New method for quantification and statistical analysis of nociceptive reflex receptive fields in humans

A method for quantifying nociceptive withdrawal reflex receptive fields in human volunteers and patients is described. The reflex receptive field (RRF) for a specific muscle denotes the cutaneous area from which a muscle contraction can be evoked by a nociceptive stimulus. The method is based on random stimulations presented in a blinded sequence to 10 stimulation sites. The sensitivity map is derived by interpolating the reflex responses evoked from the 10 sites. A set of features describing the size and location of the RRF is presented based on statistical analysis of the sensitivity map within every subject. The features include RRF area, volume, peak location and center of gravity. The method was applied to 30 healthy volunteers. Electrical stimuli were applied to the sole of the foot evoking reflexes in the ankle flexor tibialis anterior. The RRF area covered a fraction of 0.57+/-0.06 (S.E.M.) of the foot and was located on the medial, distal part of the sole of the foot. An intramuscular injection into flexor digitorum brevis of capsaicin was performed in one spinal cord injured subject to attempt modulation of the reflex receptive field. The RRF area, RRF volume and location of the peak reflex response appear to be the most sensitive measures for detecting modulation of spinal nociceptive processing. This new method has important potential applications for exploring aspects of central plasticity in volunteers and patients. It may be utilized as a new diagnostic tool for central hypersensitivity and quantification of therapeutic interventions.

Thalamic stimulation for tremor. Subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect

The aim of this study was to investigate the impact of unilateral deep brain stimulation (DBS) of the ventrointermediate (Vim) thalamic nucleus on neuropsychological functioning comparing stimulation-on with stimulation-off conditions. Nine patients [five patients with Parkinson's Disease (PD), two patients with essential tremor (ET) and 2 patients with multiple sclerosis (MS)] underwent comprehensive neuropsychological testing for cognitive functions, including general mental impairment, aphasia, agnosia, executive and constructional abilities, learning, memory, cognitive processing speed and attention as well as depression. The neuropsychological assessments were performed at least 6 months postoperatively (mean 9 months). Testing in the stimulation-on and stimulation-off condition was obtained within a period of 3 to 4 weeks. Unilateral DBS resulted in improvement of tremor in all patients. There were no significant differences between the stimulation-on and the stimulation-off condition with the exception of a decrement of word-recall in the short delay free-recall subtest of the Rey Auditory-Verbal Learning Test (RAVLT). Subgroup analysis indicated that the impairment in word-recall was related to left-sided thalamic stimulation. Our study confirms that chronic unilateral DBS is a safe method with regard to cognitive function. The subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect.

Neglect-like visual exploration behaviour after theta burst transcranial magnetic stimulation of the right posterior parietal cortex

The right posterior parietal cortex (PPC) is critically involved in visual exploration behaviour, and damage to this area may lead to neglect of the left hemispace. We investigated whether neglect-like visual exploration behaviour could be induced in healthy subjects using theta burst repetitive transcranial magnetic stimulation (rTMS). To this end, one continuous train of theta burst rTMS was applied over the right PPC in 12 healthy subjects prior to a visual exploration task where colour photographs of real-life scenes were presented on a computer screen. In a control experiment, stimulation was also applied over the vertex. Eye movements were measured, and the distribution of visual fixations in the left and right halves of the screen was analysed. In comparison to the performance of 28 control subjects without stimulation, theta burst rTMS over the right PPC, but not the vertex, significantly decreased cumulative fixation duration in the left screen-half and significantly increased cumulative fixation duration in the right screen-half for a time period of 30 min. These results suggest that theta burst rTMS is a reliable method of inducing transient neglect-like visual exploration behaviour.

Enhancing rehabilitation of motor deficits with peripheral nerve stimulation

A number of different neurorehabilitation strategies include manipulation of the somatosensory system, e.g. in the form of training by passive movement. Recently, peripheral electrical nerve stimulation has been proposed as a simple, painless method of enhancing rehabilitation of motor deficits. Several physiological studies both in animals and in humans indicate that a prolonged period of patterned peripheral electrical stimulation induces short-term plasticity at multiple levels of the motor system. Small-scale studies in humans indicate that these plastic changes are linked with improvement in motor function, particularly in patients with chronic motor deficits after stroke. Somatosensory-mediated disinhibition of motor pathways is a possible underlying mechanism and might explain why peripheral electrical stimulation is more effective when combined with active training. Further large-scale studies are needed to identify the optimal stimulation protocol and the patient groups that stand to benefit the most from this technique.

Impact of coil position and electrophysiological monitoring on determination of motor thresholds to transcranial magnetic stimulation

OBJECTIVE: We compared motor and movement thresholds to transcranial magnetic stimulation (TMS) in healthy subjects and investigated the effect of different coil positions on thresholds and MEP (motor-evoked potential) amplitudes. METHODS: The abductor pollicis brevis (APB) 'hot spot' and a standard scalp position were stimulated. APB resting motor threshold (APB MEP-MT) defined by the '5/10' electrophysiological method was compared with movement threshold (MOV-MT), defined by visualization of movements. Additionally, APB MEP-MTs were evaluated with the '3/6 method,' and MEPs were recorded at a stimulation intensity of 120% APB MEP-MT at each position. RESULTS: APB MEP-MTs were significantly lower by stimulation of the 'hot spot' than of the standard position, and significantly lower than MOV-MTs (n=15). There were no significant differences between the '3/6' and the '5/10' methods, or between APB MEP amplitudes by stimulating each position at 120% APB MEP-MT. CONCLUSIONS: Coil position and electrophysiological monitoring influenced motor threshold determinations. Performing 6 instead of 10 trials did not produce different threshold measurements. Adjustment of intensity according to APB MEP-MT at the stimulated position did not influence APB MEP amplitudes. SIGNIFICANCE: Standardization of stimulation positions, nomenclature and criteria for threshold measurements should be considered in design and comparison of TMS protocols.

Neurophysiology and neuroanatomy of reflexive and volitional saccades as revealed by lesion studies with neurological patients and transcranial magnetic stimulation (TMS)

This review discusses the neurophysiology and neuroanatomy of the cortical control of reflexive and volitional saccades in humans. The main focus is on classical lesion studies and studies using the interference method of transcranial magnetic stimulation (TMS). To understand the behavioural function of a region, it is essential to assess oculomotor deficits after a focal lesion using a variety of oculomotor paradigms, and to study the oculomotor consequences of the lesion in the chronic phase. Saccades are controlled by different cortical regions, which could be partially specialised in the triggering of a specific type of saccade. The division of saccades into reflexive visually guided saccades and intentional or volitional saccades corresponds to distinct regions of the neuronal network, which are involved in the control of such saccades. TMS allows to specifically interfere with the functioning of a region within an intact oculomotor network. TMS provides advantages in terms of temporal resolution, allowing to interfere with brain functioning in the order of milliseconds, thereby allowing to define the time course of saccade planning and execution. In the first part of the paper, we present an overview of the cortical structures important for saccade control, and discuss the pro's and con's of the different methodological approaches to study the cortical oculomotor network. In the second part, the functional network involved in reflexive and volitional saccades is presented. Finally, studies concerning recovery mechanisms after a lesion of the oculomotor cortex are discussed.

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease

OBJECT: The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. METHODS: Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. RESULTS: Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. CONCLUSIONS: This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

Null-wave giant gravitons from thermal spinning brane probes

We construct and analyze thermal spinning giant gravitons in type II/M-theory based on spherically wrapped black branes, using the method of thermal probe branes originating from the blackfold approach. These solutions generalize in different directions recent work in which the case of thermal (non-spinning) D3-brane giant gravitons was considered, and reveal a rich phase structure with various new properties. First of all, we extend the construction to M-theory, by constructing thermal giant graviton solutions using spherically wrapped M2- and M5-branes. More importantly, we switch on new quantum numbers, namely internal spins on the sphere, which are not present in the usual extremal limit for which the brane world volume stress tensor is Lorentz invariant. We examine the effect of this new type of excitation and in particular analyze the physical quantities in various regimes, including that of small temperatures as well as low/high spin. As a byproduct we find new stationary dipole-charged black hole solutions in AdS m × S n backgrounds of type II/M-theory. We finally show, via a double scaling extremal limit, that our spinning thermal giant graviton solutions lead to a novel null-wave zero-temperature giant graviton solution with a BPS spectrum, which does not have an analogue in terms of the conventional weakly coupled world volume theory.

Hard thermal loop benchmark for the extraction of the nonperturbative QQ[over ¯] potential

The extraction of the finite temperature heavy quark potential from lattice QCD relies on a spectral analysis of the Wilson loop. General arguments tell us that the lowest lying spectral peak encodes, through its position and shape, the real and imaginary parts of this complex potential. Here we benchmark this extraction strategy using leading order hard-thermal loop (HTL) calculations. In other words, we analytically calculate the Wilson loop and determine the corresponding spectrum. By fitting its lowest lying peak we obtain the real and imaginary parts and confirm that the knowledge of the lowest peak alone is sufficient for obtaining the potential. Access to the full spectrum allows an investigation of spectral features that do not contribute to the potential but can pose a challenge to numerical attempts of an analytic continuation from imaginary time data. Differences in these contributions between the Wilson loop and gauge fixed Wilson line correlators are discussed. To better understand the difficulties in a numerical extraction we deploy the maximum entropy method with extended search space to HTL correlators in Euclidean time and observe how well the known spectral function and values for the real and imaginary parts are reproduced. Possible venues for improvement of the extraction strategy are discussed.

Validation of targeting the ventrointermediate thalamic nucleus using Q-ball calculation in deep brain stimulation for tremor

Objective: Identification of the ventrointermediate thalamic nucleus (Vim) in modern 3T high-field MRI for image-based targeting in deep brain stimulation (DBS) is still challenging. To evaluate the usefulness and reliability of analyzing the connectivity with the cerebellum using Q-ball-calculation we performed a retrospective analysis. Method: 5 patients who underwent bilateral implantation of electrodes in the Vim for treatment of Essential Tremor between 2011 and 2012 received additional preoperative Q-ball imaging. Targeting was performed according to atlas coordinates and standard MRI. Additionally we performed a retrospective identification of the Vim by analyzing the connectivity of the thalamus with the dentate nucleus. The exact position of the active stimulation contact in the postoperative CT was correlated with the Vim as it was identified by Q-ball calculation. Results: Localization of the Vim by analysis of the connectivity between thalamus and cerebellum was successful in all 5 patients on both sides. The average position of the active contacts was 14.6 mm (SD 1.24) lateral, 5.37 mm (SD 0.094 posterior and 2.21 mm (SD 0.69) cranial of MC. The cranial portion of the dentato-rubro-thalamic tract was localized an average of 3.38 mm (SD 1.57) lateral and 1.5 mm (SD 1.22) posterior of the active contact. Conclusions: Connectivity analysis by Q-ball calculation provided direct visualization of the Vim in all cases. Our preliminary results suggest, that the target determined by connectivity analysis is valid and could possibly be used in addition to or even instead of atlas based targeting. Larger prospective calculations are needed to determine the robustness of this method in providing refined information useful for neurosurgical treatment of tremor.

Physiological effects of mechanical pain stimulation at the lower back measured by functional near-infrared spectroscopy and capnography

The aim was to investigate the effect of mechanical pain stimulation at the lower back on hemodynamic and oxygenation changes in the prefrontal cortex (PFC) assessed by functional near-infrared spectroscopy (fNIRS) and on the partial pressure of end-tidal carbon dioxide ( PetCO 2) measured by capnography. 13 healthy subjects underwent three measurements (M) during pain stimulation using pressure pain threshold (PPT) at three locations, i.e., the processus spinosus at the level of L4 (M1) and the lumbar paravertebral muscles at the level of L1 on the left (M2) and the right (M3) side. Results showed that only in the M2 condition the pain stimulation elicited characteristic patterns consisting of (1) a fNIRS-derived decrease in oxy- and total hemoglobin concentration and tissue oxygen saturation, an increase in deoxy-hemoglobin concentration, (2) a decrease in the PetCO 2 response and (3) a decrease in coherence between fNIRS parameters and PetCO 2 responses in the respiratory frequency band (0.2-0.5 Hz). We discuss the comparison between M2 vs. M1 and M3, suggesting that the non-significant findings in the two latter measurements were most likely subject to effects of the different stimulated tissues, the stimulated locations and the stimulation order. We highlight that PetCO 2 is a crucial parameter for proper interpretation of fNIRS data in experimental protocols involving pain stimulation. Together, our data suggest that the combined fNIRS-capnography approach has potential for further development as pain monitoring method, such as for evaluating clinical pain treatment.

Modulation of corticospinal activity by strong emotions evoked by pictures and classical music: a transcranial magnetic stimulation study.

Using transcranial magnetic stimulation and skin conductance responses, we sought to clarify if, and to what extent, emotional experiences of different valences and intensity activate the hand-motor system and the associated corticospinal tract. For that purpose, we applied a newly developed method to evoke strong emotional experiences by the simultaneous presentation of musical and pictorial stimuli of congruent emotional valence. We uncovered enhanced motor-evoked potentials, irrespective of valence, during the simultaneous presentation of emotional music and picture stimuli (Combined conditions) compared with the single presentation of the two modalities (Picture/Music conditions). In contrast, vegetative arousal was enhanced during both the Combined and Music conditions, compared with the Picture conditions, again irrespective of emotional valence. These findings strongly indicate that arousal is a necessary, but not sufficient, prerequisite for triggering the motor system of the brain. We offer a potential explanation for this discrepant, but intriguing, finding in the paper.

Enhancing treatment effects by combining continuous theta burst stimulation with smooth pursuit training

Continuous theta burst stimulation (cTBS) represents a promising approach in the treatment of neglect syndrom. However, it is not known whether cTBS in conjunction with another technique may enhance the therapeutic effects. In the present sham-controlled study, we aimed to combine cTBS with smooth pursuit training (SPT), another method known to effectively improve neglect symptoms, and to evaluate whether this combination would result in a stronger effect than SPT alone. Eighteen patients with left spatial neglect after right-hemispheric stroke were included in the study and performed a cancellation task on a large 54.6" touchscreen monitor. A sequential application of cTBS and SPT induced a significantly greater improvement of neglect than SPT alone. After the combined application of these two methods, patients detected significantly more targets and their cancellation behaviour presented a significantly greater shift towards the contralesional hemispace. We suggest that a combined, sequential application of cTBS and SPT is a promising new approach to treat neglect.

Continuous dynamic mapping of the corticospinal tract during surgery of motor eloquent brain tumors: evaluation of a new method

OBJECT The authors developed a new mapping technique to overcome the temporal and spatial limitations of classic subcortical mapping of the corticospinal tract (CST). The feasibility and safety of continuous (0.4-2 Hz) and dynamic (at the site of and synchronized with tissue resection) subcortical motor mapping was evaluated. METHODS The authors prospectively studied 69 patients who underwent tumor surgery adjacent to the CST (< 1 cm using diffusion tensor imaging and fiber tracking) with simultaneous subcortical monopolar motor mapping (short train, interstimulus interval 4 msec, pulse duration 500 μsec) and a new acoustic motor evoked potential alarm. Continuous (temporal coverage) and dynamic (spatial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device, with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS All procedures were technically successful. There was a 1:1 correlation of motor thresholds for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (24 patients, 74 stimulation points; r(2) = 0.98, p < 0.001). The lowest individual motor thresholds were as follows: > 20 mA, 7 patients; 11-20 mA, 13 patients; 6-10 mA, 8 patients; 4-5 mA, 17 patients; and 1-3 mA, 24 patients. At 3 months, 2 patients (3%) had a persistent postoperative motor deficit, both of which were caused by a vascular injury. No patient had a permanent motor deficit caused by a mechanical injury of the CST. CONCLUSIONS Continuous dynamic mapping was found to be a feasible and ergonomic technique for localizing the exact site of the CST and distance to the motor fibers. The acoustic feedback and the ability to stimulate the tissue continuously and exactly at the site of tissue removal improves the accuracy of mapping, especially at low (< 5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery.

Thermal dependence of luminescence lifetimes and radioluminescence in quartz

During time-resolved optical stimulation experiments (TR-OSL), one uses short light pulses to separate the stimulation and emission of luminescence in time. Experimental TR-OSL results show that the luminescence lifetime in quartz of sedimentary origin is independent of annealing temperature below 500 °C, but decreases monotonically thereafter. These results have been interpreted previously empirically on the basis of the existence of two separate luminescence centers LH and LL in quartz, each with its own distinct luminescence lifetime. Additional experimental evidence also supports the presence of a non-luminescent hole reservoir R, which plays a critical role in the predose effect in this material. This paper extends a recently published analytical model for thermal quenching in quartz, to include the two luminescence centers LH and LL, as well as the hole reservoir R. The new extended model involves localized electronic transitions between energy states within the two luminescence centers, and is described by a system of differential equations based on the Mott–Seitz mechanism of thermal quenching. It is shown that by using simplifying physical assumptions, one can obtain analytical solutions for the intensity of the light during a TR-OSL experiment carried out with previously annealed samples. These analytical expressions are found to be in good agreement with the numerical solutions of the equations. The results from the model are shown to be in quantitative agreement with published experimental data for commercially available quartz samples. Specifically the model describes the variation of the luminescence lifetimes with (a) annealing temperatures between room temperature and 900 °C, and (b) with stimulation temperatures between 20 and 200 °C. This paper also reports new radioluminescence (RL) measurements carried out using the same commercially available quartz samples. Gaussian deconvolution of the RL emission spectra was carried out using a total of seven emission bands between 1.5 and 4.5 eV, and the behavior of these bands was examined as a function of the annealing temperature. An emission band at ∼3.44 eV (360 nm) was found to be strongly enhanced when the annealing temperature was increased to 500 °C, and this band underwent a significant reduction in intensity with further increase in temperature. Furthermore, a new emission band at ∼3.73 eV (330 nm) became apparent for annealing temperatures in the range 600–700 °C. These new experimental results are discussed within the context of the model presented in this paper.