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PubMed2004

Extrageniculate mediation of unconscious vision in transcranial magnetic stimulation-induced blindsight.

The proposed neural mechanisms supporting blindsight, the above-chance performance of cortically blind patients on forced-choice visual discrimination tasks, are controversial. In this article, we show that although subjects were unable to perceive foveally presented visual stimuli when transcranial magnetic stimulation over the visual cortex induced a scotoma, responses nonetheless were delayed significantly by these unconscious distractors in a directed saccade but not in an indirect manual response task. These results suggest that the superior colliculus, which is involved with sensory encoding as well as with the generation of saccadic eye movements, is mediating the unconscious processing of the transcranial magnetic stimulation-suppressed distractors and implicate a role of the retinotectal pathway in many blindsight phenomena.

Adult↗

PubMed1994

Distributed processing of pain and vibration by the human brain.

Pain is a diverse sensory and emotional experience that likely involves activation of numerous regions of the brain. Yet, many of these areas are also implicated in the processing of nonpainful somatosensory information. In order to better characterize the processing of pain within the human brain, activation produced by noxious stimuli was compared with that produced by robust innocuous stimuli. Painful heat (47-48 degrees C), nonpainful vibratory (110 Hz), and neutral control (34 degrees C) stimuli were applied to the left forearm of right-handed male subjects. Activation of regions within the diencephalon and telencephalon was evaluated by measuring regional cerebral blood flow using positron emission tomography (15O-water-bolus method). Painful stimulation produced contralateral activation in primary and secondary somatosensory cortices (SI and SII), anterior cingulate cortex, anterior insula, the supplemental motor area of the frontal cortex, and thalamus. Vibrotactile stimulation produced activation in contralateral SI, and bilaterally in SII and posterior insular cortices. A direct comparison of pain and vibrotactile stimulation revealed that both stimuli produced activation in similar regions of SI and SII, regions long thought to be involved in basic somatosensory processing. In contrast, painful stimuli were significantly more effective in activating the anterior insula, a region heavily linked with both somatosensory and limbic systems. Such connections may provide one route through which nociceptive input may be integrated with memory in order to allow a full appreciation of the meaning and dangers of painful stimuli. These data reveal that pain-related activation, although predominantly contralateral in distribution, is more widely dispersed across both cortical and thalamic regions than that produced during innocuous vibrotactile stimulation. This distributed cerebral activation reflects the complex nature of pain, involving discriminative, affective, autonomic, and motoric components. Furthermore, the high degree of interconnectivity among activated regions may account for the difficulty of eliminating pathological pain with discrete CNS lesions.

Adult↗

PubMedDate not supplied

[Excitability cycles of direct cortical responses during elaboration of conditioned defense reflexes in dogs].

Direct cortical responses (DCRs) to paired stimuli were studied in chronic experiments in dogs during elaboration of classical and instrumental defensive conditioned reflexes. The DCRs were recorded with 20 to 250 ms intervals between stimuli. Paired and single electrical stimulations of the middle suprasylvian gyrus given with a frequency of one per second were used as conditioned stimuli and were reinforced in a similar way. During electrical cutaneous stimulation of the dog's paw and to an even greater extent during isolated action of the conditioned stimulus the initial negativity of the testing DCR became shorter and the degree of its depression diminished. In the case of a following period of facilitation, its degree became greater. It was higher at a distance of 4 to 5 mm from the point of stimulation than at a distance of 2 to 3 mm. During isolated action of the conditioned stimulus, the degree of facilitation was higher than at the period of the possible action of the unconditioned stimulus. The greatest shorterning of the DCR excitability cycle was observed immediately before and during the conditioned lifting of the dog's paw. Excitability cycles of DCR, and possibly of other evoked potentials as well, are a more sensitive indicator of the function state of the cerebral cortex than responses to single stimuli. For this reason it appears promising to use them in studying conditioned reflexes.

Animals↗

PubMed2002

Direction of action potential propagation influences calcium increases in distal dendrites of the cricket giant interneurons.

To understand the relationship between the propagation direction of action potentials and dendritic Ca(2+) elevation, simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and intradendritic membrane potential were performed in the wind-sensitive giant interneurons of the cricket. The dendritic Ca(2+) transients induced by synaptically-evoked action potentials had larger amplitudes than those induced by backpropagating spikes evoked by antidromic stimulation. The amplitude of the [Ca(2+)](i) changes induced by antidromic stimuli combined with subthreshold synaptic stimulation was not different from that of the Ca(2+) increases evoked by the backpropagating spikes alone. This result means that the synaptically activated Ca(2+) release from intracellular stores does not contribute to enhancement of Ca(2+) elevation induced by backpropagating spikes. On the other hand, the synaptically evoked action potentials were also increased at distal dendrites in which the Ca(2+) elevation was enhanced. When the dendritic and axonal spikes were simultaneously recorded, the delay between dendritic spike and ascending axonal spike depended upon which side of the cercal nerves was stimulated. Further, dual intracellular recording at different dendritic branches illustrated that the dendritic spike at the branch arborizing on the stimulated side preceded the spike recorded at the other side of the dendrite. These results suggest that the spike-initiation site shifts depending on the location of the activated postsynaptic site. It is proposed that the difference of spike propagation manner could change the action potential waveform at the distal dendrite, and could produce synaptic activity-dependent Ca(2+) dynamics in the giant interneurons.

Action Potentials↗

PubMed1987

Is the hemispatial deficit produced by right parietal lobe damage associated with retinal or gravitational coordinates?

The hypothesis that right posterior parietal lesions cause two attentional deficits, namely, a reduced reactivity to stimuli in the left visual field (LVF), and a reduced reactivity to any stimulus which occupies a relative left position, was tested in 8 patients with an extinction syndrome. In Experiments 1 and 2 the first hypothesis was tested by measuring reaction times (RTs) to visual stimuli presented in the LVF and in the RVF, whereas the second hypothesis was tested by measuring RTs to stimuli totally positioned in the LVF, and in the RVF. The results showed that RTs to stimuli which occupied a relative left position were longer than RTs to stimuli which occupied a relative right position independent of the visual field stimulated and RTs to LVF stimuli were longer than RTs to RVF stimuli. Experiment 3 was designed to examine whether the attentional deficit associated with right parietal damage was mostly related to the use of gravitational rather than to retinal coordinates. In this experiment the patients tilted the head either to the left or the right by 90 deg and they responded to two stimuli displayed above and on either side of a fixation mark. The results showed that the difficulty in attending to the left was related both to the gravitational and the retinal frames of reference.

Aged↗

PubMed1985

Single motor unit and fiber action potentials during fatigue.

Muscle fatigue is defined as a loss of tension development during constant stimulation. Although the relationship is not well documented, muscle fatigue has been inferred from electromyogram (EMG) signals. The purpose of this study was to determine the relationship between the amplitude and duration of single motor unit action potentials (MUAPs) and the loss of tension development (fatigue) in the medial gastrocnemius muscles of cats. Single motor units were fatigued by continuous stimulation at 10 or 80 Hz or with trains of 40-Hz stimuli. When motor units were stimulated at 10 Hz and with trains at 40 Hz (low frequency), tension declined and remained depressed during recovery. The changes in the MUAP correlated poorly with changes in tension. During and after stimulation at 80 Hz (high frequency), changes in the amplitude and duration of MUAPs correlated highly with changes in tension development. Since the EMG signal is dependent on a summation and cancellation of individual MUAPs, the EMG provides a reasonable estimate of high-frequency fatigue but an unreliable measure of low-frequency fatigue.

Action Potentials↗

PubMed2001

Microelectrode findings in the thalamus in chronic pain and other conditions.

Functional neurosurgery usually requires physiological corroboration of the target site, particularly by eliciting characteristic responses to stimulation, or else by microelectrode recording of single cell responses to appropriate stimuli. Understanding pain physiology with both strategies has proven elusive, particularly microelectrode recording in response to noxious or thermal stimuli. The limited experience with stimulation and recording in pain pathways of the brain will be reviewed as well as the apparently pathophysiological observations made in certain patients with neuropathic pain.

Causalgia↗

PubMedDate not supplied

The influence of attention on the auditory brain stem evoked responses. Preliminary report.

The purpose of this study was to investigate the effects of attention on the auditory brainstem evoked responses (ABER). This was performed by measuring and statistically evaluating the interpeak latency times of wave I to wave V in 100 test subjects. The subjects were tested in three conditions: 1) selective attention to auditory click stimulation, 2) distraction by auditory stimuli, and 3) reinforced distraction by reading a newspaper during the click stimulations. It was observed that selective attention to the auditory stimulation leads to a decrease in the interpeak latency time (I-V) of, on the average, 0.2 milliseconds (statistically significant, 1%) in comparison with conditions 2 and 3.

Adult↗

PubMed2002

Inhibition of human CD4(+)CD25(+high) regulatory T cell function.

CD4(+)CD25(+high) T cells are potent regulators of autoreactive T cells. However, it is unclear how regulatory CD4(+)CD25(+high) cells discriminate between desirable inflammatory immune responses to microbial Ags and potentially pathologic responses by autoreactive T cells. In this study, an in vitro model was created that allowed differential activation of regulatory CD4(+)CD25(+high) and responder CD4(+) T cells. If CD4(+)CD25(+high) regulatory cells were strongly activated, they maintained suppressive effector function for only 15 h, while stimulation with weaker TCR stimuli produced regulatory cells that were suppressive until 60 h after activation. In contrast, strongly activated CD4(+) responder T cells were resistant to regulation at all time points, while weakly stimulated CD4(+) cells were sensitive to suppression until 38 or 60 h after activation depending upon the strength of the stimulus. The extent of suppression mediated by CD4(+)CD25(+high) cells also depended on the strength of stimulation in an Ag-specific system. Thus, the stronger the TCR signal, the more rapidly and more completely the responder cells become refractory to suppression.

Antigens↗

PubMed2001

Voltage-sensitive dye imaging of neocortical spatiotemporal dynamics to afferent activation frequency.

The spatial and temporal patterns of neocortex activation are determined not only by the dynamic character of the input but also by the intrinsic dynamics of the cortical circuitry. To study the role of afferent input frequency on cortical activation dynamics, the electrical activity of in vitro neocortex slices was imaged during white-matter electrical stimulation. High-speed optical imaging was implemented using voltage-sensitive dyes in guinea pig visual and somatosensory cortex slices concomitantly with intracellular recordings. Single white-matter electrical stimuli activated well-defined cortical sites with a radially oriented columnar configuration. This configuration was followed, over the next few milliseconds, by a lateral spread of excitation through cortical layers 5 and 6 and layers 2 and 3. Much of the optical response was eliminated in low extracellular calcium, indicating that it was primarily synaptically mediated. Repetitive stimuli at 10 Hz reproduced the spatiotemporal pattern observed for single stimuli. In contrast, repetitive stimulation in the gamma frequency range ( approximately 40 Hz) rapidly restrained the area of excitation to a small columnar site directly above the stimulating electrode. Intracellular recordings from cells lateral to the activated column revealed increased inhibitory synaptic activity and/or decreased excitatory responses during the train at 40 Hz, but not during a 10 Hz stimulation. Localized microinjections of GABA(A) antagonist produced a reorganization of the geometrical activity pattern that was dependent on the position of the microinjection site. These findings indicate that the frequency-dependent spatial organization of neocortex activation is determined by inhibitory sculpting attributable to local network dynamics.

Afferent Pathways↗

PubMedDate not supplied

[Late components of evoked potentials in cortical projections of paired stimuli during elaboration of an alimentary conditioned reflex to electric stimulation of the lateral geniculate body].

In the process of alimentary conditioning to the stimulation of LGB the late positive-negative complex appears or increases in the EPs of the visual and sensorimotor cortical areas. Its parameters differ during isolated and combined actions of the conditioned and reinforcing stimuli. The changes in EPs in the studied cortical areas are discussed in the aspect of two-way conditioned connections.

Animals↗

PubMed2004

Effects of a go/nogo task on event-related potentials following somatosensory stimulation.

OBJECTIVE: We investigated the effects of a go/nogo task on event-related potentials (ERPs) evoked by somatosensory stimuli. METHODS: ERPs following electrical stimulation of the second (go stimulus) or fifth (nogo stimulus) left-handed digit were recorded from 9 subjects. The recordings were conducted in 3 conditions: Control, Count and Movement. The subjects were instructed to count the go stimuli silently in Count, and respond to the go stimuli by grasping right hands in Movement. Go and nogo stimuli were presented at an even probability. RESULTS: N140 was recorded in all conditions and P300 in Count and Movement. The mean amplitudes of the nogo stimuli in the interval 140-200 msec and nogo-N140 amplitude were significantly more negative than those of the go stimuli in Count or Movement. Nogo-P300 was larger in amplitude than go-P300 in Movement but not Count. The effect of P300 was applied to Fz and Cz, but not at Pz. CONCLUSIONS: In the present study, effects of a somatosensory go/nogo task on ERPs were investigated, and our findings were very similar to those of previous studies using visual and auditory go/nogo tasks. Therefore, we suggest that cortical activities relating to go/nogo tasks are not dependent on sensory modalities. SIGNIFICANCE: The present study showed for the first time the go/nogo effects on somatosensory-evoked ERPs. These effects were similar to those in visual and auditory ERP studies.

Acoustic Stimulation↗

PubMed1998

Craniofacial electromyogram activation response: another indicator of anesthetic depth.

OBJECTIVE: After finding that craniofacial EMG preceding a stimulus was a poor predictor of movement response to that stimulus, we evaluated an alternative relation between EMG and movement: the difference in anesthetic depth between the endpoint of EMG responsiveness to a stimulus and endpoint of movement responsiveness to that stimulus. We expressed this relation as the increment of isoflurane between the two endpoints. METHODS: We measured EMG over the frontalis muscle, over the corrugator muscle, and between the Fp2 and the mastoid process as patients emerged from general anesthesia during suture closing of the surgical incision. Anesthesia was decreased by controlled washout of isoflurane while maintaining 70% N2O, and brain isoflurane concentrations ((C)isoBrain) were calculated. We studied a control group of 10 patients who received only surgical stimulation, and 30 experimental patients who intermittently received test stimuli in addition to the surgical stimulation. Patients were observed for movement responses and EMG records were evaluated for EMG activation responses. We defined an EMG activation response to be a rapid voltage increase of at least 1.0 microV RMS above baseline, with a duration of at least 30 s, in at least one of the three EMG channels. Patient responses to stimuli were classified as either an EMG activation response without a move response (EMG+), a move response without an EMG activation response (MV+), both an EMG activation response and a move response (EMG+MV+), or no response. We defined the EMG+ endpoint to be the threshold between EMG+ response and nonresponse to a stimulus, and estimated (C)isoBrain at this endpoint. We similarly defined the move endpoint and estimated the move endpoint (C)isoBrain. We then calculated the increment of (C)isoBrain at the EMG+ endpoint relative to the move endpoint. MAIN RESULTS: For the 30 experimental patients, the initial response to a test stimulus was an EMG+ in 14 patients (47%), an EMG+MV+ in 12 patients (40%), and a MV+ in 1 patient (3%); no response occurred by the time surgery was completed in 3 patients (10%). No response occurred in 7 of the control patients (70%). Of the 14 patients with an initial EMG+ response to a test stimulus, 9 patients later had a move response. For these 9 patients, the increment of (C)isoBrain between the EMG+ endpoint and move endpoint was 0.11 +/- 0.04 vol%, (mean +/- SD). CONCLUSIONS: Our results suggest that, given the circumstances of our study, an EMG activation response by a nonmoving patient indicates that the patient is at an anesthetic level close to that at which movement could occur. However, because the first EMG activation response may occur simultaneously with movement, the EMG activation response cannot be relied upon to always herald a move response before it occurs. Our results also suggest that EMG responsiveness to a test stimulus may be used to estimate the anesthetic depth of an individual patient.

Adolescent↗

PubMed1983

Case of downbeat nystagmus influenced by otolith stimulation.

A patient with downbeat nystagmus and familial ataxia is described. The nystagmus was induced by static tilt away from normal upright posture, by linear acceleration of the head, and by convergence. It is inferred that the nystagmus was modulated by otolith-specific stimuli and not by stimulation of the canals. These findings demonstrate the role of otolith function in generation of eye movements in the vertical plane and support proposed interrelationships between otolith and vergence mechanisms. The nystagmus and associated oscillopsia were partially suppressed by treatment with clonazepam.

Acceleration↗

PubMed1989

Role of antitachycardia devices in the treatment of ventricular tachyarrhythmias.

Chronic recurrent ventricular tachycardia (VT) can be terminated reproducibly by programmed endocardial right ventricular stimulation. However, antitachycardia pacing is associated with possible acceleration of VT, while frequent occurrence of VT and discomfort of the patient can limit treatment with an automatic implantable cardioverter/defibrillator (AICD; Cardiac Pacemakers Inc.). The combined use of antitachycardia pacing (Tachylog pacemaker; Siemens-Elema) and AICD was therefore evaluated in 6 of 35 patients (aged 50 to 70 years, mean 60.1 +/- 7.7) in whom AICD had been implanted because of VT, which could be terminated by temporary overdrive pacing. With the interactive mode of the Tachylog, termination of VT by the pacemaker as well as by the AICD was assessed after implantation. In the automatic mode, the Tachylog functioned as a bipolar ventricular inhibited (VVI) device with antitachycardia burst stimulation: 2 to 5 stimuli, interval 260 to 300 ms, 1 to 2 interventions. During follow-up of 32 +/- 17 months, the Tachylog terminated VT reliably 50 to 505 times per patient. When burst stimulation accelerated VT, termination was achieved by AICD discharge. Thus, drug-resistant VT can be terminated by antitachycardia pacing avoiding patient discomfort. In case of acceleration, VT can be controlled by the AICD. A universal pacemaker should combine antibradycardia and antitachycardia pacing with backup cardioversion/defibrillation mode.

Electric Countershock↗

PubMed1985

Elevation of pain threshold by vaginal stimulation in women.

In 2 studies with 10 women each, vaginal self-stimulation significantly increased the threshold to detect and tolerate painful finger compression, but did not significantly affect the threshold to detect innocuous tactile stimulation. The vaginal self-stimulation was applied with a specially designed pressure transducer assembly to produce a report of pressure or pleasure. In the first study, 6 of the women perceived the vaginal stimulation as producing pleasure. During that condition, the pain tolerance threshold increased significantly by 36.8% and the pain detection threshold increased significantly by 53%. A second study utilized other types of stimuli. Vaginal self-stimulation perceived as pressure significantly increased the pain tolerance threshold by 40.3% and the pain detection threshold by 47.4%. In the second study, when the vaginal stimulation was self-applied in a manner that produced orgasm, the pain tolerance threshold and pain detection threshold increased significantly by 74.6% and 106.7% respectively, while the tactile threshold remained unaffected. A variety of control conditions, including various types of distraction, did not significantly elevate pain or tactile thresholds. We conclude that in women, vaginal self-stimulation decreases pain sensitivity, but does not affect tactile sensitivity. This effect is apparently not due to painful or non-painful distraction.

Adult↗

PubMed1983

Vagal afferent inhibition of primate thoracic spinothalamic neurons.

Spinothalamic (ST) neurons in the C8-T5 segments of the spinal cord were examined for responses to electrical stimulation of the left thoracic vagus nerve (LTV). Seventy-one ST neurons were studied in 39 anesthetized monkeys (Macaca fascicularis). Each neuron could be excited by manipulation of its somatic field and by electrical stimulation of cardiopulmonary sympathetic afferent fibers. LTV stimulation resulted in inhibition of the background activity of 43 (61%) ST neurons. Nine (13%) were excited, 3 (4%) were excited and then inhibited, while 16 (22%) did not respond. There was little difference among these groups in terms of the type of somatic or sympathetic afferent input although inhibited cells tended to be more prevalent in the more superficial laminae. The degree of inhibition resulting from LTV stimulation was related, in a linear fashion, to the magnitude of cell activity before stimulation. LTV inhibition of background activity was similar among wide dynamic range, high threshold, and high-threshold cells with inhibitory hair input. Any apparent differences in LTV inhibitory effects among these groups were accounted for by the differences in ongoing cell activity as predicted by linear regression analysis. LTV stimulation inhibited responses of 32 of 32 ST cells to somatic stimuli. In most cases the stimulus was a noxious pinch; however, LTV stimulation also inhibited responses to innocuous stimuli such as hair movement. Bilateral cervical vagotomy abolished the inhibitory effect of LTV stimulation on background activity (six cells) or responses to somatic stimuli (seven cells). Stimulation of the cardiac branch of the vagus inhibited activity of three cells to a similar degree as LTV stimulation, while stimulation of the vagus below the heart was ineffective in reducing activity of 10 cells. We conclude that LTV stimulation alters activity of ST neurons in the upper thoracic spinal cord. Vagal inhibition of ST cell activity was due to stimulation of cardiopulmonary vagal afferent fibers coursing to the brain stem, which appear to activate descending inhibitory spinal pathways. Vagal afferent activity may participate in processing of somatosensory information as well as information related to cardiac pain.

Afferent Pathways↗

PubMed1990

Changes in inositol lipids and phosphates after stimulation of the MAS-transfected NG115-401L-C3 cell line by mitogenic and non-mitogenic stimuli.

A neuronal cell line (NG115-401L-C3) was stimulated by mitogenic (angiotensin) and non-mitogenic (bradykinin) peptides and examined for the time course of changes in the levels of radiolabelled inositol phosphates and phospholipids. Both peptides stimulated the time-dependent production of Ins(1,4,5)P3 and related metabolites. Bradykinin caused a much larger increase in Ins(1,4,5)P3 than did angiotensin. However, both peptides stimulated similar rises in the levels of Ins(1,3,4)P3 and InsP4. Bradykinin, but not angiotensin, caused a rapid (within 2 s) fall in the levels of PtdIns(4,5)P2 and PtdIns(4)P. Serum pretreatment of the cells caused a 2-3-fold potentiation of both the responses to bradykinin and angiotensin. Although significant levels of PtdIns(3)P were detected in resting cells, neither mitogenic (angiotensin, insulin-like growth factor I, transforming growth factor beta) nor non-mitogenic (bradykinin, nerve growth factor, interleukin-1) receptor activation changed its levels, arguing against regulation of either PtdIns 3-kinase or PtdIns(3)P phosphatase. We conclude that, as judged by the levels of its product. PtdIns(3)P, the enzyme PtdIns 3-kinase is not activated. This questions the significance of this activity in the receptor-mediated initiation of DNA synthesis.

Angiotensin II↗