Reorganization of retinotopic maps after occipital lobe infarction

Published in final edited form as: J Cogn Neurosci. 2014 June ; 26(6): 1266–1282. doi:10.1162/jocn_a_00538.We studied patient JS, who had a right occipital infarct that encroached on visual areas V1, V2v, and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this motion coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy participants. Training on the motion coherence task generalized to another motion task, the motion discontinuity task, on which he had to detect the presence of an edge that was defined by the difference in the direction of the coherently moving dots (signal) within the display. He was much better at this task at 8 than 3 months, and this improvement was associated with an increase in the activation of the human MT complex (hMT^+) and in the kinetic occipital region as shown by repeated fMRI scans. We also used fMRI to perform retinotopic mapping at 3, 8, and 11 months after the infarct. We quantified the retinotopy and areal shifts by measuring the distances between the center of mass of functionally defined areas, computed in spherical surface-based coordinates. The functionally defined retinotopic areas V1, V2v, V2d, and VP were initially smaller in the lesioned right hemisphere, but they increased in size between 3 and 11 months. This change was not found in the normal, left hemisphere of the patient or in either hemispheres of the healthy control participants. We were interested in whether practice on the motion coherence task promoted the changes in the retinotopic maps. We compared the results for patient JS with those from another patient (PF) who had a comparable lesion but had not been given such practice. We found similar changes in the maps in the lesioned hemisphere of PF. However, PF was only scanned at 3 and 7 months, and the biggest shifts in patient JS were found between 8 and 11 months. Thus, it is important to carry out a prospective study with a trained and untrained group so as to determine whether the patterns of reorganization that we have observed can be further promoted by training.This work was supported by NIH grant R01NS064100 to L. M. V. Lucia M. Vaina dedicates this article to Charlie Gross, who has been a long-time collaborator and friend. I met him at the INS meeting in Beaune (France), and since then we often discussed the relationship between several aspects of high-level visual processing described in his work in monkeys physiology and my work in neuropsychology. In particular, his pioneering study of biological motion in monkeys' superior temporal lobe has influenced my own work on biological motion and has led us to coauthor a paper on this topic. Working with Charlie was a uniquely enjoyable experience. Alan Cowey and I often spoke fondly about Charlie, a dear friend and close colleague to us both, whose work, exquisite sense of humor, and unbound zest of living we both deeply admired and loved. (R01NS064100 - NIH)Accepted manuscrip

Stroke of the Visual Cortex

Stroke is the leading cause of homonymous visual field defect (VFD), resulting from irreversible damage of the post-chiasmatic visual pathway. From 6 to 13% of ischaemic strokes affect the supply area of the posterior cerebral artery, including the visual cortex in the occipital lobe. Besides ischaemic injury, the visual cortex can be damaged by intracerebral haemorrhage (ICH), 10% of which reside in the occipital lobe. Since occipital stroke almost always disturbs vision but can leave motor and language functions untouched, it may remain unrecognised in the acute phase, withholding the patients from receiving recanalisation treatments. Moreover, only up to 25% of stroke-related VFD recover spontaneously, whereas the rest continue to hinder patients’ independence in daily living and quality of life. Despite rigorous efforts, no evidence-based rehabilitation method to restore vision after stroke has been established. The aim of this thesis was to study the recognition, clinical characteristics, rehabilitation, neural mechanisms, and outcome of occipital stroke patients with VFD. The retrospective part of the thesis consists of two cohorts. The first cohort comprised 245 occipital ischaemic stroke patients admitted to the neurological emergency department of Helsinki University Hospital due to visual symptoms in 2010‒2015. We investigated their prehospital recognition and diagnostic delays and analysed the obstacles in their access to acute stroke treatment. The second retrospective cohort was the Helsinki ICH Study registry of 1013 consecutive non-traumatic ICH patients treated at Helsinki University Hospital in 2005‒2010, among whom we searched for isolated occipital ICH patients and analysed their clinical characteristics, aetiology, outcome, and incidence of post-stroke epilepsy in comparison to ICHs of other location. The prospective part of the thesis was based on the multicentre, randomised, sham-controlled exploratory REVIS (Restoration of Vision after Stroke) trial that studied rehabilitation of persistent VFD after chronic occipital stroke with different methods of non-invasive electrical brain stimulation. Altogether 56 patients were included in three 10-day experiments in three centres. The centres examined: 1) repetitive transorbital alternating current stimulation (rtACS) vs transcranial direct current stimulation preceding rtACS (tDCS/rtACS) vs sham in Germany, 2) rtACS vs sham in Finland, and 3) tDCS vs sham in Italy. In a functional magnetic resonance imaging spin-off study, resting-state functional connectivity of occipital stroke patients receiving rtACS or sham was compared to healthy control subjects at baseline and to each other after intervention. We found out that the prehospital delay of occipital stroke patients ranged between 20 minutes and 5 weeks and only 20% were admitted within the 4.5-hour time window of intravenous thrombolysis. Consequently, only 6.5% received thrombolysis, which is the mainstay of acute stroke treatment. One fourth of the patients arrived through at least two points of care and as many were assessed by an ophthalmologist before entering the neurological care, even though acute stroke patients should be transported directly to the neurological emergency department. The diagnostic delay was primarily caused by the patients’ late contact to health care but was also attributed to poor recognition and misdiagnosis by health-care professionals. The incidence of isolated occipital ICH was 1.9% of all non-traumatic ICHs and 5.3% of lobar ICHs. The patients with occipital ICH were younger and had more often vascular malformations as an aetiology of the bleeding than the non-occipital lobar ICH patients. They presented with milder symptoms and longer delay, and over 60% of the patients suffered solely from visual focal symptom. The haematoma volume in the occipital lobe was smaller and grew less compared to the non-occipital lobar haemorrhages. All in all, the occipital location of ICH was independently associated with favourable outcome at discharge among the patients with lobar ICH. The majority of the occipital ICH patients were able to return to independent activities of daily living, including driving a car and working, within a follow-up of a year. However, post-stroke epilepsy was as frequent as after non-occipital lobar ICH. In the prospective REVIS trial, rtACS was mostly ineffective in vision rehabilitation according to behavioural vision tests. Neither did it affect resting-state functional connectivity in comparison to sham. Transcranial DCS alone increased the monocular visual field measured with standard automated perimetry. The combined tDCS/rtACS propelled some improvements in the secondary visual outcome measures but did not differ from the sham stimulation. All the stimulation modalities were tolerated well. The functional connectivity of the chronic occipital stroke patients with VFD did not differ from the healthy control subjects when the whole brain network was considered in the analyses. However, a few occipital regions close to the infarct expressed lower local connectivity to the highly connected regions of the network according to the network graph metrics, whereas a lateral occipital region in the damaged hemisphere had higher network connectivity. These findings support the view that chronic ischaemic damage of the visual cortex affects functional connectivity within the visual network but leaves global connectivity unchanged. In conclusion, occipital stroke patients are insufficiently recognised, and thus the awareness of visual stroke symptoms should be raised especially among the public but also among health-care professionals to provide the patients with timely acute treatment and to prevent permanent disability. Occipital ICH patients have relatively favourable outcomes, but a structural cause of bleeding should be searched. Non-invasive electrical brain stimulation with the examined modalities does not cause robust improvement in vision or functional connectivity of the brain networks after a 10-day treatment, but further experiments with tDCS-based methods, potentially in combination with vision training, may be worth pursuing.Ihmisen näköaivokuori sijaitsee pääosin takaraivolohkossa ja sen vaurio johtaa tyypillisesti molempien silmien toispuoleiseen näkökenttäpuutokseen. Yleisin syy vaurioon on aivoverenkiertohäiriö: joko aivovaltimon tukoksesta johtuva infarkti tai verisuonen repeämästä aiheutuva aivoverenvuoto. Näkökenttäpuutos alentaa toiminta-, työ- ja ajokykyä ja heikentää elämänlaatua. Alle neljäsosa näkökenttäpuutoksista paranee täysin, eikä niiden kuntouttamiseksi ole kliiniseen käyttöön vakiintunutta menetelmää. Väitöskirjatyössä tutkittiin näköaivokuoren aivoverenkiertohäiriöiden tunnistamista, kliinistä kuvaa, kuntoutusta ja ennustetta. Tutkimuksessa selvisi, että ainoastaan 20,8 % HUS:in neurologian päivystyksessä vuosina 2010–2015 hoidetuista, näköoirein ilmenneen takaraivolohkon infarktin saaneista potilaista tuli hoitoon liuotushoidon mahdollistavassa aikaikkunassa ja vain 6,5 % sai liuotuksen. Viiveen yleisin syy oli potilaiden hidas hakeutuminen hoitoon, mutta kolmasosassa tapauksista myöskään terveydenhuoltohenkilökunta ei aluksi tunnistanut oireiden johtuvan aivoverenkiertohäiriöstä. Takaraivolohkoon rajautuvia aivoverenvuotoja esiintyi 1,9 %:lla HUS:issa 2005–2010 hoidetusta 1013 aivoverenvuotopotilaasta. Potilaat olivat nuorempia ja lieväoireisempia kuin muut vuotopotilaat, ja heidän vuotonsa johtuivat useammin verisuoniepämuodostumista. Vuodon sijainti takaraivolohkossa ennusti parempaa toimintakykyä sairaalasta kotiutuessa, ja suurin osa potilaista toipui vuoden sisällä päivittäistoiminnoissa itsenäisiksi. Epilepsian ilmaantuvuus ei eronnut pitkäaikaisseurannassa muista aivoverenvuotopotilaista. Satunnaistetussa, lumekontrolloidussa REVIS-monikeskustutkimuksessa selvitettiin kajoamattomien, heikkoa sähkövirtaa hyödyntävien stimulaatiomenetelmien tehoa takaraivolohkon aivoinfarktin aiheuttaman kroonisen näkökenttäpuutoksen kuntoutuksessa. Hoitokokeessa tasavirtastimulaatio (tDCS) pienensi vaurion vastapuoleisen silmän näkökenttäpuutosta verrattuna lumehoitoon, kun taas vaihtovirtastimulaatio (rtACS) oli tehotonta. Myöskään näiden yhdistelmällä (tDCS/rtACS) tulokset eivät eronneet lumeesta. Lisäksi toiminnallisella magneettikuvauksella tutkittiin 16 takaraivolohkon aivoinfarktipotilaan lepohermoverkostojen toiminnallista kytkeytyvyyttä verrattuna terveisiin koehenkilöihin. Tutkimus paljasti paikallisia muutoksia kytkeytyvyydessä potilaiden näköinformaation käsittelyyn osallistuvilla aivoalueilla, mutta laajemmin verkostojen toiminta ei eronnut verrokeista. Vaihtovirtastimulaatio ei muuttanut toiminnallista kytkeytyvyyttä

Functional neuroanatomy of time-to-passage perception

The time until an approaching object passes the observer is referred to as time-to-passage (TTP). Accurate judgment of TTP is critical for visually guided navigation, such as when walking, riding a bicycle, or driving a car. Previous research has shown that observers are able to make TTP judgments in the absence of information about local retinal object expansion. In this paper we combine psychophysics and functional MRI (fMRI) to investigate the neural substrate of TTP processing. In a previous psychophysical study, we demonstrated that when local retinal expansion cues are not available, observers take advantage of multiple sources of information to judge TTP, such as optic flow and object retinal velocities, and integrate these cues through a flexible and economic strategy. To induce strategy changes, we introduced trials with motion but without coherent optic flow (0% coherence of the background), and trials with coherent, but noisy, optic flow (75% coherence of the background). In a functional magnetic resonance imaging (fMRI) study we found that coherent optic flow cues resulted in better behavioral performance as well as higher and broader cortical activations across the visual motion processing pathway. Blood oxygen-level-dependent (BOLD) signal changes showed significant involvement of optic flow processing in the precentral sulcus (PreCS), postcentral sulcus (PostCS) and middle temporal gyrus (MTG) across all conditions. Not only highly activated during motion processing, bilateral hMT areas also showed a complex pattern in TTP judgment processing, which reflected a flexible TTP response strategy.Accepted manuscrip

Reading on the right when there’s nothing left? Probabilistic tractography reveals hemispheric asymmetry in pure alexia

We present a patient with reading inexpertise and right hemianopia following left posterior cerebral artery (PCA) stroke. We examine the extent of disruption to reading performance and the extent of white matter tract damage relative to a patient with more limited PCA infarction and isolated right hemianopia. We show white matter disconnection of the temporal occipital fusiform cortex in our pure alexia patient. Connectivity-based laterality indices revealed right hemisphere laterality in the alexia patient; this was not associated with improved reading function. We speculate that the degree of premorbid laterality may be a critical factor affecting the extent of reading dysfunction in alexia

Perceptual plasticity in damaged adult visual systems

AbstractPlasticity appears to be a ubiquitous property of nervous systems, regardless of developmental stage or complexity. In the visual system of higher mammals, perceptual plasticity has been intensively studied, both during development and in adulthood. However, the last few years have seen some significant controversies arise about the existence and properties of visual plasticity after permanent damage to the adult visual system. The study of perceptual plasticity in damaged, adult visual systems is of interest for several reasons. First, it is an important means of unmasking the relative contribution of individual visual areas to visual learning, adaptation and priming, among other plastic phenomena. Second, it can provide knowledge that is essential for the development of effective therapies to rehabilitate the increasing number of people who suffer the functional consequences of damage at different levels of their visual hierarchy. This review summarizes the available evidence on the subject and proposes that visual plasticity may be just as ubiquitous after damage as it is in the intact visual system. However, damage may alter visual plasticity in ways that are still being defined

Cerebral Metamorphopsia: Perceived spatial distortion from lesions of the adult human central visual pathway

Metamorphopsia is the perceived visual illusion of spatial distortion. Cerebral causes of metamorphopsia are much less common than retinal or ocular causes. Cerebral metamorphopsia can be caused by lesions along the central visual pathway or as a manifestation of epileptogenic discharges. Geometric visual distortions may result from structural lesions of the central visual pathway after reorganisation of the retinotopic representation in the cortex. Very few experimental investigations have been performed regarding cerebral metamorphopsia as it is often viewed as a clinical curiousity and analysis of the perceived distortion is difficult due to its subjective nature. Investigations have been undertaken to understand cortical plasticity as an explanation for visual filling-in. There has been much interest in cortical reorganisation after injuries to the peripheral and central visual pathway. Behavioural experiments aimed at quantifying the possible visual spatial distortion surrounding homonymous paracentral scotomas may be able to demonstrate cortical reorganisation after brain-damage and provide clues regarding the neural processes of visual perception. The aims of the thesis are: 1. To identify which cases of metamorphopsia, both published and unpublished, might be a consequence of cortical spatial reorganisation of retinotopic projections. 2. To investigate perceptual spatial distortion surrounding homonymous paracentral scotomas in adults with isolated unilateral injuries of the striate cortex. A review of the literature describing cases of cerebral metamorphopsia was performed. Metamorphopsia caused by retinal or ocular pathology, psychiatric conditions, drugs or medications were excluded. A retrospective case series of eight patients with metamorphopsia from a cerebral cause was performed in two clinical neurology practices specialising in vision disorders. Two cases who suffered from paracentral homonymous scotomas due to isolated unilateral primary visual cortex (V1) lesions were identified from a Neuro-ophthalmology practice. Neuropsychophysical experiments to investigate visual spatial perception surrounding their scotomas were developed and tested using MATLAB and Psychtoolbox. The use of the term 'metamorphopsia' was only in reference to cases in which contours or lines were experienced as distorted. In the published literature, few cases of cerebral metamorphopsia have been identified as being potentially due to cortical reorganisation. The main result is a statistically significant visual spatial distortion in the visual field surrounding a paracentral homonymous scotoma when compared to a normal control. There is also significant distortion of perception in the subjects' "unaffected" visual hemifield. After lesions of V1, visual perceptual spatial distortions may occur in the visual field surrounding homonymous paracentral scotomas. The spatial distortion may also occur in the normal hemifield possibly due to long-range cortical connections crossing to the other hemisphere through the corpus callosum. A collaborative approach across disciplines within vision science is required to further investigate the mechanisms responsible for perceptual visual illusions. Behavioural testing in brain-damaged cases remains important in developing theories of normal visual processing. New neuroimaging and neuroscience techniques could then test these theories, furthering our understanding of visual perception. An understanding of normal visual perception could allow future modification of neuronal processes to harness cortical reorganisation and potentially restore functional vision in humans with lesions of the central visual pathway

Residual function, spontaneous reorganisation and treatment plasticity in homonymous visual field defects

This thesis will focus on the residual function and visual and attentional deficits in human patients, which accompany damage to the visual cortex or its thalamic afferents, and plastic changes, which follow it. In particular, I will focus on homonymous visual field defects, which comprise a broad set of central disorders of vision. I will present experimental evidence that when the primary visual pathway is completely damaged, the only signal that can be implicitly processed via subcortical visual networks is fear. I will also present data showing that in a patient with relative deafferentation of visual cortex, changes in the spatial tuning and response gain of the contralesional and ipsilesional cortex are observed, which are accompanied by changes in functional connectivity with regions belonging to the dorsal attentional network and the default mode network. I will also discuss how cortical plasticity might be harnessed to improve recovery through novel treatments. Moreover, I will show how treatment interventions aimed at recruiting spared subcortical pathway supporting multisensory orienting can drive network level change

Functional Magnetic Resonance Imaging

"Functional Magnetic Resonance Imaging - Advanced Neuroimaging Applications" is a concise book on applied methods of fMRI used in assessment of cognitive functions in brain and neuropsychological evaluation using motor-sensory activities, language, orthographic disabilities in children. The book will serve the purpose of applied neuropsychological evaluation methods in neuropsychological research projects, as well as relatively experienced psychologists and neuroscientists. Chapters are arranged in the order of basic concepts of fMRI and physiological basis of fMRI after event-related stimulus in first two chapters followed by new concepts of fMRI applied in constraint-induced movement therapy; reliability analysis; refractory SMA epilepsy; consciousness states; rule-guided behavioral analysis; orthographic frequency neighbor analysis for phonological activation; and quantitative multimodal spectroscopic fMRI to evaluate different neuropsychological states

Recovery from Spatial Neglect with Intra- and Transhemispheric Functional Connectivity Changes in Vestibular and Visual Cortex Areas-A Case Study

Objective: Vestibular signals are involved in higher cortical functions like spatial orientation and its disorders. Vestibular dysfunction contributes, for example, to spatial neglect which can be transiently improved by caloric stimulation. The exact roles and mechanisms of the vestibular and visual systems for the recovery of neglect are not yet known. Methods: Resting-state functional connectivity (fc) magnetic resonance imaging was recorded in a patient with hemispatial neglect during the acute phase and after recovery 6 months later following a right middle cerebral artery infarction before and after caloric vestibular stimulation. Seeds in the vestibular [parietal operculum (OP2)], the parietal [posterior parietal cortex (PPC);7A, hIP3], and the visual cortex (VC) were used for the analysis. Results: During the acute stage after caloric stimulation the fc of the right OP2 to the left OP2, the anterior cingulum, and the para/hippocampus was increased bilaterally (i.e., the vestibular network), while the interhemispheric fc was reduced between homologous regions in the VC. After 6 months, similar fc increases in the vestibular network were found without stimulation. In addition, fc increases of the OP2 to the PPC and the VC were seen;interhemispherically this was true for both PPCs and for the right PPC to both VCs. Conclusion: Improvement of neglect after caloric stimulation in the acute phase was associated with increased fc of vestibular cortex areas in both hemispheres to the para-hippocampus and the dorsal anterior cingulum, but simultaneously with reduced interhemispheric VC connectivity. This disclosed a, to some extent, similar but also distinct short-term mechanism (vestibular stimulation) of an improvement of spatial orientation compared to the long-term recovery of neglect

Preserved Haptic Shape Processing after Bilateral LOC Lesions.

UNLABELLED: The visual and haptic perceptual systems are understood to share a common neural representation of object shape. A region thought to be critical for recognizing visual and haptic shape information is the lateral occipital complex (LOC). We investigated whether LOC is essential for haptic shape recognition in humans by studying behavioral responses and brain activation for haptically explored objects in a patient (M.C.) with bilateral lesions of the occipitotemporal cortex, including LOC. Despite severe deficits in recognizing objects using vision, M.C. was able to accurately recognize objects via touch. M.C.\u27s psychophysical response profile to haptically explored shapes was also indistinguishable from controls. Using fMRI, M.C. showed no object-selective visual or haptic responses in LOC, but her pattern of haptic activation in other brain regions was remarkably similar to healthy controls. Although LOC is routinely active during visual and haptic shape recognition tasks, it is not essential for haptic recognition of object shape. SIGNIFICANCE STATEMENT: The lateral occipital complex (LOC) is a brain region regarded to be critical for recognizing object shape, both in vision and in touch. However, causal evidence linking LOC with haptic shape processing is lacking. We studied recognition performance, psychophysical sensitivity, and brain response to touched objects, in a patient (M.C.) with extensive lesions involving LOC bilaterally. Despite being severely impaired in visual shape recognition, M.C. was able to identify objects via touch and she showed normal sensitivity to a haptic shape illusion. M.C.\u27s brain response to touched objects in areas of undamaged cortex was also very similar to that observed in neurologically healthy controls. These results demonstrate that LOC is not necessary for recognizing objects via touch