Developing and Evaluating a Flexible Wireless Microcoil Array Based Integrated Interface for Epidural Cortical Stimulation.

The purpose of this study was to understand the anatomical and functional connections between the paracentral lobule (PCL) and the primary motor cortex (M1) of the human brain. This retrospective study included 16 patients who underwent resection of lesions located near M1. Nine patients had lesions in the dominant hemisphere. Tractography was performed to visualize the connectivity between two regions of interest (ROIs)-the convexity and the interhemispheric fissure-that were shown by functional MRI to be activated during a finger tapping task. The number, mean length, and fractional anisotropy (FA) of the fibers between the ROIs were estimated. During surgery, subdural electrodes were placed on the brain surface, including the ROIs, using a navigation system. Cortico-cortical evoked potentials (CCEPs) were evoked by applying electrical stimuli to the hand region of M1 using electrodes placed on the convexity and were measured with electrodes placed on the interhemispheric fissure. To verify CCEP bidirectionality, electrical stimuli were applied to electrodes on the interhemispheric fissure that showed CCEP responses. Correlations of CCEP amplitudes and latencies with the number, mean length, and mean FA value obtained from tractography were determined. The correlations between these parameters and perioperative motor functions were also analyzed. Fibers of 14 patients were visualized by diffusion tensor imaging (DTI). Unidirectional CCEPs between the PCL and M1 were measurable in all 16 patients, and bidirectional CCEPs between them were measurable in 14 patients. There was no significant difference between the two directions in the maximum CCEP amplitude or latency (amplitude, p = 0.391; latency, p = 0.583). Neither the amplitude nor latency showed any apparent correlation with the number, mean length, or mean FA value of the fibers obtained from tractography. Pre- and postoperative motor function of the hands was not significantly correlated with CCEP amplitude or latency. The number and mean FA value of fibers obtained by DTI, as well as the maximum CCEP amplitude, varied between patients. This study demonstrated an anatomical connection and a bidirectional functional connection between the PCL, including the supplementary motor area, and M1 of the human brain. The observed variability between patients suggests possible motor function plasticity. These findings may serve as a foundation for further studies.

The Influence of Anesthesia on Corticocortical Evoked Potential Monitoring Network Between Frontal and Temporoparietal Cortices

P2-63. Functional connectivity from the dorso-lateral and medial parts of the parietal lobe: a cortico-cortical evoked potential study

Connections of the limbic network: A corticocortical evoked potentials study

ObjectiveWe aimed at clarifying the clinical significance of the responses evoked by human entorhinal cortex (EC) electrical stimulation by means of cortico‐cortical evoked potentials (CCEPs).MethodsWe enrolled nine patients with medically intractable medial temporal lobe epilepsy who underwent invasive presurgical evaluations with subdural or depth electrodes. Single‐pulse electrical stimulation was delivered to the EC and fusiform gyrus (FG), and their evoked potentials were compared. The correlation between the evoked potentials and Wechsler Memory Scale‐Revised (WMS‐R) score was analyzed to investigate whether memory circuit was involved in the generation of the evoked potentials.ResultsIn most electrodes placed on the neocortex, EC stimulation induced unique evoked potentials with positive polarity, termed as “widespread P1” (P1w). Compared with FG stimulation, P1w induced by EC stimulation were distinguished by their high occurrence rate, short peak latency (mean: 20.1 ms), small peak amplitude, and waveform uniformity among different recording sites. A stimulation of more posterior parts of the EC induced P1w with shorter latency and larger amplitude. P1w peak amplitude had a positive correlation (r = .69) with the visual memory score of the WMS‐R. In one patient, with depth electrode implanted into the hippocampus, the giant evoked potentials were recorded in the electrodes of the anterior hippocampus and EC near the stimulus site.ConclusionsThe human EC electrical stimulation evoked the short‐latency potentials in the broad neocortical regions. The origin of P1w remains unclear, although the limited evidence suggests that P1w is the far‐field potential by the volume conduction of giant evoked potential from the EC itself and hippocampus. The significance of the present study is that those evoked potentials may be a potential biomarker of memory impairment in various neurological diseases, and we provided direct evidence for the functional subdivisions along the anterior–posterior axis in the human EC.

The effects of deep brain or epidural cortical stimulation on poststroke involuntary and voluntary movement disorders were analyzed in a total of 64 patients. Among them, 22 patients underwent either deep brain or epidural cortical stimulation in order to control their poststroke involuntary movements. The remaining 42 underwent epidural cortical stimulation for the purpose of controlling their poststroke pain. In the latter group of patients, we analyzed the changes in coexistent involuntary or voluntary movement disorders during stimulation for pain control. Stimulation of either the thalamic nucleus ventralis intermedius or the motor cortex proved to be useful in 13 (59%) of the patients who underwent deep brain or epidural cortical stimulation for control of poststroke involuntary movements. Satisfactory control was often achieved in patients with hemiballismus, hemichorea or resting tremor. In 8 (19%) of the patients who underwent epidural cortical stimulation for pain control, stimulation of the motor cortex improved motor performance which had been impaired in association with hemiparesis. Such an effect was independent of pain control and apparently resulted from an inhibition of their rigidity. We believe that these findings justify further clinical studies on deep brain or epidural cortical stimulation for the control of poststroke movement disorders.

The aim was to present cortical potentials after intraoperative electrical epidural stimulation of the optic nerve (ON) in individuals with normal preoperative vision. Optic nerve potentials after flash and electrical stimulation were additionally recorded. Contact electrodes on ON and occiput were used for monopolar recording of optic nerve potentials and cortical potentials, respectively. Epidural stimulating electrodes on ON were used to deliver a rectangular current pulse (intensity 0.2-5.0mA; duration 0.1-0.3ms; rate 2Hz), and LED flash goggles were used for flash stimulation. Optic nerve potentials after flash stimulation predominantly consisted of a positive deflection with a latency around 40ms, followed by a longer-lasting negativity with the peak at around 50ms. Optic nerve potentials after electrical epidural stimulation of ON were comprised of a negative deflection at around 3ms. A positive and a negative deflection at 20 and 30ms, respectively, and a smaller positive deflection at 40ms constituted cortical potentials after electrical epidural stimulation of ON. Stable and repeatable cortical potentials after electrical epidural stimulation of ON could safely be recorded in humans during neurosurgery. The origin of these presumably far-field potentials and their potential role in intraoperative monitoring remains to be established.

Cortico-cortical evoked potentials in response to varying stimulation intensity improves seizure localization

The role of cortical connectivity in brain function and pathology is increasingly being recognized. While in vivo magnetic resonance imaging studies have provided important insights into anatomical and functional connectivity, these methodologies are limited in their ability to detect electrophysiological activity and the causal relationships that underlie effective connectivity. Here, we describe results of cortico-cortical evoked potential (CCEP) mapping using single pulse electrical stimulation in 25 patients undergoing seizure monitoring with subdural electrode arrays. Mapping was performed by stimulating adjacent electrode pairs and recording CCEPs from the remainder of the electrode array. CCEPs reliably revealed functional networks and showed an inverse relationship to distance between sites. Coregistration to Brodmann areas (BA) permitted group analysis. Connections were frequently directional with 43% of early responses and 50% of late responses of connections reflecting relative dominance of incoming or outgoing connections. The most consistent connections were seen as outgoing from motor cortex, BA6–BA9, somatosensory (SS) cortex, anterior cingulate cortex, and Broca's area. Network topology revealed motor, SS, and premotor cortices along with BA9 and BA10 and language areas to serve as hubs for cortical connections. BA20 and BA39 demonstrated the most consistent dominance of outdegree connections, while BA5, BA7, auditory cortex, and anterior cingulum demonstrated relatively greater indegree. This multicenter, large-scale, directional study of local and long-range cortical connectivity using direct recordings from awake, humans will aid the interpretation of noninvasive functional connectome studies.

Referred pain and cutaneous responses from deep tissue electrical pain stimulation in the groin

To clarify the characteristics of interhemispheric connections, we investigated cortico-cortical evoked potentials (CCEP) in human. Fourteen patients with temporal lobe epilepsy who underwent invasive EEG monitoring with bilaterally implanted subdural electrodes were studied. Electric pulse stimuli were given in a bipolar fashion at two adjacent electrodes on and around the motor area (MA) or sensory area (SA), and CCEP responses were recorded by averaging electrocorticograms from the contralateral hemisphere. Seventy-two pairs of electrodes were stimulated, and 468 recordings were analyzed. Fifty-one of 468 recordings demonstrated CCEP responses. Of 51 responses, 16 consisted of an initial positive triphasic wave (Type 1), 27 had an initial negative biphasic wave (Type 2), and 8 showed an initial positive biphasic wave (type 3). The mean latencies of the earliest peaks were 13.1, 28.9, and 29.4 ms in Types 1, 2, and 3 responses, respectively. The responses were more frequently evoked by stimulating facial MA (f-MA) and nonfacial MA (nf-MA) than by stimulating SA or noneloquent area. In both f-MA and nf-MA stimulation, the responses were more frequently recorded at the contralateral f-MA than at the contralateral nf-MA or other areas. SA stimulation never evoked CCEP responses at the contralateral MA or SA. The amplitudes were maximal when f-MA was stimulated and responses recorded at the contralateral f-MA. These findings suggest that the interhemispheric connections are uneven. Both f-MA and nf-MA send dense interhemispheric connections to the contralateral f-MA. SA may have no or only rare direct connection with the contralateral MA or SA.

The review addresses modern methods of electrical stimulation used to regulate the function of external respiration in humans. The methods include abdominal functional stimulation of respiratory muscles, diaphragmatic stimulation, phrenic nerve stimulation, epidural and transcutaneous spinal cord stimulation. The physiological rationale of their application is described along with the examples of their use in clinical practice, including stimulation parameters and electrode placement diagrams for each of the methods. We analyze the effectiveness of each of the methods in patients with respiratory muscle paresis and the features of their use depending on the level of spinal cord injury. Special attention is paid to the method of epidural spinal cord stimulation because this technique is widely used in electrophysiological studies on animal models, providing deeper insight into the spinal levels of the functional control of external respiration. The review substantiates the great potential of using the method of transcutaneous electrical spinal cord stimulation both in fundamental studies of external respiration and in clinical practice.

In this review of neurocontrol of movement after spinal cord injury, we discuss neurophysiological evidences of conducting and processing mechanisms of the spinal cord. We illustrate that external afferent inputs to the spinal cord below the level of the lesion can modify, initiate, and maintain execution of movement in absence or partial presence of brain motor control after chronic spinal cord injury. We review significant differences between spinal reflex activity elicited by single and repetitive stimulation. The spinal cord can respond with sensitization, habituation, and dis-habituation to regular repetitive stimulation. Therefore, repetitive spinal cord reflex activity can contribute to the functional configuration of the spinal network. Moreover, testing spinal reflex activity in individuals with motor complete spinal cord injury provided evidences for subclinical residual brain influence, suggesting the existence of axons traversing the injury site and influencing the activities below the level of lesion. Thus, there are two motor control models of chronic spinal cord injury in humans: "discomplete" and "reduced and altered volitional motor control." We outline accomplishments in modification and initiation of altered neurocontrol in chronic spinal cord injury people with epidural and functional electrical stimulation. By nonpatterned electrical stimulation of lumbar posterior roots, it is possible to evoke bilateral extension as well as rhythmic motor outputs. Epidural stimulation during treadmill stepping shows increased and/or modified motor activity. Finally, volitional efforts can alter epidurally induced rhythmic activities in incomplete spinal cord injury. Overall, we highlight that upper motor neuron paralysis does not entail complete absence of connectivity between cortex, brain stem, and spinal motor cells, but there can be altered anatomy and corresponding neurophysiological characteristics. With specific input to the spinal cord below the level of the lesion, the clinical status of upper motor neuron paralysis without structural modification can be modified, and movements can be initiated. Thus, external afferent input can partially replace brain control.

Brain stimulation is increasingly viewed as an effective approach to treat neuropsychiatric disease. The brain's organization in distributed networks suggests that the activity of a remote brain structure could be modulated by stimulating cortical areas that strongly connect to the target. Most connections between cerebral areas are asymmetric, and a better understanding of the relative direction of information flow along connections could improve the targeting of stimulation to influence deep brain structures. The hippocampus and amygdala, two deep-situated structures that are crucial to memory and emotions, respectively, have been implicated in multiple neurological and psychiatric disorders. We explored the directed connectivity between the hippocampus and amygdala and the cerebral cortex in patients implanted with intracranial electrodes using corticocortical evoked potentials (CCEPs) evoked by single-pulse electrical stimulation. The hippocampus and amygdala were connected with most of the cortical mantle, either directly or indirectly, with the inferior temporal cortex being most directly connected. Because CCEPs assess the directionality of connections, we could determine that incoming connections from cortex to hippocampus were more direct than outgoing connections from hippocampus to cortex. We found a similar, although smaller, tendency for connections between the amygdala and cortex. Our results support the roles of the hippocampus and amygdala to be integrators of widespread cortical influence. These results can inform the targeting of noninvasive neurostimulation to influence hippocampus and amygdala function.

Previous studies suggest that the rate of indentation of a tactile probe determines which skin mechanoreceptors are activated. To further investigate this possibility, indentations of 300 microm at velocities of 100 (T100) and 400 microm/ms (T400) were applied to the tip (FT) and the proximal phalanx of digit III (PP) and the thenar eminence (Pm) of ten healthy volunteers, and compared with responses after electrical stimulation at the FT. Compound sensory action potentials (CSAPs) were recorded from the median nerve through needle electrodes at the wrist and elbow. The maximal sensory conduction velocities (SNCVs) between wrist and elbow were similar with electrical and T400 stimulation, but on average were 15% lower with T100 stimulation (P < 0.001). With both indentation velocities, SNCVs were similar regardless of stimulation sites. Amplitudes of tactile CSAPs with FT stimulation were 1--2 microV at T400 and 0.3--0.4 microV at T100. The CSAP areas evoked by T100 stimulation showed a reduction from fingertip to proximal finger to palm (P < 0.05-0.005), whereas those obtained with T400 stimulation showed a reduction only at the palm (P < 0.05). The results support previous studies indicating that fast indentation at 400 microm/ms activated deeply placed Pacinian corpuscles as well as superficially situated Meissner corpuscles, whereas slower indentation at 100 microm/ms activated primarily Meissner corpuscles.