Shared premotor activity in spoken and written communication.

The aim of the present study was to uncover a possible common neural organizing principle in spoken and written communication, through the coupling of perceptual and motor representations. In order to identify possible shared neural substrates for processing the basic units of spoken and written language, a sparse sampling fMRI acquisition protocol was performed on the same subjects in two experimental sessions with similar sets of letters being read and written and of phonemes being heard and orally produced. We found evidence of common premotor regions activated in spoken and written language, both in perception and in production. The location of those brain regions was confined to the left lateral and medial frontal cortices, at locations corresponding to the premotor cortex, inferior frontal cortex and supplementary motor area. Interestingly, the speaking and writing tasks also appeared to be controlled by largely overlapping networks, possibly indicating some domain general cognitive processing. Finally, the spatial distribution of individual activation peaks further showed more dorsal and more left-lateralized premotor activations in written than in spoken language.

In vivo localization of cortical areas using a 3D computerized atlas of the marmoset brain.

We created a volumetric template of the marmoset (Callithrix jacchus) brain, which enables localization of the cortical areas defined in the Paxinos et al. (The marmoset brain in stereotaxic coordinates. Elsevier Academic Press, Cambridge, 2012) marmoset brain atlas, as well as seven broader cortical regions (occipital, temporal, parietal, prefrontal, motor, limbic, insular), different brain compartments (white matter, gray matter, cerebro-spinal fluid including ventricular spaces), and various other structures (brain stem, cerebellum, olfactory bulb, hippocampus). The template was designed from T1-weighted MR images acquired using a 3 T MRI scanner. It was based on a single fully segmented marmoset brain image, which was transported onto the mean of 13 adult marmoset brain images using a diffeomorphic strategy that fully preserves the brain topology. In addition, we offer an automatic segmentation pipeline which fully exploits the proposed template. The segmentation pipeline was quantitatively assessed by comparing the results of manual and automated segmentations. An associated program, written in Python, can be used from a command-line interface, or used interactively as a module of the 3DSlicer software. This program can be applied to the analysis of multimodal images, to map specific cortical areas in lesions or to define the seeds for further tractography analyses.

Processing of Egomotion-Consistent Optic Flow in the Rhesus Macaque Cortex.

The cortical network that processes visual cues to self-motion was characterized with functional magnetic resonance imaging in 3 awake behaving macaques. The experimental protocol was similar to previous human studies in which the responses to a single large optic flow patch were contrasted with responses to an array of 9 similar flow patches. This distinguishes cortical regions where neurons respond to flow in their receptive fields regardless of surrounding motion from those that are sensitive to whether the overall image arises from self-motion. In all 3 animals, significant selectivity for egomotion-consistent flow was found in several areas previously associated with optic flow processing, and notably dorsal middle superior temporal area, ventral intra-parietal area, and VPS. It was also seen in areas 7a (Opt), STPm, FEFsem, FEFsac and in a region of the cingulate sulcus that may be homologous with human area CSv. Selectivity for egomotion-compatible flow was never total but was particularly strong in VPS and putative macaque CSv. Direct comparison of results with the equivalent human studies reveals several commonalities but also some differences.

Neural changes associated to procedural learning and automatization process in Developmental Coordination Disorder and/or Developmental Dyslexia.

OBJECTIVE: Recent theories hypothesize that procedural learning may support the frequent overlap between neurodevelopmental disorders. The neural circuitry supporting procedural learning includes, among others, cortico-cerebellar and cortico-striatal loops. Alteration of these loops may account for the frequent comorbidity between Developmental Coordination Disorder (DCD) and Developmental Dyslexia (DD). The aim of our study was to investigate cerebral changes due to the learning and automatization of a sequence learning task in children with DD, or DCD, or both disorders. METHOD: fMRI on 48 children (aged 8-12) with DD, DCD or DD + DCD was used to explore their brain activity during procedural tasks, performed either after two weeks of training or in the early stage of learning. RESULTS: Firstly, our results indicate that all children were able to perform the task with the same level of automaticity, but recruit different brain processes to achieve the same performance. Secondly, our fMRI results do not appear to confirm Nicolson and Fawcett's model. The neural correlates recruited for procedural learning by the DD and the comorbid groups are very close, while the DCD group presents distinct characteristics. This provide a promising direction on the neural mechanisms associated with procedural learning in neurodevelopmental disorders and for understanding comorbidity.

White matter disruption at the prodromal stage of Alzheimer's disease: relationships with hippocampal atrophy and episodic memory performance.

White matter tract alterations have been consistently described in Alzheimer's disease (AD). In particular, limbic fronto-temporal connections, which are critical to episodic memory function, may degenerate early in the course of the disease. However the relation between white matter tract degeneration, hippocampal atrophy and episodic memory impairment at the earliest stages of AD is still unclear. In this magnetic resonance imaging study, white matter integrity and hippocampal volumes were evaluated in patients with amnestic mild cognitive impairment due to AD (Albert et al., 2011) (n = 22) and healthy controls (n = 15). Performance in various episodic memory tasks was also evaluated in each participant. Relative to controls, patients showed a significant reduction of white matter fractional anisotropy (FA) and increase of radial diffusivity (RD) in the bilateral uncinate fasciculus, parahippocampal cingulum and fornix. Within the patient group, significant intra-hemispheric correlations were notably found between hippocampal grey matter volume and FA in the uncinate fasciculus, suggesting a relationship between atrophy and disconnection of the hippocampus. Moreover, episodic recognition scores were related with uncinate fasciculus FA across patients. These results indicate that fronto-hippocampal connectivity is reduced from the earliest pre-demential stages of AD. Disruption of fronto-hippocampal connections may occur progressively, in parallel with hippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.

Incongruent object/context relationships in visual scenes: where are they processed in the brain?

Rapid object visual categorization in briefly flashed natural scenes is influenced by the surrounding context. The neural correlates underlying reduced categorization performance in response to incongruent object/context associations remain unclear and were investigated in the present study using fMRI. Participants were instructed to categorize objects in briefly presented scenes (exposure duration=100ms). Half of the scenes consisted of objects pasted in an expected (congruent) context, whereas for the other half, objects were embedded in incongruent contexts. Object categorization was more accurate and faster in congruent relative to incongruent scenes. Moreover, we found that the two types of scenes elicited different patterns of cerebral activation. In particular, the processing of incongruent scenes induced increased activations in the parahippocampal cortex, as well as in the right frontal cortex. This higher activity may indicate additional neural processing of the novel (non experienced) contextual associations that were inherent to the incongruent scenes. Moreover, our results suggest that the locus of object categorization impairment due to contextual incongruence is in the right anterior parahippocampal cortex. Indeed in this region activity was correlated with the reaction time increase observed with incongruent scenes. Representations for associations between objects and their usual context of appearance might be encoded in the right anterior parahippocampal cortex.

Neural correlates of the continuous Wagon Wheel Illusion: a functional MRI study.

After prolonged viewing of a continuous periodic motion stimulus at frequencies around 10 Hz, observers experience a fleeting impression of reversed motion: the continuous Wagon Wheel Illusion (c-WWI). To account for this phenomenon it has been proposed that attentional mechanisms discretely sample motion information. Alternative accounts argue that the illusion relies on the spurious activation of motion detectors, which under the effect of adaptation could trigger a reversed percept. We investigated the neural correlates of the c-WWI using fMRI (3T). Subjects viewed a vertically bisected ring containing a radial grating unambiguously rotating at 10 Hz; they continuously reported the perceived motion direction within each half of the ring. The two halves always rotated in opposite directions, allowing us to separately explore illusory reversals occurring within each hemifield. Comparing BOLD activity during illusory (c-WWI) or real perceptual periods revealed systematic differences in right parietal regions, in addition to the right motion complex MT+. This activation pattern did not depend on the side on which the illusion occurred, and could not be accounted for by purely perceptual switch-related activity-known to encompass parietal regions during other bistable effects. This first characterization of the fMRI correlates of the c-WWI may have implications for the different theoretical explanations of the phenomenon.

Co-registration of stereotactic MRI and isofieldlines during deep brain stimulation.

OBJECT: The parameter adjustment process during deep brain stimulation (DBS) for dystonia remains time consuming and based on clinical observation alone. The aim was to correlate the electric field with the GPi anatomy to be able to study the stimulated volume. METHODS: We developed a computer-assisted method (model) for visualizing electric field in reference to the stereotactic space. Electric field values were correlated with the GPi anatomy (stereotactic Magnetic Resonance Imaging) in one reference patient. RESULTS: Using this methodology it becomes possible to correlate the electric field distributions for patient specific parameters with the anatomical information. The application to one patient showed that the 0.1V/mm isofieldline fits best with the lateral GPi borders at the level of the stimulated contacts. CONCLUSIONS: The electric field is a crucial parameter as it is assumed to be responsible for triggering action potentials. Electric field visualisation allows the calculation of the stimulated volume for a given isoline. Its application to our whole patient population might help in determining a threshold for obtaining a therapeutic effect, to date unknown, and consequently in optimizing the parameter setting in each patient.

Deep brain stimulation in movement disorders: stereotactic coregistration of two-dimensional electrical field modeling and magnetic resonance imaging.

OBJECT: Adjusting electrical parameters used in deep brain stimulation (DBS) for dystonia remains time consuming and is currently based on clinical observation alone. The goal of this study was to visualize electrical parameters around the electrode, to correlate these parameters with the anatomy of the globus pallidus internus (GPI), and to study the relationship between the volume of stimulated tissue and the electrical parameter settings. METHODS: The authors developed a computer-assisted methodological model for visualizing electrical parameters (the isopotential and the isoelectric field magnitude), with reference to the stereotactic target, for different stimulation settings (monopolar and bipolar) applied during DBS. Electrical field values were correlated with the anatomy of the GPI, which was determined by performing stereotactic magnetic resonance imaging in one reference patient. By using this method it is possible to compare potential and electrical field distributions for different stimulation modes. In monopolar and bipolar stimulation, the shape and distribution of the potential and electrical field are different and depend on the stimulation voltage. Distributions visualized for patient-specific parameters can be subsequently correlated with anatomical information. The application of this method to one patient demonstrated that the 0.2-V/ mm isofield line fits best with the lateral GPI borders at the level of the stimulated contacts. CONCLUSIONS: The electrical field is a crucial parameter because it is assumed to be responsible for triggering action potentials. Electrical field visualization allows the calculation of the stimulated volume for a given isoline. Its application to an entire series of patients may help determine a threshold for obtaining a therapeutic effect, which is currently unknown, and consequently may aid in optimizing parameter settings in individual patients.

Stereotactic coregistration of 201Tl SPECT and MRI applied to brain tumor biopsies.

UNLABELLED: The aim of the present study was to determine the clinical feasibility of integration of stereotactic SPECT (sSPECT) with 201Tl in the stereotactic MRI (sMRI)-based planning of brain tumor biopsy. Furthermore, the predictive value of the integrated techniques was analyzed by comparison with the corresponding histologically determined metabolic activity. METHODS: Ten patients underwent combined 201Tl SPECT- and MRI-guided stereotactic biopsy of intracranial lesions according to a previously described technique. An area of abnormal 201Tl uptake was used to guide the stereotactic biopsy trajectory. Several samples were taken along the trajectory above and beneath the target. An extensive histologic diagnosis (tumor grade, mitotic index [MI], and Ki67 index) and the 201Tl index were obtained for all samples and compared statistically. RESULTS: Combined 201Tl sSPECT- and sMRI-guided biopsy could be performed on all patients. Ki67 index, MI, and tumor grade correlated significantly. The correlations between MI or Ki67 index and 201Tl index were not significant (0.18 and 0.09, respectively). A trend to significance existed between tumor grade and 201Tl index (R = 0.31; P = 0.06). Mean 201Tl index for grade III tumors (3.27 +/- 1.89 [SD]) was significantly different from that for grade IV tumors (4.34 +/- 1.29). The sample position on the trajectory correlated with the MI (R = 0.39; P = 0.01). In 4 of the 10 patients, a variation in tumor grade could be observed along the trajectory. In all patients, the highest proliferative activity was within 5-10 mm of the target. CONCLUSION: These results support the view that 201Tl SPECT may contribute to the successful management of brain tumor patients requiring stereotactic biopsy, without causing a significant increase in discomfort or morbidity. The development of similar techniques integrating sSPECT data in the planning of stereotactic biopsy should be considered by centers performing stereotactic surgery and having access to SPECT technology. In the long term, this technique could become a support for focused gene therapy and cell transfer.

Pallidal stimulation improves pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) causes a progressive generalized dystonia which remains pharmacologically intractable. We performed bilateral internal globus pallidus stimulation in six patients with genetically confirmed PKAN who obtained a major and long-lasting improvement of their painful spasms, dystonia, and functional autonomy. This study shows the benefits of pallidal DBS for the dystonia of PKAN patients.

Deep brain stimulation for dystonia confirming a somatotopic organization in the globus pallidus internus.

OBJECT: In patients with dystonia, symptoms vary greatly in their extent and severity. The efficacy of pallidal stimulation is now established, but an interindividual variability in the responses to this treatment exists. A retrospective analysis of postoperative magnetic resonance (MR) images demonstrated millimetric variations in the positions of electrode contacts inside the posterolateroventral portion of the globus pallidus internus (GPi). It therefore seemed very likely that there is a somatotopic organization within the GPi. The goal of this study was to examine the positions of specific electrode contacts according to patients' clinical evolution, so that a somatotopic organization within the GPi could be defined. METHODS: This study included 19 patients (17 of whom were right handed) with generalized dystonia who were treated by bilateral stimulation of the GPi. Patients were examined pre- and postoperatively by using the Burke-Fahn-Marsden Dystonia Rating Scale. Dividing the patient's body into three parts--cervicoaxial area, superior limb, and inferior limb--we determined the following: 1) where the dystonic symptoms started; 2) where symptoms predominated at the time of surgery; and 3) where the highest postoperative improvement was observed. Variations in clinical response were correlated to the positions of the electrode contacts. All activated electrode contacts were in the posterolateroventral portion of the GPi (Laitinen target). A correlation between the contact location measured longitudinally and the part of the body in which the highest improvement was observed (three different areas; p = 0.004) showed that a location more anterior for the inferior limb and one more posterior for the superior limb were delineated for the right side, but not for the left side. CONCLUSIONS: Inside the posterolateroventral subvolume of the GPi on the right side, three statistically different locations of electrode contacts were determined to be primary deep brain stimulation treatment sites for particular body parts in cases of dystonia.

Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results.

OBJECT: Primary generalized dystonia (PGD) is a medically refractory disease of the brain causing twisting or spasmodic movements and abnormal postures. In more than 30% of cases it is associated with the autosomal DYT1 mutation. Continuous electrical stimulation of the globus pallidus internus (GPi) has been used successfully in the treatment of PGD. The aim of this study was to examine the long-term efficacy and safety of deep brain stimulation (DBS) in the treatment of PGD in children and adults with and without the DYT1 mutation. METHODS: Thirty-one patients with PGD were selected for surgery. Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulators that were inserted subcutaneously. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) before and after implantation. The efficacy of stimulation improved with time. After 2 years, compared with preoperative values, the mean (+/- standard deviation) clinical and functional BFMDRS scores had improved by 79 +/- 19% and 65 +/- 33%, respectively. At the 2-year follow-up examination the improvement was comparable in patients with and without the DYT1 mutation in both the functional (p = 0.12) and clinical (p = 0.33) scores. Children displayed greater improvements in the clinical score than adult patients (p = 0.04) at 2 years of follow up. In contrast, there was no significant difference in functional scores between children and adults (p = 0.95). CONCLUSIONS: Electrical stimulation of the GPi is an effective, reversible, and adaptable treatment for PGD and should be considered for conditions refractory to pharmaceutical therapies.

Thallium SPECT-based stereotactic targeting for brain tumor biopsies. A technical note.

MR or CT images acquired under stereotactic conditions are often used to plan and guide brain tumor biopsies. The objective of this study was to design and test a methodology to increase target selection reliability by acquiring stereotactic 201Tl-SPECT data and by integrating them into the surgical planning. The three-headed Philips gamma camera system (Prism 3000) was adapted to stereotactic acquisitions (patient pallet, headholder). A software was developed for the stereotactic target determination based on SPECT images (pixel with the highest metabolic activity inside the tumor). The whole system accuracy was tested with the Elekta phantom adapted to SPECT imaging. The methodology was applied to one brain tumor biopsy. Comparison of the specific phantom coordinates evaluated in SPECT with the theoretical ones did not reveal any significant difference. In this way, our methodology including our homemade software (identification of the stereotactic frame, determination of the pixel with highest metabolic activity within the tumor in the stereotactic coordinate system) was validated. No significant geometric deformations were detected. Clinical feasibility was confirmed in 1 patient with a brain glioma. This study illustrates the feasibility and the accuracy of SPECT acquisitions with the stereotactic Leksell G-frame. The clinical relevance of this methodology is under evaluation. This definition of the target, based on the point with the highest metabolic activity within the tumor, might lead to improved diagnosis in biopsies and patient management. Furthermore, it might prepare the future for therapy aimed at delivering a therapeutic agent within a tumor.

Deep brain stimulation in myoclonus-dystonia syndrome.

Myoclonus-dystonia syndrome (MDS) is an autosomal dominant disorder characterized by bilateral myoclonic jerks. An 8-year-old boy presenting with early onset, medically intractable, MDS due to a mutation in the epsilon-sarcoglycan gene (SGCE) underwent chronic bilateral stimulation of the globus pallidus internus, which eliminates both myoclonus and dystonia. We conclude that deep brain stimulation can be an effective and safe treatment for MDS.

Evolution of brain impedance in dystonic patients treated by GPI electrical stimulation.

Deep Brain Stimulation is an effective treatment of generalized dystonia. Optimal stimulation parameters vary between patients. This article investigates the influence of electrical brain impedance and delivered current on the brain response to stimulation. Twenty-four patients were bilaterally stimulated in the globus pallidus internus through two implanted four-contact electrodes. The variation of brain impedance and current measurements was correlated with stimulation parameters, time course, and clinical outcome. When a contact was activated, a statistically significant and reversible decrease of brain impedance was found. Impedance and current values and their variations with time significantly differed between patients. The absolute impedance did not significantly correlate with the final outcome. We conclude that the reversible decrease of impedance reflects an adaptive long-term mechanism, which could be due to a plasticity phenomenon, but has no prognostic value. Impedance and current measurements give new complementary information for parameter adjustment and trouble shooting and should therefore be included in all patients' follow-up.

Comparison of atlas- and magnetic resonance imaging-based stereotactic targeting of the globus pallidus internus in the performance of deep brain stimulation for treatment of dystonia.

OBJECT: To assess the validity of relying on atlases during stereotactic neurosurgery, the authors compared target coordinates in the globus pallidus internus (GPi) obtained using magnetic resonance (MR) imaging with those determined using an atlas. The targets were used in deep brain stimulation (DBS) for the treatment of generalized dystonia. METHODS: Thirty-five patients, who were treated using bilateral DBS of the GPi, were included in this study. The target was selected on three-dimensional MR images by direct visual recognition of the GPi. The coordinates were automatically recorded using dedicated software. They were translated into the anterior commissure-posterior commissure (AC-PC) coordinate system by using a matrix transformation process. The same GPi target was defined, based on the locations of brain structures shown in the atlases of Schaltenbrand and Talairach. Magnetic resonance imaging-based GPi target coordinates were statistically compared with the corresponding atlas-based coordinates by applying the Student t-test. A significant difference (p < 0.001) was demonstrated in x, y, and z directions between MR imaging-based and Schaltenbrand atlas-derived target coordinates. The comparison with normalized Talairach atlas coordinates demonstrated a significant difference (p < 0.01) in the y and z directions, although not in the x direction (p = 0.12). No significant correlation existed between MR imaging-based target coordinates and patient age (p > 0.1). No significant correlation was observed between MR imaging-based target coordinates and patient sex in the y and z directions (p > 0.9), although it was significant in the x direction (p < 0.05). A significant variation in coordinates and the length of the AC-PC line was revealed only in the y direction (p < 0.005). CONCLUSIONS: A significant difference was found between target coordinates obtained by direct visual targeting on MR images (validated by postoperative clinical results) and those obtained by indirect targeting based on atlases.

Deep brain stimulation for dystonia. Surgical technique.

Stimulation electrodes are implanted under general anesthesia, without intra-operative electrophysiology or clinical testing, based only on stereotactic MRI and direct anatomical localization of the postero-ventro-basal GPi. We retrospectively analyzed the surgical procedure that has been designed and implemented in our center, using the Leksell G frame, for initiating deep brain stimulation in 65 dystonic patients. We report the surgical technique and the hardware and software complications. We recommend immediate postoperative stereotactic MRI under general anesthesia as a prerequisite to check the reliability of MR acquisition (magnet stability) and the exact localization of each electrode. This technique allowed us to reduce the duration of the operation to 4 h, including general anesthesia, frame fixation, MRI acquisition, implantation of two electrodes under radioscopic control, immediate postoperative stereotactic MRI and frame removal. Surgery-related morbidity was very low with a 0% hemorrhage rate and three delayed unilateral infections re-operated 6 months later. Hardware and software complications were rare. The advances in 3D-MR imaging permit the electrode implantation for deep brain stimulation without resorting to intraoperative localization techniques, which is especially helpful in children and for treating dystonia. The maximum follow-up period is 58 months (first case: November 1996). GPi stimulation has proven to be an effective treatment for most dystonic syndromes with particular efficacy in the disease due to the DYT1 mutation.