Alexander L. Green

Adaptive Deep Brain Stimulation In Advanced Parkinson Disease

Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof‐of‐principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.

Deep brain stimulation for pain relief: A meta-analysis

Deep brain stimulation (DBS) has been used to treat intractable pain for over 50 years. Variations in targets and surgical technique complicate the interpretation of many studies. To better understand its efficacy, we performed a meta-analysis of DBS for pain relief. MEDLINE (1966 to February 2003) and EMBASE (1980 to January 2003) databases were searched using key words deep brain stimulation, sensory thalamus, periventricular gray and pain. Inclusion criteria were based on patient characteristics and protocol clarity. Six studies (between 1977-1997) fitting the criteria were identified. Stimulation sites included the periventricular/periaqueductal grey matter (PVG/PAG), internal capsule (IC), and sensory thalamus (ST). The long-term pain alleviation rate was highest with DBS of the PVG/PAG (79%), or the PVG/PAG plus sensory thalamus/internal capsule (87%). Stimulation of the sensory thalamus alone was less effective (58% long-term success) (p < 0.05). DBS was more effective for nociceptive than deafferentation pain (63% vs 47% long-term success; p < 0.01). Long-term success was attained in over 80% of patients with intractable low back pain (failed back surgery) following successful trial stimulation. Trial stimulation was successful in approximately 50% of those with post-stroke pain, and 58% of patients permanently implanted achieved ongoing pain relief. Higher rates of success were seen with phantom limb pain and neuropathies. We conclude that DBS is frequently effective when used in well-selected patients. Neuroimaging and neuromodulation technology advances complicate the application of these results to modern practice. Ongoing investigations should shed further light on this complex clinical conundrum.

A specific and rapid neural signature for parental instinct.

Darwin originally pointed out that there is something about infants which prompts adults to respond to and care for them, in order to increase individual fitness, i.e. reproductive success, via increased survivorship of ones own offspring. Lorenz proposed that it is the specific structure of the infant face that serves to elicit these parental responses, but the biological basis for this remains elusive. Here, we investigated whether adults show specific brain responses to unfamiliar infant faces compared to adult faces, where the infant and adult faces had been carefully matched across the two groups for emotional valence and arousal, as well as size and luminosity. The faces also matched closely in terms of attractiveness. Using magnetoencephalography (MEG) in adults, we found that highly specific brain activity occurred within a seventh of a second in response to unfamiliar infant faces but not to adult faces. This activity occurred in the medial orbitofrontal cortex (mOFC), an area implicated in reward behaviour, suggesting for the first time a neural basis for this vital evolutionary process. We found a peak in activity first in mOFC and then in the right fusiform face area (FFA). In mOFC the first significant peak (p<0.001) in differences in power between infant and adult faces was found at around 130 ms in the 10–15 Hz band. These early differences were not found in the FFA. In contrast, differences in power were found later, at around 165 ms, in a different band (20–25 Hz) in the right FFA, suggesting a feedback effect from mOFC. These findings provide evidence in humans of a potential brain basis for the “innate releasing mechanisms” described by Lorenz for affection and nurturing of young infants. This has potentially important clinical applications in relation to postnatal depression, and could provide opportunities for early identification of families at risk.

Deep brain stimulation for the alleviation of post-stroke neuropathic pain.

Abstract Our aim was to asses the efficacy of deep brain stimulation in post‐stroke neuropathic pain. Since 2000, 15 patients with post‐stroke intractable neuropathic pain were treated with deep brain stimulation of the periventricular gray area (PVG), sensory thalamus (Ventroposterolateral nucleus‐VPL) or both. Pain was assessed using both a visual analogue scale and the McGills pain questionnaire. VAS scores show a mean improvement of 48.8% (SD 8.6%). However, there is a wide variation between patients. This study demonstrates that it is an effective treatment in 70% of such patients.

Deep brain stimulation: indications and evidence.

Deep brain stimulation is a minimally invasive targeted neurosurgical intervention that enables structures deep in the brain to be stimulated electrically by an implanted pacemaker. It has become the treatment of choice for Parkinson’s disease, refractory to, or complicated by, drug therapy. Its efficacy has been demonstrated robustly by randomized, controlled clinical trials, with multiple novel brain targets having been discovered in the last 20 years. Multifarious clinical indications for deep brain stimulation now exist, including dystonia and tremor in movement disorders; depression, obsessive–compulsive disorder and Tourette’s syndrome in psychiatry; epilepsy, cluster headache and chronic pain, including pain from stroke, amputation, trigeminal neuralgia and multiple sclerosis. Current research augurs for novel indications, including hypertension and orthostatic hypotension. The development, principles, indications and effectiveness of the technique are reviewed here. While deep brain stimulation is a standard and widely accepted treatment for Parkinson’s disease after 20 years of experience, in chronic pain it remains restricted to a handful of experienced, specialist centers willing to publish outcomes despite its use for over 50 years. Reasons are reviewed and novel approaches to appraising clinical evidence in functional neurosurgery are suggested.

Removing ECG noise from surface EMG signals using adaptive filtering.

Surface electromyograms (EMGs) are valuable in the pathophysiological study and clinical treatment for dystonia. These recordings are critically often contaminated by cardiac artefact. Our objective of this study was to evaluate the performance of an adaptive noise cancellation filter in removing electrocardiogram (ECG) interference from surface EMGs recorded from the trapezius muscles of patients with cervical dystonia. Performance of the proposed recursive-least-square adaptive filter was first quantified by coherence and signal-to-noise ratio measures in simulated noisy EMG signals. The influence of parameters such as the signal-to-noise ratio, forgetting factor, filter order and regularization factor were assessed. Fast convergence of the recursive-least-square algorithm enabled the filter to track complex dystonic EMGs and effectively remove ECG noise. This adaptive filter procedure proved a reliable and efficient tool to remove ECG artefact from surface EMGs with mixed and varied patterns of transient, short and long lasting dystonic contractions.

Alpha oscillations in the pedunculopontine nucleus correlate with gait performance in parkinsonism

The pedunculopontine nucleus, a component of the reticular formation, is topographically organized in animal models and implicated in locomotor control. In Parkinsons disease, pedunculopontine nucleus stimulation is an emerging treatment for gait freezing. Local field potentials recorded from pedunculopontine nucleus electrodes in such patients have demonstrated oscillations in the alpha and beta frequency bands, reactive to self-paced movement. Whether these oscillations are topographically organized or relevant to locomotion is unknown. Here, we recorded local field potentials from the pedunculopontine nucleus in parkinsonian patients during rest and unconstrained walking. Relative gait speed was assessed with trunk accelerometry. Peaks of alpha power were present at rest and during gait, when they correlated with gait speed. Gait freezing was associated with attenuation of alpha activity. Beta peaks were less consistently observed across rest and gait, and did not correlate with gait speed. Alpha power was maximal in the caudal pedunculopontine nucleus region and beta power was maximal rostrally. These results indicate a topographic distribution of neuronal activity in the pedunculopontine nucleus region and concur with animal data suggesting that the caudal subregion has particular relevance to gait. Alpha synchronization, proposed to suppress ‘task irrelevant’ distraction, has previously been demonstrated to correlate with performance of cognitive tasks. Here, we demonstrate a correlation between alpha oscillations and improved gait performance. The results raise the possibility that stimulation of caudal and rostral pedunculopontine nucleus regions may differ in their clinical effects.

Long-term outcomes of deep brain stimulation for neuropathic pain.

BACKGROUND Deep brain stimulation (DBS) to treat neuropathic pain refractory to pharmacotherapy has reported variable outcomes and has gained United Kingdom but not USA regulatory approval. OBJECTIVE To prospectively assess long-term efficacy of DBS for chronic neuropathic pain in a single-center case series. METHODS Patient reported outcome measures were collated before and after surgery, using a visual analog score, short-form 36-question quality-of-life survey, McGill pain questionnaire, and EuroQol-5D questionnaires (EQ-5D and health state). RESULTS One hundred ninety-seven patients were referred over 12 years, of whom 85 received DBS for various etiologies: 9 amputees, 7 brachial plexus injuries, 31 after stroke, 13 with spinal pathology, 15 with head and face pain, and 10 miscellaneous. Mean age at surgery was 52 years, and mean follow-up was 19.6 months. Contralateral DBS targeted the periventricular gray area (n = 33), the ventral posterior nuclei of the thalamus (n = 15), or both targets (n = 37). Almost 70% (69.4%) of patients retained implants 6 months after surgery. Thirty-nine of 59 (66%) of those implanted gained benefit and efficacy varied by etiology, improving outcomes in 89% after amputation and 70% after stroke. In this cohort, >30% improvements sustained in visual analog score, McGill pain questionnaire, short-form 36-question quality-of-life survey, and EuroQol-5D questionnaire were observed in 15 patients with >42 months of follow-up, with several outcome measures improving from those assessed at 1 year. CONCLUSION DBS for pain has long-term efficacy for select etiologies. Clinical trials retaining patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.

A role for the subthalamic nucleus in response inhibition during conflict.

The subthalamic nucleus (STN) is a key node in the network that supports response inhibition. It is suggested that the STN rapidly inhibits basal ganglia activity, to pause motor output during conflict until an appropriate motor plan is ready. Here, we recorded neural activity during a Stroop task from deep brain stimulation electrodes implanted in the human STN. We intended to determine whether cognitive psychological phenomena such as the Stroop effect can be explained via mechanisms of response inhibition involving the STN, or whether higher cognitive centers are alone responsible. We show stimulus-driven desychronization in the beta band (15–35 Hz) that lasts throughout the verbal response, in keeping with the idea that beta-band synchrony decreases to allow motor output to occur. During incongruent trials—in which response times were elongated due to the Stroop effect—a resynchronization was seen in the beta band before response. Crucially, in the incongruent trials during which the participant was unable to withhold the prepotent response, this resynchronization occurred after response onset. We suggest that this beta-band resynchronization pauses the motor system until conflict can be resolved.

Connectivity of the pedunculopontine nucleus in parkinsonian freezing of gait.

Parkinsons disease (PD) may involve sudden unintended arrests in gait or failure to initiate gait, known as gait freezing. Deep brain stimulation of the pedunculopontine nucleus (PPN) has been found to be an effective therapy for this phenomenon. In this study, we characterized the connectivity of the PPN freezing of gait (FOG) patients, compared with non-FOG PD and healthy controls using diffusion tensor imaging techniques. Differences in PPN connectivity profiles of the study groups were shown in the cerebellum and pons. The PPN showed connectivity with the cerebellum in controls and non-FOG PD. FOG patients showed absence of cerebellar connectivity, and increased visibility of the decussation of corticopontine fibres in the anterior pons. The findings suggest that corticopontine projections, which cross at the pons are increased in gait freezing, highlighting the importance and role of corticopontine–cerebellar pathways in the pathophysiology of this phenomenon.