Spinal cord stimulation may improve gait and cognition in hereditary spastic paraplegia with mental retardation: a case report.

BACKGROUND: Hereditary spastic paraplegia (HSP) include various sporadic and hereditary neurodegenerative disorders, characterized by progressive spasticity and weakness of lower limbs, possibly associated to additional features. CASE PRESENTATION: We report a male HPS patient in his 40 s, showing mental retardation associated with language impairment, dysarthria, and increased urinary frequency. Three months after treatment with electric chronic high-frequency cervical spinal cord stimulation (HF-SCS), he showed an amelioration of motor symptoms (lower limbs spasticity and gait), dysarthria, cognitive functioning (language and constructive praxic abilities), and urinary symptoms (decreased urinary frequency). Single-photon emission computed tomography (SPECT) showed a postoperative increase of cerebral perfusion in right frontal cortex and temporal cortex bilaterally. CONCLUSION: In our patient, HF-SCS might have induced an activation of ascending neural pathways, resulting in changes in activity in various cortical areas (including sensory-motor cortical areas), which may give rise to a modulation of activity in spared descending motor pathways and in neural networks involved in cognitive functions, including language. Although further studies in patients with HPS are needed to clarify whether HF-SCS can be a suitable treatment option in HSP, our observation suggests that HF-SCS, a minimally invasive neurosurgical procedure, might induce beneficial effects of on various symptoms of such orphan disease.

Selective effects of a brain tumor on the metric representation of the hand: a pre- versus post-surgery comparison.

Body representation disorders are complex, varied, striking, and very disabling in most cases. Deficits of body representation have been described after lesions to multimodal and sensorimotor cortical areas. A few studies have reported the effects of tumors on the representation of the body, but little is known about the changes after tumor resection. Moreover, the impact of brain lesions on the hand size representation has been investigated in few clinical cases. Hands are of special importance, as no other body part has the ability for movement and interaction with the environment that the hands have, and we use them for a multitude of daily activities. Studies with clinical population can add further knowledge into the way hands are represented. Here, we report a single case study of a patient (AM) who was an expert bodybuilder and underwent a surgery to remove a glioblastoma in the left posterior prefrontal and precentral cortex at the level of the hand's motor region. Pre- (20 days) and post- (4 months) surgery assessment did not show any motor or cognitive impairments. A hand localization task was used, before and after surgery (12 months), to measure possible changes of the metric representation of his right hand. Results showed a post-surgery modulation of the typically distorted hand representation, with an overall accuracy improvement, especially on width dimension. These findings support the direct involvement of sensorimotor areas in the implicit representation of the body size and its relevance on defining specific size representation dimensions.

Mini-craniotomy for intra-axial brain tumors: a comparison with conventional craniotomy in 306 patients harboring non-dural based lesions.

The use of a mini-craniotomy approach involving linear skin incision and a bone flap of about 3 cm has been reported for several neurosurgical diseases, such as aneurysms or cranial base tumors. More superficial lesions, including intra-axial tumors, may occasionally raise concerns due to insufficient control of the tumor boundaries. The convenience of a minimally invasive approach to intrinsic brain tumors was evaluated by comparing 161 patients who underwent mini-craniotomy (MC) for intra-axial brain tumors with a group of 145 patients operated on by the same surgical team through a conventional craniotomy (CC). Groups were propensity-matched for age, preoperative condition, size and location of the tumor, and pathological diagnosis. Results were analyzed focusing on operative time, the extent of resection, clinical outcome, hospitalization time, and time to start adjuvant therapy. Mini-craniotomy was equally effective in terms of extent of resection (GTR: 70.9% in the MC group vs 70.5% in the CC group) but had shorter operative time (average: 165 min in the MC group vs 205 min in the CC group p < 0.001) and lower rate of postoperative complications both superficial (1.03% vs 6.5% in the CC group p = 0.009) and deep (4% in the MC group vs 5.5% in the CC group p = 0,47). No relationship was found between the size or location of the tumor and resection rate. The MC group had reduced hospitalization time (average: 5.8 days vs 7.6 in CC group p < 0.001) and faster access to adjuvant therapies. 92.5% of the MC patients, which were scheduled for treatment, started radiotherapy within 8 weeks after surgery as opposed to 84.1% in the CC group (p = 0.04). These findings support the increasing use of mini-craniotomy for intra-axial brain tumors.

The anterior sylvian point as a reliable landmark for the anterior temporal lobectomy in mesial temporal lobe epilepsy: technical note, case series, and cadaveric dissection.

Introduction: Mesial temporal lobe epilepsy (MTLE) is one of the most prevalent forms of focal epilepsy in surgical series, particularly among adults. Over the decades, different surgical strategies have been developed to address drug-resistant epilepsy while safeguarding neurological and cognitive functions. Among these strategies, anterior temporal lobectomy (ATL), involving the removal of the temporal pole and mesial temporal structures, has emerged as a widely employed technique. Numerous modifications have been proposed to mitigate the risks associated with aphasia, cognitive issues, and visual field defects. Methods: Our approach is elucidated through intraoperative and cadaveric dissections, complemented by neuroradiological and cadaveric measurements of key anatomical landmarks. A retrospective analysis of patients with drug-resistant MTLE who were treated using our ATL technique at IRCCS Neuromed (Pozzilli) is presented. Results: A total of 385 patients were treated with our ATL subpial technique anatomically focused on the anterior Sylvian point (ASyP). The mean FU was 9.9 ± 5.4 years (range 1-24). In total, 84%of patients were free of seizures during the last follow-up, with no permanent neurological deficits. Transient defects were as follows: aphasia in 3% of patients, visual field defects in 2% of patients, hemiparesis in 2% of patients, and cognitive/memory impairments in 0.8% of patients. In cadaveric dissections, the ASyP was found at a mean distance from the temporal pole of 3.4 ± 0.2 cm (range 3-3.8) at the right side and 3.5 ± 0.2 cm (3.2-3.9) at the left side. In neuroimaging, the ASyP resulted anterior to the temporal horn tip in all cases at a mean distance of 3.2 ± 0.3 mm (range 2.7-3.6) at the right side and 3.5 ± 0.4 mm (range 2.8-3.8) at the left side. Discussion: To the best of our knowledge, this study first introduces the ASyP as a reliable and reproducible cortical landmark to perform the ATL to overcome the patients' variabilities, the risk of Meyer's loop injury, and the bias of intraoperative measurements. Our findings demonstrate that ASyP can be a safe cortical landmark that is useful in MTLE surgery because it is constantly present and is anterior to risky temporal regions such as temporal horn and language networks.

rTMS of medial parieto-occipital cortex interferes with attentional reorienting during attention and reaching tasks.

Unexpected changes in the location of a target for an upcoming action require both attentional reorienting and motor planning update. In both macaque and human brain, the medial posterior parietal cortex is involved in both phenomena but its causal role is still unclear. Here we used on-line rTMS over the putative human V6A (pV6A), a reach-related region in the dorsal part of the anterior bank of the parieto-occipital sulcus, during an attention and a reaching task requiring covert shifts of attention and planning of reaching movements toward cued targets in space. We found that rTMS increased RTs to invalidly cued but not to validly cued targets during both the attention and reaching task. Furthermore, we found that rTMS induced a deviation of reaching endpoints toward visual fixation and that this deviation was larger for invalidly cued targets. The results suggest that reorienting signals are used by human pV6A area to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly occurs in an unattended location. The current findings suggest a direct involvement of the action-related dorso-medial visual stream in attentional reorienting and a more specific role of pV6A area in the dynamic, on-line control of reaching actions.

Subpial technique in supratentorial glioma resection: state of the art and analysis of costs and effectiveness in a single institute experience.

BACKGROUND: Many neurosurgeons advocate subpial technique as the best technique to remove supratentorial gliomas. However, few authors clearly defined advantages and features of this technique. The aim of our study is to describe microsurgical subpial technique related to glioma surgery, with regard to its safety and cost effectiveness. METHODS: We analyzed retrospectively all consecutive patients surgically treated for supratentorial glioma from January 2017 to April 2018 at Neurosurgery Department of Neuromed Institute. All patients underwent to surgical glioma resection performing microsurgical subpial technique. Extent of resection and neurological complications were evaluated as primary outcomes; Karnofsky Performance Status and postoperative edema extent were secondary outcomes. Statistical analysis was obtained. RESULTS: The study included 70 patients. Gross Total Removal was obtained in 91.3% of patients with low grade glioma (LGG) and in 81% of patients with high grade glioma. Neurological complications amounted to 34% at early assessment in LGG patients, which were permanent at 3 months in 17% of patients. In high grade glioma patients, neurological complications amounted to 51% at early assessment, which were permanent at 3 months in 25% of them. CONCLUSIONS: We obtained good postoperative results with regard to the extent of tumor resection using this technique. Subpial resection is an effective surgical technique to get a safer and more complete tumor resection. It should be combined with other modern neurosurgical tools such as neuronavigation, ultrasound and cortical mapping to obtain the best tumor resection and functional neurological preservation.

Balloon-Assisted Corpus Callosotomy. Reducing the Impact of Transcallosal Approaches.

BACKGROUND: The interhemispheric transcallosal approach is widely used to remove intraventricular lesions. Corpus callosotomy gives immediate access to the ventricular chambers but is invasive in nature. Loss of callosal fibers, although normally tolerate, may cause disturbances ranging from a classical disconnection syndrome up to minor neuropsychological changes. OBJECTIVE: To open an operative window in the corpus callosum through separation rather than disconnection of the white matter fibers. METHODS: In 7 patients undergoing the interhemispheric transcallosal approach for intraventricular lesions, lying around or below the foramen of Monro, a stoma was created within the corpus callosum by using a 4F Fogarty catheter. The series included 3 colloid of the third ventricle, 2 thalamic cavernomas, 1 subependymoma, and 1 ependymoma of the foramen of Monro. We illustrate the technique and the clinico-radiological outcome, focusing on the size of callosotomy as seen on postoperative MRI. RESULTS: The balloon-assisted corpus callosotomy provided a circular, smooth-walled access to the ventricular chambers, which allowed uncomplicated removal of the lesions. On postoperative MRI, the size of the callosotomy shrinked compared with surgery (2.8-6.4 mm at follow-up vs 6-9 mm as measured intraoperatively). No signs of disconnection syndrome or new permanent deficits were observed in this series. CONCLUSION: The balloon-assisted technique produces a small callosotomy, without clinical consequences, showing a self-closing trend on postoperative MRI. This technique is a rewarding tool to reduce the impact of callosotomy while keeping the advantages of microsurgical interhemispheric approaches.

Long-term quality of life and functional outcomes in adults surgically treated for intramedullary spinal cord tumor.

Introduction: Intramedullary spinal cord tumors (IMSCTs) are rare but clinically significant entities that may cause severe neurological decline with progressive pain and motor or sensory deterioration. Beyond the beneficial effects of surgical treatment and the long-term progression-free survival, neurological deficits may still persist after surgery, and information about the long-term patients' health-related quality of life (QoL) is still lacking. In this study, we investigate the patients' health perception 15 years after the surgery in an overall patients' wellbeing framework. Methods: Patients surgically treated for IMSCT over a period from 1996 to 2011 were selected. After a mean of 15 years from the surgery, patient's self-administered questionnaire on disability, pain, sleep quality, and QoL was collected and neurological postoperative evaluation at the chronic stage was reexamined. Results: Neurological deficits are reported in half of the patients in the postoperative chronic phase. After 15 years of surgery, half of the patients still report mild or severe disability grades associated with significantly higher pain and poor sleep and QoL. In accordance, the neurological condition measured at the chronic stage is significantly related not only to disease-specific symptoms (i.e., pain) but even to sleep quality complaints and poor QoL, measured at 15 years follow-up. Conclusions: Health-related QoL is an important secondary outcome in patients. Although the progression-free survival, worse postoperative neurological conditions could predict long-term sequelae reflecting patients' poor health perception. It suggests the importance of preserving patients' functional status and globally evaluating patients' wellbeing to handle disease-specific symptoms but even more general aspects of QoL.

Continuous subcortical monitoring of motor pathways during glioma surgery with ultrasonic surgical aspirator: technical description in a single institute experience.

BACKGROUND: Actual challenge in surgical treatment of intra-axial gliomas involving eloquent areas is maximal safe resection. Mapping and monitoring of cortical and subcortical motor functionsare important tools to avoid postoperative deficits. In the present study, we present our experiencewith a continuous dynamic motor mapping technique pairing a traditional monopolar stimulatorwith a Cavitron Ultrasonic Surgical Aspirator (CUSA) to perform a continuous stimulation ofthe white matter avoiding removal interruption. METHODS: We describe a single center retrospective analysis of 1-year consecutive patients with intraxial tumors located adjacent to corticospinal tract and treated with surgical resection adopting "continuous dynamic mapping technique". With the support of a reconstruction software (3D Slicer), we classified the Extent Of Resection (EOR) as Gross Total Resection (GTR) (>98%), Sub-Total Resection (STR) (from 90% to 97%), and Partial Resection (<90%). Medical Research Council (MRC) grading was adopted to evaluate neurological outcomes (from 0 to 5), assessed on 1st post-operative day, at 1 week, 1 month and 3 months. RESULTS: From July 2017 to July 2018, 29 patients underwent to surgical removal of intraxial tumor adjacent to motor areas, using continuous dynamic subcortical mapping. Median age was 54 years old (range 12-75 years). At pre-operative MRI tractography reconstruction, mean distance between tumor and corticospinal tract was 4,4 mm (range At 1 week post-operative assessment, motor deficits were still present in 12 patients (41%). At 1 month, 10 patients (35%) had persisting deficits, which required admission to rehabilitation department. At 3 months, 4 patients (14%) had persistent motor impairment and overall 28 patients (98%) were able to walk by themselves. CONCLUSIONS: Our early experience showed that a combination of dynamic subcortical mapping with transcranial and cortical strip MEP (Motor Evoked Potentials) monitoring is useful in tumors close to motor eloquent areas to extend surgical resection avoiding permanent consequences. However, we need for further experience to consolidate and improve this technique.

Structural Brain Network Reorganization Following Anterior Callosotomy for Colloid Cysts: Connectometry and Graph Analysis Results.

Introduction: The plasticity of the neural circuits after injuries has been extensively investigated over the last decades. Transcallosal microsurgery for lesions affecting the third ventricle offers an interesting opportunity to investigate the whole-brain white matter reorganization occurring after a selective resection of the genu of the corpus callosum (CC). Method: Diffusion MRI (dMRI) data and neuropsychological testing were collected pre- and postoperatively in six patients with colloid cysts, surgically treated with a transcallosal-transgenual approach. Longitudinal connectometry analysis on dMRI data and graph analysis on structural connectivity matrix were implemented to analyze how white matter pathways and structural network topology reorganize after surgery. Results: Although a significant worsening in cognitive functions (e.g., executive and memory functioning) at early postoperative, a recovery to the preoperative status was observed at 6 months. Connectometry analysis, beyond the decrease of quantitative anisotropy (QA) near the resection cavity, showed an increase of QA in the body and forceps major CC subregions, as well as in the left intra-hemispheric corticocortical associative fibers. Accordingly, a reorganization of structural network topology was observed between centrality increasing in the left hemisphere nodes together with a rise in connectivity strength among mid and posterior CC subregions and cortical nodes. Conclusion: A structural reorganization of intra- and inter-hemispheric connective fibers and structural network topology were observed following the resection of the genu of the CC. Beyond the postoperative transient cognitive impairment, it could be argued anterior CC resection does not preclude neural plasticity and may subserve the long-term postoperative cognitive recovery.

The Impact of COVID-19 Lockdown on People With Epilepsy and Vagal Nerve Stimulation.

Objectives: Restrictive measures adopted during the COVID-19 pandemic, in order to limit contagion, have had a severe impact on mental health. The burden of lockdown has been particularly heavy on patients with chronic neurologic diseases such as People with Epilepsy (PwE). Our survey aims to describe the struggles and needs of Drug-Resistant (DR) PwE with implanted Vagal Nerve Stimulator (VNS) during the first wave of the COVID-19 lockdown in order to find strategies that help patients cope with present or future periods of restriction. Methods: We collected answers from 30 respondents who underwent an online survey including socio-demographic and clinical information and COVID-19-related information. Depression, anxiety symptoms, and sleep quality were investigated in patients through BDI II, GAD-7, and the PSQI scale. Results: In all, 46% of our sample reported an increase in the number of seizures; the entire sample complained of epilepsy-related issues (medication availability, VSN adjustments, anxiety, sleep disturbance); one out of three participants reported major epilepsy issues felt urgent; 30% had to postpone scheduled examination. Significantly higher scores for depression and anxiety scales were found in patients who perceived seizure frequency worsening and reported major epilepsy-related issues. Conclusion: Preliminary findings showed that the first lockdown influenced the clinical and psychological status of PwE and was related to seizures worsening. The lack of medical assistance and control on VNS therapy left patients to cope with the situation without a chance to contact a specialist. We discuss how a wider implementation of telemedicine programs could facilitate remote assistance of PwE with a VNS implant.

Pre-surgical fMRI Localization of the Hand Motor Cortex in Brain Tumors: Comparison Between Finger Tapping Task and a New Visual-Triggered Finger Movement Task.

Introduction: Pre-surgical mapping is clinically essential in the surgical management of brain tumors to preserve functions. A common technique to localize eloquent areas is functional magnetic resonance imaging (fMRI). In tumors involving the peri-rolandic regions, the finger tapping task (FTT) is typically administered to delineate the functional activation of hand-knob area. However, its selectivity may be limited. Thus, here, a novel cue-induced fMRI task was tested, the visual-triggered finger movement task (VFMT), aimed at eliciting a more accurate functional cortical mapping of the hand region as compared with FTT. Method: Twenty patients with glioma in the peri-rolandic regions underwent pre-operative mapping performing both FTT and VFMT. The fMRI data were analyzed for surgical procedures. When the craniotomy allowed to expose the motor cortex, the correspondence with intraoperative direct electrical stimulation (DES) was evaluated through sensitivity and specificity (mean sites = 11) calculated as percentage of true-positive and true-negative rates, respectively. Results: Both at group level and at single-subject level, differences among the tasks emerged in the functional representation of the hand-knob. Compared with FTT, VFMT showed a well-localized activation within the hand motor area and a less widespread activation in associative regions. Intraoperative DES confirmed the greater specificity (97%) and sensitivity (100%) of the VFMT in determining motor eloquent areas. Conclusion: The study provides a novel, external-triggered fMRI task for pre-surgical motor mapping. Compared with the traditional FTT, the new VFMT may have potential implications in clinical fMRI and surgical management due to its focal identification of the hand-knob region and good correspondence to intraoperative DES.

The Interhemispheric Transgenual Approach for Microsurgical Removal of Third Ventricle Colloid Cysts. Technical Note.

BACKGROUND: Colloid cysts of the third ventricle are rare benign lesions, which amount to approximately 1% of all intracranial tumors. Because these lesions grow predominantly in the anterior aspect of the third ventricle, they may cause the occlusion of the foramina of Monro, generating obstructive hydrocephalus. Surgery is mandatory in cases of large cysts and/or in symptomatic patients. Among the different surgical strategies described in colloid cysts surgery, the microsurgical transcallosal approach still constitutes the procedure of choice in many centers. In this study, we describe a modified microsurgical transcallosal approach, the interhemispheric transgenual approach, in a series of 13 consecutive patients operated on for colloid cysts of the third ventricle. METHODS: All the procedures were performed by the senior author (V.E.) at Neuromed Institute of Pozzilli (Is, Italy). The operative procedure is described in its various steps, illustrating the differences and potential advantages compared with the traditional microsurgical transcallosal approach. RESULTS: No surgical complications or new-onset neurologic deficits were observed in the postoperative period. The postoperative magnetic resonance imaging confirmed in all cases complete lesion removal without any sign of parenchymal damage. No lesion recurrence or need for permanent cerebrospinal fluid diversion was detected in the patients of this series during the follow-up period. CONCLUSIONS: In our experience, the interhemispheric transgenual approach has been effective in providing complete colloid cyst removal with minimal risk of vascular and parenchymal damage. Further studies are required to confirm its efficacy in improving the overall outcome of the microsurgical transcallosal approach.

Extradural Motor Cortex Stimulation might improve episodic and working memory in patients with Parkinson's disease.

Electric Extradural Motor Cortex Stimulation (EMCS) is a neurosurgical procedure suggested for treatment of patients with advanced Parkinson's disease (PD). We report two PD patients treated by EMCS, who experienced worsening of motor symptoms and cognition 5 years after surgery, when EMCS batteries became discharged. One month after EMCS restoration, they experienced a subjective improvement of motor symptoms and cognition. Neuropsychological assessments were carried out before replacement of batteries (off-EMCS condition) and 6 months afterward (on-EMCS condition). As compared to off-EMCS condition, in on-EMCS condition both patients showed an improvement on tasks of verbal episodic memory and backward spatial short-term/working memory task, and a decline on tasks of selective visual attention and forward spatial short-term memory. These findings suggest that in PD patients EMCS may induce slight beneficial effects on motor symptoms and cognitive processes involved in verbal episodic memory and in active manipulation of information stored in working memory.

The Functional Relevance of Diffusion Tensor Imaging in Patients with Degenerative Cervical Myelopathy.

(1) Background: In addition to conventional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) has been investigated as a potential diagnostic and predictive tool for patients with degenerative cervical myelopathy (DCM). In this preliminary study, we evaluated the use of quantitative DTI in the clinical practice as a possible measure to correlate with upper limbs function. (2) Methods: A total of 11 patients were enrolled in this prospective observational study. Fractional anisotropy (FA) values was extracted from DTI data before and after surgery using a GE Signa 1.5 T MRI scanner. The Nine-Hole Peg Test and a digital dynamometer were used to measure dexterity and hand strength, respectively. (3) Results: We found a significant increase of FA values after surgery, in particular below the most compressed level (p = 0.044) as well as an improvement in postoperative dexterity and hand strength. Postoperative FA values moderately correlate with hand dexterity (r = 0.4272, R2 = 0.0735, p = 0.19 for the right hand; r = 0.2087, R2 = 0.2265, p = 0.53 for the left hand). (4) Conclusion: FA may be used as a marker of myelopathy and could represent a promising diagnostic value in patients affected by DCM. Surgical decompression can improve the clinical outcome of these patients, especially in terms of the control of finger-hand coordination and dexterity.

A fully integrated wireless system for intracranial direct cortical stimulation, real-time electrocorticography data transmission, and smart cage for wireless battery recharge.

Wireless transmission of cortical signals is an essential step to improve the safety of epilepsy procedures requiring seizure focus localization and to provide chronic recording of brain activity for Brain Computer Interface (BCI) applications. Our group developed a fully implantable and externally rechargeable device, able to provide wireless electrocorticographic (ECoG) recording and cortical stimulation (CS). The first prototype of a wireless multi-channel very low power ECoG system was custom-designed to be implanted on non-human primates. The device, named ECOGIW-16E, is housed in a compact hermetically sealed Polyether ether ketone (PEEK) enclosure, allowing seamless battery recharge. ECOGIW-16E is recharged in a wireless fashion using a special cage designed to facilitate the recharge process in monkeys and developed in accordance with guidelines for accommodation of animals by Council of Europe (ETS123). The inductively recharging cage is made up of nylon and provides a thoroughly novel experimental setting on freely moving animals. The combination of wireless cable-free ECoG and external seamless battery recharge solves the problems and shortcomings caused by the presence of cables leaving the skull, providing a safer and easier way to monitor patients and to perform ECoG recording on primates. Data transmission exploits the newly available Medical Implant Communication Service band (MICS): 402-405 MHz. ECOGIW-16E was implanted over the left sensorimotor cortex of a macaca fascicularis to assess the feasibility of wireless ECoG monitoring and brain mapping through CS. With this device, we were able to record the everyday life ECoG signal from a monkey and to deliver focal brain stimulation with movement elicitation.

Behavioral investigation on the frames of reference involved in visuomotor transformations during peripheral arm reaching.

BACKGROUND: Several psychophysical experiments found evidence for the involvement of gaze-centered and/or body-centered coordinates in arm-movement planning and execution. Here we aimed at investigating the frames of reference involved in the visuomotor transformations for reaching towards visual targets in space by taking target eccentricity and performing hand into account. METHODOLOGY/PRINCIPAL FINDINGS: We examined several performance measures while subjects reached, in complete darkness, memorized targets situated at different locations relative to the gaze and/or to the body, thus distinguishing between an eye-centered and a body-centered frame of reference involved in the computation of the movement vector. The errors seem to be mainly affected by the visual hemifield of the target, independently from its location relative to the body, with an overestimation error in the horizontal reaching dimension (retinal exaggeration effect). The use of several target locations within the perifoveal visual field allowed us to reveal a novel finding, that is, a positive linear correlation between horizontal overestimation errors and target retinal eccentricity. In addition, we found an independent influence of the performing hand on the visuomotor transformation process, with each hand misreaching towards the ipsilateral side. CONCLUSIONS: While supporting the existence of an internal mechanism of target-effector integration in multiple frames of reference, the present data, especially the linear overshoot at small target eccentricities, clearly indicate the primary role of gaze-centered coding of target location in the visuomotor transformation for reaching.