Visual evoked potentials in multiple sclerosis: P100 latency and visual pathway damage including the lateral geniculate nucleus.

OBJECTIVE: To explore associations of the main component (P100) of visual evoked potentials (VEP) to pre- and postchiasmatic damage in multiple sclerosis (MS). METHODS: 31 patients (median EDSS: 2.5), 13 with previous optic neuritis (ON), and 31 healthy controls had VEP, optical coherence tomography and magnetic resonance imaging. We tested associations of P100-latency to the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell/inner plexiform layers (GCIPL), lateral geniculate nucleus volume (LGN), white matter lesions of the optic radiations (OR-WML), fractional anisotropy of non-lesional optic radiations (NAOR-FA), and to the mean thickness of primary visual cortex (V1). Effect sizes are given as marginal R2 (mR2). RESULTS: P100-latency, pRNFL, GCIPL and LGN in patients differed from controls. Within patients, P100-latency was significantly associated with GCIPL (mR2 = 0.26), and less strongly with OR-WML (mR2 = 0.17), NAOR-FA (mR2 = 0.13) and pRNFL (mR2 = 0.08). In multivariate analysis, GCIPL and NAOR-FA remained significantly associated with P100-latency (mR2 = 0.41). In ON-patients, P100-latency was significantly associated with LGN volume (mR2 = -0.56). CONCLUSIONS: P100-latency is affected by anterior and posterior visual pathway damage. In ON-patients, damage at the synapse-level (LGN) may additionally contribute to latency delay. SIGNIFICANCE: Our findings corroborate post-chiasmatic contributions to the VEP-signal, which may relate to distinct pathophysiological mechanisms in MS.

The role of the medial geniculate body of the thalamus in the pathophysiology of tinnitus and implications for treatment.

Tinnitus is an auditory sensation in the absence of actual external stimulation. Different clinical interventions are used in tinnitus treatment, but only few patients respond to available options. The lack of successful tinnitus treatment is partly due to the limited knowledge about the mechanisms underlying tinnitus. Recently, the auditory part of the thalamus has gained attention as a central structure in the neuropathophysiology of tinnitus. Increased thalamic spontaneous firing rate, bursting activity and oscillations, alongside an increase of GABAergic tonic inhibition have been shown in the auditory thalamus in animal models of tinnitus. In addition, clinical neuroimaging studies have shown structural and functional thalamic changes with tinnitus. This review provides a systematic overview and discussion of these observations that support a central role of the auditory thalamus in tinnitus. Based on this approach, a neuromodulative treatment option for tinnitus is proposed.

Loss and enhancement of layer-selective signals in geniculostriate and corticotectal pathways of adult human amblyopia.

How abnormal visual experiences early in life influence human subcortical pathways is poorly understood. Using high-resolution fMRI and pathway-selective visual stimuli, we investigate the influence of amblyopia on response properties and the effective connectivity of subcortical visual pathways of the adult human brain. Compared to the normal and fellow eyes, stimuli presented to the amblyopic eye show selectively reduced response in the parvocellular layers of the lateral geniculate nucleus and weaker effective connectivity to V1. Compared to the normal eye, the response of the amblyopic eye to chromatic stimulus decreases in the superficial layers of the superior colliculus, while response of the fellow eye robustly increases in the deep SC with stronger connectivity from the visual cortex. Therefore, amblyopia leads to selective parvocellular alterations of the geniculostriate and corticotectal pathways. These findings provide the neural basis for amblyopic deficits in visual acuity, ocular motor control, and attention.

Noise-induced neurophysiological alterations in the rat medial geniculate body and thalamocortical desynchronization by deep brain stimulation.

The thalamic medial geniculate body (MGB) is uniquely positioned within the neural tinnitus networks. Deep brain stimulation (DBS) of the MGB has been proposed as a possible novel treatment for tinnitus, yet mechanisms remain elusive. The aim of this study was to characterize neurophysiologic hallmarks in the MGB after noise exposure and to assess the neurophysiological effects of electrical stimulation of the MGB. Fourteen male Sprague-Dawley rats were included. Nine subjects were unilaterally exposed to a 16-kHz octave-band noise at 115 dB for 90 min, five received sham exposure. Single units were recorded from the contralateral MGB where spontaneous firing, coefficient of variation, response type, rate-level functions, and thresholds were determined. Local field potentials and electroencephalographical (EEG) recordings were performed before and after high-frequency DBS of the MGB. Thalamocortical synchronization and power were analyzed. In total, 214 single units were identified (n = 145 in noise-exposed group, n = 69 in control group). After noise exposure, fast-responding neurons become less responsive or nonresponsive without change to their spontaneous rate, whereas sustained- and suppressed-type neurons exhibit enhanced spontaneous activity without change to their stimulus-driven activity. MGB DBS suppressed thalamocortical synchronization in the ß and γ bands, supporting suppression of thalamocortical synchronization as an underlying mechanism of tinnitus suppression by high frequency DBS. These findings contribute to our understanding of the neurophysiologic consequences of noise exposure and the mechanism of potential DBS therapy for tinnitus.NEW & NOTEWORTHY Separate functional classes of MGB neurons might have distinct roles in tinnitus pathophysiology. After noise exposure, fast-responding neurons become less responsive or nonresponsive without change to their spontaneous firing, whereas sustained and suppressed neurons exhibit enhanced spontaneous activity without change to their stimulus-driven activity. Furthermore, results suggest desynchronization of thalamocortical ß and γ oscillations as a mechanism of tinnitus suppression by MGB DBS.

Abnormal Auditory Processing and Underlying Structural Changes in 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11.2 DS), one of the highest genetic risk for the development of schizophrenia, offers a unique opportunity to understand neurobiological and functional changes preceding the onset of the psychotic illness. Reduced auditory mismatch negativity response (MMN) has been proposed as a promising index of abnormal sensory processing and brain pathology in schizophrenia. However, the link between the MMN response and its underlying cerebral mechanisms in 22q11.2 DS remains unexamined. We measured auditory-evoked potentials to frequency deviant stimuli with high-density electroencephalogram and volumetric estimates of cortical and thalamic auditory areas with structural T1-weighted magnetic resonance imaging in a sample of 130 individuals, 70 with 22q11.2 DS and 60 age-matched typically developing (TD) individuals. Compared to TD group, the 22q11.2 deletion carriers reveal reduced MMN response and significant changes in topographical maps and decreased gray matter volumes of cortical and subcortical auditory areas, however, without any correlations between MMN alteration and structural changes. Furthermore, exploratory research on the presence of hallucinations (H+\H-) reveals no change in MMN response in 22q11.2DS (H+ and H-) as compared to TD individuals. Nonetheless, we observe bilateral volume reduction of the superior temporal gyrus and left medial geniculate in 22q11.2DSH+ as compared to 22q11.2DSH- and TD participants. These results suggest that the mismatch response might be a promising neurophysiological marker of functional changes within the auditory pathways that might underlie elevated risk for the development of psychotic symptoms.

Visual Dysfunction of the Superior Colliculus in De Novo Parkinsonian Patients.

OBJECTIVE: The dual hit hypothesis about the pathogenesis of Parkinson disease (PD) suggests that the brainstem is a convergent area for the propagation of pathological α-synuclein from the periphery to the brain. Although brainstem structures are likely to be affected early in the course of the disease, detailed information regarding specific brainstem regions is lacking. The aim of our study was to investigate the function of the superior colliculus, a sensorimotor brainstem structure, in de novo PD patients compared to controls using brain functional magnetic imaging and visual stimulation paradigms. METHODS: De novo PD patients and controls were recruited. PD subjects were imaged before and after starting PD medications. A recently developed functional magnetic resonance imaging protocol was used to stimulate and visualize the superior colliculus and 2 other visual structures: the lateral geniculate nucleus and the primary visual cortex. RESULTS: In the 22 PD patients, there was no modulation of the superior colliculus responses to the luminance contrasts compared to controls. This implies a hypersensitivity to low luminance contrast and abnormal rapid blood oxygenation level-dependent signal saturation to high luminance contrasts. The lateral geniculate nucleus was only modulated by 3 to 9% luminance contrasts compared to controls. No major differences were found in the primary visual cortex between both groups. INTERPRETATION: Our findings suggest that pathological superior colliculus visual responses in de novo PD patients are present early in the course of the disease. Changes in imaging the superior colliculus could play an important role as a preclinical biomarker of the disease. ANN NEUROL 2020;87:533-546.

Altered lateral geniculate nucleus functional connectivity in migraine without aura: a resting-state functional MRI study.

OBJECTIVES: To investigate the structural and functional connectivity changes of lateral geniculate nucleus (LGN) and their relationships with clinical characteristics in patients without aura. METHODS: Conventional MRI, 3D structure images and resting state functional MRI were performed in 30 migraine patients without aura (MwoA) and 22 healthy controls (HC). The lateral geniculate nucleus volumes and the functional connectivity (FC) of bilateral lateral geniculate nucleus were computed and compared between groups. RESULTS: The lateral geniculate nucleus volumes in patient groups did not differ from the controls. The brain regions with increased FC of the left LGN mainly located in the left cerebellum and right lingual gyrus in MwoA compared with HC. The increased FC of right LGN located in left inferior frontal gyrus in MwoA compared with HC. The correlation analysis showed a positive correlation between VLSQ-8 score and the increased FC of left cerebellum and right lingual gyrus. CONCLUSIONS: Photophobia in MwoA could be mediated by abnormal resting state functional connectivity in visual processing regions, the pain perception regulatory network and emotion regulation network. This result is valuable to further understanding about the clinical manifestation and pathogenesis of migraine.

Unique Features of Subcortical Circuits in a Macaque Model of Congenital Blindness.

There is an extensive modification of the functional organization of the brain in the congenital blind human, although there is little understanding of the structural underpinnings of these changes. The visual system of macaque has been extensively characterized both anatomically and functionally. We have taken advantage of this to examine the influence of congenital blindness in a macaque model of developmental anophthalmia. Developmental anophthalmia in macaque effectively removes the normal influence of the thalamus on cortical development leading to an induced "hybrid cortex (HC)" combining features of primary visual and extrastriate cortex. Here we show that retrograde tracers injected in early visual areas, including HC, reveal a drastic reduction of cortical projections of the reduced lateral geniculate nucleus. In addition, there is an important expansion of projections from the pulvinar complex to the HC, compared to the controls. These findings show that the functional consequences of congenital blindness need to be considered in terms of both modifications of the interareal cortical network and the ascending visual pathways.

Altered oscillation frequencies in the lateral geniculate complex in the rat model of absence epilepsy.

Absence epilepsy (AE) is a neurological disease that manifests in spike-wave discharges not present in healthy neuronal circuits. Mutations in ion channels directly underlying this rhythmic discharge may additionally affect rhythms in multiple brain centres which disturbances contribute to the epileptic phenotype. Malfunctioning of the light detection system (from retina to subcortical visual structures), heavily dependent on oscillatory activities, could partially explain severe problems with sleep and arousal observed in epileptic patients. Therefore, the aim of our study was to evaluate characteristics of retinal-derived oscillations in the lateral geniculate complex of the thalamus; a major gateway for the light information flow for the brain. Extracellular recordings in vivo were performed on urethane-anaesthetised WAG/Rij and Wistar rats from single units in the identified parts of lateral geniculate complex to test their basic oscillatory features as well as reaction to transient and sustained changes in ambient light conditions. Here, we show altered rhythmic activity of the lateral geniculate neurons in the absence epilepsy model with the increase of both the infra-slow and fast oscillatory frequencies. Further, we describe their disturbed reaction to sustain change in ambient light and provide evidence for major changes in the intergeniculate leaflet neuronal firing; a part of the lateral geniculate complex implicated in the circadian timekeeping. Altogether, our results are the first to show a malfunctioning of light detection mechanisms in the absence epilepsy that may in turn underpin sleep-promoting system insufficiencies and other arousal disturbances contributing to epileptic phenotype.

Visual responses in the dorsal lateral geniculate nucleus at early stages of retinal degeneration in rd1 PDE6ß mice.

Inherited retinal degenerations encompass a wide range of diseases that result in the death of rod and cone photoreceptors, eventually leading to irreversible blindness. Low vision survives at early stages of degeneration, at which point it could rely on residual populations of rod/cone photoreceptors as well as the inner retinal photoreceptor, melanopsin. To date, the impact of partial retinal degeneration on visual responses in the primary visual thalamus (dorsal lateral geniculate nucleus, dLGN) remains unknown, as does their relative reliance on surviving rod and cone photoreceptors vs. melanopsin. To answer these questions, we recorded visually evoked responses in the dLGN of anesthetized rd1 mice using in vivo electrophysiology at an age (3-5 wk) at which cones are partially degenerate and rods are absent. We found that excitatory (ON) responses to light had lower amplitude and longer latency in rd1 mice compared with age-matched visually intact controls; however, contrast sensitivity and spatial receptive field size were largely unaffected at this early stage of degeneration. Responses were retained when those wavelengths to which melanopsin is most sensitive were depleted, indicating that they were driven primarily by surviving cones. Inhibitory responses appeared absent in the rd1 thalamus, as did light-evoked gamma oscillations in firing. This description of fundamental features of the dLGN visual response at this intermediate stage of retinal degeneration provides a context for emerging attempts to restore vision by introducing ectopic photoreception to the degenerate retina.NEW & NOTEWORTHY This study provides new therapeutically relevant insights to visual responses in the dorsal lateral geniculate nucleus during progressive retinal degeneration. Using in vivo electrophysiology, we demonstrate that visual responses have lower amplitude and longer latency during degeneration, but contrast sensitivity and spatial receptive fields remain unaffected. Such visual responses are driven predominantly by surviving cones rather than melanopsin photoreceptors. The functional integrity of this visual pathway is encouraging for emerging attempts at visual restoration.

Changes in auditory thalamus neural firing patterns after acoustic trauma in rats.

Tinnitus is an abnormal phantom perception associated with cochlear trauma, and is thought to cause changes in the rates and patterns of firing neurons in the central auditory pathway. Recent studies have suggested a key role for the auditory thalamus, the medial geniculate nucleus (MGN), in the generation of tinnitus as it may serve a gating function for information en route to cortex. Dysfunctional gating would lead to abnormal activity reaching cortex and hence inappropriate perception, tinnitus, would occur. In this study we compared spontaneous MGN firing rates and burst firing parameters in Wistar rats with and without behavioural evidence of tinnitus following an acoustic trauma. Data were also compared with animals subjected to sham surgery and at an early time-point (2 weeks) after acoustic trauma. Acoustic trauma resulted in a temporary but not a permanent threshold loss and no differences were found in spontaneous firing rate between any of the groups. However, acoustic trauma, whether resulting in tinnitus or not, was accompanied by a significant decrease in the percentage of neurons showing burst firing. In bursting neurons, the number of spikes occurring in a burst and the number of burst per minutes was also significantly reduced compared to the sham group. Our results show that in our rat model without permanent threshold loss, elevated spontaneous firing rates are not associated with acoustic trauma and/or tinnitus and that burst firing parameters are associated with acoustic trauma but are not a neural signature for tinnitus.

Plasticity at Thalamo-amygdala Synapses Regulates Cocaine-Cue Memory Formation and Extinction.

Repeated drug use has long-lasting effects on plasticity throughout the brain's reward and memory systems. Environmental cues that are associated with drugs of abuse can elicit craving and relapse, but the neural circuits responsible for driving drug-cue-related behaviors have not been well delineated, creating a hurdle for the development of effective relapse prevention therapies. In this study, we used a cocaine+cue self-administration paradigm followed by cue re-exposure to establish that the strength of the drug cue association corresponds to the strength of synapses between the medial geniculate nucleus (MGN) of the thalamus and the lateral amygdala (LA). Furthermore, we demonstrate, via optogenetically induced LTD of MGN-LA synapses, that reversing cocaine-induced potentiation of this pathway is sufficient to inhibit cue-induced relapse-like behavior.

Low-intensity repetitive transcranial magnetic stimulation over prefrontal cortex in an animal model alters activity in the auditory thalamus but does not affect behavioural measures of tinnitus.

Tinnitus, a phantom auditory percept, is strongly associated with cochlear trauma. The latter leads to central changes in auditory pathways such as increased spontaneous activity and this may be involved in tinnitus generation. As not all people with cochlear trauma develop tinnitus, recent studies argue that non-auditory structures, such as prefrontal cortex (PFC), play an important role in tinnitus development. As part of sensory gating circuitry, PFC may modify activity in auditory thalamus and consequently in auditory cortex. Human studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive tool for neurostimulation, can alter tinnitus perception. This study used a guinea pig model of hearing loss and tinnitus to investigate effects of low-intensity rTMS (LI-rTMS) over PFC on tinnitus and spontaneous activity in auditory thalamus. In addition, immunohistochemistry for calbindin and parvalbumin in PFC was used to investigate the possible mechanism of action of LI-rTMS. Three treatment groups were compared: sham treatment, LI, low frequency (1 Hz) or LI, high frequency (10 Hz) rTMS (10 min/day, 2 weeks, weekdays only). None of the treatments affected the behavioural measures of tinnitus but spontaneous activity was significantly increased in auditory thalamus after 1 Hz and 10 Hz treatment. Immunostaining showed significant effects of rTMS on the density of calcium-binding protein expressing neurons in the dorsal regions of the PFC suggesting that rTMS treatment evoked plasticity in cortex. In addition, calbindin-positive neuron density in the superficial region of PFC was negatively correlated with spontaneous activity in auditory thalamus suggesting a possible mechanism for change in activity observed.

Reduced Structural Connectivity Between Left Auditory Thalamus and the Motion-Sensitive Planum Temporale in Developmental Dyslexia.

Developmental dyslexia is characterized by the inability to acquire typical reading and writing skills. Dyslexia has been frequently linked to cerebral cortex alterations; however, recent evidence also points toward sensory thalamus dysfunctions: dyslexics showed reduced responses in the left auditory thalamus (medial geniculate body, MGB) during speech processing in contrast to neurotypical readers. In addition, in the visual modality, dyslexics have reduced structural connectivity between the left visual thalamus (lateral geniculate nucleus, LGN) and V5/MT, a cerebral cortex region involved in visual movement processing. Higher LGN-V5/MT connectivity in dyslexics was associated with the faster rapid naming of letters and numbers (RANln), a measure that is highly correlated with reading proficiency. Here, we tested two hypotheses that were directly derived from these previous findings. First, we tested the hypothesis that dyslexics have reduced structural connectivity between the left MGB and the auditory-motion-sensitive part of the left planum temporale (mPT). Second, we hypothesized that the amount of left mPT-MGB connectivity correlates with dyslexics RANln scores. Using diffusion tensor imaging-based probabilistic tracking, we show that male adults with developmental dyslexia have reduced structural connectivity between the left MGB and the left mPT, confirming the first hypothesis. Stronger left mPT-MGB connectivity was not associated with faster RANln scores in dyslexics, but was in neurotypical readers. Our findings provide the first evidence that reduced cortico-thalamic connectivity in the auditory modality is a feature of developmental dyslexia and it may also affect reading-related cognitive abilities in neurotypical readers.SIGNIFICANCE STATEMENT Developmental dyslexia is one of the most widespread learning disabilities. Although previous neuroimaging research mainly focused on pathomechanisms of dyslexia at the cerebral cortex level, several lines of evidence suggest an atypical functioning of subcortical sensory structures. By means of diffusion tensor imaging, we here show that dyslexic male adults have reduced white matter connectivity in a cortico-thalamic auditory pathway between the left auditory motion-sensitive planum temporale and the left medial geniculate body. Connectivity strength of this pathway was associated with measures of reading fluency in neurotypical readers. This is novel evidence on the neurocognitive correlates of reading proficiency, highlighting the importance of cortico-subcortical interactions between regions involved in the processing of spectrotemporally complex sound.

Inhibition of Experimental Tinnitus With High Frequency Stimulation of the Rat Medial Geniculate Body.

BACKGROUND: Neuromodulation is a promising treatment modality for tinnitus, especially in chronic and severe cases. The auditory thalamus plays a key role in the pathophysiology of tinnitus, as it integrates and processes auditory and limbic information. OBJECTIVE: The effect of high frequency stimulation and low frequency stimulation of the medial geniculate bodies on tinnitus in a noise-induced tinnitus rat model is assessed. MATERIALS AND METHODS: Presence of tinnitus was verified using the gap-induced prepulse inhibition of the acoustic startle response paradigm. Hearing thresholds were determined before and after noise trauma with auditory brainstem responses. Anxiety-related side-effects were evaluated in the elevated zero maze and open field. RESULTS: Results show tinnitus development after noise exposure and preserved hearing thresholds of the ear that was protected from noise trauma. We found that high frequency stimulation of the medial geniculate bodies suppressed tinnitus. This effect maintained directly after stimulation when the stimulator was turned off. Low frequency stimulation did not have any effects on the gap:no-gap ratio of the acoustic startle response. CONCLUSION: High frequency stimulation of the MGB has a direct and residual suppressing effect on tinnitus in this animal model. Low frequency stimulation of the MGB did not inhibit tinnitus.

Blindsight relies on a functional connection between hMT+ and the lateral geniculate nucleus, not the pulvinar.

When the primary visual cortex (V1) is damaged, the principal visual pathway is lost, causing a loss of vision in the opposite visual field. While conscious vision is impaired, patients can still respond to certain images; this is known as 'blindsight'. Recently, a direct anatomical connection between the lateral geniculate nucleus (LGN) and human motion area hMT+ has been implicated in blindsight. However, a functional connection between these structures has not been demonstrated. We quantified functional MRI responses to motion in 14 patients with unilateral V1 damage (with and without blindsight). Patients with blindsight showed significant activity and a preserved sensitivity to speed in motion area hMT+, which was absent in patients without blindsight. We then compared functional connectivity between motion area hMT+ and a number of structures implicated in blindsight, including the ventral pulvinar. Only patients with blindsight showed an intact functional connection with the LGN but not the other structures, supporting a specific functional role for the LGN in blindsight.

Long-term histological changes in the macaque primary visual cortex and the lateral geniculate nucleus after monocular deprivation produced by early restricted retinal lesions and diffuser induced form deprivation.

Ocular dominance (OD) plasticity has been extensively studied in various mammalian species. While robust OD shifts are typically observed after monocular eyelid suture, relatively poor OD plasticity is observed for early eye removal or after tetrodotoxin (TTX) injections in mice. Hence, abnormal binocular signal interactions in the visual cortex may play a critical role in eliciting OD plasticity. Here, we examined the histochemical changes in the lateral geniculate nucleus (LGN) and the striate cortex (V1) in macaque monkeys that experienced two different monocular sensory deprivations in the same eye beginning at 3 weeks of age: restricted laser lesions in macular or peripheral retina and form deprivation induced by wearing a diffuser lens during the critical period. The monkeys were subsequently reared for 5 years under a normal visual environment. In the LGN, atrophy of neurons and a dramatic increase of GFAP expression were observed in the lesion projection zones (LPZs). In V1, although no obvious shift of the LPZ border was found, the ocular dominance columns (ODCs) for the lesioned eye shrunk and those for the intact eye expanded over the entirety of V1. This ODC size change was larger in the area outside the LPZ and in the region inside the LPZ near the border compared to that in the LPZ center. These developmental changes may reflect abnormal binocular interactions in V1 during early infancy. Our observations provide insights into the nature of degenerative and plastic changes in the LGN and V1 following early chronic monocular sensory deprivations.

Robust Visual Responses and Normal Retinotopy in Primate Lateral Geniculate Nucleus following Long-term Lesions of Striate Cortex.

Lesions of striate cortex (V1) trigger massive retrograde degeneration of neurons in the LGN. In primates, these lesions also lead to scotomas, within which conscious vision is abolished. Mediation of residual visual capacity within these regions (blindsight) has been traditionally attributed to an indirect visual pathway to the extrastriate cortex, which involves the superior colliculus and pulvinar complex. However, recent studies have suggested that preservation of the LGN is critical for behavioral evidence of blindsight, raising the question of what type of visual information is channeled by remaining neurons in this structure. A possible contribution of LGN neurons to blindsight is predicated on two conditions: that the neurons that survive degeneration remain visually responsive, and that their receptive fields continue to represent the region of the visual field inside the scotoma. We tested these conditions in male and female marmoset monkeys (Callithrix jacchus) with partial V1 lesions at three developmental stages (early postnatal life, young adulthood, old age), followed by long recovery periods. In all cases, recordings from the degenerated LGN revealed neurons with well-formed receptive fields throughout the scotoma. The responses were consistent and robust, and followed the expected eye dominance and retinotopy observed in the normal LGN. The responses had short latencies and preceded those of neurons recorded in the extrastriate middle temporal area. These findings suggest that the pathway that links LGN neurons to the extrastriate cortex is physiologically viable and can support residual vision in animals with V1 lesions incurred at various ages.SIGNIFICANCE STATEMENT Patients with a lesion of the primary visual cortex (V1) can retain certain visually mediated behaviors, particularly if the lesion occurs early in life. This phenomenon ("blindsight") not only sheds light on the nature of consciousness, but also has implications for studies of brain circuitry, development, and plasticity. However, the pathways that mediate blindsight have been the subject of debate. Recent studies suggest that projections from the LGN might be critical, but this finding is puzzling given that the lesions causes severe cell death in the LGN. Here we demonstrate in monkeys that the surviving LGN neurons retain a remarkable level of visual function and could therefore be the source of the visual information that supports blindsight.

Hemispheric asymmetries in the orientation and location of the lateral geniculate nucleus in dyslexia.

Human brain asymmetry reflects normal specialization of functional roles and may derive from evolutionary, hereditary, developmental, experiential, and pathological factors (Toga & Thompson, 2003). Geschwind and Galaburda (1985) suggested that processing difficulties in dyslexia are due to structural differences between hemispheres. Because of its potential significance to the controversial magnocellular theory of dyslexia, we investigated hemispheric differences in the human lateral geniculate nucleus (LGN), the primary visual relay and control nucleus in the thalamus, in subjects with dyslexia compared to normal readers. We acquired and averaged multiple high-resolution proton density (PD) weighted structural magnetic resonance imaging (MRI) volumes to measure in detail the anatomical boundaries of the LGN in each hemisphere. We observed hemispheric asymmetries in the orientation of the nucleus in subjects with dyslexia that were absent in controls. We also found differences in the location of the LGN between hemispheres in controls but not in subjects with dyslexia. Neither the precise anatomical differences in the LGN nor their functional consequences are known, nor is it clear whether the differences might be causes or effects of dyslexia.

Altered Structural Connectivity of the Left Visual Thalamus in Developmental Dyslexia.

Developmental dyslexia is a highly prevalent reading disorder affecting about 5%-10% of children [1]. It is characterized by slow and/or inaccurate word recognition skills as well as by poor spelling and decoding abilities [2]. Partly due to technical challenges with investigating subcortical sensory structures, current research on dyslexia in humans by and large focuses on the cerebral cortex [3-7]. These studies found that dyslexia is typically associated with functional and structural alterations of a distributed left-hemispheric cerebral cortex network (e.g., [8, 9]). However, findings from animal models and post mortem studies in humans suggest that dyslexia might also be associated with structural alterations in subcortical sensory pathways [10-14] (reviewed in [7]). Whether these alterations also exist in dyslexia in vivo and how they relate to dyslexia symptoms is currently unknown. Here, we used ultra-high-resolution structural magnetic resonance imaging (MRI), diffusion MRI, and probabilistic tractography to investigate the structural connections of the visual sensory pathway in dyslexia in vivo. We discovered that individuals with dyslexia have reduced structural connections in the direct pathway between the left visual thalamus (lateral geniculate nucleus [LGN]) and left middle temporal area V5/MT, but not between the left LGN and left primary visual cortex. In addition, left V5/MT-LGN connectivity strength correlated with rapid naming abilities-a key deficit in dyslexia [15]. These findings provide the first evidence of specific structural alterations in the connections between the sensory thalamus and cortex in developmental dyslexia. The results challenge current standard models and provide novel evidence for the importance of cortico-thalamic interactions in explaining dyslexia.