Somatotopic organization of the ventral nuclear group of the dorsal thalamus: deep brain stimulation for neuropathic pain reveals new insights into the facial homunculus.

Deep Brain Stimulation (DBS) is an experimental treatment for medication-refractory neuropathic pain. The ventral posteromedial (VPM) and ventral posterolateral (VPL) nuclei of the thalamus are popular targets for the treatment of facial and limb pain, respectively. While intraoperative testing is used to adjust targeting of patient-specific pain locations, a better understanding of thalamic somatotopy may improve targeting of specific body regions including the individual trigeminal territories, face, arm, and leg. To elucidate the somatotopic organization of the ventral nuclear group of the dorsal thalamus using in vivo macrostimulation data from patients undergoing DBS for refractory neuropathic pain. In vivo macrostimulation data was retrospectively collected for 14 patients who underwent DBS implantation for neuropathic pain syndromes at our institution. 56 contacts from 14 electrodes reconstructed with LeadDBS were assigned to macrostimulation-related body regions: tongue, face, arm, or leg. 33 contacts from 9 electrodes were similarly assigned to one of three trigeminal territories: V1, V2, or V3. MNI coordinates in the x, y, and z axes were compared by using MANOVA. Across the horizontal plane of the ventral nuclear group of the dorsal thalamus, the tongue was represented significantly medially, followed by the face, arm, and leg most laterally (p < 0.001). The trigeminal territories displayed significant mediolateral distribution, proceeding from V1 and V2 most medial to V3 most lateral (p < 0.001). Along the y-axis, V2 was also significantly anterior to V3 (p = 0.014). While our results showed that the ventral nuclear group of the dorsal thalamus displayed mediolateral somatotopy of the tongue, face, arm, and leg mirroring the cortical homunculus, the mediolateral distribution of trigeminal territories did not mirror the established cortical homunculus. This finding suggests that the facial homunculus may be inverted in the ventral nuclear group of the dorsal thalamus.

Pyramidal cell types drive functionally distinct cortical activity patterns during decision-making.

Understanding how cortical circuits generate complex behavior requires investigating the cell types that comprise them. Functional differences across pyramidal neuron (PyN) types have been observed within cortical areas, but it is not known whether these local differences extend throughout the cortex, nor whether additional differences emerge when larger-scale dynamics are considered. We used genetic and retrograde labeling to target pyramidal tract, intratelencephalic and corticostriatal projection neurons and measured their cortex-wide activity. Each PyN type drove unique neural dynamics, both at the local and cortex-wide scales. Cortical activity and optogenetic inactivation during an auditory decision task revealed distinct functional roles. All PyNs in parietal cortex were recruited during perception of the auditory stimulus, but, surprisingly, pyramidal tract neurons had the largest causal role. In frontal cortex, all PyNs were required for accurate choices but showed distinct choice tuning. Our results reveal that rich, cell-type-specific cortical dynamics shape perceptual decisions.

Postoperative Focal Lower Extremity Supplementary Motor Area Syndrome: Case Report and Review of the Literature.

Supplementary motor area (SMA) syndrome refers to varying degrees of transient hemiparesis and mutism following insult to the medial posterior frontal lobe. We describe a rare case of an isolated lower limb SMA deficit with associated pre- and post-operative multimodality neurophysiological monitoring data. We review the literature on SMA somatotopy and the prognostic abilities of intraoperative motor evoked potentials in suspected SMA dysfunction. A 45-year-old male underwent staged resection of a complex parasagittal WHO grade II meningioma involving the posterior superior frontal gyrus bilaterally. Intraoperative neurophysiological monitoring with transcranial motor evoked potentials (TCMEP) and direct cortical motor evoked potentials (DCMEP) were used during both stages of resection. The patient developed an isolated left foot drop despite unchanged DCMEP and TCMEP data obtained during the first stage of the procedure. During the second stage of resection 3 days later, repeat neurophysiological monitoring confirmed intact corticospinal tracts. Deep peroneal somatosensory evoked potentials (SSEPs) revealed good morphology, appropriate latency and amplitudes during the second stage of resection. These results suggested a diagnosis of focal SMA dysfunction. Left foot drop persisted 7 days post-operatively. At one month follow up, the patient was neurologically intact with full strength noted in all muscle groups of the left lower extremity. An improved understanding of the somatotopic organization of the SMA with additional neuromonitoring data can allow neurosurgeons to better predict and understand perioperative SMA dysfunctions.

Chronic, cortex-wide imaging of specific cell populations during behavior.

Measurements of neuronal activity across brain areas are important for understanding the neural correlates of cognitive and motor processes such as attention, decision-making and action selection. However, techniques that allow cellular resolution measurements are expensive and require a high degree of technical expertise, which limits their broad use. Wide-field imaging of genetically encoded indicators is a high-throughput, cost-effective and flexible approach to measure activity of specific cell populations with high temporal resolution and a cortex-wide field of view. Here we outline our protocol for assembling a wide-field macroscope setup, performing surgery to prepare the intact skull and imaging neural activity chronically in behaving, transgenic mice. Further, we highlight a processing pipeline that leverages novel, cloud-based methods to analyze large-scale imaging datasets. The protocol targets laboratories that are seeking to build macroscopes, optimize surgical procedures for long-term chronic imaging and/or analyze cortex-wide neuronal recordings. The entire protocol, including steps for assembly and calibration of the macroscope, surgical preparation, imaging and data analysis, requires a total of 8 h. It is designed to be accessible to laboratories with limited expertise in imaging methods or interest in high-throughput imaging during behavior.

Tissue Ablation Dynamics During Magnetic Resonance-Guided, Laser-Induced Thermal Therapy.

BACKGROUND: Magnetic resonance-guided, laser-induced thermal therapy is a real-time magnetic resonance thermometry-guided, minimally invasive procedure used in the treatment of intracranial tumors, epilepsy, and pain. Little is known about its dynamics and the effects of various pathologies on overall ablation. OBJECTIVE: To determine the relationship between thermal energy delivery and the time to maximal estimated thermal damage and whether differences exist between various intracranial pathologies. METHODS: We used real-time ablation data from 28 patients across 5 unique intracranial pathologies. All ablations were performed using the Visualase Thermal Therapy System (Medtronic, Inc, Minneapolis, Minnesota), which uses a 980-nm diffusing tip diode laser. The thermal damage area was plotted against time for each ablation. We then estimated the duration of time required to reach 50% (t50) and 97% (t97) of maximal damage. Comparisons were then made between different intracranial pathologies. RESULTS: The duration required to reach maximal thermal damage estimate (TDE) among all ablations was 159 ± 62 seconds, and the t50 and t97 were 43 ± 21 and 136 ± 57 seconds, respectively, where t97 was reached at an average of 23 seconds before the maximal TDE. The t97 was shorter in the recurrent metastasis/radiation necrosis and epilepsy groups compared with the previously untreated glioblastoma multiforme group. CONCLUSION: The optimal duration can be estimated by the t97, which can be achieved in less than 3 minutes and differs across ablation targets. TDE expansion decelerates with prolonged ablation. Future studies are needed to examine the radiographic and clinical outcomes as well as the effects of ablation power, irrigation speed, and the effect of previous therapies on ablation dynamics.

Fast GCaMPs for improved tracking of neuronal activity.

The use of genetically encodable calcium indicator proteins to monitor neuronal activity is hampered by slow response times and a narrow Ca(2+)-sensitive range. Here we identify three performance-limiting features of GCaMP3, a popular genetically encodable calcium indicator protein. First, we find that affinity is regulated by the calmodulin domain's Ca(2+)-chelating residues. Second, we find that off-responses to Ca(2+) are rate-limited by dissociation of the RS20 domain from calmodulin's hydrophobic pocket. Third, we find that on-responses are limited by fast binding to the N-lobe at high Ca(2+) and by slow binding to the C-lobe at lower Ca(2+). We develop Fast-GCaMPs, which have up to 20-fold accelerated off-responses and show that they have a 200-fold range of K(D), allowing coexpression of multiple variants to span an expanded range of Ca(2+) concentrations. Finally, we show that Fast-GCaMPs track natural song in Drosophila auditory neurons and generate rapid responses in mammalian neurons, supporting the utility of our approach.