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Contrasting Connectivity of the Vim and Vop Nuclei of the Motor Thalamus Demonstrated by Probabilistic Tractography.
BACKGROUND:: Targeting of the motor thalamus for the treatment of tremor has traditionally been achieved by a combination of anatomical atlases and neuro-imaging, intra-operative clinical assessment, and physiological recordings. OBJECTIVE:: To evaluate whether thalamic nuclei targeted in tremor surgery could be identified by virtue of their differing connections using non-invasive neuro-imaging, thereby providing an extra factor to aid successful targeting. METHODS:: Diffusion tensor tractography was performed in seventeen healthy control subjects using diffusion data acquired at 1.5T magnetic resonance imaging (60 directions, b-value=1000 s/mm, 2x2x2 mm voxels). The ventralis intermedius (Vim) and ventralis oralis posterior (Vop) nuclei were identified by a stereotactic neurosurgeon and these sites were used as seeds for probabilistic tractography. The expected cortical connections of these nuclei were determined a priori from the literature, namely the primary motor cortex (M1) and contralateral cerebellum for the Vim and M1, the supplementary motor area (SMA) and dorsolateral prefrontal cortex (DLPFC) for the Vop. RESULTS:: Tractogram signal intensity was highest in the DLPFC and SMA after Vop seeding (p<0.0005 using Wilcoxon signed-rank tests). High intensity was seen in M1 after seeding of both nuclei, but was greater with Vim seeding (p<0.0005). Contralateral cerebellar signal was highest with Vim seeding (p<0.0005). CONCLUSION:: Probabilistic tractography can depict differences in connectivity between intimate nuclei within the motor thalamus. These connections are consistent with published anatomical studies and therefore tractography may provide an important adjunct in future targeting in tremor surgery.
Auditory event-related potentials differ in dyslexics even when auditory psychophysical performance is normal.
Developmental dyslexia is characterized by a phonological processing deficit and impaired low-level auditory processing may contribute to this problem. However, this remains controversial because not all dyslexic individuals show psychophysical deficits on auditory processing tasks; hence it has been argued that auditory processing deficits are not a causal factor in dyslexia. Because behavioral psychophysical tasks include both bottom-up processing and top-down strategies, dyslexics' successful coping strategies may positively influence their performance on auditory behavioral measures. Therefore we have studied whether dyslexics who perform adequately on auditory psychophysical tasks nevertheless show electrophysiological evidence of impaired auditory processing. We compared auditory event-related mismatch negativity (MMN) potentials to frequency modulated (FM) tones at 5, 20 and 240 Hz between dyslexic adults and controls. Groups were matched for age, cognitive ability and psychophysical FM detection thresholds. The dyslexic group showed significantly smaller MMNs in the 20 Hz FM condition in both the early (150-300 ms, P=0.010) and late (300-500 ms, P=0.049) time frames. A 2-way ANOVA showed a significant group by FM rate interaction (P=0.012). There were no significant differences between the groups in the 5 Hz or 240 Hz conditions. The magnitude of the 20 Hz FM MMN correlated with the degree of discrepancy between cognitive and literacy skills (0.66, P=0.003) in the entire group. Thus, even among compensated dyslexics with above-average cognitive abilities and adequate performance on auditory psychophysical tasks, the MMN responses of some dyslexic adults were found to be abnormal.
Magnocellular mediated visual-spatial attention and reading ability.
This study explores the relationship between attentional processing mediated by visual magnocellular (MC) processing and reading ability. Reading ability in a group of primary school children was compared to performance on a visual cued coherent motion detection task. The results showed that a brief spatial cue was more effective in drawing attention either away or towards a visual target in the group of readers ranked in the upper 25% of the sample compared to lower ranked readers. Regression analysis showed a significant relationship between attentional processing and reading when the effects of age and intellectual ability were removed. Results suggested a stronger relationship between visual attentional and non-word reading compared to irregular word reading.
Pedunculopontine stimulation from primate to patient
Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel neurosurgical therapy developed to address symptoms of gait freezing and postural instability in Parkinson's disease and related disorders. Here we summarise our non-human primate investigations of relevance to our surgical targeting of the PPN and relate the primate research to initial clinical experience of PPN DBS. © Springer-Verlag 2010.
Application of a null-beamformer to source localisation in MEG data of deep brain stimulation.
In this paper, we present an analysis of magnetoencephalography (MEG) signals from a patient with whole-body chronic pain in order to investigate changes in neural activity induced by DBS. The patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). Using MEG to reconstruct the neural activity of interest is challenging because of interference to the signal from the DBS device. We demonstrate that a null-beamformer can be used to localise neural activity despite artefacts caused by the presence of DBS electrodes and stimulus pulses. We subsequently verified the accuracy of our source localisation by correlating the predicted DBS electrode positions with their actual positions, previously identified using anatomical imaging. We also demonstrated increased activity in pain-related regions including the pre-supplementary motor area, brainstem periaqueductal gray and medial prefrontal areas when the patient was in pain compared to when the patient experienced pain relief.
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 one's 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.
Regional cerebral perfusion differences between periventricular grey, thalamic and dual target deep brain stimulation for chronic neuropathic pain.
Regional cerebral blood flow changes were evaluated in different subcortical brain targets following deep brain stimulation (DBS) for chronic pain. Three patients with intractable neuropathic pain were assessed; one had stimulating electrodes in the ventroposterolateral thalamic nucleus (VPL), one in the periventricular grey (PVG) area, and one had electrodes in both targets. Pain relief was achieved in all patients. Cerebral perfusion was measured by single-photon emission computed tomography to determine the effects of DBS. Comparison was made between individual scans using subtraction analysis. DBS consistently increased perfusion in the posterior subcortical region between VPL and PVG, regardless of the site of stimulation. Furthermore, thalamic and dual target DBS increased thalamic perfusion, yet PVG DBS decreased perfusion in the PVG-containing midbrain region and thalamus. Dual target stimulation decreased anterior cingulate and insular cortex perfusion. The study demonstrates regional differences in cerebral perfusion between three accepted and efficacious targets for analgesic DBS.
Local field potentials reveal a distinctive neural signature of cluster headache in the hypothalamus.
Cluster headache (CH) is a debilitating neurovascular condition characterized by severe unilateral periorbital head pain. Deep brain stimulation of the posterior hypothalamus has shown potential in alleviating CH in its most severe, chronic form. During surgical implantation of stimulating macroelectrodes for cluster head pain, one of our patients suffered a CH attack. During the attack local field potentials displayed a significant increase in power of approximately 20 Hz. To the authors' knowledge, this is the first recorded account of neuronal activity observed during a cluster attack. Our results both support and extend the current literature, which has long implicated hypothalamic activation as key to CH generation, predominantly through indirect haemodynamic neuroimaging techniques. Our findings reveal a potential locus in CH neurogenesis and a potential rationale for efficacious stimulator titration.
Pedunculopontine stimulation from primate to patient.
Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel neurosurgical therapy developed to address symptoms of gait freezing and postural instability in Parkinson's disease and related disorders. Here we summarise our non-human primate investigations of relevance to our surgical targeting of the PPN and relate the primate research to initial clinical experience of PPN DBS.
Connectivity of an effective hypothalamic surgical target for cluster headache.
The purpose of this study was to look at the connectivity of the posterior inferior hypothalamus in a patient implanted with a deep brain stimulating electrode using probabilistic tractography in conjunction with postoperative MRI scans. In a patient with chronic cluster headache we implanted a deep brain stimulating electrode into the ipsilateral postero-medial hypothalamus to successfully control his pain. To explore the connectivity, we used the surgical target from the postoperative MRI scan as a seed for probabilistic tractography, which was then linked to diffusion weighted imaging data acquired in a group of healthy control subjects. We found highly consistent connections with the reticular nucleus and cerebellum. In some subjects, connections were also seen with the parietal cortices, and the inferior medial frontal gyrus. Our results illustrate important anatomical connections that may explain the functional changes associated with cluster headaches and elucidate possible mechanisms responsible for triggering attacks.
Pre-operative DTI and probabilisitic tractography in four patients with deep brain stimulation for chronic pain.
This study aimed to examine, using diffusion tensor imaging (DTI), differences in electrode placement in four patients undergoing deep brain stimulation for chronic neuropathic pain of varying aetiology. A pre-operative DTI was obtained for each patient, who was then implanted with deep brain stimulation electrodes in the periventricular/periaqueductal grey area with good pain relief. Using seeds from the postoperative MRI scan, probabilistic tractography was performed from the pre-operative DTI.
Use of surface electromyography to assess and select patients with idiopathic dystonia for bilateral pallidal stimulation.
OBJECT: The object of this study was to identify a preoperative physiological index by using surface electromyography (EMG) signals that would correlate with clinical outcome in dystonic patients following bilateral pallidal stimulation. METHODS: In 14 patients with spasmodic torticollis, generalized dystonia, and myoclonic dystonia, surface EMG signals were recorded from the most affected muscle groups. Although the dystonia affected different body segments, the EMG signals in all patients could be decomposed into bursting and sustained components. Subsequently, a ratio of the EMG amplitude was calculated between the two components and then correlated with clinical outcome. Patients who experienced rapid improvement following bilateral pallidal stimulation had a significantly higher EMG ratio compared with those who did not. Furthermore, a significant correlation was found between the EMG ratio and clinical improvement during the 12-month period following pallidal stimulation. CONCLUSIONS: The authors concluded that surface EMG studies could be used to predict the clinical outcome of and to select patients for pallidal stimulation for dystonia.
Contrasting connectivity of the ventralis intermedius and ventralis oralis posterior nuclei of the motor thalamus demonstrated by probabilistic tractography.
BACKGROUND: Targeting of the motor thalamus for the treatment of tremor has traditionally been achieved by a combination of anatomical atlases and neuroimaging, intraoperative clinical assessment, and physiological recordings. OBJECTIVE: To evaluate whether thalamic nuclei targeted in tremor surgery could be identified by virtue of their differing connections with noninvasive neuroimaging, thereby providing an extra factor to aid successful targeting. METHODS: Diffusion tensor tractography was performed in 17 healthy control subjects using diffusion data acquired at 1.5-T magnetic resonance imaging (60 directions, b value = 1000 s/mm, 2 × 2 × 2-mm³ voxels). The ventralis intermedius (Vim) and ventralis oralis posterior (Vop) nuclei were identified by a stereotactic neurosurgeon, and these sites were used as seeds for probabilistic tractography. The expected cortical connections of these nuclei, namely the primary motor cortex (M1) and contralateral cerebellum for the Vim and M1, the supplementary motor area, and dorsolateral prefrontal cortex for the Vop, were determined a priori from the literature. RESULTS: Tractogram signal intensity was highest in the dorsolateral prefrontal cortex and supplementary motor area after Vop seeding (P < .001, Wilcoxon signed-rank tests). High intensity was seen in M1 after seeding of both nuclei but was greater with Vim seeding (P < .001). Contralateral cerebellar signal was highest with Vim seeding (P < .001). CONCLUSION: Probabilistic tractography can depict differences in connectivity between intimate nuclei within the motor thalamus. These connections are consistent with published anatomical studies; therefore, tractography may provide an important adjunct in future targeting in tremor surgery.
Deep brain stimulation for the alleviation of post-stroke neuropathic pain.
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 McGill's 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 for chronic pain investigated with magnetoencephalography.
Deep brain stimulation has shown remarkable potential in alleviating otherwise treatment-resistant chronic pain, but little is currently known about the underlying neural mechanisms. Here for the first time, we used noninvasive neuroimaging by magnetoencephalography to map changes in neural activity induced by deep brain stimulation in a patient with severe phantom limb pain. When the stimulator was turned off, the patient reported significant increases in subjective pain. Corresponding significant changes in neural activity were found in a network including the mid-anterior orbitofrontal and subgenual cingulate cortices; these areas are known to be involved in pain relief. Hence, they could potentially serve as future surgical targets to relieve chronic pain.
Connectivity of the pedunculopontine nucleus in parkinsonian freezing of gait.
Parkinson's 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.
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.