Georgios Velonakis

Evaluating cognitive models of visual word recognition using fMRI: Effects of lexical and sublexical variables

In this study predictions of the dual-route cascaded (DRC) model of word reading were tested using fMRI. Specifically, patterns of co-localization were investigated: (a) between pseudoword length effects and a pseudowords vs. fixation contrast, to reveal the sublexical grapho-phonemic conversion (GPC) system; and (b) between word frequency effects and a words vs. pseudowords contrast, to reveal the orthographic and phonological lexicon. Forty four native speakers of Greek were scanned at 3T in an event-related lexical decision task with three event types: (a) 150 words in which frequency, length, bigram and syllable frequency, neighborhood, and orthographic consistency were decorrelated; (b) 150 matched pseudowords; and (c) fixation. Whole-brain analysis failed to reveal the predicted co-localizations. Further analysis with participant-specific regions of interest defined within masks from the group contrasts revealed length effects in left inferior parietal cortex and frequency effects in the left middle temporal gyrus. These findings could be interpreted as partially consistent with the existence of the GPC system and phonological lexicon of the model, respectively. However, there was no evidence in support of an orthographic lexicon, weakening overall support for the model. The results are discussed with respect to the prospect of using neuroimaging in cognitive model evaluation.

Investigating the neuroanatomical substrate of pathological laughing and crying in amyotrophic lateral sclerosis with multimodal neuroimaging techniques

Abstract Objective: Pathological laughing and crying (PLC) is common in several neurological and psychiatric diseases and is associated with a distributed network involving the frontal cortex, the brainstem and cortico-pontine-cerebellar circuits. By applying multimodal neuroimaging approach, we examined the neuroanatomical substrate of PLC in a sample of patients with amyotrophic lateral sclerosis (ALS). Methods: We studied 56 non-demented ALS patients and 25 healthy controls (HC). PLC was measured in ALS using the Center of Neurologic Study Lability Scale (CNS-LS; cutoff score: 13). All participants underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging at 3T. Voxel-based morphometry and tract-based spatial-statistics analysis was used to examine gray matter (GM) and white matter (WM) differences between ALS patients with and without PLC (ALS-PLC and ALS-nonPLC, respectively). Comparisons were restricted to regions with detected differences between ALS and HC, controlling for age, gender, total intracranial volume and depressive symptoms. Results: In regions with significant differences between ALS and HC, ALS-PLC patients showed decreased GM volume in left orbitofrontal cortex, frontal operculum, and putamen and bilateral frontal poles, compared to ALS-nonPLC. They also had decreased fractional anisotropy in left cingulum bundle and posterior corona radiata. WM abnormalities were additionally detected in WM associative and ponto-cerebellar tracts (using a more liberal threshold). Conclusions: PLC in ALS is driven by both GM and WM abnormalities which highlight the role of circuits rather than isolated centers in the emergence of this condition. ALS is suggested as a useful natural experimental model to study PLC.

Working memory impairment in aphasia: The issue of stimulus modality

Abstract The presence of short-term/working memory deficits in aphasia has been well-established in the relevant literature. Moreover, recent studies have demonstrated such deficits in both the verbal and visuospatial modalities in patients with aphasia following a left hemisphere stroke. The present study aims to investigate the prevalence and possible lesion correlates of modality-dependent and modality-independent short-term/working memory impairment in aphasia. For this purpose, 54 individuals with post-stroke aphasia were recruited. Aphasic disturbances were assessed with the Boston Diagnostic Aphasia Examination (BDAE) and memory deficits with the digit span and Corsi block-tapping tasks. Structural imaging data were obtained for each patient and lesion sites were identified and coded by two independent neuroradiologists for 16 predetermined left hemisphere areas. Results clearly showed that visuospatial deficits were relatively common, even though verbal deficits are more frequent, and further illustrate the existence of distinct performance patterns within each modality. Analyses revealed comparable lesion extent and locations between patients demonstrating modality-independent and patients demonstrating modality-dependent deficits. Hierarchical regression analyses indicated that deficient performance on digit span forward, indicating impaired verbal short-term memory, was associated with lesions encompassing the inferior frontal gyrus and the inferior parietal cortex. Similar analyses for digit span backward, and the two conditions of Corsi did not yield significant results. However, behavioral data indicate a dissociation between forward and backward visuospatial span, which could be explained by selectively impaired primacy and recency effects. The emergence of modality-dependent and modality-independent deficits is further discussed in relation to hemispheric lateralization during the course of human evolution.

The Clinical and Radiological Spectrum of Hippocampal Pathology in Amyotrophic Lateral Sclerosis

Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence from neuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely.

Verbal and Figural Fluency in Temporal Lobe Epilepsy: Does Hippocampal Sclerosis Affect Performance?

Background and Objectives: Clinicians commonly use verbal and nonverbal measures to test fluency in patients with epilepsy, either during routine cognitive assessment or as part of pre- and postsurgical evaluation. We hypothesized that patients with mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis would perform worse than patients with lateral TLE in both verbal and design fluency. Methods: We assessed semantic, phonemic, and nonverbal fluency in 49 patients with TLE: 31 with lateral TLE and 18 with mesial TLE plus hippocampal sclerosis. We also gave non-fluency cognitive measures: psychomotor speed, attentional set shifting, selective attention, abstract reasoning, verbal and visual episodic memory, and incidental memory. Results: Patients with mesial TLE performed significantly worse on figural fluency than patients with lateral TLE. Even though group differences on verbal fluency measures were not significant, the patients with mesial TLE had a pattern of poorer performance. The patients with mesial TLE scored significantly worse on measures of selective attention, verbal episodic memory, and incidental memory. Conclusions: Our study underlines differences in cognitive function between patients with mesial and lateral TLE, particularly in figural fluency. Although we cannot directly assess the role of the hippocampus in cognitive aspects of creative and divergent thinking related to figural fluency, the cognitive discrepancies between these two TLE groups could be ascribed to the mesial TLE hippocampal pathology shown in our study and addressed in the literature on hippocampal involvement in divergent thinking. Our findings could benefit cognitive rehabilitation programs tailored to the needs of patients with TLE.

Ipsilateral and contralateral cerebro-cerebellar white matter connections: A diffusion tensor imaging study in healthy adults

BACKGROUND AND PURPOSE The cerebellum has a pivotal role in regulating human behavior; yet whether this function is mediated only through contralateral cerebro-cerebellar pathways is under-investigated. Thus, we examined feed-backward and feed-forward ipsilateral and contralateral cerebro-cerebellar connections using a detereministic diffusion tensor imaging (DTI) algorithm, the robustness of which was also estimated using phantom DTI data. MATERIALS AND METHODS Fifty-one healthy controls (22-60 years old; 15 males/36 females) were scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of-interest (ROI) method was applied for the reconstruction of the ipsilateral and contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto-cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally using the Brainance DTI Suite. A realistic diffusion MR phantom was used to evaluate the fiber tracking methodology for 16 fibers containing crossing, kissing, splitting and bending configurations. RESULTS Both contralateral and ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully reconstructed; the contralateral DRTC tract was not reconstructed in all subjects. Also, the TPC tract was not reproduced in several subjects mostly regarding the contralateral connection. Descriptive DTI measures (number of fibers, fractional anisotropy, radial and axial diffusivity) are presented for each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16 fibers that almost perfectly matched the 16 ground truth fibers. CONCLUSIONS We identified ipsilateral and contralateral connections using a clinically applicable DTI sequence, a robust deterministic algorithm and an unbiased methodology, which can be applied in daily practice in different brain pathologies.

X linked Charcot-Marie-Tooth disease and multiple sclerosis: emerging evidence for an association

Objective X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, a gap junction protein expressed in Schwann cells, but also found in oligodendrocytes. Four patients with CMTX developing central nervous system (CNS) demyelination compatible with multiple sclerosis (MS) have been individually published. We presently sought to systematically investigate the relationship between CMTX and MS. Methods Over 20 years, 70 consecutive patients (36 men) with GJB1 mutations were identified at our Neurogenetics Unit, Athens, Greece, and assessed for clinical features suggestive of MS. Additionally, 18 patients with CMTX without CNS symptoms and 18 matched controls underwent brain MRI to investigate incidental findings. Serum from patients with CMTX and MS was tested for CNS immunoreactivity. Results We identified three patients with CMTX who developed clinical features suggestive of inflammatory CNS demyelination fulfilling MS diagnostic criteria. The resulting 20-year MS incidence (4.3%) differed significantly from the highest background 20-year MS incidence ever reported from Greece (p=0.00039). The search for incidental brain MRI findings identified two CMTX cases (11%) with lesions suggestive of focal demyelination compared with 0 control. Moreover, 10 cases in the CMTX cohort had hyperintensity in the splenium of the corpus callosum compared with 0 control (p=0.0002). No specific CNS-reactive humoral factors were identified in patients with CMTX and MS. Conclusions We have demonstrated a higher than expected frequency of MS in patients with CMTX and identified incidental focal demyelinating lesions on brain MRI in patients with CMTX without CNS symptoms. This provides circumstantial evidence for GJB1 mutations acting as a possible MS risk factor.

Motor and extra-motor gray matter integrity may underlie neurophysiologic parameters of motor function in amyotrophic lateral sclerosis: a combined voxel-based morphometry and transcranial stimulation study

The association between gray matter (GM) density and neurophysiologic changes is still unclear in amyotrophic lateral sclerosis (ALS). We evaluated the relationship between GM density and motor system integrity combining voxel-based morphometry (VBM) and transcranial magnetic stimulation (TMS) in ALS. We included 17 ALS patients and 22 healthy controls (HC) who underwent 3D-T1-weighted imaging. Among the ALS group, we applied left motor cortex single-pulse TMS. We used whole-brain VBM comparing ALS and HC in GM density. We also conducted regression analysis to examine correlations between GM density and the following TMS parameters: motor evoked potential (MEP)/M ratio and central motor conduction time (CMCT). We found significantly decreased GM density in ALS patients in several frontal, temporal, parietal/occipital and cerebellar regions (p < 0.001 uncorrected; cluster-extent threshold k = 100 voxels per cluster). With regards to TMS parameters, ALS patients showed mostly increased MEP/M ratio and modest prolongation of CMCT. MEP/M ratio was associated with GM density in (a) rolandic operculum/inferior frontal gyrus/precentral gyrus; anterior cingulate gyrus; inferior temporal gyrus; superior parietal lobule; cuneus; superior occipital gyrus and cerebellum (positive association) and (b) paracentral lobule/supplementary motor area (negative association). CMCT was associated with GM density in (a) inferior frontal gyrus and middle cingulated gyrus (positive association) and (b) superior parietal lobule; cuneus and cerebellum (negative association). Our findings support a significant interaction between motor and extra-motor structural and functional changes and highlight that motor and extra-motor GM integrity may underlie TMS parameters of motor function in ALS patients.

Convexity Subarachnoid Hemorrhage Due to Cardioembolic Stroke in a Woman with Thyrotoxicosis: Α Case Report

BACKGROUND Non-traumatic convexity subarachnoid hemorrhage (cSAH) is a rarely reported condition with a wide spectrum of etiologies. Cerebral ischemia secondary to extracranial or intracranial atherosclerotic disease has been identified as a relatively uncommon cause of cSAH. CASE REPORT We report a case of cSAH caused by cardioembolic stroke. A 69-year old female patient developed suddenly left-sided face and body weakness and numbness and visual neglect on the left. She was newly detected with paroxysmal atrial fibrillation on the ground of thyrotoxicosis. Brain magnetic resonance imaging revealed ischemia of embolic pattern with cSAH. Further evaluation excluded other cause of hemorrhage. Dilation of leptomeningeal collateral vessels and rupture of pial vessels in distal cortical arteries may caused cSAH. Full anticoagulation was initiated. After one month, her condition improved significantly (NIHSS from 6 to 2). CONCLUSIONS cSAH may be a rare complication of cardioembolic stroke.

Serial MRI images of an unusual presentation of anti-GAD encephalitis: A new pattern?

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