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Temporal lobe studies in motor neuron disease overwhelmingly focus on white matter alterations and cortical grey matter atrophy. Reports on amygdala involvement are conflicting and the amygdala is typically evaluated as single structure despite consisting of several functionally and cytologically distinct nuclei. A prospective, single-centre, neuroimaging study was undertaken to comprehensively characterise amygdala pathology in 100 genetically-stratified ALS patients, 33 patients with PLS and 117 healthy controls. The amygdala was segmented into groups of nuclei using a Bayesian parcellation algorithm based on a probabilistic atlas and shape deformations were additionally assessed by vertex analyses. The accessory basal nucleus (p = .021) and the cortical nucleus (p = .022) showed significant volume reductions in C9orf72 negative ALS patients compared to controls. The lateral nucleus (p = .043) and the cortico-amygdaloid transition (p = .024) were preferentially affected in C9orf72 hexanucleotide carriers. A trend of total volume reduction was identified in C9orf72 positive ALS patients (p = .055) which was also captured in inferior-medial shape deformations on vertex analyses. Our findings highlight that the amygdala is affected in ALS and our study demonstrates the selective involvement of specific nuclei as opposed to global atrophy. The genotype-specific patterns of amygdala involvement identified by this study are consistent with the growing literature of extra-motor clinical features. Mesial temporal lobe pathology in ALS is not limited to hippocampal pathology but, as a key hub of the limbic system, the amygdala is also affected in ALS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The thalamus is a key cerebral hub relaying a multitude of corticoefferent and corticoafferent connections and mediating distinct extrapyramidal, sensory, cognitive and behavioural functions. While the thalamus consists of dozens of anatomically well-defined nuclei with distinctive physiological roles, existing imaging studies in motor neuron diseases typically evaluate the thalamus as a single structure. Based on the unique cortical signatures observed in ALS and PLS, we hypothesised that similarly focal thalamic involvement may be observed if the nuclei are individually evaluated. A prospective imaging study was undertaken with 100 patients with ALS, 33 patients with PLS and 117 healthy controls to characterise the integrity of thalamic nuclei. ALS patients were further stratified for the presence of GGGGCC hexanucleotide repeat expansions in C9orf72. The thalamus was segmented into individual nuclei to examine their volumetric profile. Additionally, thalamic shape deformations were evaluated by vertex analyses and focal density alterations were examined by region-of-interest morphometry. Our data indicate that C9orf72 negative ALS patients and PLS patients exhibit ventral lateral and ventral anterior involvement, consistent with the 'motor' thalamus. Degeneration of the sensory nuclei was also detected in C9orf72 negative ALS and PLS. Both ALS groups and the PLS cohort showed focal changes in the mediodorsal-paratenial-reuniens nuclei, which mediate memory and executive functions. PLS patients exhibited distinctive thalamic changes with marked pulvinar and lateral geniculate atrophy compared to both controls and C9orf72 negative ALS. The considerable ventral lateral and ventral anterior pathology detected in both ALS and PLS support the emerging literature of extrapyramidal dysfunction in MND. The involvement of sensory nuclei is consistent with sporadic reports of sensory impairment in MND. The unique thalamic signature of PLS is in line with the distinctive clinical features of the phenotype. Our data confirm phenotype-specific patterns of thalamus involvement in motor neuron diseases with the preferential involvement of nuclei mediating motor and cognitive functions. Given the selective involvement of thalamic nuclei in ALS and PLS, future biomarker and natural history studies in MND should evaluate individual thalamic regions instead overall thalamic changes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Although hippocampal involvement in amyotrophic lateral sclerosis (ALS) has been consistently highlighted by postmortem studies, memory impairment remains under-recognized and the involvement of specific hippocampal subfields and their connectivity patterns are poorly characterized in vivo. A prospective multimodal neuroimaging study has been undertaken with 50 well-characterized ALS patients, 18 patients with Alzheimer's disease, and 40 healthy controls to evaluate their mesial temporal lobe profile. Patients with ALS and Alzheimer's disease have divergent hippocampal signatures. The cornu ammonis 2/3 subfield and the hippocampus-amygdala transition area are the most affected regions in ALS in contrast to Alzheimer's disease, where the presubiculum and subiculum are the most vulnerable regions. Tractography reveals considerable fornix and perforant pathway pathology in both patient groups. Mesial temporal lobe structures in ALS have a selective and disease-specific vulnerability profiles, and their white matter projections exhibit concomitant degeneration. Our combined gray and white matter analyses indicate a connectivity-based, network-defined involvement of interconnected temporal lobe structures as opposed to contiguous involvement of adjacent structures. Our findings underline the importance of screening for memory deficits and personalized management strategies in ALS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In the present case study, we investigated possible emotional connectedness between monozygotic twins by means of functional magnetic resonance imaging (fMRI). During the experimental condition, Twin 2 was randomly selected to participate in the neuroimaging protocol while Twin 1 participated in the experimental condition outside the MRI scanner (none of them was aware of the experimental procedure). The experimental condition included two sessions with visual and acoustic stimuli, respectively. Between the two experimental conditions, there was a 2-min break with Twin 1 (i.e., the subject outside the scanner) relaxing with eyes closed. Data analysis revealed significant brain activation in three regions, namely left orbitofrontal gyrus (during visual condition) and left cingulum and precentral gyrus (during the acoustic condition). Our findings denote emotional connectedness between a pair of monozygotic twins using fMRI. Further studies in larger sample sizes are needed to investigate if this is a generalized and systematic phenomenon or an incidental finding., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To explore the superior frontal sulcus (SFS) morphology, trajectory of the applied surgical corridor, and white matter bundles that are traversed during the superior frontal transsulcal transventricular approach., Methods: Twenty normal, adult, formalin-fixed cerebral hemispheres and 2 cadaveric heads were included in the study. The topography, morphology, and dimensions of the SFS were recorded in all specimens. Fourteen hemispheres were investigated through the fiber dissection technique whereas the remaining 6 were explored using coronal cuts. The cadaveric heads were used to perform the superior frontal transsulcal transventricular approach. In addition, 2 healthy volunteers underwent diffusion tensor imaging and tractography reconstruction studies., Results: The SFS was interrupted in 40% of the specimens studied and was always parallel to the interhemispheric fissure. The proximal 5 cm of the SFS (starting from the SFS precentral sulcus meeting point) were found to overlie the anterior ventricular system in all hemispheres. Five discrete white matter layers were identified en route to the anterior ventricular system (i.e., the arcuate fibers, the frontal aslant tract, the external capsule, internal capsule, and the callosal radiations). Diffusion tensor imaging studies confirmed the fiber tract architecture., Conclusions: When feasible, the superior frontal transsulcal transventricular approach offers a safe and effective corridor to the anterior part of the lateral ventricle because it minimizes brain retraction and transgression and offers a wide and straightforward working corridor. Meticulous preoperative planning coupled with a sound microneurosurgical technique are prerequisites to perform the approach successfully., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We aimed to investigate structural changes in vivo in memory-related white matter tracts (i.e., perforant pathway zone [PPZ]; uncinate fasciculus [UF]; fornix) using diffusion tensor tractography and evaluate possible associations with memory performance in nondemented patients with amyotrophic lateral sclerosis (ALS). Forty-two ALS patients and 25 healthy controls (HCs) underwent a 30-directional diffusion-weighted imaging on a 3T MR scanner, followed by tractography of PPZ, UF, and fornix and analysis of fractional anisotropy (FA), axial diffusivity and radial diffusivity (Dr). Patients were administered neuropsychological measures of verbal (list learning via Rey Auditory Verbal Learning Test [RAVLT] and prose memory via Babcock Story Recall Test) and nonverbal (Rey's Complex Figure Test) episodic memory. After correcting for multiple comparisons, ALS patients showed increased Dr in the left PPZ compared to HC. We then fitted a multivariate general linear model within ALS patients with neuropsychological measures as dependent variables and age, age 2 , gender, verbal IQ, and diffusion tensor tractography metrics with at least medium effect size differences between ALS and HC as independent variables. We found that (1) left PPZ FA, gender, and verbal IQ contributed to RAVLT-Total Learning; (2) left PPZ FA, left UF Dr, and gender contributed to RAVLT-Immediate Recall; and (3) left PPZ FA and left UF axial diffusivity contributed to Babcock Story Recall Test-Immediate and Delayed Recall. Advanced neuroimaging techniques verified in this study previously reported neuropathological findings regarding PPZ degeneration in ALS. We also detected a unique contribution of microstructural changes in hippocampal and frontotemporal white matter tracts on patients' memory profile., (Copyright © 2016 Elsevier Inc. All rights reserved.)