Megalencephalic Leukoencephalopathy With Subcortical Cysts (mlc) - A Case With Clinical And Magnetic Resonance Imaging (mri) Dissociation.

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Defining a role for the subthalamic nucleus within operative theoretical models of subcortical participation in language

Objective:To investigate the effects of bilateral, surgically induced functional inhibition of the subthalamic nucleus (STN) on general language, high level linguistic abilities, and semantic processing skills in a group of patients with Parkinson’s disease. Methods:Comprehensive linguistic profiles were obtained up to one month before and three months after bilateral implantation of electrodes in the STN during active deep brain stimulation (DBS) in five subjects with Parkinson’s disease (mean age, 63.2 years). Equivalent linguistic profiles were generated over a three month period for a non-surgical control cohort of 16 subjects with Parkinson’s disease (NSPD) (mean age, 64.4 years). Education and disease duration were similar in the two groups. Initial assessment and three month follow up performance profiles were compared within subjects by paired t tests. Reliability change indices (RCI), representing clinically significant alterations in performance over time, were calculated for each of the assessment scores achieved by the five STN-DBS cases and the 16 NSPD controls, relative to performance variability within a group of 16 non-neurologically impaired adults (mean age, 61.9 years). Proportions of reliable change were then compared between the STN-DBS and NSPD groups. Results:Paired comparisons within the STN-DBS group showed prolonged postoperative semantic processing reaction times for a range of word types coded for meanings and meaning relatedness. Case by case analyses of reliable change across language assessments and groups revealed differences in proportions of change over time within the STN-DBS and NSPD groups in the domains of high level linguistics and semantic processing. Specifically, when compared with the NSPD group, the STN-DBS group showed a proportionally significant (p

Discourse priming of homophones in individuals with dominant subcortical lesions, cortical lesions, and Parkinson’s disease

An on-line priming experiment was used to investigate discourse-level processing in four matched groups of subjects: individuals with nonthalamic subcortical lesions (NSL) ( n =10), normal control subjects ( n =10), subjects with Parkinsons disease (PD) ( n =10), and subjects with cortical lesions ( n =10). Subjects listened to paragraphs that ended in lexical ambiguities, and then made speeded lexical decisions on visual letter strings that were: nonwords, matched control words, contextually appropriate associates of the lexical ambiguity, contextually inappropriate associates of the ambiguity, and inferences (representing information which could be drawn from the paragraphs but was not explicitly stated). Targets were presented at an interstimulus interval (ISI) of 0 or 1000ms. NSL and PD subjects demonstrated priming for appropriate and inappropriate associates at the short ISI, similar to control subjects and cortical lesion subjects, but were unable to demonstrate selective priming of the appropriate associate and inference words at the long ISI. These results imply intact automatic lexical processing and a breakdown in discourse-based meaning selection and inference development via attentional/strategic mechanisms.

Use of SVM Methods with Surface-Based Cortical and Volumetric Subcortical Measurements to Detect Alzheimer`s Disease

Here, we examine morphological changes in cortical thickness of patients with Alzheimer`s disease (AD) using image analysis algorithms for brain structure segmentation and study automatic classification of AD patients using cortical and volumetric data. Cortical thickness of AD patients (n = 14) was measured using MRI cortical surface-based analysis and compared with healthy subjects (n = 20). Data was analyzed using an automated algorithm for tissue segmentation and classification. A Support Vector Machine (SVM) was applied over the volumetric measurements of subcortical and cortical structures to separate AD patients from controls. The group analysis showed cortical thickness reduction in the superior temporal lobe, parahippocampal gyrus, and enthorhinal cortex in both hemispheres. We also found cortical thinning in the isthmus of cingulate gyrus and middle temporal gyrus at the right hemisphere, as well as a reduction of the cortical mantle in areas previously shown to be associated with AD. We also confirmed that automatic classification algorithms (SVM) could be helpful to distinguish AD patients from healthy controls. Moreover, the same areas implicated in the pathogenesis of AD were the main parameters driving the classification algorithm. While the patient sample used in this study was relatively small, we expect that using a database of regional volumes derived from MRI scans of a large number of subjects will increase the SVM power of AD patient identification.

Long-Term Astroglial Reaction and Neuronal Plasticity in the Subcortical Visual Pathways After a Complete Ablation of Telencephalon in Pigeons (Columba livia)

This paper analyzes the astroglial and neuronal responses in subtelencephalic structures, following a bilateral ablation of the telencephalon in the Columba livia pigeons. Control birds received a sham operation. Four months later the birds were sacrificed and their brains processed for glial fribillary acid protein (GFAP) and neurofilament immunohistochemistry, markers for astrocytes and neurons, respectively. Computer-assisted image analysis was employed for quantification of the immunoreactive labeling in the nucleus rotundus (N.Rt) and the optic tectum (OT) of the birds. An increased number of GFAP immunoreactive astrocytes were found in several subregions of the N.Rt (p .001), as well as in layers 1, 2cd, 3, and 6 of the OT (p .001) of the lesioned animals. Neurofilament immunoreactivity decreased massively in the entire N.Rt of the lesioned birds; however, remaining neurons with healthy aspect showing large cytoplasm and ramified branches were detected mainly in the periphery of the nucleus. In view of the recently described paracrine neurotrophic properties of the activated astrocytes, the data of the present study may suggest a long-lasting neuroglial interaction in regions of the lesioned bird brain far from injury. Such events may trigger neuronal plasticity in remaining brain structures that may lead spontaneous behavior recovery as the one promoted here even after a massive injury.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy): an Australian perspective

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is a recently described cause of stroke or stroke-like episodes. It is caused by mutations in the Notch3 gene on chromosome 19p. We sought to demonstrate mutations of the Notch3 gene in Australian patients suspected of having CADASIL. Patients from several families were referred to the study. A diagnosis was determined clinically and by neuroimaging. Those suspected of having CADASIL had sequencing of exons 3 and 4 of the Notch3 gene. Eight patients, two of whom were siblings, were suspected of having CADASIL. Five patients (including the siblings) had mutations. Because of strong clustering of Notch3 mutations in CADASIL, this has potential as a reliable test for the disease in Australian patients. (C) 2001 Harcourt Publishers Ltd.

Subcortical brain mechanisms in speech and language

This paper reviews current research and contemporary theories of subcortical participation in the motor control of speech production and language processing. As a necessary precursor to the discussion of the functional roles of the basal ganglia and thalamus, the neuroanatomy of the basal ganglial-thalamocortical circuitry is described. Contemporary models of hypokinetic and hyperkinetic movement disorders based on recent neuroanatomical descriptions of the multi-segmented circuits that characterise basal ganglion anatomy are described. Reported effects of surgically induced lesions in the globus pallidus and thalamus on speech production are reviewed. In addition, contemporary models proposed to explain the possible contribution of various subcortical structures to language processing are described and discussed in the context of evidence gained from observation of the effects of circumscribed surgically induced lesions in the basal ganglia and thalamus on language function. The potential of studies based on examination of the speech/language outcomes of patients undergoing pallidotomy and thalamotomy to further inform the debate relating to the role of subcortical structures in speech motor control and language processing is highlighted. Copyright (C) 2001 S. Karger AG, Basel.

Complex language functions and subcortical mechanisms: evidence from Huntington's disease and patients with non-thalamic subcortical lesions

The neuropathological changes associated with Huntington's disease (HD) are most marked in the head of the caudate nucleus and, to a lesser extent, in the putamen and globus pallidus, suggesting that at least part of the language impairments found in patients with HD may result from non-thalamic subcortical (NTS) pathology. The present study aimed to test the hypothesis that a signature profile of impaired language functions is found in patients who have sustained damage to the non-thalamic subcortex, either focally induced or resulting from neurodegenerative pathology. The language abilities of a group of patients with Huntington's disease (n=13) were compared with those of an age- and education-matched group of patients with chronic NTS lesions following stroke (n=13) and a non-neurologically impaired control group (n=13). The three groups were compared on language tasks that assessed both primary and more complex language abilities. The primary language battery consisted of The Western Aphasia Battery and The Boston Naming Test, whilst the more complex cognitive-linguistic battery employed selected subtests from The Test of Language Competence-Expanded, The Test of Word Knowledge and The Word Test-Revised. On many of the tests of primary language function from the Western Aphasia Battery, both the HD and NTS participants performed in a similar manner to the control participants. The language performances of the HD participants were significantly more impaired (p<0.05 using modified Bonferroni adjustments) than the control group, however, on various lexico-semantic tasks (e. g. the Boston Naming Test and providing definitions), on both single-word and sentence-level generative tasks (e. g. category fluency and formulating sentences), and on tasks which required interpretation of ambiguous, figurative and inferential meaning. The difficulties that patients with HD experienced with tasks assessing complex language abilities were strikingly similar, both qualitatively and quantitatively, to the language profile produced by NTS participants. The results provide evidence to suggest that a signature language profile is associated with damage to the non-thalamic subcortex resulting from either focal neurological insult or a degenerative disease.

The basal ganglia and semantic engagement: Potential insights from semantic priming in individuals with subcortical vascular lesions, Parkinson's disease, and cortical lesions

The impact of basal ganglia dysfunction on semantic processing was investigated by comparing the performance of individuals with nonthalamic subcortical (NS) vascular lesions, Parkinson's disease (PD), cortical lesions, and matched controls on a semantic priming task. Unequibiased lexical ambiguity primes were used in auditory prime-target pairs comprising 4 critical conditions; dominant related (e.g., bank-money), subordinate related (e.g., bank-river), dominant unrelated (e.g.,foot-money) and subordinate unrelated (e.g., bat-river). Participants made speeded lexical decisions (word/nonword) on targets using a go-no-go response. When a short prime-target interstimulus interval (ISI) of 200 ins was employed, all groups demonstrated priming for dominant and subordinate conditions, indicating nonselective meaning facilitation and intact automatic lexical processing. Differences emerged at the long ISI (1250 ms), where control and cortical lesion participants evidenced selective facilitation of the dominant meaning, whereas NS and PD groups demonstrated a protracted period of nonselective meaning facilitation. This finding suggests a circumscribed deficit in the selective attentional engagement of the semantic network on the basis of meaning frequency, possibly implicating a disturbance of frontal-subcortical systems influencing inhibitory semantic mechanisms.

Noninvasive functional and structural exploration of human subcortical structures with high resolution

Projecte de recerca elaborat a partir d’una estada al Max Planck Institute for Human Cognitive and Brain Sciences, Alemanya, entre 2010 i 2012. El principal objectiu d’aquest projecte era estudiar en detall les estructures subcorticals, en concret, el rol dels ganglis basals en control cognitiu durant processament lingüístic i no-lingüístic. Per tal d’assolir una diferenciació minuciosa en els diferents nuclis dels ganglis basals s’utilitzà ressonància magnètica d’ultra-alt camp i alta resolució (7T-MRI). El còrtex prefrontal lateral i els ganglis basals treballant conjuntament per a mitjançar memòria de treball i la regulació “top-down” de la cognició. Aquest circuit regula l’equilibri entre respostes automàtiques i d’alt-ordre cognitiu. Es crearen tres condicions experimentals principals: frases/seqüències noambigües, no-gramatical i ambigües. Les frases/seqüències no-ambigües haurien de provocar una resposta automàtica, mentre les frases/seqüències ambigües i no-gramaticals produïren un conflicte amb la resposta automàtica, i per tant, requeririen una resposta de d’alt-ordre cognitiu. Dins del domini de la resposta de control, la ambigüitat i no-gramaticalitat representen dues dimensions diferents de la resolució de conflicte, mentre per una frase/seqüència temporalment ambigua existeix una interpretació correcte, aquest no és el cas per a les frases/seqüències no-gramaticals. A més, el disseny experimental incloïa una manipulació lingüística i nolingüística, la qual posà a prova la hipòtesi que els efectes són de domini-general; així com una manipulació semàntica i sintàctica que avaluà les diferències entre el processament d’ambigüitat/error “intrínseca” vs. “estructural”. Els resultats del primer experiment (sintax-lingüístic) mostraren un gradient rostroventralcaudodorsal de control cognitiu dins del nucli caudat, això és, les regions més rostrals sostenint els nivells més alts de processament cognitiu