Measuring complex behaviors of local oscillatory networks in deep brain local field potentials.

BACKGROUND: Multiple oscillations emerging from the same neuronal substrate serve to construct a local oscillatory network. The network usually exhibits complex behaviors of rhythmic, balancing and coupling between the oscillations, and the quantification of these behaviors would provide valuable insight into organization of the local network related to brain states. NEW METHOD: An integrated approach to quantify rhythmic, balancing and coupling neural behaviors based upon power spectral analysis, power ratio analysis and cross-frequency power coupling analysis was presented. Deep brain local field potentials (LFPs) were recorded from the thalamus of patients with neuropathic pain and dystonic tremor. t-Test was applied to assess the difference between the two patient groups. RESULTS: The rhythmic behavior measured by power spectral analysis showed significant power spectrum difference in the high beta band between the two patient groups. The balancing behavior measured by power ratio analysis showed significant power ratio differences at high beta band to 8-20 Hz, and 30-40 Hz to high beta band between the patient groups. The coupling behavior measured by cross-frequency power coupling analysis showed power coupling differences at (theta band, high beta band) and (45-55 Hz, 70-80 Hz) between the patient groups. COMPARISON WITH EXISTING METHOD: The study provides a strategy for studying the brain states in a multi-dimensional behavior space and a framework to screen quantitative characteristics for biomarkers related to diseases or nuclei. CONCLUSIONS: The work provides a comprehensive approach for understanding the complex behaviors of deep brain LFPs and identifying quantitative biomarkers for brain states related to diseases or nuclei.

A randomised double-blind placebo-controlled trial investigating the behavioural effects of vitamin, mineral and n-3 fatty acid supplementation in typically developing adolescent schoolchildren.

Nutrient deficiencies have been implicated in anti-social behaviour in schoolchildren; hence, correcting them may improve sociability. We therefore tested the effects of vitamin, mineral and n-3 supplementation on behaviour in a 12-week double-blind randomised placebo-controlled trial in typically developing UK adolescents aged 13-16 years (n 196). Changes in erythrocyte n-3 and 6 fatty acids and some mineral and vitamin levels were measured and compared with behavioural changes, using Conners' teacher ratings and school disciplinary records. At baseline, the children's PUFA (n-3 and n-6), vitamin and mineral levels were low, but they improved significantly in the group treated with n-3, vitamins and minerals (P=0·0005). On the Conners disruptive behaviour scale, the group given the active supplements improved, whereas the placebo group worsened (F=5·555, d=0·35; P=0·02). The general level of disciplinary infringements was low, thus making it difficult to obtain improvements. However, throughout the school term school disciplinary infringements increased significantly (by 25 %; Bayes factor=115) in both the treated and untreated groups. However, when the subjects were split into high and low baseline infringements, the low subset increased their offences, whereas the high-misbehaviour subset appeared to improve after treatment. But it was not possible to determine whether this was merely a statistical artifact. Thus, when assessed using the validated and standardised Conners teacher tests (but less clearly when using school discipline records in a school where misbehaviour was infrequent), supplementary nutrition might have a protective effect against worsening behaviour.

Tractography Study of Deep Brain Stimulation of the Anterior Cingulate Cortex in Chronic Pain: Key to Improve the Targeting.

BACKGROUND: Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) is a new treatment for alleviating intractable neuropathic pain. However, it fails to help some patients. The large size of the ACC and the intersubject variability make it difficult to determine the optimal site to position DBS electrodes. The aim of this work was therefore to compare the ACC connectivity of patients with successful versus unsuccessful DBS outcomes to help guide future electrode placement. METHODS: Diffusion magnetic resonance imaging (dMRI) and probabilistic tractography were performed preoperatively in 8 chronic pain patients (age 53.4 ± 6.1 years, 2 females) with ACC DBS, of whom 6 had successful (SO) and 2 unsuccessful outcomes (UOs) during a period of trialing. RESULTS: The number of patients was too small to demonstrate any statistically significant differences. Nevertheless, we observed differences between patients with successful and unsuccessful outcomes in the fiber tract projections emanating from the volume of activated tissue around the electrodes. A strong connectivity to the precuneus area seems to predict unsuccessful outcomes in our patients (UO: 160n/SO: 27n), with (n), the number of streamlines per nonzero voxel. On the other hand, connectivity to the thalamus and brainstem through the medial forebrain bundle (MFB) was only observed in SO patients. CONCLUSIONS: These findings could help improve presurgical planning by optimizing electrode placement, to selectively target the tracts that help to relieve patients' pain and to avoid those leading to unwanted effects.

Characteristics of thalamic local field potentials in patients with disorders of consciousness.

A functioning thalamus is essential for treatment of patients with disorders of consciousness (DOC) using deep brain stimulation (DBS). This work aims to identify the potential biomarkers related to consciousness from the thalamic deep brain local field potentials (LFPs) in DOC patients. The frequency features of central thalamic LFPs were characterized with spectral analysis. The features were further compared to those of LFPs from the ventroposterior lateral nucleus of the thalamus (VPL) in patients with pain. There are several distinct characteristics of thalamic LFPs found in patients with DOC. The most important feature is the oscillation around 10Hz which could be relevant to the existence of residual consciousness, whereas high power below 8Hz seemed to be associated with loss of consciousness. The invasive deep brain recording tool opens a unique way to explore the brain function in consciousness, awareness and alertness and clarify the potential mechanisms of thalamic stimulation in DOC.

Dyslexia: the Role of Vision and Visual Attention.

Dyslexia is more than just difficulty with translating letters into sounds. Many dyslexics have problems with clearly seeing letters and their order. These difficulties may be caused by abnormal development of their visual "magnocellular" (M) nerve cells; these mediate the ability to rapidly identify letters and their order because they control visual guidance of attention and of eye fixations. Evidence for M cell impairment has been demonstrated at all levels of the visual system: in the retina, in the lateral geniculate nucleus, in the primary visual cortex and throughout the dorsal visuomotor "where" pathway forward from the visual cortex to the posterior parietal and prefrontal cortices. This abnormality destabilises visual perception; hence, its severity in individuals correlates with their reading deficit. Treatments that facilitate M function, such as viewing text through yellow or blue filters, can greatly increase reading progress in children with visual reading problems. M weakness may be caused by genetic vulnerability, which can disturb orderly migration of cortical neurones during development or possibly reduce uptake of omega-3 fatty acids, which are usually obtained from fish oils in the diet. For example, M cell membranes require replenishment of the omega-3 docosahexaenoic acid to maintain their rapid responses. Hence, supplementing some dyslexics' diets with DHA can greatly improve their M function and their reading.

Reciprocal interactions between the human thalamus and periaqueductal gray may be important for pain perception.

Pain perception can be altered by activity in the periaqueductal gray (PAG). The PAG can decrease the incoming nociceptive signals at the level of the spinal dorsal horn, but it is not clear whether the PAG can also affect the sensory thalamus, ventral posterolateral and ventral posteromedial thalamic nuclei, to modulate pain. However, the PAG and the thalamus have direct connections with each other; so we postulated that the PAG may also modulate pain by inhibiting the sensory nuclei in the thalamus, and that these may also reciprocally influence the PAG. Here, by analyzing the local field potentials recorded from the sensory thalamus and the PAG in chronic pain patients with deep brain stimulation electrodes, we show that PAG stimulation inhibited the sensory thalamus with decreasing thalamic delta, theta, alpha and beta power, and sensory thalamus stimulation excited the PAG with increasing PAG delta and theta power. We demonstrate that the PAG and the sensory thalamus interact reciprocally at short latency, which may be related to pain modulation.

Federal seafood safety response to the Deepwater Horizon oil spill.

Following the 2010 Deepwater Horizon oil spill, petroleum-related compounds and chemical dispersants were detected in the waters of the Gulf of Mexico. As a result, there was concern about the risk to human health through consumption of contaminated seafood in the region. Federal and Gulf Coast State agencies worked together on a sampling plan and analytical protocols to determine whether seafood was safe to eat and acceptable for sale in the marketplace. Sensory and chemical methods were used to measure polycyclic aromatic hydrocarbons (PAHs) and dispersant in >8,000 seafood specimens collected in federal waters of the Gulf. Overall, individual PAHs and the dispersant component dioctyl sodium sulfosuccinate were found in low concentrations or below the limits of quantitation. When detected, the concentrations were at least two orders of magnitude lower than the level of concern for human health risk. Once an area closed to fishing was free of visibly floating oil and all sensory and chemical results for the seafood species within an area met the criteria for reopening, that area was eligible to be reopened. On April 19, 2011 the area around the wellhead was the last area in federal waters to be reopened nearly 1 y after the spill began. However, as of November 9, 2011, some state waters off the Louisiana coast (Barataria Bay and the Delta region) remain closed to fishing.

Long-term outcome in patients with a Gleason score ≤ 6 prostate cancer treated by radical prostatectomy.

OBJECTIVE: • To determine the actual recurrence risk of patients with a Gleason score (GS) ≤ 6 treated with radical retropubic prostatectomy (RRP) and bilateral lymphadenectomy in a cohort with long-term follow-up. PATIENTS AND METHODS: • The USC/Norris Comprehensive Cancer Center database included 3235 consecutive patients who underwent RRP for prostate cancer between January 1972 and December 2005. We identified 1383 patients with a GS ≤ 6 in prostatectomy specimens. Median follow-up was 8.3 years. Data on pathological and clinical characteristics and outcome were prospectively recorded. • Statistical analysis was performed using the stratified log-rank test and stepwise Cox regression analysis. RESULTS: • A GS of 6 was present in 66%, 5 in 27%, 4 in 5% and 3 or 2 in 3% of cases. Tumour classification was pT2N0 (83%), pT3N0 (14%), pT4N0 (0.1%) and any TN1 (2%). • Positive margins were seen in 18%. Estimated PSA and clinical recurrence rate were 14% and 4% after 10 years and 18% and 6% after 15 years, respectively. In multivariate analysis, N-stage (P < 0.001), T-stage (P= 0.02) and margin status (P < 0.001) were associated with PSA recurrence. • N-stage (P < 0.001) and T-stage (P= 0.01) were associated with clinical recurrence. • Overall, patients with a GS ≤ 6 accounted for 26% of all PSA recurrences and for 20% of all patients with clinical recurrences in the database. CONCLUSION: • A relatively small proportion of patients with a GS ≤ 6 cancer developed PSA recurrence and/or overt metastasis. However, these patients account for a substantial minority of those who experienced recurrence and metastasis.

Sustained reduction of hypertension by deep brain stimulation.

Deep brain stimulators were implanted in the left periaqueductal gray matter (PAG) and sensory thalamus for right sided neuropathic facial pain refractory to other treatments in a man aged 58 years. PAG stimulation 8 months later acutely reduced systolic blood pressure by 25 mm Hg during revision surgery. One year post procedure, ambulatory blood pressure monitoring demonstrated significant and sustained reduction in blood pressure with PAG stimulation. Mean systolic blood pressure decreased by 12.6mm Hg and diastolic by 11.0mm Hg, alongside reductions in variability of heart rate and pulse pressure. This neurosurgical treatment may prove beneficial for medically refractory hypertension.

Effects on cognition of stereotactic lesional surgery for the treatment of tremor in multiple sclerosis.

OBJECTIVE: To assess the effect of stereotactic lesional surgery for treatment of tremor in multiple sclerosis on cognition. METHODS: Eleven patients (3 males, 8 females) with multiple sclerosis participated in the study. Six subjects comprised the surgical group and five the matched control group. All patients were assessed at baseline and three months using a neuropsychological test battery that included measures of intellectual ability, memory, language, perception and executive function. RESULTS: There were no significant differences between the surgical and control groups and no change from pre to post testing except for a decline in scores on the Mini-Mental State Examination (MMSE), WAIS-R Digit Span and Verbal Fluency in the surgical group. CONCLUSIONS: The results indicate that stereotactic lesional surgery does not result in major cognitive impairment in multiple sclerosis. However, the decline in MMSE scores, digit span and verbal fluency require further investigation in a larger sample.

Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting.

OBJECT: The pedunculopontine nucleus (PPN) region of the brainstem has become a new stimulation target for the treatment of gait freezing, akinesia, and postural instability in advanced Parkinson disease (PD). Because PD locomotor symptoms are probably caused by excessive gamma-aminobutyric acidergic inhibition of the PPN, low-frequency stimulation of the PPN may overcome this inhibition and improve the symptoms. However, the anatomical connections of this region in humans are not known in any detail. METHODS: Diffusion weighted magnetic resonance (MR) images were acquired at 1.5 teslas, and probabilistic tractography was used to trace the connections of the PPN region in eight healthy volunteers. A single seed voxel (2 x 2 x 2 mm) was chosen in the PPN just lateral to the decussation of the superior cerebellar peduncle, and the Diffusion Toolbox of the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain was used to process the acquired MR images. The connections of each volunteer's PPN region were analyzed using a human brain MR imaging atlas. RESULTS: The PPN region was connected with the cerebellum and spinal cord below and to the thalamus, pallidum, subthalamic nucleus, and motor cortex above. The regions of the primary motor cortex that control the trunk and upper and lower extremities had the highest connectivity compared with other parts of motor cortex. CONCLUSIONS: These findings suggest that connections of the PPN region with the primary motor cortex, basal ganglia, thalamus, cerebellum, and spinal cord may play important roles in the regulation of movement by the PPN region. Diffusion tensor imaging tractography of the PPN region may be used preoperatively to optimize placement of stimulation electrodes and postoperatively it may also be useful to reassess electrode positions.

A dominant bursting electromyograph pattern in dystonic conditions predicts an early response to pallidal stimulation.

Although chronic pallidal deep brain stimulation (DBS) is effective in the treatment of medically intractable dystonia, there is no way of predicting the variations in clinical outcome, partly due to our limited understanding of the pathophysiological mechanisms underlying this condition. We recorded electromyographic (EMG) activity from the most severely affected muscle groups in seven dystonia patients before and after pallidal DBS. Patient EMG recordings could be classified into two groups: one consisting of patients who at rest demonstrated a dominant low frequency component of activity on power spectral analysis (ranging from 2 to 5 Hz), and one group in which this dominant pattern was absent. Early postoperative improvements (within 2-3 days) were observed in the former group, whereas the latter group benefited more gradually (over several months). Analysis of EMG activity may provide a sensitive means of identifying dystonic patients who are likely to be most responsive to functional neurosurgical intervention.

Connectivity of the human periventricular-periaqueductal gray region.

OBJECT: The periventricular gray (PVG) zone and its continuation, the periaqueductal gray (PAG) substance, have been targets for deep brain stimulation (DBS) in the alleviation of intractable pain for longer than two decades. Nevertheless, the anatomical connectivity of this region has been fairly poorly defined. The effects of DBS in this region are probably related to the release of endogenous endorphins, but until the connectivity of this region is better understood the mechanisms will remain unclear. METHODS: Diffusion tractography was used to trace the pathways of the PVG-PAG region in seven healthy human volunteers. Images were acquired with the aid of a 1.5-tesla magnetic resonance imaging system. The region of interest was located just lateral to the posterior commissure and extended caudally to the level of the superior colliculus. Probabilistic diffusion tractography was performed from each voxel in each patient's PVG-PAG region. The PVG-PAG region was found to yield descending projections to the spinal cord and cerebellum. Ascending projections to the thalamus and frontal lobes were also observed. CONCLUSIONS: These findings suggest that the PVG-PAG region may modulate pain by two mechanisms: one involving the antinociceptive system in the spinal cord and the other involving influences on the central pain network.

Thalamotomy versus thalamic stimulation for multiple sclerosis tremor.

Disabling intractable tremor occurs frequently in patients with multiple sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable. Thalamotomy has been the mainstay of neurosurgical therapy for intractable MS tremor, however the popularisation of deep brain stimulation (DBS) has led to the adoption of chronic thalamic stimulation in an attempt to ameliorate this condition. With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both thalamotomy and thalamic stimulation produced improvements in postural and intention tremor. The mean improvement in postural tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor improved by 72% in the group undergoing thalamotomy, a significantly larger gain than the 36% tremor reduction following DBS (P < 0.05). Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall. Following thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised hemiparesis and seizures. Only one patient in the thalamic stimulation group experienced a permanent deficit (monoparesis). We conclude that thalamotomy is a more efficacious surgical treatment for intractable MS tremor, however the higher incidence of persistent neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.

Reversal of hypertonic co-contraction after bilateral pallidal stimulation in generalised dystonia: a clinical and electromyogram case study.

In a patient of generalised dystonia treated with bilateral pallidal stimulation, serial surface EMGs recorded from the neck muscles during alternating head movements revealed progressive reduction in hypertonic activity and reversal of co-contraction to reciprocal contraction, which preceded clinical improvement.

Globus pallidus internus deep brain stimulation for dystonic conditions: a prospective audit.

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured target in the treatment of patients with dystonia. The results of 25 consecutive patients with medically intractable dystonia (12 with generalised dystonia, 7 with spasmodic torticollis, and 6 with other types of dystonia) treated with GPi stimulation are reported. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS benefited all groups, resulting in clear and progressive improvements in their condition. This study clearly demonstrates that DBS of the GPi provides amelioration of intractable dystonia.

Thalamic field potentials in chronic central pain treated by periventricular gray stimulation -- a series of eight cases.

Chronic deep brain stimulation (DBS) of the periventricular gray (PVG) has been used for the treatment of chronic central pain for decades. In recent years motor cortex stimulation (MCS) has largely supplanted DBS in the surgical management of intractable neuropathic pain of central origin. However, MCS provides satisfactory pain relief in about 50-75% of cases, a range comparable to that reported for DBS (none of the reports are in placebo-controlled studies and hence the further need for caution in evaluating and comparing these results). Our experience also suggests that there is still a role for DBS in the control of central pain. Here we present a series of eight consecutive cases of intractable chronic pain of central origin treated with PVG DBS with an average follow-up of 9 months. In each case, two electrodes were implanted in the PVG and the ventroposterolateral thalamic nucleus, respectively, under guidance of corneal topography/magnetic resonance imaging image fusion. The PVG was stimulated in the frequency range of 2-100 Hz in alert patients while pain was assessed using the McGill-Melzack visual analogue scale. In addition, local field potentials (FPs) were recorded from the sensory thalamus during PVG stimulation. Maximum pain relief was obtained with 5-35 Hz stimulation while 50-100 Hz made the pain worse. This suggests that pain suppression was frequency dependent. Interestingly, we detected low frequency thalamic FPs at 0.2-0.4 Hz closely associated with the pain. During 5-35 Hz PVG stimulation the amplitude of this potential was significantly reduced and this was associated with marked pain relief. At the higher frequencies (50-100 Hz), however, there was no reduction in the FPs and no pain suppression. We have found an interesting and consistent correlation between thalamic electrical activity and chronic pain. This low frequency potential may provide an objective index for quantifying chronic pain, and may hold further clues to the mechanism of action of PVG stimulation. It may be possible to use the presence of these slow FPs and the effect of trial PVG DBS on both the clinical status and the FPs to predict the probable success of future pain control in individual patients.

Peri-ventricular grey stimulation versus motor cortex stimulation for post stroke neuropathic pain.

Central post stroke pain is often difficult to manage satisfactorily with conventional treatment modalities for pain. In the last decade functional neurosurgery has offered hope with motor cortex stimulation achieving significant alleviation of pain in some patients. Unfortunately this has led to the neglect of chronic stimulation of deep grey matter as another modality of treating this condition. In this article we present our experience with motor cortex stimulation and that with deep grey matter stimulation in patients with post stroke pain. We argue that both modalities have a significant role and that what is required are better methods of identifying particular patients who are more likely to respond to one or the other.