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      Functional magnetic resonance imaging: cerebral function alterations in subthreshold and suprathreshold spinal cord stimulation

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          Background and purpose

          Failed back surgery syndrome (FBSS) is a common and devastating chronic neuropathic pain disorder. Conventional spinal cord stimulation (SCS) applies electrical suprathreshold pulses to the spinal cord at a frequency of 40–60 Hz and relieves pain in FBSS patients. During the last decade, two major changes have emerged in the techniques of stimulating the spinal cord: paresthesia-free or subthreshold stimulation and administration of higher frequency or higher amounts of energy to the spinal cord. Despite the positive clinical results, the mechanism of action remains unclear. A functional MRI (fMRI) study was conducted to investigate the brain alterations during subthreshold and suprathreshold stimulation at different frequencies.


          Ten subjects with FBSS, treated with externalized SCS, received randomly four different stimulation frequencies (4 Hz, 60 Hz, 500 Hz, and 1 kHz) during four consecutive days. At every frequency, the patient underwent sub- and suprathreshold stimulation. Cerebral activity was monitored and assessed using fMRI.


          Suprathreshold stimulation is generally accompanied with more activity than sub-threshold SCS. Suprathreshold SCS resulted in increased bilateral activation of the frontal cortex, thalamus, pre- and postcentral gyri, basal ganglia, cingulate gyrus, insula, thalamus, and claustrum. We observed deactivation of the bilateral parahippocampus, amygdala, precuneus, posterior cingulate gyrus, postcentral gyrus, and unilateral superior temporal gyrus.


          Suprathreshold stimulation resulted in greater activity (both activation and deactivation) of the frontal brain regions; the sensory, limbic, and motor cortices; and the diencephalon in comparison with subthreshold stimulation. Each type of frequency at suprathreshold stimulation was characterized by an individual activation pattern.

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          Most cited references 33

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          Estimating sample size in functional MRI (fMRI) neuroimaging studies: statistical power analyses.

          Estimation of statistical power in functional MRI (fMRI) requires knowledge of the expected percent signal change between two conditions as well as estimates of the variability in percent signal change. Variability can be divided into intra-subject variability, reflecting noise within the time series, and inter-subject variability, reflecting subject-to-subject differences in activation. The purpose of this study was to obtain estimates of percent signal change and the two sources of variability from fMRI data, and then use these parameter estimates in simulation experiments in order to generate power curves. Of interest from these simulations were conclusions concerning how many subjects are needed and how many time points within a scan are optimal in an fMRI study of cognitive function. Intra-subject variability was estimated from resting conditions, and inter-subject variability and percent signal change were estimated from verbal working memory data. Simulations derived from these parameters illustrate how percent signal change, intra- and inter-subject variability, and number of time points affect power. An empirical test experiment, using fMRI data acquired during somatosensory stimulation, showed good correspondence between the simulation-based power predictions and the power observed within somatosensory regions of interest. Our analyses suggested that for a liberal threshold of 0.05, about 12 subjects were required to achieve 80% power at the single voxel level for typical activations. At more realistic thresholds, that approach those used after correcting for multiple comparisons, the number of subjects doubled to maintain this level of power. Copyright 2002 Elsevier Science B.V.
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            Functional connectivity mapping of the human precuneus by resting state fMRI.

            Precuneus responds to a wide range of cognitive processes. Here, we examined how the patterns of resting state connectivity may define functional subregions in the precuneus. Using a K-means algorithm to cluster the whole-brain "correlograms" of the precuneus in 225 adult individuals, we corroborated the dorsal-anterior, dorsal-posterior, and ventral subregions, each involved in spatially guided behaviors, mental imagery, and episodic memory as well as self-related processing, with the ventral precuneus being part of the default mode network, as described extensively in earlier work. Furthermore, we showed that the lateral/medial volumes of dorsal anterior and dorsal posterior precuneus are each connected with areas of motor execution/attention and motor/visual imagery, respectively. Compared to the ventral precuneus, the dorsal precuneus showed greater connectivity with occipital and posterior parietal cortices, but less connectivity with the medial superior frontal and orbitofrontal gyri, anterior cingulate cortex as well as the parahippocampus. Compared to dorsal-posterior and ventral precuneus, the dorsal-anterior precuneus showed greater connectivity with the somatomotor cortex, as well as the insula, supramarginal, Heschl's, and superior temporal gyri, but less connectivity with the angular gyrus. Compared to ventral and dorsal-anterior precuneus, dorsal-posterior precuneus showed greater connectivity with the middle frontal gyrus. Notably, the precuneus as a whole has negative connectivity with the amygdala and the lateral and inferior orbital frontal gyri. Finally, men and women differed in the connectivity of precuneus. Men and women each showed greater connectivity with the dorsal precuneus in the cuneus and medial thalamus, respectively. Women also showed greater connectivity with ventral precuneus in the hippocampus/parahippocampus, middle/anterior cingulate gyrus, and middle occipital gyrus, compared to men. Taken together, these new findings may provide a useful platform upon which to further investigate sex-specific functional neuroanatomy of the precuneus and to elucidate the pathology of many neurological illnesses. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses.

              This review describes unique neuromodulatory influences on working memory prefrontal cortical (PFC) circuits that coordinate cognitive strength with arousal state. Working memory arises from recurrent excitation within layer III PFC pyramidal cell NMDA circuits, which are afflicted in aging and schizophrenia. Neuromodulators rapidly and flexibly alter the efficacy of these synaptic connections, while leaving the synaptic architecture unchanged, a process called dynamic network connectivity (DNC). Increases in calcium-cAMP signaling open ion channels in long, thin spines, gating network connections. Inhibition of calcium-cAMP signaling by stimulating α2A-adrenoceptors on spines strengthens synaptic efficacy and increases network firing, whereas optimal stimulation of dopamine D1 receptors sculpts network inputs to refine mental representation. Generalized increases in calcium-cAMP signaling during fatigue or stress disengage dlPFC recurrent circuits, reduce firing and impair top-down cognition. Impaired DNC regulation contributes to age-related cognitive decline, while genetic insults to DNC proteins are commonly linked to schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                24 October 2018
                : 11
                : 2517-2526
                [1 ]Department of Neurosurgery, Universitair Ziekenhuis Brussel, Brussels, Belgium, mtmoens@ 123456gmail.com
                [2 ]Department of Radiology, Universitair Ziekenhuis Brussel, Brussels, Belgium, mtmoens@ 123456gmail.com
                [3 ]Department of Radiology, Universitair Ziekenhuis Leuven, Leuven, Belgium
                [4 ]COMETRIX, Leuven, Belgium
                [5 ]Pain in Motion International Research Group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussel, Belgium
                [6 ]Department Anesthesiology, Universitair Ziekenhuis Brussel, Brussels, Belgium
                [7 ]Department of Neurology, Universitair Ziekenhuis Brussel, Brussels, Belgium
                [8 ]Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium, mtmoens@ 123456gmail.com
                Author notes
                Correspondence: Maarten Moens, Department of Neurosurgery, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, Brussels B-1090, Belgium, Tel +32 2 477 5514, Fax +32 2 477 8689, Email mtmoens@ 123456gmail.com
                © 2018 De Groote et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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