Biomedical subjects

F A Lenz

Publications and source records attributed to F A Lenz.

At least 19 recordsLinked to original sources

PubMed2007

Internal pallidal neuronal activity during mild drug-related dyskinesias in Parkinson's disease: decreased firing rates and altered firing patterns.

The neuronal basis of hyperkinetic movement disorders has long been unclear. We now test the hypothesis that changes in the firing pattern of neurons in the globus pallidus internus (GPi) are related to dyskinesias induced by low doses of apomorphine in patients with advanced Parkinson's disease (PD). During pallidotomy for advanced PD, the activity of single neurons was studied both before and after administration of apomorphine at doses just adequate to induce dyskinesias (21 neurons, 17 patients). After the apomorphine injection, these spike trains demonstrated an initial fall in firing from baseline. In nine neurons, the onset of on was simultaneous with that of dyskinesias. In these spike trains, the initial fall in firing rate preceded and was larger than the fall at the onset of on with dyskinesias. Among the three neurons in which the onset of on occurred before that of dyskinesias, the firing rate did not change at the time of onset of dyskinesias. After injection of apomorphine, dyskinesias during on with dyskinesias often fluctuated between transient periods with dyskinesias and those without. Average firing rates were not different between these two types of transient periods. Transient periods with dyskinesias were characterized by interspike interval (ISI) independence, stationary spike trains, and higher variability of ISIs. A small but significant group of neurons demonstrated recurring ISI patterns during transient periods of on with dyskinesias. These results suggest that mild dyskinesias resulting from low doses of apomorphine are related to both low GPi neuronal firing rates and altered firing patterns.

Aged↗

PubMed2006

Analysis of synchrony demonstrates 'pain networks' defined by rapidly switching, task-specific, functional connectivity between pain-related cortical structures.

Imaging studies indicate that experimental pain is processed in multiple cortical areas which are often characterized as a network. However, the functional connectivity within the network and the other properties of the network is poorly understood. Substantial evidence demonstrates that synchronous oscillations between two cortical areas may indicate functional connectivity between those areas. We test the hypothesis that cortical areas with pain-related activity are functionally connected during attention to a painful stimulus. We stimulated with a painful, cutaneous, laser stimulus and recorded the response directly from the cortical surface (electrocorticography--ECoG) over primary somatosensory (SI), parasylvian (PS), and medial frontal (MF) cortex through subdural electrodes implanted for treatment of epilepsy. The results demonstrate synchrony of ECoGs between cortical structures receiving input from nociceptors, as indicated by the occurrence of laser-evoked potentials (LEPs) and/or event-related desynchronization (ERD). Prior to the stimulus, directed attention to the painful stimulus consistently increased the degree of synchrony between SI and PS regions, as the subject anticipated the stimulus. After the laser stimulus, directed attention to the painful stimulus consistently increased the degree of synchrony between SI and MF cortex, as the subject responded by counting the stimulus. Therefore, attention to painful stimuli always enhanced synchrony between cortical pain-related structures. The pattern of this synchrony changed as the patient switched tasks from anticipation of the stimulus to counting the stimulus. These results are the first compelling evidence of pain networks characterized by rapidly switching, task-specific functional connectivity.

Adult↗

PubMed2006

Fractal characteristics of human Parkinsonian neuronal spike trains.

Fractal analysis was applied to human pallidal neuronal spike trains recorded from patients with Parkinson's disease during ablative surgery of the internal segment of the globus pallidus. Fractal dynamics was quantified by computing the scaling exponent with the average wavelet coefficient approach. We observed fractal persistent correlation in the fluctuation of the interspike intervals of neuronal spike trains recorded in the internal segment of the globus pallidus both before and after the administration of dopamine agonist apomorphine. However, there was a significant increase in the scaling exponent during the "on" state after apomorphine administration as compared with the parkinsonian "off" state prior to apomorphine. In addition, we observed a statistically significant decrease in the average firing rate in the transition from the "off" to the "on" state. We conclude that robust fractal dynamics can be observed in single neurons in the human CNS, indicating that human neuronal dynamics of the internal segment of the globus pallidus are essentially a nonlinear and nonequilibrium process, with a long-range correlation or memory extending across many time scales. Accompanying the "on" state after apomorphine administration was an improvement in the long-range persistent correlation as compared with the more random dynamics in the "off" state. A scaling exponent signaling a breakdown or modification in long-range correlation in a single neuron may serve as a useful indicator of a dysfunctional network in the human CNS.

Apomorphine↗

PubMed2006

Modulation of somatosensory event-related potential components in a tactile-visual cross-modal task.

Human tactile discrimination studies have shown that visual stimuli enhance tactile performance. Other studies on event-related potentials showed that somatosensory N140 was enhanced when attention of human subjects was directed to tactile stimuli. Therefore, we hypothesized that N140 would be modulated when human subjects performed tactile cross-modal delay tasks. Scalp-event-related potentials were recorded from normal subjects performing either a tactile-tactile unimodal, or a tactile-visual cross-modal delayed matching-to-sample task. Identical tactile stimuli were used in both tasks. N140 component evoked by the tactile stimuli was enhanced in the cross-modal task. Enhancement of this component was also observed in control cross-modal tasks. The results suggest that tactile-visual cross-modal association affects tactile sensory-perceptual processes in humans.

Adult↗

PubMed2006

Plasticity of pain-related neuronal activity in the human thalamus.

Strokes and other forms of injury to the central nervous system cause changes in function because of the injuries themselves and indirectly because injuries cause expression of neural plasticity. Studies in humans undergoing neurosurgical procedures for implantation of electrodes for deep brain stimulation and for making lesions in the brain have contributed understanding of both normal and abnormal functions of the somatic sensory system. This chapter will specifically discuss the reorganization of the ventral caudal (Vc) sensory nucleus of the thalamus that occurs in connection with pain conditions after strokes and spinal cord injuries. It is shown that pain is associated with expression of neural plasticity that alters maps of noxious and innocuous stimulation in the thalamus and affect processing of sensory information. Results from studies of neural activity in the thalamus in humans will be compared with results from animal studies.

Brain Injuries↗

PubMed2006

Psychophysics of CNS pain-related activity: binary and analog channels and memory encoding.

The forebrain neuronal system signaling pain has been poorly characterized. The pain pathway afferent to the thalamus may be a labeled line consisting of neurons in the pain-signaling pathway to the brain (spinothalamic tract, STT) that respond only to painful stimuli. It has recently been proposed that the STT contains a series of analog-labeled lines, each signaling a different aspect of the internal state of the body (interoception), for example, visceral/cold/itch sensations. In this view, pain is the unpleasant emotion produced by disequilibrium of the internal state. The authors now show that stimulation of an STT receiving zone (thalamic principal somatic sensory nucleus, ventral caudal) in awake humans produces two different exteroceptive responses. The first is a binary response signaling the presence of painful stimuli. The second is an analog response in which nonpainful and painful sensations are graded with intensity of the stimulus. Such stimulation can evoke both the sensory and emotional components of previously experienced pain. These results illustrate the diverse functions of human pain signaling pathways.

Animals↗

PubMed2005

Psychophysical elements of place and modality specificity in the thalamic somatic sensory nucleus (ventral caudal, vc) of awake humans.

Discrete anatomic structures in the monkey somatic sensory thalamus may segregate input arising from different peripheral receptors and from different parts of the body. It has been proposed that these structures serve as components of modality- and place-specific pathways from the periphery to the cortex. We now test this hypothesis by examining the modality- and place-specific segregation of sensations at sites where microstimulation (microA currents) within the region of ventral caudal (Vc; human principal somatic sensory nucleus) evokes somatic sensations. Microstimulation was delivered in an ascending staircase protocol consisting of different numbers of pulses (4-100) presented at different frequencies (10-200 Hz) during awake thalamic surgery for movement disorders. The results demonstrate that the part of the body where microstimulation evoked sensation (projected field) and the descriptors of nonpainful sensations were usually uniform across the staircase. These results strongly support the existence of psychophysical elements of place and modality specificity in the Vc thalamus. The proportion of sites at which the sensation included more than one part of the body almost always stayed constant over current intervals (plateaus) of 10 microA. Similar plateaus were not found for sites with more than one descriptor, suggesting that elements of modality-specificity are smaller than and located within those for place-specificity. The intensity of sensations varied with the number of stimulation pulses for mechanical/tingle and cool sensations. The results provide strong evidence for psychophysically defined elements that are responsible for modality specificity of nonpainful sensations, place specificity, and intensity coding of somatic sensation in the human thalamus.

Deep Brain Stimulation↗

PubMed2005

Pain and temperature encoding in the human thalamic somatic sensory nucleus (Ventral caudal): inhibition-related bursting evoked by somatic stimuli.

Stimulus-evoked inhibitory events have not been demonstrated in thalamic spike trains encoding of pain and temperature stimuli. We have now tested the hypothesis that the human thalamic response to mechanical and thermal stimuli is characterized by low-threshold calcium spike (LTS)-associated bursts of high-frequency action potentials preceded by prolonged inhibition. The results included 57 neurons recorded in the human thalamic principal somatic sensory nucleus (ventral caudal, Vc) of 24 patients during awake surgery. Neurons were classified by the grading of their response with stimulus intensity into the painful range (graded or non-graded) and the stimulus response (to mechanical, cold, or heat stimuli). Firing rates were analyzed by the response to all stimuli combined (stimuli overall) and to the stimulus characteristic of the stimulus response type (optimal stimulus), e.g., cold stimuli for neurons of the cold stimulus response type. All neuronal categories had clear stimulus-evoked LTS bursting as identified by the criteria for selecting bursts in the spike train, by significant preburst inhibition, and by preburst inter-spike interval not significantly <100 ms. Stimulus-evoked LTS burst rates were significantly higher for neurons in the cold stimulus response type independent of the firing rate between bursts. The parameters of preburst inhibition were largely independent of the neuronal category and the stimuli included in the analysis, which suggests inhibitory mechanisms are similar across neuronal types. Therefore LTS bursting is a substantial, nonlinear component of the spontaneous and stimulus-evoked activity of thalamic neurons in awake humans.

Action Potentials↗

PubMed2004

Attention to a painful cutaneous laser stimulus modulates electrocorticographic event-related desynchronization in humans.

OBJECTIVE: To test the hypothesis that attention to painful cutaneous laser stimuli enhances event-related desynchronization (ERD) in cortical regions receiving nociceptive input. METHODS: We used wavelet time-frequency analysis and bandpass filtering to measure ERD quantitatively in subdural electrocorticographic recordings while subjects either attended to, or were distracted from, a painful cutaneous laser stimulus. RESULTS: ERD were observed over primary somatosensory and parasylvian (PS) cortices in all 4 subjects, and over medial frontal cortex in 1 subject. Laser-evoked potentials were also observed in all 3 regions. In all subjects, ERD was more widespread and intense, particularly over PS, during attention to laser stimuli (counting stimuli) than during distraction from the stimuli (reading for comprehension). CONCLUSIONS: These findings suggest that pain-associated ERD is modulated by attention, particularly over PS. SIGNIFICANCE: This study suggests that thalamocortical circuits are involved in attentional modulation of pain because of the proposed role of these circuits in the mechanisms of ERD.

Adult↗

PubMed2004

Amplitudes of laser evoked potential recorded from primary somatosensory, parasylvian and medial frontal cortex are graded with stimulus intensity.

Intensity encoding of painful stimuli in many brain regions has been suggested by imaging studies which cannot measure electrical activity of the brain directly. We have now examined the effect of laser stimulus intensity (three energy levels) on laser evoked potentials (LEPs) recorded directly from the human primary somatosensory (SI), parasylvian, and medial frontal cortical surfaces through subdural electrodes implanted for surgical treatment of medically intractable epilepsy. LEP N2* (early exogenous/stimulus-related potential) and LEP P2** (later endogenous potential) amplitudes were significantly related to the laser energy levels in all regions, although differences between regions were not significant. Both LEP peaks were also significantly correlated with the pain intensity evoked by the laser stimulus, excepting N2* over the parasylvian region. Peak latencies of both LEP peaks were independent of laser energy levels. N2* and P2** amplitudes of the maxima in all regions showed significant positive linear correlations with laser energy, excepting N2* over the parasylvian region. The lack of correlation of parasylvian cortical N2* with laser energy and pain intensity may be due to the unique anatomy of this region, or the small sample, rather than the lack of activation by the laser. Differences in thresholds of the energy correlation with amplitudes were not significant between regions. These results suggest that both exogenous in endogenous potentials evoked by painful stimuli, and recorded over SI, parasylvian, and medial frontal cortex of awake humans, encode the intensity of painful stimuli and correlate with the pain evoked by painful stimuli.

Adult↗

PubMed2003

Cutaneous painful laser stimuli evoke responses recorded directly from primary somatosensory cortex in awake humans.

Negative and positive laser evoked potential (LEP) peaks (N2*, P2**) were simultaneously recorded from the primary somatosensory (SI), parasylvian, and medial frontal (MF: anterior cingulate and supplementary motor area) cortical surfaces through subdural electrodes implanted for the surgical treatment of intractable epilepsy. Distribution of the LEP N2* and P2** peaks was estimated to be in cortical areas (SI, parasylvian, and MF) identified by anatomic criteria, by their response to innocuous vibratory stimulation of a finger (v-SEP), and to electrical stimulation of the median nerve (e-SEP). The maximum of the LEP N2* peak was located on the CS, medial (dorsal) to the finger motor area, as determined by cortical stimulation, and to the finger somatosensory area, as determined from the e-SEP and v-SEP. This finding suggests that the generator source of the LEP N2* peak in SI was different from that of e-SEP or v-SEP in Brodmann's areas 3b or 1. In parasylvian and MF, polarity reversal was often observed, indicating tangential current sources in these regions. In contrast to e-SEP and v-SEP, the LEP N2* latency over SI was not shorter than that over the parasylvian region. The amplitude of N2* was larger over SI than over MF and the latencies of the LEP peaks in those 2 regions were different. These findings provide evidence for a significant LEP generator in the postcentral gyrus, perhaps SI cortex, that is situated outside the tactile homunculus in SI and that receives its input arising from nociceptors simultaneously with parasylvian and MF cortex.

Adult↗

PubMed2003

Physiological changes in primate somatosensory thalamus induced by deafferentation are dependent on the spinal funiculi that are sectioned and time following injury.

The importance of spike bursts in thalamo-cortical processing of sensory information has received an increasing amount of interest over the past several years. Previously it has been reported that short high-frequency spike trains (3-8 action potentials occurring at 67-167 Hz), or spike bursts, are increased in both human and non-human primate thalamus following deafferentation. Here we examine the effects of lesion of the ventral spinal quadrant alone versus combined lesion of the ventral and dorsal spinal quadrants on the evoked and spontaneous spike trains in thalamic neurons. A total of 1175 neurons were sampled from 13 animals, three intact, six with ventral quadrant lesions (three with prolonged survival and three with short-term survival after spinal lesion) and four with combined ventral and dorsal quadrant lesions. Detailed analysis was conducted on 256 of these neurons, which revealed that thalamic neurons of animals with ventral quadrant lesions had elevated burst and non-burst spike rates while neurons from animals with combined ventral-dorsal lesions showed two types of change. Neurons in the forelimb areas showed increased bursts without a change in non-burst activity, while neurons in lateral VPL without receptive fields showed very low non-burst activity, but high burst spike rates. The magnitude of the effects produced by ventral-lateral spinal lesions was more pronounced in the short-term survival animals than in the long-term survival animals. These results show that the effects of deafferentation on the physiological properties of thalamic neurons are dependent on the afferent tract or tracts that are lesioned and the time after lesion.

Action Potentials↗

PubMed2003

ET-1- and NO-mediated signal transduction pathway in human brain capillary endothelial cells.

Previous studies have demonstrated that functional interaction between endothelin (ET)-1 and nitric oxide (NO) involves changes in Ca(2+) mobilization and cytoskeleton in human brain microvascular endothelial cells. The focus of this investigation was to examine the possible existence of analogous interplay between these vasoactive substances and elucidate their signal transduction pathways in human brain capillary endothelial cells. The results indicate that ET-1-stimulated Ca(2+) mobilization in these cells is dose-dependently inhibited by NOR-1 (an NO donor). This inhibition was prevented by ODQ (an inhibitor of guanylyl cyclase) or Rp-8-CPT-cGMPS (an inhibitor of protein kinase G). Treatment of endothelial cells with 8-bromo-cGMP reduced ET-1-induced Ca(2+) mobilization in a manner similar to that observed with NOR-1 treatment. In addition, NOR-1 or cGMP reduced Ca(2+) mobilization induced by mastoparan (an activator of G protein), inositol 1,4,5-trisphosphate, or thapsigargin (an inhibitor of Ca(2+)-ATPase). Interestingly, alterations in endothelial cytoskeleton (actin and vimentin) were associated with these effects. The data indicate for the first time that the cGMP-dependent protein kinase colocalizes with actin. These changes were accompanied by altered levels of phosphorylated vasodilator-stimulated phosphoprotein, which were elevated in endothelial cells incubated with NOR-1 and significantly reduced by ODQ or Rp-8-CPT-cGMPS. The findings indicate a potential mechanism by which the functional interrelationship between ET-1 and NO plays a role in regulating capillary tone, microcirculation, and blood-brain barrier function.

Actins↗

PubMed2002

Single-neuron analysis of human thalamus in patients with intention tremor and other clinical signs of cerebellar disease.

Tremor that occurs as a result of a cerebellar lesion, cerebellar tremor, is characteristically an intention tremor. Thalamic activity may be related to cerebellar tremor because transmission of some cerebellar efferent signals occurs via the thalamus and cortex to the periphery. We have now studied thalamic neuronal activity in a cerebellar relay nucleus (ventral intermediate-Vim) and a pallidal relay nucleus (ventralis oral posterior-Vop) during thalamotomy in patients with intention tremor and other clinical signs of cerebellar disease (tremor patients). The activity of single neurons and the simultaneous electromyographic (EMG) activity of the contralateral upper extremity in tremor patients performing a pointing task were analyzed by spectral cross-correlation analysis. EMG spectra during intention tremor often showed peaks of activity in the tremor-frequency range (1.9-5.8 Hz). There were significant differences in thalamic neuronal activity between tremor patients and controls. Neurons in Vim and Vop had significantly lower firing rates in tremor patients than in patients undergoing thalamic surgery for pain (pain controls). Other studies have shown that inputs to Vim from the cerebellum are transmitted through excitatory connections. Therefore the present results suggest that tremor in these tremor patients is associated with deafferentation of the thalamus from cerebellar efferent pathways. The thalamic X EMG cross-correlation functions were studied for cells located in Vim and Vop. Neuronal and EMG activity were as likely to be significantly correlated for cells in Vim as for those in Vop. Cells in Vim were more likely to have a phase lag relative to EMG than were cells in Vop. In monkeys, cells in the cerebellar relay nucleus of the thalamus, corresponding to Vim, are reported to lead movement during active oscillations at the wrist. In view of these monkey studies, the present results suggest that cells in Vim are deafferented and have a phase lag relative to tremor that is not found in normal active oscillations. The difference in phase of thalamic spike X EMG activity between Vim and Vop may contribute to tremor because lesions of pallidum or Vop are reported to relieve cerebellar tremor.

Action Potentials↗

PubMed2001

Reorganization of somatic sensory function in the human thalamus after stroke.

A patient with thalamic stroke underwent microelectrode-guided stereotactic thalamic exploration during surgery for control of tremor. The results of somatic sensory mapping in this patient were compared with explorations carried out during stereotactic surgery for the control of essential tremor (70 patients). There was evidence both of somatotopic reorganization and of anatomic reorganization of the representation of deep structures in the principal somatic sensory nucleus of the thalamus and the nuclei located anterior to it. This case demonstrates that thalamic reorganization can occur after a thalamic stroke and may play a role in recovery from such a stroke.

Brain Ischemia↗

PubMed2001

Human "memories" can be evoked by stimulation of the lateral temporal cortex after ipsilateral medial temporal lobe resection.

A patient with medically intractable seizures and mesial temporal sclerosis underwent a left anterior temporal lobectomy and amygdalohippocampectomy. After 4 months, his seizures recurred and a left temporal, subdural grid of electrodes was placed to localise his seizure focus. Stimulation through the grid evoked four distinct "memories", or experiential phenomena, despite absence of the ipsilateral medial temporal lobe. To our knowledge, this is the first documented case of experiential phenomena evoked by cortical stimulation in the absence of the ipsilateral medial temporal lobe.

Adult↗

PubMed2000

Human brain capillary endothelium: 2-arachidonoglycerol (endocannabinoid) interacts with endothelin-1.

In brain, the regulatory mechanism of the endothelial reactivity to nitric oxide and endothelin-1 may involve Ca(2+), cytoskeleton, and vasodilator-stimulated phosphoprotein changes mediated by the cGMP/cGMP kinase system.(1) Endothelium of human brain capillaries or microvessels is used to examine the interplay of endothelin-1 with the putative vasorelaxant 2-arachidonoyl glycerol, an endogenous cannabimimetic derivative of arachidonic acid. This study demonstrates that 2-arachidonoyl glycerol counteracts Ca(2+) mobilization and cytoskeleton rearrangement induced by endothelin-1. This event is independent of nitric oxide, cyclooxygenase, and lipoxygenase and is mediated in part by cannabimimetic CB1 receptor, G protein, phosphoinositol signal transduction pathway, and Ca(2+)-activated K(+) channels. The induced rearrangements of cellular cytoskeleton (actin or vimentin) are partly prevented by inhibition of protein kinase C or high levels of potassium chloride. The 2-arachidonoyl glycerol-induced phosphorylation of vasodilator-stimulated phosphoprotein is mediated by cAMP. These findings suggest that 2-arachidonoyl glycerol may contribute to the regulation of cerebral capillary and microvascular function.

Actins↗

PubMed2000

Different generators in human temporal-parasylvian cortex account for subdural laser-evoked potentials, auditory-evoked potentials, and event-related potentials.

In order to localize cortical areas mediating pain we now report subdural cortical potentials evoked by auditory stimulation (auditory-evoked potentials - AEPs) and by cutaneous stimulation with a laser (laser-evoked potentials - LEPs). Stimulation with the laser evokes a pure pain sensation by selective activation of nociceptors. LEPs were maximal over the inferior aspect of the central sulcus and had the same polarity on either side of the sylvian fissure. AEPs were maximal posterior to the LEP maximum and had opposite polarity on opposite sides of the sylvian fissure, consistent with the location of a known generator in the temporal operculum. Auditory P3 (event-related) potentials were maximal over the temporal base. These findings demonstrate that the LEP generator is not in secondary somatosensory cortex on the parietal operculum and is different from the P3 generator.

Adult↗