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

Short-term memory for colour following posterior hemispheric lesions in man.

SHORT-TERM memory for colour was studied in ®ve patients with circumscribed posterior hemispheric lesions. It was impaired independently of colour discrimination in one and more than colour discrimination in two patients. Two patients were normal in colour short-term memory, one with normal and one with de®cient colour discrimination performance. De®cient performance in colour short-term memory was associated with bilateral lesions of the inferior occipitotemporal junction including the lateral part of the fusiform gyrus or with a unilateral lesion of the left parieto-occipital convexity

An adaptable metric shapes perceptual space

How do we derive a sense of the separation of points in the world within a space-variant visual system? Visual directions are thought to be coded directly by a process referred to as local sign, in which a neuron acts as a labeled line for the perceived direction associated with its activation. The separations of visual directions are however not given. Nor are they directly related to the separations of signals on the receptive surface or in the brain which are modified by retinal and cortical magnification, respectively. To represent the separation of directions veridically the corresponding neural signals need to be scaled in some way. We considered this scaling process may be influenced by adaptation. Here we describe a novel adaptation paradigm, which can alter both apparent spatial separation and size. We measured the perceived separation of two dots and the size of geometric figures after adaptation to random dot patterns. We show that adapting to high density texture not only increases the apparent sparseness (average element separation) of a lower density pattern, as expected, but paradoxically, it reduces the apparent separation of dot pairs and induces apparent shrinkage of geometric form. This demonstrates for the first time a contrary linkage between perceived density and perceived extent. Separation and size appear to be expressed relative to a variable spatial metric whose properties, while not directly observable, are revealed by reductions in both apparent size and texture density

Phosphene Perception Relates to Visual Cortex Glutamate Levels and Covaries with Atypical Visuospatial Awareness

Phosphenes are illusory visual percepts produced by the application of transcranial magnetic stimulation to occipital cortex. Phosphene thresholds, the minimum stimulation intensity required to reliably produce phosphenes, are widely used as an index of cortical excitability. However, the neural basis of phosphene thresholds and their relationship to individual differences in visual cognition are poorly understood. Here, we investigated the neurochemical basis of phosphene perception by measuring basal GABA and glutamate levels in primary visual cortex using magnetic resonance spectroscopy. We further examined whether phosphene thresholds would relate to the visuospatial phenomenology of grapheme-color synesthesia, a condition characterized by atypical binding and involuntary color photisms. Phosphene thresholds negatively correlated with glutamate concentrations in visual cortex, with lower thresholds associated with elevated glutamate. This relationship was robust, present in both controls and synesthetes, and exhibited neurochemical, topographic, and threshold specificity. Projector synesthetes, who experience color photisms as spatially colocalized with inducing graphemes, displayed lower phosphene thresholds than associator synesthetes, who experience photisms as internal images, with both exhibiting lower thresholds than controls. These results suggest that phosphene perception is driven by interindividual variation in glutamatergic activity in primary visual cortex and relates to cortical processes underlying individual differences in visuospatial awareness

LUMINOS-102: Lerapolturev with and without α-PD- 1 in unresectable α-PD- 1 refractory melanoma

Lerapolturev (lera, formerly PVSRIPO) is a novel poliovirus based intratumoral immunotherapy that infects both cancer cells and antigen-presenting cells (APCs) via CD155, the poliovirus receptor. Lera has direct anticancer effects while also generating type I/III interferon-dominated inflammation and anti-tumor T-cell priming and activation via infection of local APCs. LUMINOS-102 (NCT04577807) is a multi-center, open-label, two-arm randomized Phase 2 study investigating the efficacy and safety of lera ± α-PD- 1 in patients with unresectable melanoma who failed prior α-PD- 1 therapy. Cross-over to the α-PD- 1 arm is permitted after progression, PR for ≥6 mo or 6 mo on treatment with SD. The maximum initial lera dose was 6x108 TCID50 /visit every 3 or 4 weeks (Q3/4 W). As of March 2022, the maximum lera dose was increased to 1.6 x 109 TCID50/visit, every week (QW) for 7 weeks (induction), followed by Q3/4 W dosing (maintenance). As of 20-Jun- 2022, 21 participants (10 male, 11 female, median 64 yrs) received lera (n = 14 at initial dose, Q3/4 W; n = 4 at increased dose, Q3/4 W; n = 3 at increased dose, QW) ± αPD-1. Five patients are currently on treatment. With the initial regimen, no objective responses and a CBR of 7% were observed. However, with the higher dose regimen, 1 complete response and a CBR of 71% (5/7) has been observed. Two of 4 participants with stable disease have evidence of response (1 with resolution of uninjected lung metastasis, 1 with decreased PET signal in injected and uninjected lesions receiving combination therapy). The only treatment related AE in \u3e1 pt was fatigue (19%, all grade 1 or 2). No dose-limiting toxicities or treatment-related SAEs were reported. Multiplex-IF analysis of on-treatment tumor biopsies will be presented. Lera ± αPD-1 is well tolerated, with early signs of efficacy at the higher dose level. Enrollment and randomization are ongoing

Human frontal eye fields and visual search

This thesis tested whether the human frontal eye fields (FEFs) have visuospatial functions that are dissociable from FEF oculomotor functions. Functional magnetic resonance imaging (fMRI) was used to localize the FEFs, and transcranial magnetic stimulation (TMS) was applied in a series of experiments to transiently disrupt information processing in the FEFs. It was shown that TMS applied over the right FEFs degrades subjects' performance on a visual conjunction search task in which eye movements were not required and were not made. A TMS timing protocol subsequently showed that computations in the FEFs that occur between 40 and 80ms after the onset of a visual search array are critical for accurate performance. This suggests that, as in the monkey, the human FEFs may accumulate and use visual evidence from extrastriate cortex, which forms the basis for accurate visuospatial discrimination. A training protocol showed that the right FEFs are no longer critical for accurate visuospatial discrimination performance once a search task has been extensively practised. This study further suggested that the FEFs may have a previously unknown role in the perception of left-right rotated shapes. A study on feature and spatial priming indicated that these two phenomena have distinct causal mechanisms. The left FEFs appear to access a spatial memory signal during the process of saccade programming. When TMS is applied during this period, the spatial priming benefit is abolished. Altogether, this thesis presents evidence that visuospatial and oculomotor functions can be dissociated in the human FEFs. The data on timing and the effects of learning correspond well with results reported in monkeys. The priming experiment offers the first evidence that the left FEFs are crucial for spatial priming, while the learning study suggests the novel hypothesis that the FEFs are crucial for left-right rotated shape perception.</p