Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 x 0.39 x 1.0 mm³) 7.0T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans

The eVects of local and global processing demands on perception and action

Abstract The line-bisection task, adapted to utilise a wooden rod as the bisection stimulus, has revealed that patients with visuo-spatial neglect may be more accurate at bisection when asked to pick up the rod, compared to pointing to its centre. We recently reported that neurologically intact participants show a similar dissociation on this task-demonstrating a rightward bias when pointing to the centre, which was not present when grasping the rod by the centre. The current paper examined how pointing and grasping responses were aVected by adapted rod-bisection tasks that emphasised local or global processing. In Experiment 1, 26 participants completed four rod-bisection tasks. The rods were compound stimuli and the participants directed to focus on either the local or global level. The results demonstrated that when participants focused on the global level, the previous dissociations found for pointing and grasping conditions were evident. However, the perception of centre did change when participants focused on the local level: both the pointing and grasping responses were rightward biased. In Experiment 2, 42 participants completed three bisection tasks which again emphasised either the local or global level, but in diVerent sets of stimuli. The results of this task further support the Wndings in Experiment 1: the rightward bias in the local-bisection task was again evident and in addition, the global-bisection task resulted in no bias and no diVerence between the pointing and grasping bisections. These results demonstrate how task demands can similarly aVect the pointing and grasping responses, and indicate that local and global processing may be involved in perception/action dissociations on rod bisection

Datasets 2 and 3: Percentage accuracy and mean RTs (ms) for the group by visual field by validity ANOVA.

<p>Dataset 2: For each participant, percentage accuracy was calculated within each of the levels of visual field and validity. The group data were subjected to a repeated measures ANOVA. The analyses of percentage accuracy are not reported, as they resulted in similar results with regards to the experimental hypotheses as the analysis of mean RTs. L = leftward-shifting prism group; R = rightward-shifting prism group; N=neutral pointing group; LVF = left visual field; RVF = right visual field.</p> <p>Dataset 3: For each participant, RTs (ms) were averaged within each of the levels of visual field and validity. The group data were subjected to a repeated measures ANOVA, as reported in the text. L = leftward-shifting prism group; R = rightward-shifting prism group; N=neutral pointing group; LVF = left visual field; RVF = right visual field.</p

Effects of symmetry and apparent distance in a parasagittal-mirror variant of the rubber hand illusion paradigm

When I see my face in a mirror, its apparent position (behind the glass) is not one that my own face could be in. I accept the face I see as my own because I have an implicit understanding of how mirrors work. The situation is different if I look at the reflection of my right hand in a parasagittal mirror (parallel to body midline) when my left hand is hidden behind the mirror. It is as if I were looking through a window at my own left hand. The experience of body ownership has been investigated using rubber hand illusion (RHI) paradigms, and several studies have demonstrated ownership of a rubber hand viewed in a frontal mirror. Our “proof of concept” study was the first to combine use of a parasagittal mirror and synchronous stroking of both a prosthetic hand (viewed in the mirror) and the participant’s hand, with a manipulation of distance between the hands. The strength of the RHI elicited by our parasagittal-mirror paradigm depended not on physical distance between the hands (30, 45, or 60 cm) but on apparent distance between the prosthetic hand (viewed in the mirror) and the participant’s hand. This apparent distance was reduced to zero when the prosthetic hand and participant’s hand were arranged symmetrically (e.g., 30 cm in front of and behind the mirror). Thus, the parasagittal-mirror paradigm may provide a distinctive way to assess whether competition for ownership depends on spatial separation between the prosthetic hand and the participant’s hand

Datasets 4 and 5: Percentage accuracy and mean RTs (ms) for the group by horizontal location ANOVA.

<p>Dataset 4: For each participant, percentage accuracy was calculated within each of the four horizontal location conditions. The group data were subjected to a repeated measures ANOVA. The analyses of percentage accuracy are not reported, as they resulted in similar results with regards to the experimental hypotheses as the analysis of mean RTs. L = leftward-shifting prism group; R = rightward-shifting prism group; N=neutral pointing group; LVF = left visual field; RVF = right visual field; leftloc = left location; rightloc = right location.</p> <p>Dataset 5: For each participant, RTs (ms) were averaged within each of the four horizontal location conditions. The group data were subjected to a repeated measures ANOVA, as reported in the text. L = leftward-shifting prism group; R = rightward-shifting prism group; N=neutral pointing group; LVF = left visual field; RVF = right visual field; leftloc = left location; rightloc = right location.</p

Datasets 6 and 7: Percentage accuracy and mean RTs (ms) for the group by visual field x shift type x horizontal shift direction ANOVA.

<p>Dataset 6: For each participant, percentage accuracy was calculated within each level of visual field and horizontal shift direction. The group data were subjected to a repeated measures ANOVA. The analyses of percentage accuracy are not reported, as they resulted in similar results with regards to the experimental hypotheses as the analysis of mean RTs. L = leftward-shifting prism group; R = rightward-shifting prism group; N=neutral pointing group; LVF = left visual field; RVF = right visual field.</p> <p>Dataset 7: For each participant, RTs (ms) were averaged within each level of visual field and horizontal shift direction. The group data were subjected to a repeated measures ANOVA, as reported in the text. L = leftward-shifting prism group; R = rightward-shifting prism group; N=neutral pointing group; LVF = left visual field; RVF = right visual field; </p