Hiroki Nishibayashi

Cortically evoked responses of human pallidal neurons recorded during stereotactic neurosurgery

Responses of neurons in the globus pallidus (GP) to cortical stimulation were recorded for the first time in humans. We performed microelectrode recordings of GP neurons in 10 Parkinsons disease (PD) patients and 1 cervical dystonia (CD) patient during surgeries to implant bilateral deep brain stimulation electrodes in the GP. To identify the motor territories in the external (GPe) and internal (GPi) segments of the GP, unitary responses evoked by stimulation of the primary motor cortex were observed by constructing peristimulus time histograms. Neurons in the motor territories of the GPe and GPi responded to cortical stimulation. Response patterns observed in the PD patients were combinations of an early excitation, an inhibition, and a late excitation. In addition, in the CD patient, a long‐lasting inhibition was prominent, suggesting increased activity along the cortico‐striato‐GPe/GPi pathways. The firing rates of GPe and GPi neurons in the CD patient were lower than those in the PD patients. Many GPe and GPi neurons of the PD and CD patients showed burst or oscillatory burst activity. Effective cathodal contacts tended to be located close to the responding neurons. Such unitary responses induced by cortical stimulation may be of use to target motor territories of the GP for stereotactic functional neurosurgery. Future findings utilizing this method may give us new insights into understanding the pathophysiology of movement disorders.

Reduced pallidal output causes dystonia

Dystonia is a neurological disorder characterized by sustained or repetitive involuntary muscle contractions and abnormal postures. In the present article, we will introduce our recent electrophysiological studies in hyperkinetic transgenic mice generated as a model of DYT1 dystonia and in a human cervical dystonia patient, and discuss the pathophysiology of dystonia on the basis of these electrophysiological findings. Recording of neuronal activity in the awake state of DYT1 dystonia model mice revealed reduced spontaneous activity with bursts and pauses in both internal (GPi) and external (GPe) segments of the globus pallidus. Electrical stimulation of the primary motor cortex evoked responses composed of excitation and subsequent long-lasting inhibition, the latter of which was never observed in normal mice. In addition, somatotopic arrangements were disorganized in the GPi and GPe of dystonia model mice. In a human cervical dystonia patient, electrical stimulation of the primary motor cortex evoked similar long-lasting inhibition in the GPi and GPe. Thus, reduced GPi output may cause increased thalamic and cortical activity, resulting in the involuntary movements observed in dystonia.

Unilateral spatial neglect due to a haemorrhagic contusion in the right frontal lobe

We report two cases of unilateral spatial neglect associated with an isolated right frontal lobe lesion. Case 1 was a 59-year-old, right-handed man, who developed a left hemiplegia, disorientation, and frontal lobe neglect associated with a haemorrhagic contusion following a head injury. Case 2 was a 55-year-old, right-handed man, who also developed disorientation and frontal lobe neglect secondary to a haemorrhagic contusion following a head injury.99mTc HM-PAO SPECT revealed an isolated reduction in the regional cerebral blood flow (CBF) around the haematoma in the frontal lobe; blood flow to remaining parts of the brain was normal. Damage to the right frontal lobes of these patients was confirmed as being the cause of the unilateral spatial neglect in accordance with the results of CBF studies.

Ictal asomatognosia due to dominant superior parietal cortical dysplasia

We report a 23-year-old man with left dominant parietal cortical dysplasia manifesting as ictal asomatognosia. The man had experienced seizures, during which he underwent ictal asomatognosia as a feeling of loss of his right extremities. Scalp electroencephalography (EEG) showed interictal discharges in the left parietal region of his brain. Magnetic resonance fluid-attenuated inversion recovery (FLAIR) imaging revealed a hyperintense lesion in the left superior parietal lobule. A [(123)I]-iomazenil (IMZ) single-photon-emission CT scan demonstrated an area of low IMZ binding coincident with the lesion observed in the MRI scan. Invasive EEG monitoring showed ictal discharges in the cortex posterior to the postcentral sulcus. High-frequency electrical stimulation of the same area of the cortex also induced asomatognosia of the patients right forearm. We performed a corticectomy of the anterior part of the superior parietal lobule, which resulted in no new neurological deficits. The seizures disappeared after surgery with the maintenance of preoperative medication. Therefore, the anterior part of the superior parietal lobule may be a symptomatogenic zone for ictal asomatognosia.

Surgical Technique of Brain Stimulation

Deep brain stimulation (DBS) is a well-established treatment for movement disorders, such as Parkinson’s disease (PD), essential tremor, and dystonia. Best clinical effects depend on precise placement of electrodes in the motor territory of the target nuclei by stereotactic neurosurgery. Patient selection is important. Careful surgical interventions and microelectrode recordings are necessary in aged patients. General anesthesia can be required for frame placement in dystonia case. Correct framing from three directions should be verified. Combinations of AC(anterior commissure)–PC(posterior commissure)-based targeting and imaging-based targeting may approach the optimal target. Care should be taken for continuous cerebrospinal fluid leak after dural opening. Optimal trajectory should be selected to avoid injuries of cortical and sulcal vessels, or lateral ventricle penetration, which may increase hemorrhagic risk and electrode malposition. Because of the brain shift as the operating time progresses, target should be modified according to intraoperative neurophysiological examinations such as microelectrode recording and macroelectrode stimulation test. Implantation of devices should be reminded of delayed skin complication or infection. On the background of extended application, surgical technique of DBS would be modified in the future, preserving principal concept and surgical technique.

MRI Based Sulcal Pattern Analysis for Diagnosis and Clinical Application in Neurosurgery

MRI is used not only for anatomical location and characterization but also for 3D views of sulci and gyri. T1WI-MRI captured with 3D-volume acquired 3D-views of sulci and gyri on fifty healthy volunteers and two patients. The software that we developed analyzed and labeled sulcal patterns of cerebral cortex automatically comparing to a standard brain model. We focused the post-central sulcus (PoC) and 2 neighboring sulci with an inter-sulcal analysis (Relations) including an inter-sulci junction (PoC and cingulate sulcus posterior [Cing]). The value of PoC-Cing Relations of focal cortical dysplasia (FCD) is higher than that of normal, while the value of glioma is much less among that of normal. The PoC of FCD and a few normal brains have junction with Cing. This informative value and a presence of inter-sulci junction suggest that cortical folding dynamics might influence the folding patterns of cerebral cortex. This sulcal labeling can analyze normal and abnormal patient’s brains for clinical use.

Reply: Cortically evoked responses of human pallidal neurons†‡

Regarding Nishibayashi et al, a description of human pallidal neuronal responses to cortical stimulation, there are 2 sets of concerns. First, the latencies of 22 ms are far longer than reported elsewhere in laboratory animals, as noted by the authors. Their explanation of longer conduction times based on larger human brain sizes is improbable. Their latencies are far longer than those reported in human studies as well. Thalamic neuronal responses latencies to globus pallidus interna (GPi) deep brain stimulation (DBS) are approximately 3.5 ms. Reese et al reported latencies of GPi neuronal responses to subthalamic nucleus (STN) DBS ranging from 0.265 to 1.0 ms. Further, STN DBS corticalevoked potentials to single pulses demonstrate latencies of much less than the 22 ms. The observations by Baker et al are particularly relevant, as the evoked potentials reflect antidromic activation of the cortical projections to the STN and thus reflect at least conduction velocities of some of the components that Nishibayashi et al posited as mediating the pallidal neuronal responses. The range of latencies of GPi responses to STN DBS in the study by Reese et al is much faster than antidromic responses described above. Stimulus artifact could obscure earlier extracellular antidromic potentials in the other studies; however, intracellular recordings in cortical neurons to STN stimulation show latencies on the order of 2 6 0.5 ms in the rodent. Rather, the response reported by Reese et al probably represents reentrant activities from DBS pulses earlier than the immediately preceding DBS pulse. The actual latencies probably ranged from n*5.6 þ 0.265 ms to n*5.6 þ 1 ms, where n is some integer and 5.6 ms is the interstimulus interval of 180 pps DBS. This is relevant, as the responses described by Nishibayashi et al could reflect later reentrant activity in the basal ganglia-thalamic-cortical system, which is very different from the presumption of an open-loop feed-forward mechanism by Nishibayashi et al. The second concern relates to the attribution of the sequential changes in neuronal activities to excitation, then inhibition and then excitation from which they inferred a sequence of orthodromic influences. This is an unwarranted conclusion as there are alternatives that cannot be excluded based on the data presented. These alternatives include refractory periods reducing neuronal activity following excitation and a post–refractory period of increased excitability producing increased neuronal activity following the reduction. At the least, alternatives should be considered. Erwin Montgomery, Jr., MD* Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA *E-mail: emontgom@uab.edu