Evaluating Current Density Modeling of Non-Invasive Eye and Brain Electrical Stimulation Using Phosphene Thresholds.

Because current flow cannot be measured directly in the intact retina or brain, current density distribution models were developed to estimate it during magnetic or electrical stimulation. A paradigm is now needed to evaluate if current flow modeling can be related to physiologically meaningful signs of true current distribution in the human brain. We used phosphene threshold measurements (PTs) as surrogate markers of current-flow to determine if PTs, evoked by transcranial alternating current stimulation (tACS), can be matched with current density estimates generated by head model-based computer simulations. Healthy, male subjects (n=15) were subjected to three-staged PT measurements comparing six unilateral and one bilateral stimulation electrode montages according to the 10/20 system: Fp2-Suborbital right (So), Fp2-right shoulder (rS), Fp2-Cz, Fp2- O2, So-rS, Cz-F8 and F7-F8. The stimulation frequency was set at 16 Hz. Subjects were asked to report the appearance and localization of phosphenes in their visual field for every montage. Current density models were built using multi-modal imaging data of a standard brain, meshed with isotropic conductivities of different tissues of the head using the SimBio and SCIRun software packages. We observed that lower PTs were associated with higher simulated current levels in the unilateral montages of the model head, and shorter electrode distances to the eye had lower PTs. The lowest mean PT and the lowest variability were found in the F7-F8 montage ( [Formula: see text]). Our results confirm the hypothesis that phosphenes are primarily of retinal origin, and they provide the first in vivo evidence that computer models of current flow using head models are a valid tool to estimate real current flow in the human eye and brain.

Personality and stress influence vision restoration and recovery in glaucoma and optic neuropathy following alternating current stimulation: implications for personalized neuromodulation and rehabilitation.

PURPOSE: Identifying factors that affect recovery or restoration of neurological function is a key goal of rehabilitation in neurology and ophthalmology. One such factor can be prolonged mental stress, which may be not only the consequence of nervous system damage but also a major risk factor, or cause, of neural inactivation. Using the visual system as a model of neural injury, we wished to study how patients' stress and personality profiles correlate with vision recovery as induced by therapy with alternating current stimulation (ACS) in patients with optic nerve damage. METHODS: Personality and stress questionnaires were sent retrospectively to a clinical convenience sample of patients who suffer low vision due to optic nerve damage, which had previously been treated with ACS. The questionnaires included the NEO Five-Factor Inventory (NEO-FFI), the Trier Inventory of Chronic Stress (TICS), and the Flammer syndrome (FS) checklist, which probes signs of vascular dysregulation (VD). These scores were then correlated with the extent of ACS-induced vision restoration as recorded 1-3 years earlier by perimetric visual field tests. RESULTS: Two NEO-FFI personality factors (lower neuroticism, higher conscientiousness) and the presence of physiological Flammer signs were associated with greater recovery as were individual items of the factors openness and agreeableness. Single NEO-FFI item analysis revealed that recovery relates to greater extraversion (optimistic and happy), openness (less guided by authorities for decisions on moral issues), and agreeableness (argue less, like working with others, thoughtful, considerate) as well as the presence of FS signs (cold hands/feet, hypotension, slim body shapes, tinnitus). This suggests that patients with better recovery were more calm, peaceful and secure, hard-working, and reliable, and with high organizational skills. In contrast, patients with poor recovery had a tendency to be emotionally unstable, anxious, unhappy and prone to negative emotions, impulsive, careless, and unorganized. Chronic stress assessed with TICS did not correlate with recovery. CONCLUSION: Vision restoration induced by ACS is greater in patients with less stress-prone personality traits and those who show signs of VD. Prospective studies are now needed to determine if personality has (i) a causal influence, i.e., patients with less stress-prone personalities and greater VD signs recover better, and/or (ii) if personality changes are an effect of the treatment, i.e., successful recovery induces personality changes. Though the cause-effect relationship is still open, we nevertheless propose that psychosocial factors and VD contribute to the highly variable outcome of vision restoration treatments in low vision rehabilitation. This has implications for preventive and personalized vision restoration and is of general value for our understanding of outcome variability in neuromodulation and neurological rehabilitation.

[The 2-Scale Model of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to Assess Vision-Related Quality of Life]. / Das 2-Skalen-Modell des National Eye Institute Visual Function Questionnaire (NEI-VFQ) zur Erfassung der sehbezogenen Lebensqualität.

Aim This study addresses the examination of the factorial validity of the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ 39) and the neuro-ophthalmological supplement in a German sample. Method Eighty-one patients with visual field defects affecting at least one eye answered the NEI-VFQ 39 and the supplement. Theoretical factor structures reported in the manuals were examined in confirmatory factor analysis. Because of a misfit, items retained after item analysis were subjected to exploratory factor analysis. Results The originally postulated factor structures could not be replicated. Many items revealed floor effects. The 21 remaining items could be assigned to two factors - "visual functioning" and "socio-emotional impairment". Conclusion The weakness of the theoretical factors can be avoided by using the 2-scale model.

[Are Visual Field Defects Reversible? - Visual Rehabilitation with Brains]. / Sind Gesichtsfelddefekte doch reversibel? ­ Visuelle Rehabilitation mit Gehirn.

Visual field defects are considered irreversible because the retina and optic nerve do not regenerate. Nevertheless, there is some potential for recovery of the visual fields. This can be accomplished by the brain, which analyses and interprets visual information and is able to amplify residual signals through neuroplasticity. Neuroplasticity refers to the ability of the brain to change its own functional architecture by modulating synaptic efficacy. This is actually the neurobiological basis of normal learning. Plasticity is maintained throughout life and can be induced by repetitively stimulating (training) brain circuits. The question now arises as to how plasticity can be utilised to activate residual vision for the treatment of visual field loss. Just as in neurorehabilitation, visual field defects can be modulated by post-lesion plasticity to improve vision in glaucoma, diabetic retinopathy or optic neuropathy. Because almost all patients have some residual vision, the goal is to strengthen residual capacities by enhancing synaptic efficacy. New treatment paradigms have been tested in clinical studies, including vision restoration training and non-invasive alternating current stimulation. While vision training is a behavioural task to selectively stimulate "relative defects" with daily vision exercises for the duration of 6 months, treatment with alternating current stimulation (30 min. daily for 10 days) activates and synchronises the entire retina and brain. Though full restoration of vision is not possible, such treatments improve vision, both subjectively and objectively. This includes visual field enlargements, improved acuity and reaction time, improved orientation and vision related quality of life. About 70 % of the patients respond to the therapies and there are no serious adverse events. Physiological studies of the effect of alternating current stimulation using EEG and fMRI reveal massive local and global changes in the brain. These include local activation of the visual cortex and global reorganisation of neuronal brain networks. Because modulation of neuroplasticity can strengthen residual vision, the brain deserves a better reputation in ophthalmology for its role in visual rehabilitation. For patients, there is now more light at the end of the tunnel, because vision loss in some areas of the visual field defect is indeed reversible.

Repetitive Transcorneal Alternating Current Stimulation Reduces Brain Idling State After Long-term Vision Loss.

BACKGROUND: Deafferentation of visual system structures following brain or optic nerve injury leaves cortical areas deprived of visual input. Deprived cortical areas have a reduced sensory information processing and are characterized with localized enhanced or synchronized rhythms believed to represent an "idling state". OBJECTIVE/HYPOTHESIS: We hypothesized that cortical idling can be modified with transcorneal alternating current stimulation (tACS) known to modulate cortical oscillations and thus change the functional state of the deafferented areas. METHODS: tACS was applied in rat model of severe optic nerve crush using a protocol similar to our clinical studies (200 µA, 2-8 Hz) for 5 treatment days right after the lesion and at the chronic stage (3 months later). EEG and VEP were recorded over the visual cortices. In vivo confocal neuroimaging of the retina and histology of the optic nerves were performed. RESULTS: Morphological investigations showed massive retinal ganglion cells death and degeneration of the optic nerves after crush. Visual loss was associated with increased EEG spectral power and lower coherence, indicating an "idling state". Stimulation induced a significant decrease of EEG power towards normal values. These effects were especially pronounced in the chronic stage. CONCLUSION: Our results suggest that alternating current injected via the eye is able to modulate visually deprived brain areas and thus reduce cortical idling.

Structural abnormalities in early Tourette syndrome children: a combined voxel-based morphometry and tract-based spatial statistics study.

Tourette Syndrome (TS) is characterized with chronic motor and vocal tics beginning in childhood. Abnormality of both gray (GM) and white matter (WM) has been observed in cortico-striato-thalamo-cortical circuits and sensory-motor cortex of adult TS patient. It is not clear if these morphological changes are also present in TS children and if there are any microstructural changes of WM. To understand the developmental cause of such changes, we investigated volumetric changes of GM and WM using VBM and microstructural changes of WM using DTI, and correlated these changes with tic severity and duration. T1 images and Diffusion Tensor Images (DTI) from 21 TS children were compared with 20 age and gender matched health control children using a 1.5T Philips scanner. All of the 21 TS children met the DSM-IV-TR criteria. T1 images were analyzed using DARTEL-VBM in conjunction with statistical parametric mapping (SPM). Diffusion tensor imaging (DTI) analysis was performed using Tract-Based Spatial Statistics (TBSS). Brain volume changes were found in left superior temporal gyrus, left and right paracentral gyrus, right precuneous cortex, right pre- and post-central gyrus, left temporal occipital fusiform cortex, right frontal pole, and left lingual gyrus. Significant axial diffusivity (AD) and mean diffusivity (MD) increases were found in anterior thalamic radiation, right cingulum bundle projecting to the cingulate gurus and forceps minor. Decreases in white matter volume (WMV) in the right frontal pole were inversely related with tic severity (YGTSS), and increases in AD and MD were positively correlated with tic severity and duration, respectively. These changes in TS children can be interpreted as signs of neural plasticity in response to the experiential demand. Our findings may suggest that the morphological and microstructural measurements from structural MRI and DTI can potentially be used as a biomarker of the pathophysiologic pattern of early TS children.

Altered white matter integrity in adolescents with prelingual deafness: a high-resolution tract-based spatial statistics imaging study.

BACKGROUND AND PURPOSE: Prelingual deafness is a hearing loss that occurs before language is acquired and may result in brain structural alterations. We studied microstructural WM alterations in prelingually deaf adolescents by using DTI. We hypothesized that any morphologic alterations are mainly located in the auditory association areas. Furthermore, considering that the developing brain is both more vulnerable to deprivation and more plastic than the adult brain, we speculated that the affected areas should be larger than those previously reported in adult deafness. MATERIALS AND METHODS: Diffusion tensor images were obtained from 16 prelingually deaf adolescents (age range, 10-18 years) and 16 healthy control adolescents matched for age and sex. Both groups were compared in fractional anisotropy and radial diffusivity by tract-based spatial statistics. In addition, we examined the correlation between the structural data (FA, RD) differences and the duration of sign language use and hearing aid experience. RESULTS: Prelingually deaf adolescents had significantly lower FA and increased RD in the bilateral superior temporal gyri, Heschl gyrus, planum polare, and the splenium of the corpus callosum. Only RD values in the right superior temporal gyrus correlated significantly and negatively (r = -0.518; P = .040) with duration of sign language use. These alterations were larger than those previously reported in adult deafness. CONCLUSIONS: As expected, we found severe morphologic changes of decreased FA and increased RD in multiple auditory association areas and in the corpus callosum. These changes are signs of development impairments in prelingually deaf adolescents, possibly reflecting axonal loss or lack of myelination.

Quantification of the human lateral geniculate nucleus in vivo using MR imaging based on morphometry: volume loss with age.

BACKGROUND AND PURPOSE: Because it is a small subcortical structure, the precise measurement of the human LGN is still a technical challenge. In this article, we identify the LGN in vivo, measure its volume based on high-resolution MR imaging, and then relate its volume to subject age to evaluate the potential clinical application. MATERIALS AND METHODS: A semiautomatic LGN isolation method was developed on scans obtained with 1.5T MR imaging, which involves highlighting the surrounding landmarks, obtaining candidate LGN voxels with a region-growing algorithm, and isolating the LGN from the ventral diencephalon. The method was accessed with a test-retest reliability on the results from 55 healthy subjects at different ages. RESULTS: This method showed high test-retest within-subject reliability (ICC, 0.950 and 0.948 in left and right hemispheres, respectively) among 3 independent measurements in each subject. The unilateral volume was highly variable, ranging from 52 to 102 mm(3) in the left and 66 to 105 mm(3) in the right hemisphere, with significantly larger volumes on the right (86 mm(3)) than on the left (77 mm(3)). The combined bilateral volumes (controlled for ICV) significantly decreased in size with progressing age from 20 to 65 years (r = -0.512, P = .000). There was no sex difference in bilateral LGN volumes (male/female: 163.1 ± 18.2/162.2 ± 21.4 mm(3)). CONCLUSIONS: Using our new technique, we were able to reliably determine the human LGN volume in vivo, which was found to decline with age. The volumes obtained by our method corresponded well with previously reported postmortem values, so our method may be considered to be superior for investigating the pathology of LGN.

Restoration of vision after optic nerve lesions with noninvasive transorbital alternating current stimulation: a clinical observational study.

BACKGROUND: Non-invasive current stimulation can induce neuroplastic changes in the normal brain, including visual system structures. Because it is not known if such plasticity is of clinical value, we wished to learn if vision restoration can be induced after optic nerve damage. METHODS: In an open-label, clinical observational study 446 patients with optic nerve lesions were treated with non-invasive repetitive transorbital alternating current stimulation (rtACS). Current bursts (<1000 µA, 5-20 Hz) were applied to induce phosphenes for one or two 10-day stimulation periods. Efficacy was assessed by monocular measurements of visual acuity and visual field (VF) size. EEG recordings at rest (n = 68) were made before and after treatment and global power spectra changes were analyzed. RESULTS: rtACS improved VF size in the right and left eye by 7.1% and 9.3% (p < 0.001), respectively. VF enlargements were present in 40.4% of right and 49.5% of left eyes. Visual acuity (VA) significantly increased in both eyes (right = 0.02, left = 0.015; p < 0.001). A second 10-day course was conducted 6 months in a subset of 62 patients and resulted in additional significant improvements of VA. Analysis of EEG power spectra revealed that VA and VF improvements were associated with increased alpha power. Increased theta power was observed in patients that had only VF enlargements but no VA change. In contrast, non-responders had increased delta power spectra in frontal and occipital areas. CONCLUSIONS: rtACS leads to long-lasting improvements in VA and VF size and after-effects in EEG power spectra. Because physiological and clinical parameters are correlated we hypothesize that rtACS enhances plasticity by inducing synchronization in different cortical regions, but the precise mechanisms needs further clarification. These encouraging results require confirmation by controlled clinical trials.

[The neuroophthalmic supplement to the NEI-VFQ: test statistics and validation with a cohort of patients with pre- and postchiasmatic damage]. / Das neuroophthalmologische Supplement des NEI-VFQ: Teststatistische Überprüfung und Validierung an einer Stichprobe prä- und postchiasmatisch geschädigter Patienten.

BACKGROUND: The National Eye Institute Visual Function Questionnaire (NEI-VFQ) is not sufficient to assess vision-related quality of life in patients with vision impairments caused by neuroophthalmic deficits. The neuroophthalmic supplement to the NEI-VFQ is currently only available in an English version. The supplement was translated into German and three items concerning visual field loss were added. MATERIAL AND METHODS: NEI-VFQ and supplement data were collected from 62 pre- and postchiasmatic patients with visual field defects and from 245 healthy reference persons. NEI-VFQ and supplement were psychometrically tested and validated. Relations between visual field variables and vision-related quality of life were assessed. RESULTS: The patient group showed diminished quality of life in 10 NEI-VFQ subscales and in eight supplement items when compared to age-matched healthy controls. Correlations between supplement and visual field diagnostic variables demonstrate moderate relations between visual field loss and deterioration of vision-related quality of life. A Cronbach's α of 0.81 for the supplement can be increased to 0.92 in combination with the NEI-VFQ, the sole application of the NEI-VFQ generates an alpha of 0.93 in this sample. A factor analysis reveals four factors that cover the 13 items capturing the following issues: 'severity/problems due to the visual field defect", "unusual eyelid appearances", "blurry vision/double vision" and "diverse vision of both eyes"; 72 % of the variance can be explained by these four factors. CONCLUSION: The German translation of the neuroophthalmic supplement to the NEI-VFQ captures additional vision-specific problems beyond the sole NEI-VFQ that are often reported by patients with vision impairments after brain damage. Although the relevance of some items can be questioned, nevertheless the supplement qualifies for an enhanced outline of subjective vision impairments that are not included in the previous NEI-VFQ.

[Impairments of vision- and health-related quality of life in stroke patients with homonymous visual field defects depend on severity of visual function loss]. / Beeinträchtigung der seh- und gesundheitsbezogenen Lebensqualität bei Schlaganfallpatienten mit homonymen Gesichtsfelddefekten in Abhängigkeit von der Schwere des visuellen Funktionsverlustes.

BACKGROUND AND PURPOSE: Little is known about whether and to what extent health- and vision-related quality of life in stroke patients with visual field defects is influenced by the severity of visual function loss and which quality of life is achieved compared to healthy control persons. PATIENTS/MATERIALS AND METHODS: Results of the National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ) and the Medical Outcome Study Short-Form 36 Health Survey (SF-36) of 177 first stroke patients with visual field defects were compared with scores of age- and sex-matched healthy reference persons. The influence of visual field loss, perimetric data, reduced visual acuity and demographic variables on NEI-VFQ and SF-36 scores were estimated by analyses of variance. RESULTS: First stroke patients showed worse results in 11/12 NEI-VFQ and in 6/8 SF-36 subscales when compared to healthy controls. The factor "intact central visual field" influenced 9/12 NEI-VFQ subscales (F-range 3.16 - 14.11; all p < 0.05), but only one SF-36 scale (F = 3.15; p < 0.05). Patients with larger intact visual fields, shorter reaction times in the visual field test and better visual acuity reached higher NEI-VFQ and SF-36 scores. Male patients reported worse scores for SF-36 subscale General Health Perceptions than female patients (F = 8.61; p = 0.004), but no differences in vision-related quality of life due to the factor gender could be detected. CONCLUSIONS: Patients with visual field defects showed considerable reductions in vision- and health-related quality of life compared to healthy control persons. These were mainly influenced by variables of visual functioning such as size of intact visual field, reaction times or visual acuity. The size of the intact central visual field influenced vision-related quality of life rather than health-related quality of life.

Special issues in brain plasticity, repair and rehabilitation: 20 years of a publishing strategy.

The journal Restorative Neurology and Neuroscience (RNN) is focused on the emerging field of brain plasticity, repair and rehabilitation, including original and review papers both in basic research (in vitro studies, animal experiments) and in the clinical domain, including brain imaging studies. The publication of special issues on vital topics, summarizing the work of leading experts in the field of restoration and plasticity has become a major strategy of RNN and has attracted worldwide attention. Special issues are typically organized by specialized guest-editors familiar with the respective science field. Special issues cover a particular sub-discipline and often contain laboratory review papers. The first special issue appeared in 1990, and until today RNN has published a total of 25 special issues on a variety of basic science and clinical matters. In this way, RNN promotes the dissemination of information in the field of neuroplasticity, repair and rehabilitation, providing the reader with up-to-date information prepared by leading experts in the field.

Publishing in the field of brain plasticity, repair and rehabilitation: The 20th Anniversary issue of Restorative Neurology and Neuroscience.

The journal Restorative Neurology and Neuroscience (RNN) now celebrates its 20th anniversary. Since 1989 RNN has published scientific findings in the emerging fields of brain plasticity, repair and rehabilitation via original scientific publications and review papers in basic research (animal experiments, in vitro studies) and clinical science. During the last decade RNN had a steady progress in reference value and scientific impact, reaching an ISI-impact factor of 1.978 (2008) and has published a total of 717 papers. The journal's success can be explained by different factors: (1) neuroplasticity, regeneration, recovery and rehabilitation have developed to main stream subjects with a worldwide increase in the number of publications and their citation rate, (2) RNN has published numerous special issues which summarize the work of leading experts in specialized sub-fields, (3) a dedicated, highly qualified editorial board (4) the quality of papers submitted to RNN has increased over time. RNN has now become a visible and leading source of original scientific information in the space of brain plasticity, rehabilitation and repair.

[Do patients undergo changes of their personality due to visual field defects? An investigation with FPI-R and NEI-VQ]. / Zeigen Patienten aufgrund ihres Gesichtsfeldausfalls Veränderungen in ihrer Persönlichkeit? Eine Untersuchung mittels FPI-R und NEI-VFQ.

BACKGROUND: Visual restrictions can lead to anxiety and possibly to social retirement. Therefore it makes sense to assess the patients' degree of handicap. The goal of the present study was to investigate if patients show changes in their personality or a reduced quality of life as a result of their visual field defect. METHODS: 15 patients with visual field defects were asked to fill out the revised version of the Freiburger Persönlichkeitsinventar (FPI-R) and the National Eye Institute Visual Function Questionnaire (NEI-VFQ). The FPI-R encompasses the standardised recording of many personality traits whereas the NEI-VFQ addresses the visual quality of life. RESULTS: In the total sample all FPI-R scales were appropriate for the study in the inconspicuous standard range. Slight shifts resulted toward increased willingness to make contacts (scale 4, ST 4.2), reduced physical strain (scale 7, ST 4.3) and lower physical discomfort (scale 8, ST 3.7). The size of the visual field defect does not correlate with the satisfaction with life, with the physical discomfort and with the state of health but with the dependency on others (p = 0.047) and with the exertion of their social roles (p = 0.043). The scale "satisfaction with life" of the FPI-R correlated with the scale "psychic condition" of the NEI-VFQ (p = 0.028) and the physical discomfort showed a significant correlation with the scale "eye strain" (p = 0.006) in the NEI-VFQ. DISCUSSION: Contrary to our presumptions, patients with visual field defects did not show any changes in their personality. It is supposed that they have learned to compensate for their reduced visual functions.

[Visual field defects after cerebral lesions from the patient's perspective: health- and vision-related quality of life assessed by SF-36 and NEI-VFQ]. / Zerebral bedingte Gesichtsfelddefekte aus Patientensicht : Gesundheitsbezogene und sehspezifische Lebensqualität unter Verwendung des SF-36 und des NEI-VFQ.

BACKGROUND: In patients with visual field defects, measurement of health-related quality of life (hQoL) and vision-related quality of life (vQoL) is an important adjunct to clinical measures such as perimetry. The purpose of this study was to describe hQoL and vQoL of patients with visual field defects after cerebral lesions such as infarction, traumatic brain injury, and tumor. METHODS: The National Eye Institute -- Visual Function Questionnaire (NEI-VFQ) for vQoL and the SF-36 Health Survey for hQoL were administered to 24 patients about 2 years after occurrence of the visual field defect. Visual fields were measured by standard perimetry and a near-threshold campimetric method. Visual acuity was measured by the Landolt-Ring-Test. RESULTS: The NEI-VFQ scores -- but not SF-36 scores -- were not only lower than those of a disease-free group but also lower than those of patients with visual impairments not caused by cerebral damage. Rank correlations between the size of the visual field defect and NEI-VFQ subscales were significantly high or modest. With SF-36 scores these correlations were generally low and moderate at best. CONCLUSION: The NEI-VFQ is a valuable measure of self-reported visual impairment in patients with visual field defects after cerebral lesions. The measurement of unspecific hQoL is not sufficient to reflect the problems of patients with visual field defects.

Two faces of calcium activation after optic nerve trauma: life or death of retinal ganglion cells in vivo depends on calcium dynamics.

Calcium elevations after neurotrauma are not only implicated in cell death but may contribute to adaptive plasticity. We now wished to resolve this contradiction by following calcium dynamics after optic nerve crush in vivo. Adult rats received no injury (n = 5), unilateral mild (n = 10) or moderate optic nerve crush (n = 10) (ONC), or axotomy (n = 5). Before surgery, retinal ganglion cells (RGCs) were retrogradely labelled with Oregon Green BAPTA-dextran, a fluorescent calcium marker. Calcium-related fluorescence intensity (FI) was repeatedly measured in individual RGCs in vivo using the in vivo confocal neuroimaging (ICON) method. Four different RGC types were found. Normal RGCs without FI change were found in sham rats and also in both ONC groups. RGCs with mild damage were seen only after mild ONC, showing an initial calcium depression of 26% at day 4 followed by a 169% increase 15 days after ONC. RGCs with moderate damage were found only after moderate ONC and showed calcium hypoactivation followed by a slower return toward baseline and a delayed calcium increase of 72% above baseline. Sixty to sixty-five per cent of the RGCs in both ONC groups and all RGCs in the axotomy group died within 6 days following a fast and massive calcium increase of 316% with a concomitant 156% soma size increase. In conclusion rapid calcium elevation leads to cell death, while an initial calcium depression followed by a delayed and moderate calcium hyperactivation is associated with cell survival. We propose that immediate, massive calcium activation is maladaptive whereas delayed and moderate hyperactivation of surviving cells is adaptive. Implications for pharmacotherapy are discussed.

Visual hallucinations during spontaneous and training-induced visual field recovery.

Visual hallucinations after post-geniculate visual system lesions were shown to be associated with spontaneous recovery of visual functions. We investigated the occurrence of hallucinations during spontaneous recovery and additionally tested whether hallucinations were re-instated in a phase of vision restoration therapy (VRT). Nineteen patients with post-geniculate lesions and homonymous visual loss participated in a prospective study, and 121 patients with various lesions were included in a retrospective study using a questionnaire including verbal descriptions as well as drawings of hallucinations experienced by the patients. In both samples, visual-field size was determined before and after 6 months of VRT. Many patients in both groups experienced post-lesion hallucinations (mostly colors, objects, motion) which subsided after spontaneous recovery of visual functions (increase of visual field size, recovery of more complex visual function) was ended. Hallucinations re-emerged during training. However, the majority of patients reported simple, unformed visual hallucinations (uncolored phosphenes, spots, flashes), especially when visual field recovery was most intense. Hallucinations were mainly found in patients with large shifts of the visual field border. They occurred in blind areas, particularly in areas of residual vision where recovery was predominantly observed. Hallucinations may reflect functional recovery in partially lesioned brain areas. While the colored/formed hallucinations during spontaneous recovery may represent non-specific activation of higher visual areas, the simple, unformed training-related hallucinations may indicate recovery in the primary visual cortex during treatment. Hallucinations should not generally be discarded as pathological or unimportant symptoms, but they may be functional indicators of visual system plasticity.

Publishing in the field of brain plasticity, repair and rehabilitation: an emerging neuroscience niche journal.

The journal Restorative Neurology and Neuroscience (RNN) is now published in its 25th volume since its inception in 1989. RNN focuses on the emerging field of brain plasticity, repair and rehabilitation, including original and review papers both in basic research (animal experiments, in vitro studies) and in the clinical domain, including brain imaging studies. During the last decade RNN has experienced a steady progress in its reference value and scientific impact. The ISI-impact factor has risen from 1.117 (1997) to 2.862 (2006). This places the journal at the 81st rank among all 200 neuroscience journals, i.e. 60% of all neuroscience journals have a lower impact factor. When compared to other journals in the field of rehabilitation, RNN ranks number 1. Causes for this positive development are, among others: (1) the field of neuroplasticity, regeneration, recovery and rehabilitation is an emerging field in medicine and therefore the number of publications and their citation rate overall increases, (2) the special issues strategy, (3) a top level editorial board, and (4) the quality of papers submitted to RNN continuously improves as RNN is gaining increasing acceptance in the scientific community. Thus, in the space of neuroscience in general, and rehabilitation in particular, RNN has become a visible, high impact journal and a leading source of original scientific information pertaining to brain plasticity , rehabilitation and repair. RNN is likely to gain more momentum as the field matures further.