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Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease., Methods: This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396., Findings: Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p<0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation., Interpretation: This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes., Funding: Boston Scientific., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Recognition of human behavioral activities using local field potential (LFP) signals recorded from the Subthalamic Nuclei (STN) has applications in developing the next generation of deep brain stimulation (DBS) systems. DBS therapy is often used for patients with Parkinson's disease (PD) when medication cannot effectively tackle patients' motor symptoms. A DBS system capable of adaptively adjusting its parameters based on patients' activities may optimize therapy while reducing the stimulation side effects and improving the battery life., Method: STN-LFP reveals motor and language behavior, making it a reliable source for behavior classification. This paper presents LFP-Net, an automated machine learning framework based on deep convolutional neural networks (CNN) for classification of human behavior using the time-frequency representation of STN-LFPs within the beta frequency range. CNNs learn different features based on the beta power patterns associated with different behaviors. The features extracted by the CNNs are passed through fully connected layers and then to the softmax layer for classification., Results: Our experiments on ten PD patients performing three behavioral tasks including "button press", "target reaching", and "speech" show that the proposed approach obtains an average classification accuracy of ∼88 %. Comparison with existing methods: The proposed method outperforms other state-of-the-art classification methods based on STN-LFP signals. Compared to well-known deep neural networks such as AlexNet, our approach gives a higher accuracy using significantly fewer parameters., Conclusions: CNNs show a high performance in decoding the brain neural response, which is crucial in designing the automatic brain-computer interfaces and closed-loop systems., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This paper presents the results of our recent work on studying the effects of deep brain stimulation (DBS) and medication on the dynamics of brain local field potential (LFP) signals used for behavior analysis of patients with Parkinson's disease (PD). DBS is a technique used to alleviate the severe symptoms of PD when pharmacotherapy is not very effective. Behavior recognition from the LFP signals recorded from the subthalamic nucleus (STN) has application in developing closed-loop DBS systems, where the stimulation pulse is adaptively generated according to subjects' performing behavior. Most of the existing studies on behavior recognition that use STN-LFPs are based on the DBS being "off". This paper discovers how the performance and accuracy of automated behavior recognition from the LFP signals are affected under different paradigms of stimulation on/off. We first study the notion of beta power suppression in LFP signals under different scenarios (stimulation on/off and medication on/off). Afterward, we explore the accuracy of support vector machines in predicting human actions ("button press" and "reach") using the spectrogram of STN-LFP signals. Our experiments on the recorded LFP signals of three subjects confirm that the beta power is suppressed significantly when the patients take medication (p-value < 0.002) or stimulation (p-value < 0.0003). The results also show that we can classify different behaviors with a reasonable accuracy of 85% even when the high-amplitude stimulation is applied.

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become standard care for the surgical treatment of Parkinson's disease (PD). Reliable interpretation of microelectrode recording (MER) data, used to guide DBS implantation surgery, requires expert electrophysiological evaluation. Recent efforts have endeavored to use electrophysiological signals for automatic detection of relevant brain structures and optimal implant target location.The authors conducted an observational case-control study to evaluate a software package implemented on an electrophysiological recording system to provide online objective estimates for entry into and exit from the STN. In addition, they evaluated the accuracy of the software in selecting electrode track and depth for DBS implantation into STN, which relied on detecting changes in spectrum activity., Methods: Data were retrospectively collected from 105 MER-guided STN-DBS surgeries (4 experienced neurosurgeons; 3 sites), in which estimates for entry into and exit from the STN, DBS track selection, and implant depth were compared post hoc between those determined by the software and those determined by the implanting neurosurgeon/neurophysiologist during surgery., Results: This multicenter study revealed submillimetric agreement between surgeon/neurophysiologist and software for entry into and exit out of the STN as well as optimal DBS implant depth., Conclusions: The results of this study demonstrate that the software can reliably and accurately estimate entry into and exit from the STN and select the track corresponding to ultimate DBS implantation.

Deep brain stimulation (DBS) provides significant therapeutic benefit for movement disorders, such as Parkinson's disease (PD). Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and side effects by adjusting stimulation parameters based on patient's behavior. Subthalamic nucleus (STN) local field potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. In this paper, we introduce a behavior detection method capable of asynchronously detecting the finger movements of PD patients. Our study indicates that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from the STN. We utilize a non-linear regression method to measure this inter-hemispheric connectivity for detecting finger movement. Our experimental results, using the recordings from 11 patients with PD, demonstrate that this approach is applicable for behavior detection in the majority of subjects (average area under curve of 70±12%).

Background: Classification of human behavior from brain signals has potential application in developing closed-loop deep brain stimulation (DBS) systems. This paper presents a human behavior classification using local field potential (LFP) signals recorded from subthalamic nuclei (STN)., Method: A hierarchical classification structure is developed to perform the behavior classification from LFP signals through a multi-level framework (coarse to fine). At each level, the time-frequency representations of all six signals from the DBS leads are combined through an MKL-based SVM classifier to classify five tasks (speech, finger movement, mouth movement, arm movement, and random segments). To lower the computational cost, we alternatively use the inter-hemispheric synchronization of the LFPs to make three pairs out of six bipolar signals. Three classifiers are separately trained at each level of the hierarchical approach, which lead to three labels. A fusion function is then developed to combine these three labels and determine the label of the corresponding trial., Results: Using all six LFPs with the proposed hierarchical approach improves the classification performance. Moreover, the synchronization-based method reduces the computational burden considerably while the classification performance remains relatively unchanged., Comparison With Existing Methods: Our experiments on two different datasets recorded from nine subjects undergoing DBS surgery show that the proposed approaches remarkably outperform other methods for behavior classification based on LFP signals., Conclusion: The LFP signals acquired from STNs contain useful information for recognizing human behavior. This can be a precursor for designing the next generation of closed-loop DBS systems., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Subthalamic nucleus (STN) local field potentials (LFP) are neural signals that have been shown to reveal motor and language behavior, as well as pathological parkinsonian states. We use a research-grade implantable neurostimulator (INS) with data collection capabilities to record STN-LFP outside the operating room to determine the reliability of the signals over time and assess their dynamics with respect to behavior and dopaminergic medication. Seven subjects were implanted with the recording augmented deep brain stimulation (DBS) system, and bilateral STN-LFP recordings were collected in the clinic over twelve months. Subjects were cued to perform voluntary motor and language behaviors in on and off medication states. The STN-LFP recorded with the INS demonstrated behavior-modulated desynchronization of beta frequency (13-30 Hz) and synchronization of low gamma frequency (35-70 Hz) oscillations. Dopaminergic medication did not diminish the relative beta frequency oscillatory desynchronization with movement. However, movement-related gamma frequency oscillatory synchronization was only observed in the medication on state. We observed significant inter-subject variability, but observed consistent STN-LFP activity across recording systems and over a one-year period for each subject. These findings demonstrate that an INS system can provide robust STN-LFP recordings in ambulatory patients, allowing for these signals to be recorded in settings that better represent natural environments in which patients are in a variety of medication states., Competing Interests: A.O.H. receives consulting and research support from Medtronic, Inc. The other authors declare no conflict of interest.

Deep Brain Stimulation (DBS) has gained increasing attention as an effective method to mitigate Parkinson's disease (PD) disorders. Existing DBS systems are open-loop such that the system parameters are not adjusted automatically based on patient's behavior. Classification of human behavior is an important step in the design of the next generation of DBS systems that are closed-loop. This paper presents a classification approach to recognize such behavioral tasks using the subthalamic nucleus (STN) Local Field Potential (LFP) signals. In our approach, we use the time-frequency representation (spectrogram) of the raw LFP signals recorded from left and right STNs as the feature vectors. Then these features are combined together via Support Vector Machines (SVM) with Multiple Kernel Learning (MKL) formulation. The MKL-based classification method is utilized to classify different tasks: button press, mouth movement, speech, and arm movement. Our experiments show that the lp-norm MKL significantly outperforms single kernel SVM-based classifiers in classifying behavioral tasks of five subjects even using signals acquired with a low sampling rate of 10 Hz. This leads to a lower computational cost.

Deep Brain Stimulation (DBS) provides significant therapeutic benefit for movement disorders such as Parkinson's disease. Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and DBS side effects. In such systems, DBS parameters are adjusted based on patient's behavior, which means that behavior detection is a major step in designing such systems. Various physiological signals can be used to recognize the behaviors. Subthalamic Nucleus (STN) Local Field Potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. A practical behavior detection method should be able to detect behaviors asynchronously meaning that it should not use any prior knowledge of behavior onsets. In this paper, we introduce a behavior detection method that is able to asynchronously detect the finger movements of Parkinson patients. As a result of this study, we learned that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from STN. We used non-linear regression method to measure this connectivity and use it to detect the finger movements. Performance of this method is evaluated using Receiver Operating Characteristic (ROC).

Cortical networks and quantitative measures of connectivity are integral to the study of brain function. Despite lack of direct connections between left and right subthalamic nuclei (STN), there are apparent physiological connections. During clinical examination of patients with Parkinson's disease (PD), this connectivity is exploited to enhance signs of PD, yet our understanding of this connectivity is limited. We hypothesized that movement leads to synchronization of neural oscillations in bilateral STN, and we implemented phase coherence, a measure of phase-locking between cortical sites in a narrow frequency band, to demonstrate this synchronization. We analyzed task specific phase synchronization and causality between left and right STN local field potentials (LFPs) recorded from both hemispheres simultaneously during a cued movement task in four subjects with PD who underwent Deep Brain Stimulation (DBS) surgery. We used a data driven approach to determine inter-hemispheric channel pairs and frequencies with a task specific increase in phase locking.We found significant phase locking between hemispheres in alpha frequency (8-12 Hz) in all subjects concurrent with movement of either hand. In all subjects, phase synchronization increased over baseline upon or prior to hand movement onset and lasted until the motion ceased. Left and right hand movement showed similar patterns. Granger causality (GC) at the phase-locking frequencies between synchronized electrodes revealed a unidirectional causality from right to left STN regardless of which side was moved.Phase synchronization across hemispheres between basal ganglia supports existence of a bilateral network having lateralized regions of specialization for motor processing. Our results suggest this bilateral network is activated by a unilateral motor program. Understanding phase synchronization in natural brain functions is critical to development of future DBS systems that augment goal directed behavioral function.

Current DBS therapy delivers a train of electrical pulses at set stimulation parameters. This open-loop design is effective for movement disorders, but therapy may be further optimized by a closed loop design. The technology to record biosignals has outpaced our understanding of their relationship to the clinical state of the whole person. Neuronal oscillations may represent or facilitate the cooperative functioning of brain ensembles, and may provide critical information to customize neuromodulation therapy. This review addresses advances to date, not of the technology per se, but of the strategies to apply neuronal signals to trigger or modulate stimulation systems., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Deep Brain Stimulation (DBS) has been a successful technique for alleviating Parkinson's disease (PD) symptoms especially for whom drug therapy is no longer efficient. Existing DBS therapy is open-loop, providing a time invariant stimulation pulse train that is not customized to the patient's current behavioral task. By customizing this pulse train to the patient's current task the side effects may be suppressed. This paper introduces a method for single trial recognition of the patient's current task using the local field potential (LFP) signals. This method utilizes wavelet coefficients as features and support vector machine (SVM) as the classifier for recognition of a selection of behaviors: speech, motor, and random. The proposed method is 82.4% accurate for the binary classification and 73.2% for classifying three tasks. These algorithms will be applied in a closed loop feedback control system to optimize DBS parameters to the patient's real time behavioral goals.

Regionalization of language function within the left thalamus has been established with language and verbal memory effects of thalamic stimulation during surgery for movement disorders. Three distinct language effects of thalamic stimulation were established: anomia from posterior ventrolateral (VL) and pulvinar regions; perseveration from mid-VL regions; and, a memory and acceleratory effect from anterior VL, described as a "specific alerting response" (SAR). These studies are reviewed in context of pertinent contemporary and recent literature on the thalamic role in memory and language. An explicit mechanistic model for the anomia and SAR effect is proposed. The suggested model for the SAR effect involves secondary switching in the striatum by the activation of thalamostriatal projections, whereas the anomia effect implicates the disruption of the cortical synchronization action of pulvinar via the cortico-pulvinar-cortical projection system. Further experimental data is required to firmly establish these mechanisms., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre- and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: Exclusive right hemisphere language lateralization is rarely observed in the Wada angiography results of epilepsy surgery patients. Cortical stimulation mapping (CSM) is infrequently performed in such patients, as most undergo nondominant left hemisphere resections, which are presumed not to pose any risk to language. Early language reorganization is typically assumed in such individuals, taking left hemisphere epileptiform activity as confirmation of change resulting from a pathologic process. We present data from CSM and Wada studies demonstrating that right hemisphere language occurs in the absence of left hemisphere pathology, suggesting it can exist as a normal, but rare variant, in some individuals. Furthermore, these data confirm the Wada test findings of atypical dominance., Methods: Cortical stimulation mapping data were examined for all right hemisphere surgical patients with right hemisphere speech at our center between 1974 and 2006. Of 1,209 interpretable Wada procedures, 89 patients (7.4%) had exclusive right hemisphere speech, and 21 (1.7%) of these patients underwent surgery involving the right hemisphere. Language site location was determined by examining intraoperative photographs, and site distribution was statistically compared to published findings from left hemisphere language dominant patients., Key Findings: Language cortex was identified in the right hemisphere during CSM for all patients with available data. All sites could be classified in superior or middle temporal gyri, inferior parietal lobe, or inferior frontal gyrus, all of which were common zones where language was identified in the left hemisphere dominant comparison sample., Significance: Results suggest that the Wada procedure is a valid measure for identifying right hemisphere language processing without any false lateralization found in the patients mapped with CSM (i.e., a positive Wada is 100% sensitive for finding right hemisphere language sites), and that the distribution of language sites is consistent across right hemisphere and left hemisphere language dominant patients, supporting the theory that right hemisphere language can occur as a normal variant of language lateralization., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Object: Posttraumatic epilepsy (PTE) is a common cause of medically intractable epilepsy. While much of PTE is extratemporal, little is known about factors associated with good outcomes in extratemporal resections in medically intractable PTE. The authors investigated and characterized the long-term outcome and patient factors associated with outcome in this population., Methods: A single-institution retrospective query of all epilepsy surgeries at Regional Epilepsy Center at the University of Washington was performed for a 17-year time span with search terms indicative of trauma or brain injury. The query was limited to adult patients who underwent an extratemporal resection (with or without temporal lobectomy), in whom no other cause of epilepsy could be identified, and for whom minimum 1-year follow-up data were available. Surgical outcomes (in terms of seizure reduction) and clinical data were analyzed and compared., Results: Twenty-one patients met inclusion and exclusion criteria. In long-term follow-up 6 patients (28%) were seizure-free and an additional 6 (28%) had a good outcome of 2 or fewer seizures per year. Another 5 patients (24%) experienced a reduction in seizures, while only 4 (19%) did not attain significant benefit. The presence of focal encephalomalacia on imaging was associated with good or excellent outcomes in 83%. In 8 patients with the combination of encephalomalacia and invasive intracranial EEG, 5 (62.5%) were found to be seizure free. Normal MRI examinations preoperatively were associated with worse outcomes, particularly when combined with multifocal or poorly localized EEG findings. Two patients suffered complications but none were life threatening or disabling., Conclusions: Many patients with extratemporal PTE can achieve good to excellent seizure control with epilepsy surgery. The risks of complications are acceptably low. Patients with focal encephalomalacia on MRI generally do well. Excellent outcomes can be achieved when extratemporal resection is guided by intracranial EEG electrodes defining the extent of resection.

Signs of Parkinson's disease (PD) are augmented by speech and repetitive motor tasks. The neurophysiological basis for this phenomenon is unknown, but may involve augmentation of β (13-30 Hz) oscillations within the subthalamic nucleus (STN). We hypothesized that speech and motor tasks increase β power in STN and propose a mechanism for clinical observations of worsening motor state during such behaviors. Subjects undergoing deep brain stimulation (DBS) surgery performed tasks while STN local field potential (LFP) data were collected. Power in the β frequency range was analyzed across the entire recording to observe slow shifts related to block design and during time epochs synchronized to behavior to evaluate immediate fluctuations related to task execution. Bilaterally symmetric β event related desynchronization was observed in analysis time-locked to subject motor and speech tasks. We also observed slow shifts of β power associated with blocks of tasks. Repetitive combined speech and motor, and isolated motor blocks were associated with the highest bilateral β power state. Overt speech alone and imagined speech were associated with a low bilateral β power state. Thus, changing behavioral tasks is associated with bilateral switching of β power states. This offers a potential neurophysiologic correlate of worsened PD motor signs experienced during clinical examination with provocative tasks: switching into a high β power state may be responsible for worsening motor states in PD patients when performing unilateral repetitive motor tasks and combined speech and motor tasks. Beta state changes could be chronically measured and potentially used to control closed loop neuromodulatory devices in the future., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

The functional significance of electrical rhythms in the mammalian brain remains uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently decrease in amplitude during movement, and to be altered in many motor diseases. Here we show that the activity of neuronal populations is phase-coupled with the beta rhythm on rapid timescales, and describe how the strength of this relation changes with movement. To investigate the relationship of the beta rhythm to neuronal dynamics, we measured local cortical activity using arrays of subdural electrocorticographic (ECoG) electrodes in human patients performing simple movement tasks. In addition to rhythmic brain processes, ECoG potentials also reveal a spectrally broadband motif that reflects the aggregate neural population activity beneath each electrode. During movement, the amplitude of this broadband motif follows the dynamics of individual fingers, with somatotopically specific responses for different fingers at different sites on the pre-central gyrus. The 12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent within sulcal boundaries and decreases in amplitude across the pre- and post-central gyri in a diffuse manner that is not finger-specific. We find that the amplitude of this broadband motif is entrained on the phase of the beta rhythm, as well as rhythms at other frequencies, in peri-central cortex during fixation. During finger movement, the beta phase-entrainment is diminished or eliminated. We suggest that the beta rhythm may be more than a resting rhythm, and that this entrainment may reflect a suppressive mechanism for actively gating motor function.

The presurgical evaluation of patients with epilepsy often requires an intracranial study in which both subdural grid electrodes and depth electrodes are needed. Performing a craniotomy for grid placement with a stereotactic frame in place can be problematic, especially in young children, leading some surgeons to consider frameless stereotaxy for such surgery. The authors report on the use of a system that uses electromagnetic impulses to track the tip of the depth electrode. Ten pediatric patients with medically refractory focal lobar epilepsy required placement of both subdural grid and intraparenchymal depth electrodes to map seizure onset. Presurgical frameless stereotaxic targeting was performed using a commercially available electromagnetic image-guided system. Freehand depth electrode placement was then performed with intraoperative guidance using an electromagnetic system that provided imaging of the tip of the electrode, something that has not been possible using visually or sonically based systems. Accuracy of placement of depth electrodes within the deep structures of interest was confirmed postoperatively using CT and CT/MR imaging fusion. Depth electrodes were appropriately placed in all patients. Electromagnetic-tracking-based stereotactic targeting improves the accuracy of freehand placement of depth electrodes in patients with medically refractory epilepsy. The ability to track the electrode tip, rather than the electrode tail, is a major feature that enhances accuracy. Additional advantages of electromagnetic frameless guidance are discussed.

Object: Emerging research in evoked broadband electrocorticographic (ECoG) measurement from the cortical surface suggests that it might cleanly delineate the functional organization of cortex. The authors sought to demonstrate whether this could be done in a same-session, online manner to identify receptive and expressive language areas., Methods: The authors assessed the efficacy of simple integration of "χ-band" (76-200 Hz) change in the ECoG signal by implementing a simple band-pass filter to estimate broadband spectral change. Following a brief (less than 10-second) period to characterize baseline activity, χ-band activity was integrated while 7 epileptic patients with implanted ECoG electrodes performed a verb-generation task., Results: While the patients were performing verb-generation or noun-reading tasks, cortical activation was consistently identified in primary mouth motor area, superior temporal gyrus, and Broca and Wernicke association areas. Maps were robust after a mean time of 47 seconds (using an "activation overlap" measure). Correlation with electrocortical stimulation was not complete and was stronger for noun reading than verb generation., Conclusions: Broadband ECoG changes can be captured online to identify eloquent cortex. This demonstrates the existence of a powerful new tool for functional mapping in the operative and chronic implant setting.

Central pain syndromes associated with damage to the thalamic sensory relay nuclei have been described predominantly in the stroke literature; however, pain syndromes associated with thalamic neoplasms are much less common. We describe a woman with dyspareunia secondary to vaginal allodynia as the presenting sign of a left thalamic juvenile pilocytic astrocytoma. Subsequent to an uneventful stereotactic biopsy, her vaginal allodynia progressed to hemi-body allodynia. We believe that this is the first reported case of isolated vaginal allodynia associated with a thalamic neoplasm or any other structural pathology of the central nervous system. Dyspareunia secondary to vaginal allodynia as the presenting sign of a left thalamic juvenile pilocytic astrocytoma is reported, in a rare case underscoring that thalamic pathology including neoplasms should be considered in evaluating patients with longstanding and unexplained pain syndromes., (Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Object: Where no society-based or manufacturer guidance on radiation limits to neuromodulation devices is available, this research provides the groundwork for neurosurgeons and radiation oncologists who rely on the computerized treatment plan clinically for cancer patients. The focus of the article is to characterize radiation parameters of attenuation and scatter when an incident therapeutic x-ray beam is directed upon them. At the time of this writing, manufacturers of Neuromodulation products do not recommend direct exposure of the device in the beam nor provide guidance for the maximum dose for these devices., Methods: Ten neuromodulation models were chosen to represent the finite class of devices marketed by Medtronic before 2011. CT simulations permitted computer treatment modeling for dose distribution analysis as used routinely in radiation oncology for patients. Phantom case results were directly compared to actual clinical patient cases. Radiation detection measurements were then correlated to computational results. Where the x-ray beam passes through the device and is attenuated, dose reduction was identified with Varian Eclipse computer modeling for these posterior locations., Results: Although the computer algorithm did not identify physical processes of side-scatter and back-scatter, these phenomena were proven by radiation measurement to occur. In general, the computer results underestimated the level of change seen by measurement., Conclusions: For these implantable neurostimulators, the spread in dose changes were found to be -6.2% to -12.5% by attenuation, +1.7% to +3.8% by side-scatter, and +1.1% to +3.1% by back-scatter at 6 MV. At 18 MV, these findings were observed to be -1.4% to -7.0% by attenuation, +1.8% to 5.7% by side-scatter, and 0.8% to 2.7% by back-scatter. No pattern for the behavior of these phenomena was deduced to be a direct consequence of device size.

Background: The technique of sub-pial resection, first described in the early 1900s, was later refined by Penfield and Jasper for removal of supratentorial epileptic cortex. This technique has not been widely adopted for intrinsic tumor resection, for which the most widely used technique involves piecemeal aspiration of the tumor. This technique of "staying within the tumor" results in persistent bleeding, with obscuration of the tumor/brain interface, potentially yielding less than satisfactory results. In our experience, the sub-pial technique is useful for resections of supratentorial intrinsic tumor. We report the use of sub-pial resection technique and present illustrative cases., Methods: The sub-pial resection technique is described along with important clinical decision-making guidelines. Representative cases are presented to discuss application of the sub-pial technique and to demonstrate surgical results., Results: The sub-pial technique preserves the pia during cortical resections and makes it easier to protect and identify normal anatomy, including sulci, gyri, cranial nerves, and major vascular structures. This reduces bleeding, making surgery safer and more efficient. In most cases, an en bloc resection can be accomplished, permitting more accurate histopathology and more extensive tissue acquisition for research purposes., Conclusion: The sub-pial technique can be incorporated into strategies for supratentorial intrinsic tumor resections, including temporal, frontal, occipital, and insular tumors, at para-Sylvian or para-insular-sulcus locations.

Brain rhythms are more than just passive phenomena in visual cortex. For the first time, we show that the physiology underlying brain rhythms actively suppresses and releases cortical areas on a second-to-second basis during visual processing. Furthermore, their influence is specific at the scale of individual gyri. We quantified the interaction between broadband spectral change and brain rhythms on a second-to-second basis in electrocorticographic (ECoG) measurement of brain surface potentials in five human subjects during a visual search task. Comparison of visual search epochs with a blank screen baseline revealed changes in the raw potential, the amplitude of rhythmic activity, and in the decoupled broadband spectral amplitude. We present new methods to characterize the intensity and preferred phase of coupling between broadband power and band-limited rhythms, and to estimate the magnitude of rhythm-to-broadband modulation on a trial-by-trial basis. These tools revealed numerous coupling motifs between the phase of low-frequency (δ, θ, α, β, and γ band) rhythms and the amplitude of broadband spectral change. In the θ and β ranges, the coupling of phase to broadband change is dynamic during visual processing, decreasing in some occipital areas and increasing in others, in a gyrally specific pattern. Finally, we demonstrate that the rhythms interact with one another across frequency ranges, and across cortical sites.

Objective: Corpora amylacea (CA) normally accumulate within perivascular, subpial, and subependymal astrocytic processes. CA are associated with a number of conditions including normal aging, hippocampal sclerosis associated with temporal lobe epilepsy, multiple sclerosis, Lafora-type progressive myoclonic epilepsy, and adult polyglucosan body disease. Reports of massive localized accumulation of CA in the brain outside of these conditions are rare., Clinical Presentation: A 49-year-old woman, with a long-standing history of migraine headaches, presented to her primary care provider for increased headache duration. Brain magnetic resonance imaging (MRI) revealed a left parahippocampal lesion, suggestive of low-grade glioma., Intervention: Given the MRI suggestive of left parahippocampal glioma, left-sided frontotemporal craniotomy was performed for resection of the lesion. Specimens obtained during the operation revealed focal high-density accumulation of CA with no evidence of neoplasm, ischemia, or hypoxic injury., Conclusion: This case illustrates the possibility that localized high-density CA accumulation can present as an intrinsic lesion on brain MRI. CA should be included in the differential diagnosis for patients presenting with brain MRI suggestive of nonenhancing space-occupying lesions.

Deep Brain Stimulation (DBS) is a routine therapy for movement disorders, and has several emerging indications. We present a novel protocol to define the stereotactic coordinates of metallic DBS implants that may be routinely employed for validating therapeutic anatomical targets. Patients were referred for troubleshooting or new DBS implantation. A volumetric MRI of the brain obtained prior to or during this protocol was formatted to the Anterior Commissure-Posterior Commissure (AC-PC) coordinate system. Patients underwent a CT scan of the brain in an extended Hounsfield unit (EHU) mode. A semi-automatic detection algorithm based on a Normalized Mutual Information (NMI) co-registration method was implemented to measure the AC-PC coordinates of each DBS contact. This algorithm was validated using manual DBS contact identification. Fifty MRI-CT image pairs were available in 39 patients with a total of 336 DBS electrodes. The median and mean Euclidean distance errors for automatic identification of electrode locations were 0.20mm and 0.22 mm, respectively. This method is an accurate method of localization of active DBS contacts within the sub-cortical region. As the investigational indications of DBS expand, this method may be used for verification of final implant coordinates, critical for understanding clinical benefit and comparing efficacy between subjects., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Electrocorticographic recording is now being used in a wide variety of experimental settings. We present a simple method which can be used to estimate electrode position with respect to brain gyral anatomy using a pre-implantation MRI and post-implantation coronal and sagittal x-rays. It is semi-automated, with the user manually rotating and scaling an x-ray to fit brain outline, identifying threshold values for brain surface rendering, and clicking on electrodes on an x-ray. Electrode positions can be rapidly identified and rendered in about 20 minutes from start to finish. This approach is useful when the MRI quality is poor, there is no quality CT, but one would like to understand the relationship between experimental result and brain anatomy.

Deep brain stimulation (DBS) has become a routine therapy for Parkinson's disease. Standard CT imaging, often used to evaluate DBS electrodes in patients with limited benefit or significant side effects, has limitations including inability to distinguish different metallic components of the DBS lead. CT imaging with an extended Hounsfield unit (EHU) scale allows advanced image processing techniques to detect individual electrodes. EHU-CT may be co-registered to MRI volumes to provide accurate anatomical visualization of DBS lead contacts., (2009 S. Karger AG, Basel.)

Foreign accent syndrome is a rare language output disorder characterized by changes in various speech features leading to a perceived foreign accent. There are few cases reported in the literature. Due to the rarity of this condition, information regarding the functional neuroanatomy of FAS is lacking. We present the case of a 60-year-old woman with a left anterior parietal lobe breast carcinoma metastasis who developed foreign accent syndrome (FAS). This patient presented to the emergency room with right upper extremity weakness, facial weakness, and altered speech. Neurological examination revealed the patient's speech to be dysarthric and accented, but otherwise appropriate. Brain magnetic resonance (MR) imaging demonstrated a 3cm x 3cm x 3cm lesion in the left anterior parietal lobe. The patient underwent craniotomy for resection of the mass. Intra-operative cortical stimulation mapping demonstrated the lesion to be confined to somatosensory cortex and gross total resection was performed. There were no new neurological deficits post-operatively. To our knowledge, this is a unique case of FAS due to breast carcinoma metastasis. Additionally, this is the first documented case of electrocortical function stimulation mapping of language and Rolandic cortex in a patient with FAS.

Medically refractory epilepsy accounts for more than 30% of the epilepsy population. Scalp EEG electrodes have limited ability to localize seizure onset from deep structures and implantation of subdural electrodes with long term monitoring provides additional information. Apart from clinical application, this patient population provides a unique opportunity for acquiring electrocorticography data in research paradigms. We present a method for rapid localization of electrodes using lateral and anterior-posterior X-rays. Skull landmarks and proportions are used for co-registration with the standardized Talairach coordinate system. This MATLAB-based "Location on Cortex" (LOC) package facilitates rapid visualization of clinical and experimental data in a user-friendly manner.

We address the application of a modified form of Principal Component Analysis (PCA) to data which is characterized by sparse, but known, event times. The sparsity of such event times makes it unlikely that they have a major contribution to the overall covariance in the data, and standard PCA components generated from this covariance may not give us useful insight about the task. A simple method is shown here which generates an orthogonal, "task-related PCA" (trPCA) transform based upon correlations between non-simultaneous, event-time locked, subsets of data. Non-simultaneity is the constraint that epochs of data are only compared to epochs of data from other points in time, which explicitly selects for reproducible effects. The prescription for trPCA is presented within the context of a fusiform face area experiment for illustration. In this experiment, a reproducible, face-stimulus specific, negative potential deflection is observed 200ms (N200) after presentation. We demonstrate how this N200 phenomenon, initially distributed across a subtemporal electrocorticographic (ECoG) array, may be isolated in a single component using trPCA.

Object: Transplantation of fetal dopaminergic tissue is being investigated in animal models and clinical trials for its potential as a treatment for advanced Parkinson disease. At the same time, the availability of fetal tissue is limited, making its storage time prior to transplantation a key practical issue. Although it results in a smaller percentage of surviving cells. a longer storage time enables fetal tissue obtained over several days to be pooled for transplantation in a recipient. Glial cell line-derived neurotrophic factor (GDNF) has been shown to improve survival of human dopaminergic tissue that has been stored prior to transplantation. The objective of this study was to evaluate the effects on fetal dopaminergic tissue of GDNF-supplemented hibernation for extended periods of 6 to 15 days., Methods: The ventral mesencephalon (VM) was harvested in a total of 27 14-day-old rat fetuses, and three VMs were cultured immediately (fresh control group). The remaining 24 VMs were divided sagittally along the midline to yield 48 equal pieces of hemimesencephalon. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 "partner" hemimesencephalon pieces were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and double-stained with cresyl violet. Cell counts for all cultures and the percentage of TH-immunoreactive cells were obtained. The percentage of TH-immunoreactive cells for the fresh control group was 6.3 +/- 0.5%. The percentage of TH-immunoreactive cells in cultures derived from tissue stored in GDNF-supplemented medium was significantly increased at 6 and 9 days posthibernation compared with the fresh control group and the "partner" groups stored in hibernation medium only. No significant increase in the percentage of TH-immunoreactive cells was observed in the 12- and 15-day groups., Conclusions: In this study the authors have demonstrated that fetal dopaminergic tissue can be safely stored for up to 9 days in GDNF-supplemented hibernation medium. Furthermore, the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-immunoreactive cells prior to transplantation. These observations have practical clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.

Object: Investigation of fetal dopaminergic tissue transplantation is being conducted in animal models and clinical trials as a potential treatment for advanced Parkinson disease (PD). Because the availability of fetal tissue is limited, however, the duration of its storage prior to transplantation is a key practical issue. Longer storage times may enable fetal tissue obtained over several days to be pooled together for transplantation in a recipient. Glial cell line-derived neurotrophic factor (GDNF) has been shown to improve survival of stored human dopaminergic tissue prior to transplantation. The objective of this study was to evaluate GDNF-supplemented hibernation of fetal dopaminergic tissue for extended periods of 6 to 15 days., Methods: A total of 27 rat ventral mesencephalons (VMs) were obtained in gestation Day 14 rat fetuses, and three were cultured immediately (fresh-culture control group). The remaining 24 VMs were divided sagittally along the midline to form 48 equal pieces of hemimesencephalons. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 "partner" hemimesencephalons were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and cresyl violet. Cell counts for all cultures and percentage of TH-immunoreactive cells were obtained. The percentage of TH-positive cells for the fresh control group was 6.3 +/- 0.5%; that measured in cultures derived from tissue hibernated in GDNF-supplemented medium was significantly increased at 6 and 9 days posthibernation compared with the fresh-culture control group and the partner groups stored in hibernation medium only. No significant increase in percentage of TH-immunoreactive cells was observed in the 12- and 15-day hibernation groups., Conclusions: In summary the authors found that fetal dopaminergic tissue can safely be stored up to 9 days in GDNF-supplemented hibernation medium. Furthermore the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-positive cells prior to transplantation. These observations may have important clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.

Objective: Patient selection for cerebrospinal fluid diversion is difficult, because idiopathic normal pressure hydrocephalus (INPH) mimics other neurodegenerative disorders and no findings reliably predict outcome. The literature was reviewed to identify diagnostic criteria that predict shunt response and to formulate prognostic expectations., Methods: MEDLINE was searched, and 44 articles meeting predetermined criteria were included., Results: Clinical series were frequently retrospective with small patient numbers and unstandardized outcome evaluation. Clinical findings suggestive of shunt responsiveness were the complete triad (gait disturbance, urinary incontinence, and dementia) with early gait disturbance. Degree of hydrocephalus was not correlated with clinical improvement. Reduction of the subcortical low-blood flow area was correlated with improvement in three small studies. Clinical response to prolonged cerebrospinal fluid drainage predicted shunt outcome in all cases in two small series. Overall, 59% (range, 24-100%) of patients improved after shunting, and 29% (range, 10-100%) of patients experienced prolonged improvement. Complications occurred in 38% (range, 5-100%) of patients, additional surgery was required in 22% (range, 0-47%) of patients, and there was a 6% (range, 0-35%) combined rate of permanent neurological deficit and death., Conclusion: Shunting INPH is associated with an approximately 29% rate of significant improvement and a 6% significant complication rate. Enlargement of the subcortical low-flow area and clinical improvement secondary to prolonged lumbar drainage may provide additive predictive value above clinical and computed tomographic criteria. A multicenter clinical trial that focuses on the value of ancillary tests, defines the clinical course of a patient with a ventriculoperitoneal shunt, and evaluates the cost effectiveness of shunting INPH is needed to better describe outcome from shunting in INPH.