Modeling of post-stroke stimulation of cortical tissue.

Following a stroke, cortical networks in the penumbra area become fragmented and partly deactivated. We develop a model to study the propagation of waves of electric potential in the cortical tissue with integro-differential equations arising in neural field models. The wave speed is characterized by the tissue excitability and connectivity determined through parameters of the model. Post-stroke tissue damage in the penumbra area creates a hypoconnectivity and decreases the speed of wave propagation. It is proposed that external stimulation could restore the wave speed in the penumbra area under certain conditions of the parameters. Model guided cortical stimulation could be used to improve the functioning of cortical networks.

Speech and language adverse effects after thalamotomy and deep brain stimulation in patients with movement disorders: A meta-analysis.

BACKGROUND: The thalamus has been a surgical target for the treatment of various movement disorders. Commonly used therapeutic modalities include ablative and nonablative procedures. A major clinical side effect of thalamic surgery is the appearance of speech problems. OBJECTIVE: This review summarizes the data on the development of speech problems after thalamic surgery. METHODS: A systematic review and meta-analysis was performed using nine databases, including Medline, Web of Science, and Cochrane Library. We also checked for articles by searching citing and cited articles. We retrieved studies between 1960 and September 2014. RESULTS: Of a total of 2,320 patients, 19.8% (confidence interval: 14.8-25.9) had speech difficulty after thalamotomy. Speech difficulty occurred in 15% (confidence interval: 9.8-22.2) of those treated with a unilaterally and 40.6% (confidence interval: 29.5-52.8) of those treated bilaterally. Speech impairment was noticed 2- to 3-fold more commonly after left-sided procedures (40.7% vs. 15.2%). Of the 572 patients that underwent DBS, 19.4% (confidence interval: 13.1-27.8) experienced speech difficulty. Subgroup analysis revealed that this complication occurs in 10.2% (confidence interval: 7.4-13.9) of patients treated unilaterally and 34.6% (confidence interval: 21.6-50.4) treated bilaterally. After thalamotomy, the risk was higher in Parkinson's patients compared to patients with essential tremor: 19.8% versus 4.5% in the unilateral group and 42.5% versus 13.9% in the bilateral group. After DBS, this rate was higher in essential tremor patients. CONCLUSION: Both lesioning and stimulation thalamic surgery produce adverse effects on speech. Left-sided and bilateral procedures are approximately 3-fold more likely to cause speech difficulty. This effect was higher after thalamotomy compared to DBS. In the thalamotomy group, the risk was higher in Parkinson's patients, whereas in the DBS group it was higher in patients with essential tremor. Understanding the pathophysiology of speech disturbance after thalamic procedures is a priority. © 2017 International Parkinson and Movement Disorder Society.

Repeated BOLD-fMRI imaging of deep brain stimulation responses in rats.

Functional magnetic resonance imaging (fMRI) provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol) with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP) thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1). The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91), and location (overlap ratio from 0.61 to 0.67). The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI.

Temporal patterns of deep brain stimulation generated with a true random number generator and the logistic equation: effects on CNS arousal in mice.

Deep brain stimulation (DBS) has shown promise in the treatment of many neurological and psychiatric disorders as well as a disorder of consciousness, the minimally conscious state (MCS). In the clinic, DBS is always monotonic standard pulses; however, we have hypothesized that temporally patterned pulses might be more efficient in achieving desired behavioral responses. Here we present two experiments on DBS of the central thalamus to increase arousal, as measured by motor activity, and to affect the electroencephalogram (EEG). In the first, we optimized amplitude and frequency in standard stimulation of the central thalamus in intact mice. In the second, the optimized fixed frequency was compared to two alternative temporal patterns, chaotic and random, which were physically identical to each other and fixed frequency in all ways except temporal pattern. In both experiments and with all types of stimulation, DBS of the central thalamus increased arousal as measured by motor activity. These data also revealed that temporal patterning of pulses can modulate response to stimulation. That temporal patterns in DBS of the central thalamus were found to alter motor activity response implies possible usefulness of temporal patterns in DBS of other contexts. More investigation into exactly how temporally patterned stimulation may affect neuronal circuit dynamics is necessary.

Hidden semi-Markov models in the computerized decoding of microelectrode recording data for deep brain stimulator placement.

OBJECTIVE: To describe an approach to the analysis of deep brain stimulation (DBS) of the subthalamic nucleus (STN) using a hidden semi-Markov model (HsMM) and early results of the analysis of microelectrode recordings for STN DBS. METHODS: The author simulated the anatomy and electrophysiology of STN DBS and built a seven-state model to compare Hidden Markov model (HMM) and HsMM approaches. RESULTS: Accuracy of these competing models was similar for correctly identifying brain nuclei; however, HsMMs showed superior specificity in detecting microelectrode passes traversing the STN. CONCLUSIONS: Further clinical work must be done; however, based on these data, HsMMs may be best suited to computer-assisted anatomic delineation for DBS.

Deep brain stimulation: from neurology to psychiatry?

Functional stereotaxy was introduced in the late 1940s to reduce the morbidity of lobotomy in psychiatric disease by using more focal lesions. The advent of neuroleptics led to a drastic decline in psychosurgery for several decades. Functional stereotactic neurosurgery has recently been revitalized, starting with treatment of Parkinson's disease, in which deep brain stimulation (DBS) facilitates reversible focal neuromodulation of altered basal ganglia circuits. DBS is now being extended to treatment of neuropsychiatric conditions such as Gilles de la Tourette syndrome, obsessive-compulsive disorder, depression and addiction. In this review, we discuss the concept that dysfunction of motor, limbic and associative cortico-basal ganglia-thalamocortical loops underlies these various disorders, which might now be amenable to DBS treatment.

Intracranial neurostimulation for pain control: a review.

Intracranial neurostimulation for pain relief is most frequently delivered by stimulating the motor cortex, the sensory thalamus, or the periaqueductal and periventricular gray matter. The stimulation of these sites through MCS (motor cortex stimulation) and DBS (deep brain stimulation) has proven effective for treating a number of neuropathic and nociceptive pain states that are not responsive or amenable to other therapies or types of neurostimulation. Prospective randomized clinical trials to confirm the efficacy of these intracranial therapies have not been published. Intracranial neurostimulation is somewhat different than other forms of neurostimulation in that its current primary application is for the treatment of medically intractable movement disorders. However, the increasing use of intracranial neurostimulation for the treatment of chronic pain, especially for pain not responsive to other neuromodulation techniques, reflects the efficacy and relative safety of these intracranial procedures. First employed in 1954, intracranial neurostimulation represents one of the earliest uses of neurostimulation to treat chronic pain that is refractory to medical therapy. Currently, 2 kinds of intracranial neurostimulation are commonly used to control pain: motor cortex stimulation and deep brain stimulation. MCS has shown particular promise in the treatment of trigeminal neuropathic pain and central pain syndromes such as thalamic pain syndrome. DBS may be employed for a number of nociceptive and neuropathic pain states, including cluster headaches, chronic low back pain, failed back surgery syndrome, peripheral neuropathic pain, facial deafferentation pain, and pain that is secondary to brachial plexus avulsion. The unique lack of stimulation-induced perceptual experience with MCS makes MCS uniquely suited for blinded studies of its effectiveness. This article will review the scientific rationale, indications, surgical techniques, and outcomes of intracranial neuromodulation procedures for the treatment of chronic pain.

Deep brain stimulation for dystonia: outcome at long-term follow-up.

OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic option for patients with insufficient benefit from conservative treatment. METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4), generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige syndrome (1) were available for formal follow-up at three years postoperatively, and beyond up to 10 years. All patients had undergone pallidal stimulation except one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS: Maintained improvement was seen in all patients with pallidal stimulation up to 10 years after surgery except in one patient who had a relative loss of benefit in dystonia ratings but continued to have improved disability scores. After nine years of chronic thalamic stimulation there was a mild loss of efficacy which was regained when the target was changed to the pallidum in the patient with paroxysmal dystonia. There were no major complications related to surgery or to chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in general. CONCLUSION: DBS maintains marked long-term symptomatic and functional improvement in the majority of patients with dystonia.

Mesial temporal inhibition in a patient with deep brain stimulation of the anterior thalamus for epilepsy.

We investigated the electrophysiological effects of high-frequency anterior thalamic deep brain stimulation using intracerebral mesial and lateral temporal depth electrodes in a patient with intractable focal epilepsy. Monopolar and bipolar stimulation delivered to the thalamic anterior nucleus using the programmable ITREL II stimulation device led to a significant decrease of cross power spectral density and a nonsignificant decrease of coherence in ipsilateral hippocampal structures. No such effect was found in lateral temporal or contralateral sites. The hippocampal inhibition was clearly related to the voltage (> or =7 V) and frequency (> or =70 Hz) of the thalamic stimulus and occurred with a delay of approximately 60 s after stimulus onset.

Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology.

BACKGROUND: Essential tremor (ET) is one of the most common tremor disorders in adults and is characterized by kinetic and postural tremor. To develop this practice parameter, the authors reviewed available evidence regarding initiation of pharmacologic and surgical therapies, duration of their effect, their relative benefits and risks, and the strength of evidence supporting their use. METHODS: A literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was performed to identify clinical trials in patients with ET published between 1966 and August 2004. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. RESULTS AND CONCLUSIONS: Propranolol and primidone reduce limb tremor (Level A). Alprazolam, atenolol, gabapentin (monotherapy), sotalol, and topiramate are probably effective in reducing limb tremor (Level B). Limited studies suggest that propranolol reduces head tremor (Level B). Clonazepam, clozapine, nadolol, and nimodipine possibly reduce limb tremor (Level C). Botulinum toxin A may reduce hand tremor but is associated with dose-dependent hand weakness (Level C). Botulinum toxin A may reduce head tremor (Level C) and voice tremor (Level C), but breathiness, hoarseness, and swallowing difficulties may occur in the treatment of voice tremor. Chronic deep brain stimulation (DBS) (Level C) and thalamotomy (Level C) are highly efficacious in reducing tremor. Each procedure carries a small risk of major complications. Some adverse events from DBS may resolve with time or with adjustment of stimulator settings. There is insufficient evidence regarding the surgical treatment of head and voice tremor and the use of gamma knife thalamotomy (Level U). Additional prospective, double-blind, placebo-controlled trials are needed to better determine the efficacy and side effects of pharmacologic and surgical treatments of ET.