Pure alexia as a disconnection syndrome: new diffusion imaging evidence for an old concept

Functional neuroimaging and studies of brain-damaged patients made it possible to delineate the main components of the cerebral system for word reading. However, the anatomical connections subtending the flow of information within this network are still poorly defined. Here we study the connectivity of the Visual Word Form Area (VWFA), a pivotal component of the reading network achieving the invariant identification of letter strings, and reproducibly located in the left lateral occipitotemporal sulcus. Diffusion images and functional imaging data were gathered in a patient who developed pure alexia following a small surgical lesion in the vicinity of his VWFA. We had a unique opportunity to compare images obtained before, early after, and late after surgery. Analysis of diffusion images with white matter tractography and voxel-based morphometry showed that the VWFA was mainly linked to the occipital cortex through the inferior longitudinal fasciculus (ILF), and to perisylvian language areas (supramarginal gyrus) through the arcuate fasciculus. After surgery, we observed the progressive and selective degeneration of the ILF, while the VWFA was anatomically intact. This allowed us to establish the critical causal role of this fiber tract in normal reading, and to show that its disruption is one pathophysiological mechanism of pure alexia, thus clarifying a long-standing debate on the role of disconnection in neurocognitive disorders.     

Mucosal intraepithelial T-lymphocytes in refractory celiac disease: a neoplastic population with a variable CD8 phenotype

Celiac disease (CD) is characterized by villous atrophy and an increase in intraepithelial lymphocytes (IEL). The IEL usually exhibit a suppressor/cytotoxic phenotype (CD3 and CD8) and display a polyclonal profile for T-cell receptor (TCR) rearrangement as opposed to the monoclonality of refractory CD (RCD) with CD8 IEL. A complication of CD is the loss of response to a gluten-free diet called RCD that may progress to an enteropathy-associated T-cell lymphoma. We reviewed 20 uncomplicated CD and 23 complicated CD (19 RCD and 4 diagnosed at the same time as enteropathy-associated T-cell lymphoma). In complicated CD, the IEL phenotype was CD8 in 9 cases and CD8 in 14 cases. In 100% of cases, IEL showed a monoclonal TCR rearrangement. All the 9 CD8 complicated CD exhibited a monoclonal TCR rearrangement and 3 of them were associated with a T-cell lymphoma (2 at the same time as CD and 1 after 43-mo follow-up) and bore the same monoclonal rearrangement in IEL and in lymphoma. Interestingly, the 13 cases (100%) of CD with a CD8 phenotype were also found monoclonal and 2 of them were associated with a T-cell lymphoma diagnosed at the same time as CD and exhibiting the same rearrangement in IEL and in lymphoma. An aberrant CD3 CD8 IEL phenotype is a good criterion for RCD diagnosis. However, cases with a normal CD3 CD8 IEL phenotype may correspond to RCD. In such cases, we suggest that molecular analysis of TCR-gamma genes is a useful method for identifying cases with RCD.     

Changes in local and network brain activity after stereotactic thermocoagulation in patients with drug-resistant epilepsy

Objective

Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) aims to reduce seizure frequency by modifying epileptogenic networks through local thermocoagulative lesions. Although RF-TC is hypothesized to functionally modify brain networks, reports of changes in functional connectivity (FC) following the procedure are missing. We evaluated, by means of SEEG recordings, whether variation in brain activity after RF-TC is related to clinical outcome.

Methods

Interictal SEEG recordings from 33 patients with drug-resistant epilepsy (DRE) were analyzed. Therapeutic response was defined as a >50% reduction in seizure frequency for at least 1 month following RF-TC. Local (power spectral density [PSD]) and FC changes were evaluated in 3-min segments recorded shortly before (baseline), shortly after, and 15 min after RF-TC. The PSD and FC strength values after thermocoagulation were compared with baseline as well as between the responder and nonresponder groups.

Results

In responders, we found a significant reduction in PSD after RF-TC in channels that were thermocoagulated for all frequency bands (p = .007 for broad, delta and theta, p <.001 for alpha and beta bands). However, we did not observe such PSD decrease in nonresponders. At the network level, nonresponders displayed a significant FC increase in all frequency bands except theta (broad, delta, beta band: p <.001; alpha band: p <.01), although responders showed a significant FC decrease in delta (p <.001) and alpha bands (p <.05). Nonresponders showed stronger FC changes with respect to responders exclusively in TC channels (broad, alpha, theta, beta: p >.05; delta: p = .001).

Significance

Thermocoagulation induces both local and network-related (FC) changes in electrical brain activity of patients with DRE lasting for at least 15 min. This study demonstrates that the observed short-term modifications in brain network and local activity significantly differ between responders and nonresponders and opens new perspectives for studying the longer-lasting FC changes after RF-TC.     

A RGG motif protein is involved in Toxoplasma gondii stress-mediated response

The molecular mechanisms controlling gene expression are still poorly understood in apicomplexan parasites. Here, we report the characterization of a homolog of the single strand binding proteins (named TgSsossB) in Toxoplasma gondii. We previously showed that TgSsossB interacts with the TgAlba proteins that are involved in translation regulation. We examined the role of TgSsossB in stress-mediated response, and particularly the role of its arginine–glycine–glycine (RGG) repeats domain. TgSsossB recombinant protein is able to bind to single strand DNA and RNA in a sequence-independent manner, but not to double stranded DNA. We showed that the RGG motif is not involved in this ability to bind to nucleic acid. We produced a mutant tagged strain lacking the RGG motif of TgSsossB using the knock-in strategy. We observed that this strain exhibited a fitness defect compared with the parental parasites. Moreover, the mutant strain produced fewer plaques in stress conditions, a defect that is due to a slow growth phenotype when extracellular parasites are exposed to stress. At the molecular level, we showed that the TgSsossB protein lacking a RGG motif lost its ability to interact with TgAlba2 and an isoform of TgAlba1, indicating that the TgAlba complex is likely non-functional in those parasites. Thus, our findings define the RGG domain of TgSsossB as a protein–protein interaction platform and underline the role of the TgAlba–TgSsossB complex in stress-mediated response.     

Cerebral bases of subliminal and supraliminal priming during reading

Several studies have investigated the neural correlates of conscious perception by contrasting functional magnetic resonance imaging (fMRI) activation to conscious and nonconscious visual stimuli. The results often reveal an amplification of posterior occipito-temporal activation and its extension into a parieto-frontal network. However, some of these effects might be due to a greater deployment of attentional or strategical processes in the conscious condition. Here, we examined the brain activity evoked by visible and invisible stimuli, both of which were irrelevant to the task. We collected fMRI data in a masking paradigm in which subliminal versus supraliminal letter strings were presented as primes while subjects focused attention on another subsequent, highly visible target word. Under those conditions, prime visibility was associated with greater activity confined to bilateral posterior occipito-temporal cortices, without extension into frontal and parietal cortices. However, supraliminal primes, compared with subliminal primes, evoked more extensive repetition suppression in a widely distributed set of parieto-frontal areas. Furthermore, only supraliminal primes caused phonological repetition enhancement in left inferior frontal and anterior insular cortex. Those results suggest a 2-stage view of conscious access: Relative to masked stimuli, unmasked stimuli elicit increased occipito-temporal activity, thus allowing them to compete for global conscious access and to induce priming in multiple distant areas. In the absence of attention, however, their access to a second stage of distributed parieto-frontal processing may remain blocked.