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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.

BCIs for rehabilitation integrate BCIs with conventional methods and devices for rehabilitation like functional electrical stimulation (FES)-based neuroprostheses (Colachis et al.; Remsik et al.), transcranial direct current stimulation (tDCS) (Rodriguez-Ugarte et al.) etc. to enhance the brain's reorganization of corticospinal and cortico-muscular connections after acute, sub-acute, or chronic lesions. Beside motor deficits, BCI-induced brain plasticity might contribute to the treatment of high-order cortical dysfunctions, such as improving social and emotional behaviors in autism spectrum disorder (Amaral et al.), training inhibitory control and working memory in ADHD, as well as contributing to the rehabilitation of cognitive deficits related to dementia. [...]BCI-based brain training can help preserve cognitive performance in healthy older adults, promoting successful aging and reducing the social burden of the population's increasing aging. [...]BCIs may increase the diagnostic accuracy of brain disorders.

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.

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. 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. 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. 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. Boston Scientific.

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.

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in particular is highly effective in relieving symptoms of Parkinson′s disease (PD). However, it can also have marked psychiatric side effects, including delirium, mania, and psychosis. The etiologies of those effects are not well-understood, and both surgeons and consulting psychiatrists are in need of treatment strategies. Case Description: Two patients with young onset of PD and without significant prior psychiatric problems presented for bilateral STN DBS when medications became ineffective. Both had uneventful operative courses but developed florid psychosis 1-2 weeks later, before stimulator activation. Neither showed signs of delirium, but both required hospitalization, and one required treatment with a first-generation antipsychotic drug. Use of that drug did not worsen PD symptoms, contrary to usual expectations. Conclusion: These cases describe a previously unreported post-DBS syndrome in which local tissue reaction to lead implantation produces psychosis even without electrical stimulation of subcortical circuits. The lesion effect also appears to have anti-Parkinsonian effects that may allow the safe use of otherwise contraindicated medications. These cases have implications for management of PD DBS patients postoperatively, and may also be relevant as DBS is further used in other brain regions to treat behavioral disorders.

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. 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. 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. 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.

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 3 cm × 3 cm × 3 cm 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.

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. 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. 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. 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.

INTRODUCTION Subthalamic Deep Brain Stimulation (STN-DBS) is an established therapeutic option for managing the motor symptoms of Parkinson's disease (PD); however, it has not been previously evaluated in a double-blind, randomized controlled trial (RCT) with sham control. METHODS INTREPID (Clinicaltrials.gov identifier: NCT01839396) is a multi-center, prospective, double-blinded randomized controlled trial (RCT) sponsored by Boston Scientific. Subjects with advanced PD were implanted bilaterally in the STN with a multiple-source, constant-current DBS system (Vercise, Boston Scientific). Subjects were randomized to either receive active versus control settings for 12 weeks. Upon completion of the 12-week blinded period, subjects received their best therapeutic settings in the open-label phase up to 5 years. During long-term follow-up, motor improvement and quality of life was evaluated using UPRDS, PDQ39, Schwann and England, etc. Adverse events were also collected. RESULTS The study met the primary endpoint demonstrated by a mean difference of 3.03 ± 4.52 hours (p < 0.001) between active and control groups in ON time without troublesome dyskinesia and with no increase in antiparkisonian medication, from post-implant baseline to 12-weeks post-randomization. At 2 years, a 46% improvement in UPDRS III scores was reported (sustained since last follow-up at 1 year) and overall improvement in quality of life was maintained compared to pre-surgery screening. Three-year follow up data will be presented. CONCLUSION Results of the INTREPID RCT demonstrate that use of a multiple-source, constant current DBS system is safe and effective for treatment of PD motor symptoms. Long-term follow up on the use of this system and associated outcomes will be presented.