Intense peripheral electrical stimulation differentially inhibits tail vs. limb withdrawal reflexes in the rat

In an on-going study on mechanisms by which activation of sensory afferents regulates nociception, high-intensity, low-frequency electrical stimulation was applied to previously defined meridian and non-meridian points of the hindlimb or forelimb, and the effects measured on the withdrawal reflex of the tail or limb in the lightly anesthetized rat. Withdrawal was evoked by application of noxious radiant heat to the tip of the tail or to the plantar surface of a hindpaw or forepaw. Parameters of conditioning electrical stimulation were 2 ms pulses at 4 Hz for 20 min at 20 × threshold (20–30 mA) where threshold was the minimum intensity which evoked muscle twitch. In experiments on tail withdrawal, stimulation applied to meridian points fengshi (GB-31), femur-futu (ST-32) and zusanli (ST-36) of the hindlimb or to wai-kuan (TH-5) and hoku (LI-4) of the forelimb increased the latency of the withdrawal reflex to 70–100% of the maximum possible inhibition (MPI) during the stimulation. Inhibition persisted for more than 1 h after the end of stimulation. Bilateral stimulation of hindlimb meridian points evoked a greater inhibition during the stimulation ( > 95% of the MPI); the inhibition persisted for 40 min. Stimulation of non-meridian sites in hindlimb or forelimb inhibited the withdrawal reflexes by 45–50% of the MPI during the stimulation only. Thus, the evoked inhibition has two components, a brief effect elicited by non-meridian point stimulation and a persistent post-stimulation effect produced only upon stimulation of meridian points. Stimulation produced little effect on nociceptive limb withdrawal reflexes. The results suggest that high-intensity, low-frequency electrical stimulation of meridian points produced a long-lasting, extrasegmental inhibition of the tail withdrawal but not of limb withdrawal reflexes. This differential inhibition may be due to differences in neuronal circuitry and CNS modulatory control mechanisms. The persistent inhibition appears to be dependent on the site of stimulation because it is not evoked by stimulation of sites outside of meridian points.     

Parametric Studies on Electroacupuncture-Like Stimulation in a Rat Model: Effects of Intensity, Frequency, and Duration of Stimulation on Evoked Antinociception

We have found that electroacupuncture-like stimulation of defined sites in the hindlimb of the rat inhibits a nociceptive withdrawal reflex. The lightly anaesthetized rat was used and tail withdrawal from a noxious radiant heat stimulus was the nociceptive reflex. Standard stimulation of hindlimb meridian points femur-futu (ST-32), fengshi (GB-31), and zusanli (ST-36) consisted of a 2-ms square voltage pulse at 4 Hz for a duration of 20 min, applied at 20 times the threshold to evoke muscle twitch. This produced two types of inhibition of the reflex; one was an increase in the latency of up to 80% during the stimulation, termed the brief antinociception, and the other was a post stimulation increase of up to 60% lasting greater than 1 h, termed the persistent antinociception. When the stimulus intensity was reduced to 10 times threshold, the latency during stimulation increased up to 50%, but the persistent response did not occur. Stimulation at threshold produced neither effect. When the train duration was altered, 10 min of stimulation produced only the brief effect, whereas 40 min of stimulation produced both effects, although the persistent effect lasted only 20 min. Stimulation at 6 Hz produced responses similar to those at 4 Hz, whereas stimulation at 2 Hz produced smaller effects. At 8 Hz, only the brief antinociception was elicited. With a pulse duration of 0.2 ms, the brief response was observed but the persistent response was markedly attenuated, whereas 5 ms produced responses similar to those with 2 ms. These data suggest that high-intensity, low-frequency electrical stimulation of meridian points in the rat hindlimb produces both brief and persistent antinociceptive effects on the tail withdrawal reflex, and both effects are dependent upon the parameters of stimulation. The persistence of the latter effect beyond the period of stimulation suggests events occurring after direct synaptic activity, possibly mediated via plastic changes at spinal and/or supraspinal levels.     

Readjustment of the efferent activity of the scratching generator in response to stimulation of cutaneous afferents of the hindlimb of the decerebrate immobilized cat

Rebuildings of the scratching generator efferent activity caused by the phasic electrical stimulation of ipsilateral hindlimb skin nerves during different hindlimb positions were studied in decerebrated immobilized cats. Stimulation was followed by short latency inhibition of the efferent activity. Stimulation did not cause correlation shifts in the common "aiming" and "scratching" activity. Changes in the efferent activity cycle duration and intensity depended on the stimulation phase. Inversion of intensity changes occurred with transition from the middle-force to strong stimulation. A functional role of the dependence of the efferent activity rebuilding on the stimulation phase is considered. The scratching generator is supposed to contain a model of the afferent inflow which enters the spinal cord during real scratching.     

Neuropathy reduces viscero-somatic inhibition via segmental mechanisms in rats

The effect of an experimental neuropathy on the viscero-somatic inhibition was studied in lightly anesthetized rats. In controls, colo-rectal distension at noxious intensities produced a multisegmental prolongation of the withdrawal response induced by noxious stimulation of the skin. In rats with a spinal nerve-ligation induced neuropathy this viscero-somatic inhibition was significantly reduced within the neuropathic segment (the hindlimb) but not outside of it (the tail). Naloxone, an opioid antagonist, attenuated this viscero-somatic inhibition in controls and it did not restore the inhibition in neuropathic rats. The results indicate that somatic neuropathy produces a segmental attenuation of viscero-somatic inhibition and this attenuation cannot be explained by a nerve injury-induced release of endogenous opioids. The decreased inhibition of somatic signals may contribute to the hypersensitivity observed in neuropathic conditions.     

Centrifugal modulation of the rat tail flick reflex evoked by graded noxious heating of the tail

Centrifugal modulation from the midbrain, pons and medulla of the spinal nociceptive tail flick (TF) reflex evoked by graded noxious heating of the tail was studied in lightly pentobarbital-anaesthetized rats. In initial experiments, the relationship between the intensity of the noxious thermal stimulus and the TF latency was characterized. The thermal stimulus was provided by a lamp focused on the ventral surface of a rat's tail. Five different rates of heating of the tail were varied systematically by altering the voltage supplied to the lamp and were characterized using a thermocouple to measure the temperature of tissue exposed to the radiant heat. A linear stimulus-response function relating the inverse of the latency of the TF to the rate of heating of the tail was established. However, the mean cutaneous tissue temperature of the exposed tail at the time of the TF was found to be invariant and independent of the rate of heating. Focal electrical stimulation in the midbrain, pons and medulla modulated the TF reflex in two different ways, analogous to modulations of stimulus-response functions of single-cell recordings of spinal dorsal horn neurons. A Type I modulation, analogous to the parallel shift in response threshold seen in spinal dorsal horn neurons, was an absolute increase in the thermal threshold of the TF reflex. A Type II modulation, analogous to a change in slope or gain seen in spinal dorsal horn neurons, was a linear increase in the thermal threshold of the TF reflex as a function of the rate of heating. Type I modulations were produced by electrical stimulation in the ventromedial medulla (n. raphe magnus and n. reticularis gigantocellularis) and lateral periaqueductal gray of the midbrain. Type II modulations were produced by electrical stimulation in the dorsolateral pons, locus coeruleus-subcoeruleus and in the medial periaqueductal gray. This experimental approach has shown itself to be useful in the characterization of descending inhibition of nociception. Much simpler and less invasive than analogous spinal dorsal horn single cell electrophysiologic studies, it can be used to study the mechanisms of centrifugal modulation of nociceptive flexion reflexes and further establishes the utility of the lightly anaesthetized rat preparation for studies of nociception-antinociception.     

Antihistamine-selective vasodilatation in the canine hindlimb evoked by electrical stimulation rostral to the hypothalamus

Electrical stimulation was carried out at various sites in the brain of anaesthetized dogs pretreated with guanethidine. Stimulation at some sites elicited cholinergic vasodilator responses in the femoral vascular bed while stimulation at other sites produced non-cholinergic vasodilator responses which were prevented by histamine antagonists administered into the hindlimb. The central sites mediating the two types of responses were anatomically distinct.     

Differential Effects of a Distant Noxious Stimulus on Hindlimb Nociceptive Withdrawal Reflexes in the Rat

Recent studies indicate that the nociceptive withdrawal reflexes to individual muscles are evoked by separate reflex pathways. The present study examines whether nociceptive withdrawal reflexes to different muscles are subject to differential supraspinal control in rats. A distant noxious stimulus was used to activate a bulbospinal system which selectively inhibits 'multireceptive' neurons (i.e. neurons receiving excitatory tactile and nociceptive inputs) in the dorsal horn of the spinal cord. Withdrawal reflexes, recorded with electromyographic techniques in single hindlimb muscles, were evoked by standardized noxious pinch. Thirty-seven rats, anaesthetized with halothane and nitrous oxide, were used. Whereas withdrawal reflexes to the extensor digitorum longus and brevis, tibialis anterior and biceps posterior muscles were strongly inhibited, reflexes to interossei muscles were potentiated during noxious pinch of the nose. Reflexes to peronei muscles were not significantly changed. The effects on the reflexes usually had an onset latency of <0.5 s and outlasted the conditioning stimulation by up to 2 s. The monosynaptic la reflex to the deep peroneal nerve, innervating dorsiflexors of the digits and ankle, was not significantly changed during noxious pinch of the nose. Hence, the inhibitory effects on the hindlimb withdrawal reflexes induced by the conditioning stimulation were presumably exerted on reflex interneurons. It is concluded that nociceptive withdrawal reflexes to different hindlimb muscles are differentially controlled by descending pathways activated by a distant noxious stimulus. The results support our previous conclusion that there are separate nociceptive withdrawal reflex pathways to different hindlimb muscles.     

Involvement of spinal α2‐adrenoceptors in prolonged modulation of hind limb withdrawal reflexes following acute noxious stimulation in the anaesthetized rabbit

The role of spinal α ₂‐adrenoceptors in mediating long‐lasting modulation of hind limb withdrawal reflexes following acute noxious chemical stimulation of distant heterotopic and local homotopic locations has been investigated in pentobarbitone‐anaesthetized rabbits. Reflexes evoked in the ankle extensor muscle medial gastrocnemius (MG) by electrical stimulation of the ipsilateral heel, and reflexes elicited in the ankle flexor tibialis anterior and the knee flexor semitendinosus by stimulation at the base of the ipsilateral toes, could be inhibited for over 1 h after mustard oil (20%) was applied to either the snout or into the contralateral MG. The heel–MG response was also inhibited after applying mustard oil across the plantar metatarsophalangeal joints of the ipsilateral foot, whereas this homotopic stimulus facilitated both flexor responses. Mustard oil also caused a significant pressor effect when applied to any of the three test sites. The selective α₂‐adrenoceptor antagonist, RX 821002 (100–300 μg, intrathecally), had no effect on reflexes per se, but did cause a decrease in mean arterial blood pressure. In the presence of the α₂‐blocker, inhibitory and facilitatory effects of mustard oil on reflexes were completely abolished. These data imply that long‐lasting inhibition of spinal reflexes following acute noxious stimulation of distant locations involves activation of supraspinal noradrenergic pathways, the effects of which are dependent on an intact α₂‐adrenoceptor system at the spinal level. These pathways and receptors also appear to be involved in facilitation (sensitization) as well as inhibition of reflexes following a noxious stimulus applied to the same limb.     

Sleep, subcortical stimulation and kindling in the cat.

A longitudinal study of the effects of sleep on amygdaloid kindling showed that kindling disrupted normal sleep patterns by reducing REM sleep and increasing awake time. Few interictal spike discharges were observed during the awake stage, while a marked increase in discharge was observed during the light and deep sleep stages. No discharges were observed during REM sleep. During the immediate post-stimulation period the nonstimulated amygdala showed a much higher rate of spike discharge. On the other hand, there was an increase in spike discharge in the stimulated amygdala during natural sleep without preceding amygdaloid stimulation. Amygdaloid stimulation at the generalized seizure threshold during each sleep stage resulted in a generalized convulsion. The influence of subcortical electrical stimulation on kindled amygdaloid convulsions was investigated in a second experiment. Stimulation of the centre median and the caudate nucleus was without effect on kindled convulsions, while stimulation of the mesencephalic reticular formation at high frequency (300 Hz) reduced the latency of onset of kindled generalized convulsions. Stimulation of the nucleus ventralis lateralis of the thalamus at low frequency (10 Hz) prolonged the convulsion latency, and at high current levels blocked the induced convulsion. Stimulation in the central gray matter at low frequency (10 Hz) also blocked kindled amygdaloid convulsions.     

Inhibitory effect of stimulation of the anterior pretectal nucleus on the jaw-opening reflex

The anterior pretectal nucleus (APT) has been recently implicated in sensorimotor integration and has been shown to have suppressive influences on tail flick behaviour and on nociceptive responses of spinal dorsal horn neurones in rats. The present study tested the effect of stimulation of the APT on the rat's digastric jaw-opening reflex elicited by orofacial stimuli. Either ipsilateral or contralateral electrical stimulation at histologically confirmed sites within and immediately subjacent to the APT produced a suppression of the reflex that had an onset of 20–30 ms, peaked around 50 ms and lasted for 200–300 ms; in some cases, a brief period of reflex facilitation preceded the onset of inhibition was sometimes followed by a facilitatory period. No prolonged period of suppression induced by electrical stimulation was noted in these anaesthetized rats. The injection of monosodium glutamate at comparable sites within and subjacent to APT induced reflex suppression that lasted several minutes. These findings represent the first documentation of APT-induced modulation in the trigeminal sensorimotor system, but support recent evidence suggesting the involvement of APT in sensorimotor integration and modulation.     

Influence of spinalization on spinal withdrawal reflex responses varies depending on the submodality of the test stimulus and the experimental pathophysiological condition in the rat

The influence of midthoracic spinalization on thermally and mechanically induced spinal withdrawal reflex responses was studied in the rat. There were three experimental groups of rats: healthy controls, rats with a spinal nerve ligation-induced unilateral neuropathy, and rats with a carrageenan-induced inflammation of one hindpaw. Tail flick response was induced by radiant heat. Hindlimb withdrawal was induced by radiant heat, ice water, and innocuous or noxious mechanical stimulation of the paw. Prior to spinalization, spinal nerve ligated and carrageenan-treated animals had a marked unilateral allodynia and hyperalgesia. Spinalization tended to induce a facilitation of noxious heat-evoked reflexes. This spinalization-induced facilitation was stronger on tail than hindlimb withdrawal. Spinalization-induced skin temperature change did not explain the facilitation of noxious heat-evoked reflexes. In contrast, spinal withdrawal responses induced by noxious cold or mechanical stimulation were significantly suppressed following spinalization. The spinalization-induced facilitatory effects as well as inhibitory ones on spinal reflexes were enhanced in inflamed/neuropathic animals. The results indicate that the tonic descending control of spinal nocifensive responses varies depending on the submodality of the test stimulus, the segmental level of the reflex (tail vs. hindlimb), and on the pathophysiological condition.     

Studies of the habenulo-interpeduncular pathway in cats

Electrophysiological studies with extracellular macroelectrodes and microelectrodes of the habenulo-interpeduncular pathway in cats revealed spontaneous rhythmic oscillations in the interpeduncular nucleus, ranging from 3–4 Hz to 9–10 Hz under different anesthetics. There was little obvious correlation between these waves and the spontaneous firing patterns of interpeduncular units. Possible origins of the waves are discussed. Stimulation of the habenula evoked in the interpeduncular nucleus brief positive-negative deflections followed by a slow negative, and then a slow positive wave. The majority of interpeduncular neurons excited by habenular stimulation initially fired during the brief early waves. The unit discharge was either a constant latency spike, which followed repetitive stimulation at 100/sec or more, or at relatively variable latency, a single spike or a short burst of two to six spikes at 400–1000/sec. Some units showed sequences of initial excitation followed by inhibition, while other units showed pure inhibition. Over 80% of units either excited or inhibited by habenular stimulation were excited by acetylcholine applied microiontophoretically; this excitation was potentiated by neostigmine and blocked by atropine (0.3–1.0 mg/kg iv), although atropine did not affect responses to habenular stimulation. These findings are only partly consistent with cholinergic transmission in the habenulo-interpeduncular pathway which was suggested by previous histochemical findings of intense choline acetyltransferase and cholinesterase activity.     

Axon-to-axon transmission in tullidora (buckthorn) neuropathy

Oral administration of ether extracts of the tullidora (Karwinskia humboldtiana) fruit, which contains an identified neurotoxin, produced flaccid hind limb paralysis in cats after a latency of 4 to 7 weeks. Acute experiments were conducted after the paralysis was evident. Spinal roots of lumbar and sacral segments were transected as close as possible to the spinal cord and divided into several filaments. Stimulation of some filaments distal to the transection evoked action potentials in other filaments (axon-to-axon transmission or cross talk) after a latency of at least 8 ms. Cross-talk responses frequently consisted of multiple discharges. Axon-to-axon transmission was seen only between motor axons and disappeared when hind limb nerves were transected 10 to 15 cm from the spinal cord. Twin pulses were applied to a filament at various intervals; the pulse intensity was adjusted so that the conditioning pulse was subthreshold to elicit cross talk, but the test pulse frequently elicited it (temporal facilitation). In three fully studied fibers the facilitation was prolonged to 50 to 80 ms. In some cases, no cross talk was evoked in a given filament by individual stimulation of two other filaments, but simultaneous stimulation of the same filaments did evoke cross talk (spatial facilitation). Series of periodic bursts of activity spontaneously occurred in those axons responding with multiple discharges to single stimulation of other axons. At low temperatures (about 30°C) the stimulus could trigger essentially similar series of bursts. Single motoneurons were intracellularly stimulated by brief depolarizing pulses. The action potential elicited by the stimulus was followed after several msec by a secondary train of discharges generated at the periphery (“back firing”).     

Analgesia from electrical stimulation of the hypothalamic arcuate nucleus in pentobarbital-anesthetized rats

Inhibition of noxious heat-induced tail flick by electrical stimulation of the arcuate nucleus of the hypothalamus (ARH) was examined and characterized in pentobarbital-anesthetized rats. Systematic mapping studies revealed that inhibition of the tail flick reflex could be induced by stimulating widespread areas in the ventromedial parts of the hypothalamus, which include the paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus, anterior hypothalamic area as well as the ARH areas. The ARH stimulation-produced tail flick suppression could be completely blocked by systemic naloxone (2 mg/kg) which shows the involvement of an opiate mechanism in this effect. Although the tail flick reflex in the lightly anesthetized state is of significantly shorter latency than in the unanesthetized state, thresholds of the ARH stimulation for suppressing spinal nociceptive reflexes in the lightly anesthetized state were not significantly different from the thresholds at the same ARH sites in the awake state.     

红核在大脑皮质下行调控脊髓伤害感受性传递中的作用

以电刺激外周感受野诱发的大鼠脊髓背角WDR和NS神经元的晚串放电（C-反应）为指标，以串脉中刺激对侧大脑脚（CP）作为条件刺激，在C-反应受到明显抑制的神经元。分别观察了电解损毁红核（RN）和RN内注射兴奋性氨基酸的受体拮抗剂对刺激CP的下行抑制作用的影响。结果发现：损毁同侧RN后，刺激CP对C反应的抑制作用明显减弱，而损毁同侧RN背侧结构，对侧RN及假损毁RN均无此效应；RN内微量注射兴奋性氨基酸受体拮抗剂AP5和DNQX均可减弱刺激CP对C-反应的抑制。提示RN至少部分参与大脑皮质对脊髓伤害感受性传递的下行抑制作用。且以同侧RN为主；在与痛觉调制有关的皮质-RN通路中既有NMDA受体又有非NMDA受体的参与。     

Developmental tuning in a spinal nociceptive system: effects of neonatal spinalization.

Recent studies indicate a modular organization of the nociceptive withdrawal reflex system. Each module has a characteristic receptive field, closely matching the withdrawal movement caused by its effector muscle. In the rat, the strength of the sensory input to each module is tuned during the first postnatal weeks, i.e., erroneous spinal connections are depressed, and adequate connections are strengthened. To clarify if this tuning is dependent on supraspinal structures, the effect of a complete neonatal spinal cord transection on the postnatal tuning of withdrawal reflexes was studied. The nociceptive receptive fields of single hindlimb muscles and compound withdrawal reflexes were examined in decerebrate unanesthetized and awake rats, respectively. Noxious thermal CO(2) laser stimulation was used to evoke reflex responses. Neonatal spinal cord transection resulted in a disrupted reflex organization in the adult rat, resembling that previously found in neonatal rats. The receptive fields of single hindlimb muscles exhibited abnormal distribution of sensitivity not matching the withdrawal action of the effector muscles. Likewise, the composite nocifensive movements, as documented in the awake rat, often resulted in erroneous movements toward the stimulus. It is concluded that withdrawal reflexes do not become functionally adapted in rats spinalized at birth. These findings suggest a critical role for supraspinal systems in the postnatal tuning of spinal nociceptive systems.     

Intrathecal 5-hydroxytryptamine and electrical stimulation of the nucleus raphe magnus in rats both reduce the antinociceptive potency of intrathecally administered noradrenaline

The antinociceptive potency of noradrenaline (NA), as assessed by suppression of the spinal nocifensive tail flick and paw withdrawal reflexes was examined. The tail flick latency (TFL) was increased to the cut-off value for a period of approximately 120 min following the intrathecal microinjection of a standard 15 nmol dose of NA. A similar intrathecal dose of NA produced an increase in threshold to elicit the paw withdrawal reflex for a period of approximately 20 min. When preceded by a standard intrathecal microinjection of 260 nmol 5-hydroxytryptamine, the antinociceptive potency of NA was significantly reduced as reflected by both the tail flick and paw withdrawal tests. In addition, electrical stimulation of the posterior raphe complex immediately before and during the NA-induced increase in TFL, significantly reduced the antinociceptive potency of NA. It is concluded that spinal tryptaminergic activity can reduced the duration of the antinociceptive action of intrathecally applied NA.     

Reticulospinal tracts involved in the spino-bulbo-spinal reflex in cats

Twenty-three chloralosed cats were used to examine the spinal descending pathways of the spino-bulbo-spinal (SBS) reflex.Transection of the ventrolateral funiculus in the spinal cord at the thoracic level abolished the SBS reflex of caudal spinal segments ipsilateral to the transection, but did not abolish the ascending propriospinal reflex and SBS reflex of rostral segments.Unit discharges elicited in axons of the ventrolateral funiculus at L₃ by sural nerve stimulation had the appropriate latency for mediating the SBS reflex. These axons originated in the medial bulbar reticular formation, since the responses had a consistent short latency and followed repetitive stimulation of the bulbar reticular formation (up to a rate of 300 Hz). Conduction velocities of reticulospinal axons ranged widely from 20 to 120 m/sec. There were two peaks, fast (95 m/sec) and slow (35 m/sec). The fast conducting fibers showed oligo-spikes, high amplitude and wide distribution of latency. Almost 90% of the axons with slow conduction exhibited multi-spikes, low amplitude and narrow distribution.Unitary responses of the ventral rootlet at L₇ were elicited by sural nerve stimulation and correlated with the latency of the SBS reflex. The unitary response was also evoked by train pulse stimulation of the ventrolateral funiculus in the spinal cord. Conduction velocities of descending spinal tracts ranged from 20 to 60 (mean±S.D.,35 ± 8) m/sec.We may conclude that the descending spinal pathway of the SBS reflex is the slowly conducting reticulospinal tract which originates in the medial bulbar reticular formation and passes through the ventrolateral funiculus of the spinal cord.     

Precision mapping of the epileptogenic network with low- and high-frequency stimulation of anterior nucleus of thalamus

ObjectiveThe goal of thalamic deep brain stimulation in epilepsy is to engage and modulate the epileptogenic network. We demonstrate how the anterior nucleus of thalamus (ANT) stimulation engages the epileptogenic network using electrophysiological measures (gamma response and post-stimulation excitability).MethodsFive patients with suspected temporal lobe epilepsy syndrome, undergoing stereo-electroencephalography (SEEG), were enrolled in the IRB approved study to undergo recording and stimulation of the ANT. We analyzed the extent of gamma-band response (activation or suppression) and post-stimulation change in excitability in various cortical regions during low (10 Hz) and high (50 Hz) frequency stimulations.Results10 Hz stimulation increased cortical gamma, whereas 50 Hz stimulation suppressed the gamma responses. The maximum response to stimuli was in the hippocampus. High epileptogenicity regions were more susceptible to stimulation. Both 10-and 50 Hz stimulations decreased post-stimulation cortical excitability. The greater the gamma-band activation with 10 Hz stimulation, the greater was the decrease in post-stimulation excitability.ConclusionsWe define an EEG marker that delineates stimulation-specific nodal engagement. We proved that nodes that were engaged with the thalamus during stimulation were more likely to show a short term decrease in post-stimulation excitability.SignificancePatient-specific engagement patterns during stimulation can be mapped with SEEG that can be used to optimize stimulation parameters.     

Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats. Part II: Stimulation of cerebral cortex and hypothalamus

This experimental work was carried out to examine whether activation of autonomic cortical and hypothalamic areas by electrical stimulation is related to changes in the intracranial pressure (ICP) in cats anaesthetized lightly with sodium pentobarbital. Electrical stimulation was performed using a concentric electrode with a train of electrical pulses (pulse duration, 0.4 ms; frequency, 40 Hz; intensity, 50-400 microA). Stimulation of sites in the anterior cingulate gyrus produced a rise in ICP associated with a fall in systemic arterial blood pressure (BP) or with no change in BP. Stimulation of sites in the anterior hypothalamus produced a fall in BP with an increase in ICP. Stimulation of sites in the area extending from the anterior hypothalamus to the posterior hypothalamus produced rises in BP and ICP. These observations suggest that activation of autonomic cortical and hypothalamic areas is involved in changes in ICP.