A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations

BackgroundThe Perturbational Complexity Index (PCI) was recently introduced to assess the capacity of thalamocortical circuits to engage in complex patterns of causal interactions. While showing high accuracy in detecting consciousness in brain-injured patients, PCI depends on elaborate experimental setups and offline processing, and has restricted applicability to other types of brain signals beyond transcranial magnetic stimulation and high-density EEG (TMS/hd-EEG) recordings.ObjectiveWe aim to address these limitations by introducing PCI^ST, a fast method for estimating perturbational complexity of any given brain response signal.MethodsPCI^ST is based on dimensionality reduction and state transitions (ST) quantification of evoked potentials. The index was validated on a large dataset of TMS/hd-EEG recordings obtained from 108 healthy subjects and 108 brain-injured patients, and tested on sparse intracranial recordings (SEEG) of 9 patients undergoing intracranial single-pulse electrical stimulation (SPES) during wakefulness and sleep.ResultsWhen calculated on TMS/hd-EEG potentials, PCI^ST performed with the same accuracy as the original PCI, while improving on the previous method by being computed in less than a second and requiring a simpler set-up. In SPES/SEEG signals, the index was able to quantify a systematic reduction of intracranial complexity during sleep, confirming the occurrence of state-dependent changes in the effective connectivity of thalamocortical circuits, as originally assessed through TMS/hd-EEG.ConclusionsPCI^ST represents a fundamental advancement towards the implementation of a reliable and fast clinical tool for the bedside assessment of consciousness as well as a general measure to explore the neuronal mechanisms of loss/recovery of brain complexity across scales and models.     

Characterizing and predicting cortical evoked responses to direct electrical stimulation of the human brain

BackgroundDirect electrical stimulation of the human brain has been used to successfully treat several neurological disorders, but the precise effects of stimulation on neural activity are poorly understood. Characterizing the neural response to stimulation, however, could allow clinicians and researchers to more accurately predict neural responses, which could in turn lead to more effective stimulation for treatment and to fundamental knowledge regarding neural function.ObjectiveHere we use a linear systems approach in order to characterize the response to electrical stimulation across cortical locations and then to predict the responses to novel inputs.MethodsWe use intracranial electrodes to directly stimulate the human brain with single pulses of stimulation using amplitudes drawn from a random distribution. Based on the evoked responses, we generate a simple model capturing the characteristic response to stimulation at each cortical site.ResultsWe find that the variable dynamics of the evoked response across cortical locations can be captured using the same simple architecture, a linear time-invariant system that operates separately on positive and negative input pulses of stimulation. We demonstrate that characterizing the response to stimulation using this simple and tractable model of evoked responses enables us to predict the responses to subsequent stimulation with single pulses with novel amplitudes, and the compound response to stimulation with multiple pulses.ConclusionOur data suggest that characterizing the response to stimulation in an approximately linear manner can provide a powerful and principled approach for predicting the response to direct electrical stimulation.     

Co-occurrence of high-frequency oscillations and delayed responses evoked by intracranial electrical stimulation in stereo-EEG studies

Objective

To perform a side-by-side comparison of two epileptogenicity biomarkers, high frequency oscillations (HFOs) and delayed responses (DRs), as a result of single-pulse electrical stimulation.

The role of the right parietal cortex in sound localization: a chronometric single pulse transcranial magnetic stimulation study

Auditory spatial functions, including the ability to discriminate between the positions of nearby sound sources, are subserved by a large temporo-parieto-frontal network. With the aim of determining whether and when the parietal contribution is critical for auditory spatial discrimination, we applied single pulse transcranial magnetic stimulation on the right parietal cortex 20, 80, 90 and 150 ms post-stimulus onset while participants completed a two-alternative forced choice auditory spatial discrimination task in the left or right hemispace. Our results reveal that transient TMS disruption of right parietal activity impairs spatial discrimination when applied at 20 ms post-stimulus onset for sounds presented in the left (controlateral) hemispace and at 80 ms for sounds presented in the right hemispace. We interpret our finding in terms of a critical role for controlateral temporo-parietal cortices over initial stages of the building-up of auditory spatial representation and for a right hemispheric specialization in integrating the whole auditory space over subsequent, higher-order processing stages.     

Comparison of cortical responses to the activation of retina by visual stimulation and transcorneal electrical stimulation

Background

Electrical stimulation has been widely used in many ophthalmic diseases to modulate neuronal activities or restore partial visual function. Due to the different processing pathways and mechanisms, responses to visual and electrical stimulation in the primary visual cortex and higher visual areas might be different. This differences would shed some light on the properties of cortical responses evoked by electrical stimulation.

皮层电刺激技术在语言区附近病变手术中的应用

目的探讨唤醒状态下皮层电刺激技术在语言区附近病变手术中的应用价值。方法 79例语言区附近病变的患者,在唤醒状态下利用皮层电刺激技术,通过执行三类语言任务:数数字、图片命名与语言理解来进行语言区定位,避开语言区在显微镜下切除病变。结果本组患者51例术前语言功能正常,28例有不同程度语言功能障碍。75例患者完成了语言区定位。病变全切除30例,次全切除26例,大部切除23例。术后语言功能19例较前好转,53例无变化,4例出现短暂性运动性失语,3例出现短暂性感觉性失语,均于2周内基本恢复正常。结论唤醒状态下多种语言任务的联合应用可以提高皮层电刺激语言区定位的准确性,减少术后语言功能障碍的发生;语言区与切除皮层之间的相对安全距离是10mm。     

Autonomic responses are elicited by electrical stimulation of the medial but not lateral frontal cortex in rabbits

Conscious rabbits received electrical stimulation of the anterior midline frontal cortex or lateral somatosensory and motor cortex, through chronically-implanted electrodes. Active sites for cardiovascular responses were found in the anterior midline cortex, but stimulation of the frontolateral sensory-motor cortex either did not elicit cardiovascular changes or elicited only small and variable changes when stimulated. The heart-rate response elicited was, in all cases, bradycardia. All blood pressure changes consisted of depressor responses. Stimulation of the lateral frontal cortex almost always resulted in increases in EMG activity, although many placements were observed in the medial frontal cortex that were unaccompanied by movement. In all cases in which depressor responses and bradycardia were elicited, increases in respiration rate and decreases in depth also occurred. The active area from which bradycardia and depressor responses were elicited forms the medial portion of the cortical projection area of the mediodorsal nucleus of the thalamus and thus may be involved in the autonomic accompaniments of the behavioral activities, i.e. learning and memory processes, associated with this nucleus.     

Differentiating transcranial magnetic stimulation cortical and auditory responses via single pulse and paired pulse protocols: A TMS-EEG study

ObjectiveWe measured the neurophysiological responses of both active and sham transcranial magnetic stimulation (TMS) for both single pulse (SP) and paired pulse (PP; long interval cortical inhibition (LICI)) paradigms using TMS-EEG (electroencephalography).MethodsNineteen healthy subjects received active and sham (coil 90° tilted and touching the scalp) SP and PP TMS over the left dorsolateral prefrontal cortex (DLPFC). We measured excitability through SP TMS and inhibition (i.e., cortical inhibition (CI)) through PP TMS.ResultsCortical excitability indexed by area under the curve (AUC_(25-275ms)) was significantly higher in the active compared to sham stimulation (F(1,18) = 43.737, p < 0.001, η² = 0.708). Moreover, the amplitude of N100-P200 complex was significantly larger (F(1,18) = 9.118, p < 0.01, η² = 0.336) with active stimulation (10.38 ± 9.576 µV) compared to sham (4.295 ± 2.323 µV). Significant interaction effects were also observed between active and sham stimulation for both the SP and PP (i.e., LICI) cortical responses. Finally, only active stimulation (CI = 0.64 ± 0.23, p < 0.001) resulted in significant cortical inhibition.ConclusionThe significant differences between active and sham stimulation in both excitatory and inhibitory neurophysiological responses showed that active stimulation elicits responses from the cortex that are different from the non-specific effects of sham stimulation.SignificanceOur study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity.     

Changes in the perioral muscle responses to cortical TMS induced by decrease of sensory input and electrical stimulation to lower facial region.

OBJECTIVE: To determine the changes in the motor cortex due to repetitive electrical stimulation and cutaneous anesthesia in lower facial region. METHODS: A total of 11 subjects participated in the study of repetitive electrical stimulation, and 10 other subjects in the study of lower facial anesthesia. Facial nerve root and face associated cortical MEPs by transcranial magnetic stimulation (eight-shaped coil) were recorded from perioral muscles pre- and post- electrical stimulation and lower facial anesthesia. Cheek near to the corner of the mouth was transcutaneously stimulated by bipolar surface electrode giving repetitive electrical shocks at 5 Hz. Five percent lidocain/prilocain local anesthetic cream was applied to left or right lip-cheek region. RESULTS: There was no significant change in perioral MEP responses after 10-30 min of 5 Hz electrical stimulation. We found a significant increase of amplitude in cortical MEP recordings during lower facial anesthesia especially in cases of cortical magnetic stimulations ipsilateral and contralateral to the anaesthetized side and in perioral recordings contralateral to the anaesthetized side. CONCLUSIONS: The present study demonstrates that topical anesthesia to the lower facial region leads to cortical modulation and fast plastic changes in both hemispheres that are directed to the normal side.     

双语脑语言转换和语言代表区的术中直接电刺激研究（附2例分析）

目的通过对双语病人进行术中直接电刺激研究,探讨参与双语过程的脑结构。方法对2例左额叶低级别胶质瘤汉-英双语病人在术中唤醒麻醉下进行中文、英文以及双语转换任务的脑定位,依据功能边界切除肿瘤。评价术前、术后语言功能。结果2例病人均定位出Broca区,无语种特异性,但两种语言的命名阳性点是分离的：在前额叶背外侧区发现负责双语转换的阳性点,并在皮质下找到相应的特异性纤维;电刺激尾状核头表现为双语转换障碍。术后MRI显示肿瘤全切除。术后语速减慢1例,另1例自发言语减少．3个月后均恢复,未遗留语言转换障碍。结论大脑存在负责语言转换的脑结构。在实施语言功能区定位手术时,应对每种语言及其转换进行监测。     

Motor cortex electrical stimulation promotes axon outgrowth to brain stem and spinal targets that control the forelimb impaired by unilateral corticospinal injury

We previously showed that electrical stimulation of motor cortex (M1) after unilateral pyramidotomy in the rat increased corticospinal tract (CST) axon length, strengthened spinal connections, and restored forelimb function. Here, we tested: (i) if M1 stimulation only increases spinal axon length or if it also promotes connections to brain stem forelimb control centers, especially magnocellular red nucleus; and (ii) if stimulation‐induced increase in axon length depends on whether pyramidotomy denervated the structure. After unilateral pyramidotomy, we electrically stimulated the forelimb area of intact M1, to activate the intact CST and other corticofugal pathways, for 10 days. We anterogradely labeled stimulated M1 and measured axon length using stereology. Stimulation increased axon length in both the spinal cord and magnocellular red nucleus, even though the spinal cord is denervated by pyramidotomy and the red nucleus is not. Stimulation also promoted outgrowth in the cuneate and parvocellular red nuclei. In the spinal cord, electrical stimulation caused increased axon length ipsilateral, but not contralateral, to stimulation. Thus, stimulation promoted outgrowth preferentially to the sparsely corticospinal‐innervated and impaired side. Outgrowth resulted in greater axon density in the ipsilateral dorsal horn and intermediate zone, resembling the contralateral termination pattern. Importantly, as in spinal cord, increase in axon length in brain stem also was preferentially directed towards areas less densely innervated by the stimulated system. Thus, M1 electrical stimulation promotes increases in corticofugal axon length to multiple M1 targets. We propose the axon length change was driven by competition into an adaptive pattern resembling lost connections.     

Effects of diazepam or haloperjdol on convulsion and behavioral responses induced by bilateral electrical stimulation in the medial prefrontal cortex

Nakamura-Palacios, Ester Miyuki, Roney Welinton de Oliveira, Cristiano Freitas Gomes: Effects of diazepam or haloperidol on convulsion and behavioral responses induced by bilateral electrical stimulation in the medial prefrontal cortex. Prog Neuro-Psychopharmacol. & Biol.Psychiat. 1999, : pp. 1369–1388.

1. 1. Effects of diazepam (DZP) or haloperidol (HAL) on convulsions and behavioral responses (locomotion, circling, spying and head shaking) induced by bilateral electrical stimulation in the medial prefrontal cortex (mPFC) were examined.

2. 2. Male Wistar rats were electrically stimulated (ten 30-sec trains, 60 Hz, 80 – 100 μA) bilaterally in the mPFC and their behavior was simultaneously observed in an open field in daily session

3. 3. DZP and HAL dose-response curves (0, 0. 5, 1 25, 2. 5 and 5 mg/kg, i p , 30 min before electrical stimulation session) were determined after a baseline of behavioral responses was established.

4. 4. DZP dose-dependently decreased head shaking and convulsions, had no effect in circling and spying behaviors, and increased locomotion except at the highest dose HAL reduced locomotion, circling and spying behaviors in a dose-dependent manner, but did not affect convulsions or head shaking.

5. 5. These results demonstrated that convulsion and behavioral responses induced by electrical activation of the mPFC were modified by DZP or HAL. Therefore, the mPFC is involved in the mediation of neural and/or behavioral activity that may be implicated in some central effects of psychoactive drugs.

     

Age-dependent alteration of metabolic response to photic stimulation in the human brain measured by P MR-spectroscopy

Effects of photic stimulation (PS) on energy metabolism were examined in the occipital cortex of 25 healthy volunteers aged 23–69 years old using phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS). A significant effect of photic stimulation was found only for intracellular pH (p<0.05 by repeated measures analysis of variance) but not for any peak area ratios. An interaction between intracellular pH and age were statistically significant (p<0.005), and the interaction between phosphocreatine and age was close to significance (p=0.06). In subjects aged more than 40 years old, phosphocreatine was significantly decreased during the photic stimulation (p<0.05, multiple comparison by Dunnett's method), and intracellular pH tended to be elevated just after the stimulation (p=0.07). There were no significant changes in these values in younger subjects. These results suggest that no significant effect of photic stimulation on brain energy metabolism was found in younger subjects, and that significant effects of photic stimulation on intracellular pH and phosphocreatine were found in middle-aged subjects. Metabolic response of the human brain to photic stimulation may be dependent on age.     

Sources of cortical responses to painful CO(2) laser skin stimulation of the hand and foot in the human brain.

OBJECTIVES: To investigate whether the same dipolar model could explain the scalp CO(2) laser evoked potential (LEP) distribution after either hand or foot skin stimulation. METHODS: LEPs were recorded in 14 healthy subjects after hand and foot skin stimulation and brain electrical source analysis of responses obtained in each individual was performed. RESULTS: A 5 dipolar sources model explained the scalp LEP topography after both hand and foot stimulation. In particular, we showed that the co-ordinates of the two earliest activated dipoles were compatible with source locations in the upper bank of the Sylvian fissure on both sides. These sources did not change their location when the stimulation site was moved from the upper to the lower limb. The other 3 dipoles of our model were activated in the late LEP latency range with a biphasic profile and a location compatible with activation of the cingulate gyrus and deep temporo-insular structures. CONCLUSIONS: The dipolar model previously proposed for the hand stimulation LEPs can also satisfactorily explain the LEP distribution obtained after foot stimulation. The earliest activated Sylvian dipolar sources did not change their location when the upper or lower limb was stimulated, as expected from the close projections of hand and foot in the second somatosensory area. No source in the primary somatosensory area was necessary to model the scalp topography of LEPs to hand and foot stimulation.     

Morphological identification of brain stem neurones associated with predatory behaviour elicited by lateral hypothalamic electrical stimulation in the cat: a retrograde transport study using horseradish peroxidase subsequent to an electrolytic lesion

The combination of electrical stimulation of the lateral hypothalamus to elicit predatory behaviour, an electrolytic lesion and a subsequent HRP injection was used to identify brain stem neurones whose axons were affected by such hypothalamic stimulation. In contrast, the injection of HRP into such hypothalamic sites, without a prior lesion, resulted in a significant reduction in the number of labelled neurones. This suggests that an important contribution, namely those neurones which give rise to fibres which pass through the stimulated region, is underestimated by the later procedure.     

Intense and sustained pain reduces cortical responses to auditory stimuli: Implications for the interpretation of the effects of heterotopic noxious conditioning stimulation in humans

Phasic pain stimuli are inhibited when they are applied concomitantly with a conditioning tonic stimulus at another body location (heterotopic noxious conditioning stimulation, HNCS). While the effects of HNCS are thought to rely on a spino‐bulbo‐spinal mechanism in animals (termed diffuse noxious inhibitory controls, DNIC), the underlying neurophysiology in humans may involve other pathways. In this study, we investigated the role of concomitant supraspinal mechanisms during HNCS by presenting auditory stimuli during a conditioning tonic painful stimulus (the cold pressor test, CPT). Considering that auditory stimuli are not conveyed through the spinal cord, any changes in brain responses to auditory stimuli during HNCS can be ascribed entirely to supraspinal mechanisms. Electroencephalography (EEG) was recorded during HNCS, and auditory stimuli were administered in three blocks, before, during and after HNCS. Nociceptive withdrawal reflexes (NWRs) were recorded at the same time points to investigate spinal processing. Our results showed that AEPs were significantly reduced during HNCS. Moreover, the amplitude of the NWR was significantly diminished during HNCS in most participants. Given that spinal and supraspinal mechanisms operate concomitantly during HNCS, the possibility of isolating their individual contributions in humans is questionable. We conclude that the net effects of HCNS are not independent from attentional/cognitive influences.     

The distribution of fos immunoreactivity in rat brain following freezing and escape responses elicited by electrical stimulation of the inferior colliculus

Several sources of evidence indicate that the inferior colliculus also integrates acoustic information of an aversive nature besides its well-known role as a relay station for auditory pathways. Gradual increases of the electrical stimulation of this structure cause in a hierarchical manner alertness, freezing and escape behaviors. Independent groups of animals implanted with bipolar electrodes into the inferior colliculus received electrical stimulation at one of these aversive thresholds. Control animals were submitted to the same procedure but no current was applied. Next, analysis of Fos protein expression was used to map brain areas activated by the inferior colliculus stimulation at each aversive threshold and in the controls. Whereas alertness elicited by stimulation of the inferior colliculus did not cause any significant labeling in any structure studied in relation to the respective control, electrical stimulation applied at the freezing threshold increased Fos-like immunoreactivity in the central amygdaloid nucleus and entorhinal cortex. In contrast, escape response enhanced Fos-like immunoreactivity in the nucleus cuneiform and the dorsal periaqueductal gray matter of the mesencephalon. This evidence supports the notion that freezing and escape behaviors induced by electrical stimulation of the inferior colliculus activate different neural circuitries in the brain. Both defensive behaviors caused significant expression of c-fos in the frontal cortex, hippocampus and basolateral amygdaloid nucleus. This indistinct pattern of c-fos distribution may indicate a more general role for these structures in the modulation of fear-related behaviors. Therefore, the present data bring support to the notion that amygdala, dorsal hippocampus, entorhinal cortex, frontal cortex, dorsal periaqueductal gray matter and cuneiform nucleus altogether play a role in the integration of aversive states generated at the level of the inferior colliculus.