Histopathological Correlations of Qualitative and Quantitative Temporopolar MRI Analyses in Patients With Hippocampal Sclerosis

Hippocampal sclerosis (HS) is a common cause of pharmacoresistant focal epilepsy. Here, we (1) performed a histological approach to the anterior temporal pole of patients with HS to evaluate cortical and white matter (WM) cell populations, alteration of myelin integrity and markers of neuronal activity, and (2) correlated microscopic data with magnetic resonance imaging (MRI) findings. Our aim was to contribute with the understanding of neuroimaging and pathophysiological mechanisms of temporal lobe epilepsy (TLE) associated with HS. We examined MRIs and surgical specimens from the anterior temporal pole from TLE-HS patients (n = 9) and compared them with 10 autopsy controls. MRIs from healthy volunteers (n = 13) were used as neuroimaging controls. Histological techniques were performed to assess oligodendrocytes, heterotopic neurons, cellular proliferative index, and myeloarchitecture integrity of the WM, as well as markers of acute (c-fos) and chronic (ΔFosB) activities of neocortical neurons. Microscopic data were compared with neuroimaging findings, including T2-weighted/FLAIR MRI temporopolar blurring and values of fractional anisotropy (FA) from diffusion-weighed imaging (DWI). We found a significant increase in WM oligodendrocyte number, both in hematoxylin and eosin, and in Olig2-stained sections. The frequencies of oligodendrocytes in perivascular spaces and around heterotopic neurons were significantly higher in patients with TLE–HS compared with controls. The percentage of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase; a marker of myeloarchitecture integrity) immunopositive area in the WM was significantly higher in TLE-HS, as well as the numbers of c-fos- and ΔFosB-immunostained neocortical neurons. Additionally, we demonstrated a decrease in axonal bundle integrity on neuroimaging, with a significant reduction in the FA in the anterior temporal pole. No differences were detected between individuals with and without temporopolar blurring on visual MRI analysis, considering the number of oligodendroglial cells and percentage of WM CNPase-positive areas. Also, there was no relationship between T2 relaxometry and oligodendrocyte count. In conclusion, our histopathological data support the following: (1) the hypothesis that repetitive neocortical neuronal activity could induce changes in the WM cellular constitution and myelin remodeling in the anterior temporal pole from patients with TLE-HS, (2) that oligodendroglial hyperplasia is not related to temporal blurring or T2 signal intensity on MRI, and (3) that reduced FA is a marker of increase in Olig2-immunopositive cells in superficial temporopolar WM from patients with TLE-HS.

A nested cortical hierarchy of neural states underlies event segmentation in the human brain

A fundamental aspect of human experience is that it is segmented into discrete events. This may be underpinned by transitions between distinct neural states. Using an innovative data-driven state segmentation method, we investigate how neural states are organized across the cortical hierarchy and where in cortex neural state and perceived event boundaries overlap. Our results show that neural state boundaries are organized in a temporal cortical hierarchy, with short states in primary sensory regions and long states in anterior temporal pole and lateral and medial prefrontal cortex. Neural state boundaries overlap with event boundaries across large parts of this hierarchy. State boundaries are shared within and between groups of brain regions that resemble well known functional networks, such as the default mode network that fractionates into two subnetworks – one fast, one slow. Together these findings suggest that a nested cortical hierarchy of neural states forms the basis of event segmentation.

Distinguishing syntactic operations in the brain: Dependency and phrase-structure parsing

Finding the structure of a sentence — the way its words hold together to convey meaning — is a fundamental step in language comprehension. Several brain regions, including the left inferior frontal gyrus, the left posterior superior temporal gyrus, and the left anterior temporal pole, are supposed to support this operation. The exact role of these areas is nonetheless still debated. In this paper we investigate the hypothesis that different brain regions could be sensitive to different kinds of syntactic computations. We compare the fit of phrase-structure and dependency structure descriptors to activity in brain areas using fMRI. Our results show a division between areas with regard to the type of structure computed, with the left ATP and left IFG favouring dependency structures and left pSTG favouring phrase structures.

Words in context: tracking context-processing during language comprehension using computational language models and MEG

The meaning of a word depends on its lexical semantics and on the context in which it is embedded. At the basis of this lays the distinction between lexical retrieval and integration, two basic operations supporting language comprehension. In this paper, we investigate how lexical retrieval and integration are implemented in the brain by comparing MEG activity to word representations generated by computational language models. We test both non-contextualized embeddings, representing words independently from their context, and contextualized embeddings, which instead integrate contextual information in their representations. Using representational similarity analysis over cortical regions and over time, we observed that brain activity in the left anterior temporal pole and inferior frontal regions shows higher similarity with contextualized word embeddings compared to non-contextualized embeddings, between 300 and 500 ms after word presentation. On the other hand, non-contextualized word embeddings show higher similarity with brain activity in the left lateral and anterior temporal lobe at earlier latencies – areas and latencies related to lexical retrieval. Our results highlight how lexical retrieval and context integration can be tracked in the brain using word embeddings obtained with computational models. These results also suggest that the distinction between lexical retrieval and integration might be framed in terms of context-independent and contextualized representations.

Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally.Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally).Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions.Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.Highlights⍰ Anterior temporal lobe (ATL) degeneration is most often caused by FTLD-TDP type C pathology⍰ Cases can present with predominantly left (60%) or right (40%) ATL atrophy⍰ Within ATLs, medial regions are more vulnerable than lateral ones⍰ The observed spectrum of clinical phenotypes is driven by atrophy lateralization⍰ Left and right temporal variants of FTD should be considered the same disease

Genotypic and phenotypic variation of CADASIL among Chinese, Indians and Rungus in Malaysia

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of small cerebral arteries. This case series aims to describe the mutations in NOTCH3 and their phenotypes in Malaysia. We included patients who were genetically confirmed to have CADASIL, diagnosed at the University of Malaya Medical Centre, Malaysia. Family members who fulfilled clinical or imaging criteria, and patients from two previous published Malaysian families were also included. Six families (eleven cases) were included in this series. Genetic testing revealed NOTCH3 mutations in c.328C>T (p.Arg110Cys, R110C), c.533T>G (p.Cys185Gly, C185G), c.1630C>T (p.Arg544Cys, R544C) and c.160C>T (p.Arg54Cys, R54C). Two out of four Chinese families had R544C mutation in exon 11, with a later age of onset, absence of migraine and lack of anterior temporal pole involvement on MRI. One family with mixed Indian and Chinese ancestry had a mutation in exon 3 with R110C and another Indian family exon 4 with C185G mutation. This case series highlights the genotypic and phenotypic variability of CADASIL in a multiethnic country. The finding of p.Arg544Cys mutation among the older Chinese families, similar to those reported in Jeju Island and Taiwan, suggest the need to screen the older Chinese stroke patients with typical MRI changes.

Acute Ischemic Lesions Associated With Impairments in Expression and Recognition of Affective Prosody

Purpose We aimed to: (a) review existing data on the neural basis of affective prosody; (b) test the hypothesis that there are double dissociations in impairments of expression and recognition of affective prosody; and (c) identify areas of infarct associated with impaired expression and/or recognition of affective prosody after acute right hemisphere (RH) ischemic stroke. Methods Participants were tested on recognition of emotional prosody in content-neutral sentences. Expression was evaluated by measuring variability in fundamental frequency. Voxel-based symptom mapping was used to identify areas associated with severity of expressive deficits. Results We found that 9/23 patients had expressive prosody impairments; 5/9 of these patients also had impaired recognition of affective prosody; 2/9 had selective deficits in expressive prosody; recognition was not tested in 2/9. Another 6/23 patients had selective impairment in recognition of affective prosody. Severity of expressive deficits was associated with lesions in right temporal pole; patients with temporal pole lesions had deficits in expression and recognition. Conclusions Expression and recognition of prosody can be selectively impaired. Damage to right anterior temporal pole is associated with impairment of both, indicating a role of this structure in a mechanism shared by expression and production of affective prosody.