Resting-state network mapping in neurosurgical practice: a review.

Resting-state functional MRI (rs-fMRI) is a well-established method for studying intrinsic connectivity and mapping the topography of functional networks in the human brain. In the clinical setting, rs-fMRI has been used to define functional topography, typically language and motor systems, in the context of preoperative planning for neurosurgery. Intraoperative mapping of critical speech and motor areas with electrocortical stimulation (ECS) remains standard practice, but preoperative noninvasive mapping has the potential to reduce operative time and provide functional localization when awake mapping is not feasible. Task-based fMRI has historically been used for this purpose, but it can be limited by the young age of the patient, cognitive impairment, poor cooperation, and need for sedation. Resting-state fMRI allows reliable analysis of all functional networks with a single study and is inherently independent of factors affecting task performance. In this review, the authors provide a summary of the theory and methods for resting-state network mapping. They provide case examples illustrating clinical implementation and discuss limitations of rs-fMRI and review available data regarding performance in comparison to ECS. Finally, they discuss novel opportunities for future clinical applications and prospects for rs-fMRI beyond mapping of regions to avoid during surgery but, instead, as a tool to guide novel network-based therapies.

Facial motor evoked potential with paired transcranial magnetic stimulation: prognostic value following microvascular decompression for hemifacial spasm.

OBJECTIVE: Microvascular decompression (MVD) is widely considered the treatment of choice for hemifacial spasm (HFS), but not all patients immediately benefit from it. Numerous electrophysiological tests have been employed to monitor the integrity of the facial nerve prior to, during, and after MVD treatment. The authors sought to verify if facial motor evoked potential (FMEP) with paired transcranial magnetic stimulation (pTMS) can be utilized as a tool to predict prognosis following MVD for HFS. METHODS: FMEP using pTMS was performed preoperatively and postoperatively for 527 HFS patients who underwent an MVD treatment. Various interstimuli intervals (ISIs), which included 2, 10, 20, 25, 30, 75, and 100 msec, were applied for each paired stimulation and pTMS(%) was obtained. A graph of pTMS(%) versus each ISI was drawn for every patient and its pattern was analyzed in accordance with patients' clinical outcomes. RESULTS: With ISIs of 75 and 100 msec, pTMS(%) was physiologically further inhibited, whereas it was relatively facilitated under ISIs of 20, 25, and 30 msec; loss of this specific pattern, that is, further inhibition-relative facilitation, indicated impaired integrity of the facial nerve. Those patients who immediately benefited from an MVD and experienced no relapse tended to show proper restoration of this further inhibition-relative facilitation pattern (p = 0.01). Greater resemblance between the physiological pattern of pTMS(%) and postoperative pTMS(%) was correlated to better outcome (p = 0.019). CONCLUSIONS: A simple linear graph of pTMS(%) versus each ISI may be a helpful tool to predict prognosis for HFS following an MVD.

Deep brain stimulation for the treatment of disorders of consciousness and cognition in traumatic brain injury patients: a review.

Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.

Neuromodulation with transcranial focused ultrasound.

The understanding of brain function and the capacity to treat neurological and psychiatric disorders rest on the ability to intervene in neuronal activity in specific brain circuits. Current methods of neuromodulation incur a tradeoff between spatial focus and the level of invasiveness. Transcranial focused ultrasound (FUS) is emerging as a neuromodulation approach that combines noninvasiveness with focus that can be relatively sharp even in regions deep in the brain. This may enable studies of the causal role of specific brain regions in specific behaviors and behavioral disorders. In addition to causal brain mapping, the spatial focus of FUS opens new avenues for treatments of neurological and psychiatric conditions. This review introduces existing and emerging FUS applications in neuromodulation, discusses the mechanisms of FUS effects on cellular excitability, considers the effects of specific stimulation parameters, and lays out the directions for future work.

Resection of primary motor cortex tumors: feasibility and surgical outcomes.

OBJECTIVE: Brain tumors involving the primary motor cortex are often deemed unresectable due to the potential neurological consequences that result from injury to this region. Nevertheless, we have challenged this dogma for many years and used asleep, as well as awake, intraoperative stimulation mapping to maximize extent of resection. It remains unclear whether these tumors can be resected with acceptable morbidity, whether performing the surgery with the patient awake or asleep impacts extent of resection, and how stimulation mapping influences outcomes. METHODS: A retrospective chart review was performed on the senior author's cohort to identify patients treated between 1998 and 2016 who underwent resection of tumors that were located within the primary motor cortex. Clinical notes, operative reports, and radiographic images were reviewed to identify intraoperative stimulation mapping findings and functional outcomes following tumor resection. Extent of resection was quantified volumetrically. Characteristics of patients were analyzed to identify factors associated with postoperative motor deficits. RESULTS: Forty-nine patients underwent 53 resections of tumors located primarily within the motor cortex. Stimulation mapping was performed in all cases. Positive cortical sites for motor response were identified in 91% of cases, and subcortical sites in 74%. Awake craniotomy was performed in 65% of cases, while 35% were done under general anesthesia. The mean extent of resection was 91%. There was no statistically significant difference in extent of resection in cases done awake compared with those done under general anesthesia. New or worsened postoperative motor deficits occurred in 32 patients (60%), and 20 patients (38%) had a permanent deficit. Of the permanent deficits, 14 were mild, 4 were moderate, and 2 were severe (3.8% of cases). Decreased intraoperative motor response and diffusion restriction on postoperative MRI were associated with permanent deficit. Awake motor mapping surgery was associated with increased diffusion signal on postoperative MRI. CONCLUSIONS: Resection of tumors from the primary motor cortex is associated with an increased risk of motor deficit, but most of these deficits are transient or mild and have little functional impact. Excellent extent of resection can be achieved with intraoperative stimulation mapping, suggesting that these tumors are indeed amenable to resection and should not be labeled unresectable. Injury to small perforating or en passage blood vessels was the most common cause of infarction that led to moderate or severe deficits. Awake motor mapping was not superior to mapping done under general anesthesia with regard to long-term functional outcome.

Resection of gliomas deemed inoperable by neurosurgeons based on preoperative imaging studies.

OBJECTIVE Maximal safe resection is a primary objective in the management of gliomas. Despite this objective, surgeons and referring physicians may, on the basis of radiological studies alone, assume a glioma to be unresectable. Because imaging studies, including functional MRI, may not localize brain functions (such as language) with high fidelity, this simplistic approach may exclude some patients from what could be a safe resection. Intraoperative direct electrical stimulation (DES) allows for the accurate localization of functional areas, thereby enabling maximal resection of tumors, including those that may appear inoperable based solely on radiological studies. In this paper the authors describe the extent of resection (EOR) and functional outcomes following resections of tumors deemed inoperable by referring physicians and neurosurgeons. METHODS The authors retrospectively examined the cases of 58 adult patients who underwent glioma resection within 6 months of undergoing a brain biopsy of the same lesion at an outside hospital. All patients exhibited unifocal supratentorial disease and preoperative Karnofsky Performance Scale scores ≥ 70. The EOR and 6-month functional outcomes for this population were characterized. RESULTS Intraoperative DES mapping was performed on 96.6% (56 of 58) of patients. Nearly half of the patients (46.6%, 27 of 58) underwent an awake surgical procedure with DES. Overall, the mean EOR was 87.6% ± 13.6% (range 39.0%-100%). Gross-total resection (resection of more than 99% of the preoperative tumor volume) was achieved in 29.3% (17 of 58) of patients. Subtotal resection (95%-99% resection) and partial resection (PR; < 95% resection) were achieved in 12.1% (7 of 58) and 58.6% (34 of 58) of patients, respectively. Of the cases that involved PR, the mean EOR was 79.4% ± 12.2%. Six months after surgery, no patient was found to have a new postoperative neurological deficit. The majority of patients (89.7%, 52 of 58) were free of neurological deficits both pre- and postoperatively. The remainder of patients exhibited either residual but stable deficits (5.2%, 3 of 58) or complete correction of preoperative deficits (5.2%, 3 of 58). CONCLUSIONS The use of DES enabled maximal safe resections of gliomas deemed inoperable by referring neurosurgeons. With rare exceptions, tumor resectability cannot be determined solely by radiological studies.

Efficacy of deep rTMS for neuropathic pain in the lower limb: a randomized, double-blind crossover trial of an H-coil and figure-8 coil.

OBJECTIVE Electrical motor cortex stimulation can relieve neuropathic pain (NP), but its use requires patients to undergo an invasive procedure. Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) using a figure-8 coil can relieve NP noninvasively, but its ability to relieve lower limb pain is still limited. Deep rTMS using an H-coil can effectively stimulate deep brain regions and has been widely used for the treatment of various neurological diseases; however, there have been no clinical studies comparing the effectiveness of figure-8 coils and H-coils. This study assessed the clinical effectiveness of 5 once-daily stimulations with H-coils and figure-8 coils in patients with NP. METHODS This randomized, double-blind, 3-way crossover trial examined 18 patients with NP who sequentially received 3 types of stimulations in the M1 for 5 consecutive days; each 5-day stimulation period was followed by a 17-day follow-up period before crossing over to the next type of stimulation. During each rTMS session, patients received a 5-Hz rTMS to the M1 region corresponding to the painful lower limb. The visual analog scale (VAS) and the Japanese version of the short-form McGill Pain Questionnaire 2 (SF-MPQ2-J) were used to measure pain intensity. The primary outcome was VAS score reduction immediately after and 1 hour after intervention. RESULTS Both the VAS and SF-MPQ2-J showed significant pain improvement immediately after deep rTMS with an H-coil as compared with the sham group (p < 0.001 and p = 0.049, respectively). However, neither outcome measure showed significant pain improvement when using a figure-8 coil. The VAS also showed significant pain improvement 1 hour after deep rTMS with an H-coil (p = 0.004) but not 1 hour after rTMS using a figure-8 coil. None of the patients exhibited any serious adverse events. CONCLUSIONS The current findings suggest that the use of deep rTMS with an H-coil in the lower limb region of the M1 in patients with NP was tolerable and could provide significant short-term pain relief. Clinical trial registration no.: UMIN000010536 ( http://www.umin.ac.jp/ctr/ ).

Language pathway tracking: comparing nTMS-based DTI fiber tracking with a cubic ROIs-based protocol.

OBJECTIVE Diffusion tensor imaging (DTI) fiber tracking (FT) has been widely used in glioma surgery in recent years. It can provide helpful information about subcortical structures, especially in patients with eloquent space-occupying lesions. This study compared the newly developed navigated transcranial magnetic stimulation (nTMS)-based DTI FT of language pathways with the most reproducible protocol for language pathway tractography, using cubic regions of interest (ROIs) for the arcuate fascicle. METHODS Thirty-seven patients with left-sided perisylvian lesions underwent language mapping by repetitive nTMS. DTI FT was performed using the cubic ROIs-based protocol and the authors' nTMS-based DTI FT approach. The same minimal fiber length and fractional anisotropy were chosen (50 mm and 0.2, respectively). Both protocols were performed with standard clinical tractography software. RESULTS Both methods visualized language-related fiber tracts (i.e., corticonuclear tract, arcuate fascicle, uncinate fascicle, superior longitudinal fascicle, inferior longitudinal fascicle, arcuate fibers, commissural fibers, corticothalamic fibers, and frontooccipital fascicle) in all 37 patients. Using the cubic ROIs-based protocol, 39.9% of these language-related fiber tracts were detected in the examined patients, as opposed to 76.0% when performing nTMS-based DTI FT. For specifically tracking the arcuate fascicle, however, the cubic ROIs-based approach showed better results (97.3% vs 75.7% with nTMS-based DTI FT). CONCLUSIONS The cubic ROIs-based protocol was designed for arcuate fascicle tractography, and this study shows that it is still useful for this intention. However, superior results were obtained using the nTMS-based DTI FT for visualization of other language-related fiber tracts.

Intermittent bilateral deep brain stimulation of the nucleus accumbens shell reduces intravenous methamphetamine intake and seeking in Wistar rats.

OBJECTIVE There is increasing interest in neuromodulation for addiction. Methamphetamine abuse is a global health epidemic with no proven treatment. The objective of this study was to examine the effects of intermittent nucleus accumbens shell (AcbSh) deep brain stimulation (DBS) on operant methamphetamine intake and on methamphetamine seeking when stimulation is delivered in an environment different from that of drug use. METHODS Eighteen rats were implanted with intravenous (IV) catheters and bilateral AcbSh electrodes and subsequently underwent daily sessions in 2-lever (active/methamphetamine and inactive/no reward) operant chambers to establish IV methamphetamine self-administration. After stable responding was achieved, 3 hours of DBS or sham treatment was administered (sham: 0 µA, n = 8; active: 200 µA, n = 10) in a separate nondrug environment prior to the daily operant sessions for 5 consecutive days. Immediately following each DBS/sham treatment, rats were placed in the operant chambers to examine the effects of remote stimulation on methamphetamine intake. After the 5 days of therapy were finished, rats reestablished a posttreatment baseline, followed by extinction training, abstinence, and 1 day of relapse testing to assess methamphetamine-seeking behavior. RESULTS There was a decrease in total methamphetamine intake in rats receiving active DBS versus sham on Days 1 (42%) and 2 (44%). Methamphetamine administration returned to baseline levels following the cessation of DBS therapy. Compared with baseline drug responding, methamphetamine seeking was reduced (57%) in the DBS group but not in the sham group. CONCLUSIONS It is feasible to deliver noncontinuous DBS outside of the drug use environment with a resultant decrease in IV methamphetamine intake and seeking. The AcbSh is a neuroanatomical substrate for psychostimulant reinforcement and may be a target for intermittent neuromodulatory therapies that could be administered during brief periods of sobriety.

Functional cortical reorganization in cases of cervical spondylotic myelopathy and changes associated with surgery.

OBJECTIVE The physiological mechanisms underlying the recovery of motor function after cervical spondylotic myelopathy (CSM) surgery are poorly understood. Neuronal plasticity allows neurons to compensate for injury and disease and to adjust their activities in response to new situations or changes in their environment. Cortical reorganization as well as improvement in corticospinal conduction happens during motor recovery after stroke and spinal cord injury. In this study the authors aimed to understand the cortical changes that occur due to CSM and following CSM surgery and to correlate these changes with functional recovery by using blood oxygen level-dependent (BOLD) functional MRI (fMRI). METHODS Twenty-two patients having symptoms related to cervical cord compression due to spondylotic changes along with 12 age- and sex-matched healthy controls were included in this study. Patients underwent cervical spine MRI and BOLD fMRI at 1 month before surgery (baseline) and 6 months after surgery. RESULTS Five patients were excluded from analysis because of technical problems; thus, 17 patients made up the study cohort. The mean overall modified Japanese Orthopaedic Association score improved in patients following surgery. Mean upper-extremity, lower-extremity, and sensory scores improved significantly. In the preoperative patient group the volume of activation (VOA) was significantly higher than that in controls. The VOA after surgery was reduced as compared with that before surgery, although it remained higher than that in the control group. In the preoperative patient group, activations were noted only in the left precentral gyrus (PrCG). In the postoperative group, activations were seen in the left postcentral gyrus (PoCG), as well as the PrCG and premotor and supplementary motor cortices. In postoperative group, the VOA was higher in both the PrCG and PoCG as compared with those in the control group. CONCLUSIONS There is over-recruitment of sensorimotor cortices during nondexterous relative to dexterous movements before surgery. After surgery, there was recruitment of other cortical areas such as the PoCG and premotor and supplementary motor cortices, which correlated with improvement in dexterity, but activation in these areas was greater than that found in controls. The results show that improvement in dexterity and finer movements of the upper limbs is associated with recruitment areas other than the premotor cortex to compensate for the damage in the cervical spinal cord.

Neurorestoration after stroke.

Recent advancements in stem cell biology and neuromodulation have ushered in a battery of new neurorestorative therapies for ischemic stroke. While the understanding of stroke pathophysiology has matured, the ability to restore patients' quality of life remains inadequate. New therapeutic approaches, including cell transplantation and neurostimulation, focus on reestablishing the circuits disrupted by ischemia through multidimensional mechanisms to improve neuroplasticity and remodeling. The authors provide a broad overview of stroke pathophysiology and existing therapies to highlight the scientific and clinical implications of neurorestorative therapies for stroke.

Intraoperative mapping during repeat awake craniotomy reveals the functional plasticity of adult cortex.

OBJECT To avoid iatrogenic injury during the removal of intrinsic cerebral neoplasms such as gliomas, direct electrical stimulation (DES) is used to identify cortical and subcortical white matter pathways critical for language, motor, and sensory function. When a patient undergoes more than 1 brain tumor resection as in the case of tumor recurrence, the use of DES provides an unusual opportunity to examine brain plasticity in the setting of neurological disease. METHODS The authors examined 561 consecutive cases in which patients underwent DES mapping during surgery forglioma resection. "Positive" and "negative" sites-discrete cortical regions where electrical stimulation did (positive) or did not (negative) produce transient sensory, motor, or language disturbance-were identified prior to tumor resection and documented by intraoperative photography for categorization into functional maps. In this group of 561 patients, 18 were identified who underwent repeat surgery in which 1 or more stimulation sites overlapped with those tested during the initial surgery. The authors compared intraoperative sensory, motor, or language mapping results between initial and repeat surgeries, and evaluated the clinical outcomes for these patients. RESULTS A total of 117 sites were tested for sensory (7 sites, 6.0%), motor (9 sites, 7.7%), or language (101 sites, 86.3%) function during both initial and repeat surgeries. The mean interval between surgical procedures was 4.1 years. During initial surgeries, 95 (81.2%) of 117 sites were found to be negative and 22 (18.8%) of 117 sites were found to be positive. During repeat surgeries, 103 (88.0%) of 117 sites were negative and 14 (12.0%) of 117 were positive. Of the 95 sites that were negative at the initial surgery, 94 (98.9%) were also negative at the repeat surgery, while 1 (1.1%) site was found to be positive. Of the 22 sites that were initially positive, 13 (59.1%) remained positive at repeat surgery, while 9 (40.9%) had become negative for function. Overall, 6 (33.3%) of 18 patients exhibited loss of function at 1 or more motor or language sites between surgeries. Loss of function at these sites was not associated with neurological impairment at the time of repeat surgery, suggesting that neurological function was preserved through neural circuit reorganization or activation of latent functional pathways. CONCLUSIONS The adult central nervous system reorganizes motor and language areas in patients with glioma. Ultimately, adult neural plasticity may help to preserve motor and language function in the presence of evolving structural lesions. The insight gained from this subset of patients has implications for our understanding of brain plasticity in clinical settings.

Neurosurgery for schizophrenia: an update on pathophysiology and a novel therapeutic target.

The main objectives of this review were to provide an update on the progress made in understanding specific circuit abnormalities leading to psychotic symptoms in schizophrenia and to propose rational targets for therapeutic deep brain stimulation (DBS). Refractory schizophrenia remains a major unsolved clinical problem, with 10%-30% of patients not responding to standard treatment options. Progress made over the last decade was analyzed through reviewing structural and functional neuroimaging studies in humans, along with studies of animal models of schizophrenia. The authors reviewed theories implicating dysfunction in dopaminergic and glutamatergic signaling in the pathophysiology of the disorder, paying particular attention to neurosurgically relevant nodes in the circuit. In this context, the authors focused on an important pathological circuit involving the associative striatum, anterior hippocampus, and ventral striatum, and discuss the possibility of targeting these nodes for therapeutic neuromodulation with DBS. Finally, the authors examined ethical considerations in the treatment of these vulnerable patients. The functional anatomy of neural circuits relevant to schizophrenia remains of great interest to neurosurgeons and psychiatrists and lends itself to the development of specific targets for neuromodulation. Ongoing progress in the understanding of these structures will be critical to the development of potential neurosurgical treatments of schizophrenia.

Anterior cingulate implants for tinnitus: report of 2 cases.

Tinnitus can be distressful, and tinnitus distress has been linked to increased beta oscillatory activity in the dorsal anterior cingulate cortex (dACC). The amount of distress is linked to alpha activity in the medial temporal lobe (amygdala and parahippocampal area), as well as the subgenual (sg)ACC and insula, and the functional connectivity between the parahippocampal area and the sgACC at 10 and 11.5 Hz. The authors describe 2 patients with very severely distressing intractable tinnitus who underwent transcranial magnetic stimulation (TMS) with a double-cone coil targeting the dACC and subsequent implantation of electrodes on the dACC. One of the patients responded to the implant and one did not, even though phenomenologically they both expressed the same tinnitus loudness and distress. The responder has remained dramatically improved for more than 2 years with 6-Hz burst stimulation of the dACC. The 2 patients differed in functional connectivity between the area of the implant and a tinnitus network consisting of the parahippocampal area as well as the sgACC and insula; that is, the responder had increased functional connectivity between these areas, whereas the nonresponder had decreased functional connectivity between these areas. Only the patient with increased functional connectivity linked to the target area of repetitive TMS or implantation might transmit the stimulation current to the entire tinnitus network and thus clinically improve.

Electrophysiological assessments of the motor pathway in diabetic patients with compressive cervical myelopathy.

OBJECT: The occurrence of compressive cervical myelopathy (CCM) increases in adults over 50 years of age. In addition, diabetes mellitus (DM) is a frequent comorbidity for people of this age and may impact the severity of CCM. The authors assessed motor pathway function in diabetic patients with CCM to investigate the correlation between electrophysiological parameters and clinical symptoms. METHODS: Motor evoked potentials (MEPs) were measured from the abductor digiti minimi muscle (ADM) and the abductor hallucis muscle (AH) following transcranial magnetic stimulation, as were M- and F-waves following electrical stimulation of the ulnar and tibial nerves, in 22 patients with CCM and diabetes mellitus (DM) who had not experienced symptomatic diabetic neuropathy (CCM-DM group), in 92 patients with CCM alone (CCM group), and in 24 healthy adults (control group). The peripheral conduction time (PCT; measured from the ADM and AH) was calculated as follows: (M-wave latency + F-wave latency -1)/2. The central motor conduction time (CMCT; measured from the ADM and AH) was calculated by subtracting the PCT from the onset latency of the MEPs. The Japanese Orthopaedic Association (JOA) score for cervical myelopathy was obtained before and 1 year after surgery as a clinical outcome measure. RESULTS: MEP, PCT, and CMCT parameters in the CCM-DM and CCM groups were significantly longer than those in the control group (p = 0.000-0.007). The PCTs in the CCM-DM group were significantly longer than those in the CCM group (p = 0.001-0.003). No significant differences were detected in the MEP and CMCT parameters between the CCM-DM and CCM groups (p = 0.080-1.000). The JOA score before surgery in the CCM-DM group was 10.7 ± 2.0 points and was significantly lower than that in the CCM group (12.2 ± 2.5 points, p = 0.015). In the CCM-DM group, JOA scores before surgery correlated with MEP-AH (r = -0.610, p = 0.012) and PCT-AH (r = -0.676, p = 0.004) values, but not with CMCT values, while the JOA scores were related to both MEP and CMCT parameters in the CCM group. The JOA scores improved to 13.8 ± 2.2 points after surgery (p = 0.001) and correlated with MEP-AH (r = -0.667, p = 0.005) and PCT-AH (r = -0.611, p = 0.012) in the CCM-DM group. CONCLUSIONS: The results suggest that MEP, PCT, and CMCT parameters each reveal abnormalities in the upper and lower motor neurons even in patients with DM. The results also show a prolonged PCT in CCM-DM patients, despite having no history of diabetic neuropathy. Corticospinal tract impairments are similar between CCM and CCM-DM patients, while the JOA score of the CCM-DM patients is lower than that in the CCM patients. The JOA score in CCM-DM patients may be influenced by additional impairments in peripheral nerves or other diabetic complications. These electrophysiological studies may be useful for screening motor pathway function for CCM in patients with DM.

Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study.

OBJECT: Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions. METHODS: Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions. RESULTS: The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%). CONCLUSIONS: Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.

Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation.

OBJECT: Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods. METHODS: The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery. RESULTS: The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%. CONCLUSIONS: In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.

Neurostimulation for traumatic brain injury.

Traumatic brain injury (TBI) remains a significant public health problem and is a leading cause of death and disability in many countries. Durable treatments for neurological function deficits following TBI have been elusive, as there are currently no FDA-approved therapeutic modalities for mitigating the consequences of TBI. Neurostimulation strategies using various forms of electrical stimulation have recently been applied to treat functional deficits in animal models and clinical stroke trials. The results from these studies suggest that neurostimulation may augment improvements in both motor and cognitive deficits after brain injury. Several studies have taken this approach in animal models of TBI, showing both behavioral enhancement and biological evidence of recovery. There have been only a few studies using deep brain stimulation (DBS) in human TBI patients, and future studies are warranted to validate the feasibility of this technique in the clinical treatment of TBI. In this review, the authors summarize insights from studies employing neurostimulation techniques in the setting of brain injury. Moreover, they relate these findings to the future prospect of using DBS to ameliorate motor and cognitive deficits following TBI.

Electrophysiological evidence of functional improvement in the corticospinal tract after laminoplasty in patients with cervical compressive myelopathy: clinical article.

OBJECT: Cervical laminoplasty is a surgical procedure for cervical compressive myelopathy (CCM), and satisfactory outcomes have been reported. However, few reports have examined the pathophysiology of improvements in spinal cord function. The aim of this study was to investigate the variation in central motor conduction time (CMCT) before and after cervical laminoplasty in patients with CCM. METHODS: Motor evoked potentials (MEPs) following transcranial magnetic stimulation and compound muscle action potentials (CMAPs) and F-waves following electrical stimulation of the ulnar and tibial nerves at the wrist and ankle were measured from the abductor digiti minimi muscle (ADM) and abductor hallucis muscle (AH) in 42 patients with CCM before and 1 year after cervical laminoplasty. The peripheral conduction time (PCT) was calculated as follows: (latency of CMAPs + latency of F-waves - 1)/2. The CMCT was calculated by subtracting the PCT from the onset latency of the MEPs. The CMCT recovery ratio was defined and calculated as the ratio of CMCT values 1 year after surgery to those before surgery. The CMCT data were analyzed as longer or shorter CMCT between the patients' right and left ADMs and AHs. The Japanese Orthopaedic Association (JOA) score for cervical myelopathy was obtained as a clinical outcome before and 1 year after surgery. The recovery rate (RR) 1 year after surgery was calculated using the following formula: (postoperative JOA score 1 year after surgery - preoperative JOA score)/(17 - preoperative JOA score) × 100. Correlations among CMCT parameters, patient age, JOA score, and RR were determined. RESULTS: The longer and shorter CMCTs from the ADM (longer, p = 0.000; shorter, p = 0.008) and the longer CMCT from the AH (longer, p = 0.000) before surgery decreased significantly 1 year after surgery; the shorter CMCT from the AH did not significantly differ (shorter, p = 0.078). The mean JOA score before surgery was 10.1 ± 3.0 and improved significantly to 12.9 ± 2.7 at 1 year after surgery (p = 0.000). The mean CMCT recovery ratio and RR were 0.91 ± 0.18 and 0.43 ± 0.27, respectively. The longer/shorter CMCT parameters in the ADM and AH before or 1 year after surgery correlated significantly with the JOA score both before and 1 year after surgery. The CMCT recovery ratio from the longer CMCT in the ADM correlated significantly with the RR (r = - 3090, p = 0.011). There were no significant correlations between age and any CMCT parameters or CMCT recovery ratios. CONCLUSIONS: These results suggest that cervical laminoplasty improves corticospinal tract function 1 year after surgery, which may be one of the reasons for the JOA score improvements in patients with CCM. The degree of improvement in corticospinal tract function did not correlate with patient age in this case series. The results demonstrated quantitative evidence of the pathophysiology of functional recovery in the corticospinal tract following cervical laminoplasty in patients with CCM.

Surgery for a giant arteriovenous malformation without motor deterioration: preoperative transcranial magnetic stimulation in a non-cooperative patient.

Transcranial magnetic stimulation (TMS) is a noninvasive activation method that is increasingly used for motor mapping. Preoperative functional mapping in vascular surgery is not routinely performed; however, in cases of high-grade arteriovenous malformations (AVMs), it could play a role in preoperative decision making. A 16-year-old male was suffering from a giant, right-sided insular, Spetzler-Martin Grade V AVM. This patient's history included 3 hemorrhagic strokes in the past 3 years, resulting in Medical Research Council Grade 2-3 (proximal) and 2-4 (distal) paresis of the left side of the body and hydrocephalus requiring a ventriculoperitoneal shunt. Preoperative TMS showed absent contralateral innervation of the remaining left-sided motor functions. Subsequently, the AVM was completely resected without any postoperative increase of the left-sided paresis. This case shows that TMS can support decision making in AVM treatment by mapping motor functions.