circuits. Neuroplasticity is the ability to adapt and reorganize the structure or function to internal or external stimuli and occurs at the cellular, population, network or behavioral level and is reflected in the cytological and network architecture as well as in intrinsic properties of hippocampal neurons and circuits. The high degree of hippocampal neuroplasticity might, however, be also negatively reflected in the pronounced vulnerability of the hippocampus to deleterious conditions such as ischemia, epilepsy, chronic stress, neurodegeneration and aging targeting hippocampal structure and function and leading to cognitive deficits. Considering this framework of plasticity and vulnerability, we here review basic principles of hippocampal anatomy and neuroplasticity on various levels as well as recent findings regarding the functional organization of the hippocampus in light of the regional vulnerability in Alzheimer's disease, ischemia, epilepsy, neuroinflammation and aging.

Imaging of autoimmune encephalitis--Relevance for clinical practice and hippocampal function.

The field of autoimmune encephalitides associated with antibodies targeting cell-surface antigens is rapidly expanding and new antibodies are discovered frequently. Typical clinical presentations include cognitive deficits, psychiatric symptoms, movement disorders and seizures and the majority of patients respond well to immunotherapy. Pathophysiological mechanisms and clinical features are increasingly recognized and indicate hippocampal dysfunction in most of these syndromes. Here, we review the neuroimaging characteristics of autoimmune encephalitides, including N-methyl-d-aspartate (NMDA) receptor, leucine-rich glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2) encephalitis as well as more recently discovered and less frequent forms such as dipeptidyl-peptidase-like protein 6 (DPPX) or glycine receptor encephalitis. We summarize findings of routine magnetic resonance imaging (MRI) investigations as well as (18)F-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET) and single photon emission tomography (SPECT) imaging and relate these observations to clinical features and disease outcome. We furthermore review results of advanced imaging analyses such as diffusion tensor imaging, volumetric analyses and resting-state functional MRI. Finally, we discuss contributions of these neuroimaging observations to the understanding of the pathophysiology of autoimmune encephalitides.

Voxel seed coherent source analysis on transient global amnesia patients.

Transient global amnesia (TGA) is a rare neurological disorder with a sudden, temporary episode of memory loss which usually occurs in old age. The episodic loss of memory becomes normal after a stipulated time of approximately 24 hours. The precise pathology is not yet completely understood. Moreover, there is no proper neuroimaging method to assess this condition. In this study, the EEG was measured at two time points one with the occurrence of the episode (acute) and the second time point after the patient returns to the normal memory condition (follow-up). The aim of the study was to look at the pathological network involved during the acute phase and the follow up phase in these patients for the five frequency bands, namely, delta, theta, alpha, beta, and gamma. The method used for the source analyses was a beamforming approach called dynamic imaging of coherent sources in the frequency domain. The seed voxel was the lesion area taken from the anatomical MRI of each patient. The cortical and subcortical network comprised of the caudate and cerebellum in case of the delta band frequency. Two temporal sources in case of the theta band. Temporal, medial frontal, parietal, putamen, and thalamus sources were found in case of the alpha band. Prefrontal, parietal, and thalamus sources were found in case of the beta band. Temporal and thalamus in case of the gamma band frequency. All these sources were involved in the acute phase. Moreover, in the follow-up phase the motor area, in all frequency bands except gamma band, was additionally active followed by parietal and occipital regions in alpha and gamma frequencies. The differences involved in the network of sources between the two phases gives us better understanding of this neurological disorder.

Neurologic outcome of controlled compressed-air diving.

The authors compared the neurologic, neuropsychological, and neuroradiologic status of military compressed-air divers without a history of neurologic decompression illness and controls. No gross differences in the neuropsychometric test results or abnormal neurologic findings were found. There was no correlation between test results, diving experience, and number and size of cerebral MRI lesions. Prevalence of cerebral lesions was not increased in divers. These results suggest that there are no long-term CNS sequelae in military divers if diving is performed under controlled conditions.

Differential modulation of nociceptive dural input to [hypocretin] orexin A and B receptor activation in the posterior hypothalamic area.

The novel neuropeptides orexin A and B are selectively synthesised in the lateral and posterior hypothalamus and are involved in hypothalamic regulation of autonomic and neuroendocrine functions. Recent findings point also to a role in nociception. As the posterior hypothalamus is involved in the central modulation of nociception we studied the effects of hypocretin/orexin receptor activation in the posterior hypothalamic area (PH) of the rat on dural nociceptive input. Orexins were microinjected into the PH and the effects on responses of neurones in the caudal trigeminal nucleus studied. Injection of orexin A decreased the A- and C-fibre responses to dural electrical stimulation as well as spontaneous activity. Responses to noxious thermal stimulation of the facial skin were also decreased by orexin A. Injection of orexin B into the PH, however, elicited increased responses to dural stimulation in A- and C-fibre responses and resulted in increased spontaneous activity. Responses to facial thermal stimulation were also increased by orexin B. Control injection of saline into the PH had no significant effect. The results show a differential modulation of dural nociceptive input by orexin A and B receptor activation in the PH. The results support the role of the PH in the nociceptive processing of meningeal input. As both peptides are also involved in hypothalamic regulation of neuroendocrine and autonomic functions, orexinergic mechanisms in the PH may provide a link for endocrine and autonomic changes as well as nociceptive phenomena seen in primary headache disorders.

The ORL-1 (NOP1) receptor ligand nociceptin/orphanin FQ (N/OFQ) inhibits neurogenic dural vasodilatation in the rat.

The effects of the ORL-1 (NOP(1)) receptor ligand nociceptin (N/OFQ) and the nociceptin antagonists [Nphe(1)]N/OFQ-(1-13)-NH(2) (Nphe) and nocistatin (NST) on neurogenic dural vasodilatation (NDV) in the rat dura mater evoked by electrical stimulation of a closed cranial window were studied. The middle meningeal artery was visualised using intravital microscopy, and the vessel diameter analysed using a video dimension analyser. N/OFQ (1, 10, 100 nmol kg(-1); i.v., n=10) significantly and dose-dependently suppressed NDV maximally by 65% (P<0.01). Neither Nphe (100 nmol kg(-1); n=5) nor NST (100 nmol kg(-1); n=4) alone had an effect on NDV (P>0.05). Baseline vessel diameter was not significantly affected by application of N/OFQ, NST or Nphe. Application of the selective N/OFQ antagonist Nphe (10, 100 nmol kg(-1) i.v., n=8) dose-dependently and significantly (P<0.01) reversed the inhibition of NDV induced by application of N/OFQ (10 nmol kg(-1)). NST (10, 100 nmol kg(-1); n=7) failed to reverse the effects elicited by N/OFQ. Application of N/OFQ elicited a dose-dependent transient decrease in arterial blood pressure (P<0.01). Nphe dose-dependently reversed the cardiovascular effects induced by application of N/OFQ (10 nmol kg(-1)) (P<0.01),while NST did not alter the blood pressure reaction elicited by N/OFQ. The results show that N/OFQ inhibits NDV, an effect which is antagonised by Nphe, but not by NST. ORL-1 (NOP(1)) receptors located on trigeminal sensory fibres may be involved in the regulation of dural vessel diameter and hence may play a role in migraine pathophysiology.

Responses of rat postganglionic sympathetic vasoconstrictor neurons following blockade of nitric oxide synthesis in vivo.

The hypothesis was tested that the activation of postganglionic sympathetic neurons contributes to the peripheral vasoconstriction and the blood pressure increase which are observed in rats after systemic blockade of nitric oxide synthase by substituted L-arginine analogues. Single and multifiber postganglionic sympathetic activity supplying hindlimb hairy skin and the activity in the caudal lumbar sympathetic trunk supplying mainly hindlimb skeletal muscle were recorded in anaesthetized, paralysed and artificially ventilated Wistar rats before, during and up to 1 h after intravenous injection of a supramaximal dose (10 or 35 mg/kg) of N(G)-nitro-L-arginine methyl ester. This elicited a sustained rise of arterial blood pressure, a long-lasting decrease in heart rate and vasoconstriction in hindlimb skin and skeletal muscle as measured by laser Doppler flowmetry. With intact buffer nerves all sympathetic neurons analysed responded with a decrease in their ongoing activity in parallel with the vasoconstriction and the increased blood pressure, except for one neuron which was unresponsive. These responses were probably mediated by the arterial baroreceptors. since it was shown that N(G)-nitro-L-arginine methyl ester did not impair the function of both the afferent and the efferent limb of the reflex. Furthermore, baroreceptor denervation almost abolished the inhibitory responses in sympathetic neurons. In baroreceptor denervated animals, with a latency of about 15 min after N(G)-nitro-L-arginine methyl ester there was an increase in sympathetic activity without a further increase in blood pressure. It was concluded that sympathetic vasoconstrictor neurons which supply the rat hindlimb do not contribute by neurogenic means to the vasoconstriction and the blood pressure increase occurring after blockade of the nitric oxide synthase. Instead, the results suggest that sympathetic vasoconstrictor neurons, via the baroreceptor loop, counteract the vasoconstriction caused by the blockade of endothelium-derived nitric oxide. Therefore nitric oxide does not seem to play a role in the central regulation of activity in the sympathetic vasoconstrictor pathways studied here. The long latency increase in sympathetic activity observed after N(G)-nitro-L-arginine methyl ester in baroreceptor-denervated animals may be due to an impairment of blood flow in the brainstem.

Influence of magnetic fields on electron-Ion recombination at very low energies

Radiative recombination (inverse photoionization) is believed to be well understood since the beginning of quantum mechanics. Still, modern experiments consistently reveal excess recombination rates at very low electron-ion center-of-mass energies. In a detailed study on recombination of F6+ and C6+ ions with magnetically guided electrons we explored the yet unexplained rate enhancement, its dependence on the magnetic field B, the electron density n(e), and the beam temperatures T( perpendicular) and T( ||). The excess scales as T(-1/2)( perpendicular) and, surprisingly, as T(-1/2)( ||), increases strongly with B, and is insensitive to n(e). This puts strong constraints on explanations of the enhancement.

Cervico-thoracic disc protrusions in controlled compressed-air diving: clinical and MRI findings.

Prevalence of cervical and thoracic disc protrusions was investigated by MRI in 24 military long-term compressed-air divers and 24 controls. A total of 26 disc protrusions (17 cervical disc protrusions) were detected in 58% of the divers whereas 18 protrusions were detected in 38 % of the controls (13 disc cervical protrusions). There was no significant difference between groups and no correlation with the diving experience. Neurological examination revealed no clinical abnormalities. In contrast to a recent study, our results suggest that long-term divers are at no increased risk for accumulating spinal disc protrusions or intramedullary abnormalities.

Functional properties of postganglionic sympathetic neurones supplying the submandibular gland in the anaesthetized rat.

Sympathetic neurones supplying the submandibular salivary gland innervate blood vessels, secretory and myoepithelial cells. Here we examined whether these functionally different sympathetic neurones show distinct reflex response patterns. In anaesthetized rats, single unit activity was recorded from postganglionic axons projecting to the gland. Neurones were tested for their responses to stimulation of baroreceptors, cutaneous nociceptors and cold receptors and to gustatory stimuli applied to the tongue. Respiratory modulation was also analysed. Only a few postganglionic neurones identified electrically (5-10%) were spontaneously active. They were excited by noxious and cold stimuli, inhibited by baroreceptor stimulation and exhibited respiratory modulation. None of the units responded to gustatory stimuli. Thus, in anaesthetized rats spontaneously active sympathetic neurones supplying the submandibular gland behave like vasoconstrictor neurones. Sympathetic neurones with other functions are probably silent.

Reflex patterns in preganglionic sympathetic neurons projecting to the superior cervical ganglion in the rat.

Reflex patterns in preganglionic neurons projecting in the cervical sympathetic trunk (CST) were analyzed in response to stimulation of various afferent systems. We focused on the question whether these preganglionic neurons can be classified into functionally distinct subpopulations. Reflex responses were elicited by stimulation of trigeminal and spinal nociceptive, thermoreceptive as well as baroreceptor and chemoreceptor afferents. Multi- and single fiber preparations were studied in baroreceptor intact and sino-aortically denervated animals. Spontaneous activity of 36 preganglionic single neurons ranged from 0.2 to 3.5 imp/s (median= 1.11 imp/s). The degree of cardiac rhythmicity (CR) in the activity of sympathetic neurons was 69.5+/-13% (mean+/-S.D.; N=52; range=39-95%). Noxious stimulation of acral skin activated the majority (67%) of sympathetic preparations by 37+/-25% (N=35) above pre-stimulus activity; 15% were inhibited. In these neurons the response to noxious stimulation of acral skin was significantly correlated with the degree of CR (P<0.001, N=52) in that neurons showing the strongest excitation to noxious stimulation displayed the strongest CR. Noxious mechanical stimulation of body trunk skin (N=60) inhibited the majority (80%) of fiber preparations tested (by 34+/-18% of pre-stimulus activity, N=48); an activation was not observed. Cold stimulation of acral (N=9) and body trunk skin (N=42) activated most fiber preparations. Trigeminal stimulation evoked a uniform reflex activation of preganglionic neurons (+79+/-73% of pre-stimulus activity, N=32). Chemoreceptor stimulation by systemic hypercapnia elicited inhibitory (-31+/-19%, N=8) as well as excitatory (+59+/-5%, N=4) responses. These results show that preganglionic sympathetic neurons projecting to target organs in the head exhibit distinct reflex patterns to stimulation of various afferent systems; however, a clear classification into different functional subgroups did not emerge. Furthermore, reflex patterns showed a segmental organization to noxious cutaneous stimulation of acral parts and body trunk reflecting a differential central integration of spinal afferent input. Compared with the cat the reflex organization of sympathetic neurons projecting to the head seems to be less differentiated in the anesthetized rat.