Mesial temporal sclerosis is linked with more widespread white matter changes in temporal lobe epilepsy

AbstractTemporal lobe epilepsy patients with unilateral mesial temporal sclerosis (TLE+uMTS) have been demonstrated to have extensive white matter abnormalities both ipsilateral and contralateral to the seizure onset zone. However, comparatively less is known about the white matter integrity of TLE patients without MTS (non-lesional TLE, nl-TLE). The purpose of the study was to investigate the diffusion properties of thirteen major white matter tracts in patients with TLE+uMTS and nl-TLE. Diffusion tensor imaging (DTI) was performed on 23 TLE+uMTS (15 left MTS and 8 right MTS), 15nl-TLE and 21 controls. Thirteen tracts were delineated by tractography and their diffusion parameters compared for the two TLE groups relative to controls, with left and right hemispheres combined per tract. A subgroup analysis investigated left and right MTS separately. Compared to controls, reduced anisotropy was detected in ten tracts for TLE+uMTS, but only the parahippocampal cingulum and tapetum for nl-TLE. Right MTS subgroup showed reduced anisotropy in 7 tracts bilaterally (3 limbic, 3 association, 1 projection) and 2 tracts ipsilaterally (1 association, 1 projection) and the body of the corpus callosum whereas the left MTS subgroup showed reduced anisotropy in 4 tracts bilaterally (2 limbic, 1 association, 1 projection) and 2 tracts ipsilaterally (1 limbic, 1 association). Diffusion abnormalities in tracts were observed within and beyond the temporal lobe in TLE+uMTS and were more widespread than in nl-TLE. Patients with right MTS had more extensive, bilateral abnormalities in comparison to left MTS. These findings suggest different dysfunctional networks in TLE patients with and without MTS

Neuronal underpinnings of stuttering

Fluent speech production depends on robust connections between brain regions that are crucial for auditory processing, motor planning and execution. The ability of the speech apparatus to produce effortless, continuous and uninterrupted flow of speech is compromised in people who stutter (PWS). Stuttering is a multifactorial speech fluency disorder that results in unintended occurrences of sound syllable repetitions, prolongations, and blocks, particularly on the initial part of words and sentences. Decades of research on the topic have produced an extensive amount of data but the mechanism behind the symptoms associated with stuttering is not clear. The aim of the present study was to investigate the neuronal basis of stuttering by looking at the brains neurochemistry utilizing the proton magnetic resonance spectroscopy (1H - MRS) technique. In particular, we looked at the neurotransmitters N-acetyl Aspartate (NAA), an aggregate of Glutamate and Glutamine (Glx) and myo-inositol (mI) as potential candidates for understanding the biochemical manifestations of stuttering. We have also collected behavioral data from the PWS group and correlated it with their spectroscopy results. Finally, we combined the measurements of neuronal activity behind speech production, probed with functional magnetic resonance imaging (fMRI), with 1H-MRS measurements in order to achieve information on the interaction between neuronal activation and underlying neurochemical function. The inferior frontal gyrus (IFG) was chosen as a target region for this investigation, given its' involvement in speech motor control. Neurotransmitter mI showed the main group effect. The cerebral metabolite pattern of PWS is characterized by the pronounced reduction in myo-inositol level in the IFG. Myo- inositol is considered a glial marker and its concentration may reflect the condition of myelin in the brain. The myelination process is referred to as the maturation process of the fibers that facilitates rapid neural innervation of speech muscles underlying speech fluency. Hence, given the existing literature on the topic and our main findings we suggested that delayed or impaired myelination of the speech-related neuronal network in the postnatal period might be responsible for the later development of stuttering.Flytende tale er avhengig av solide forbindelser mellom hjerneområder involvert i auditorisk prosessering, motorisk planlegging og utførelse. Taleapparatets evne til uanstrengt å produsere flytende uforstyrret tale er forstyrret hos personer som stammer (PWS). Stamming er en sammensatt forstyrrelse av taleflyt som resulterer i ufrivillige gjentagelser av stavelser, utvidelser, og blokkeringer, spesielt i begynnelsen av ord og setninger. Gitt tiår med forskning på området er det ennå ikke klart hvilke mekanismer som ligger til grunn for stammingen. Hensikten med dette studiet har vært å utforske det nevrale grunnlaget til stamming ved å se på hjernens nevrokjemi ved å ta i bruk proton-magnetisk resonsansspektroskopi (1H-MRS) teknikk. Vi har sett på om nevrotransmitterene: N-acetyl Asparatate (NAA); glutamat og glutamin (Glx) og myo-inositol kan bidra til forståelsen av de biokjemiske manifestasjonene av stamming. Vi har også samlet inn atferdsdata fra PWS-gruppen og korrelert dette med spektroskopi-dataen. Til slutt kombinerte vi målingene av den nevral aktiviteten av taleproduksjon med 1H-MRS målingene for å se på interaksjon mellom nevral aktivering og underliggende nevrokjemisk funksjon. Inferior frontal gyrus (IFG) var målområdet for undersøkelsen, siden området er viktig for motorisk kontroll av tale. Nevrotransmitteren myo-inositol viste en hovedgruppeeffekt. Metabolittene i hjernen til personer som stammer var karakterisert av en tydelig reduksjon i nivå av myo-inositol i IFG. Myo-inositol er ansett som en glial markør, og dets konsentrasjon kan muligens fortelle om myelinets tilstand i hjernen. Myelineringsprosessen av nerveceller er en modningsprosess som fasiliterer rask signaloverføring fra hjernen til muskelfibrene involvert i tale. Vi foreslår derfor på bakgrunn av foreliggende litteratur på området og våre resultater at forsinket eller hemmet myelinering av tale-relaterte nevrale nettverk i spedbarnsperioden kan føre til senere utvikling av stamming.LOGO345MAPS-LOG0

Nuclear imaging for localization and surgical outcome prediction in epilepsy: A review of latest discoveries and future perspectives

BackgroundEpilepsy is one of the most common neurological disorders. Approximately, one-third of patients with epilepsy have seizures refractory to antiepileptic drugs and further require surgical removal of the epileptogenic region. In the last decade, there have been many recent developments in radiopharmaceuticals, novel image analysis techniques, and new software for an epileptogenic zone (EZ) localization.ObjectivesRecently, we provided the latest discoveries, current challenges, and future perspectives in the field of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in epilepsy.MethodsWe searched for relevant articles published in MEDLINE and CENTRAL from July 2012 to July 2022. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis was conducted using the keywords “Epilepsy” and “PET or SPECT.” We included both prospective and retrospective studies. Studies with preclinical subjects or not focusing on EZ localization or surgical outcome prediction using recently developed PET radiopharmaceuticals, novel image analysis techniques, and new software were excluded from the review. The remaining 162 articles were reviewed.ResultsWe first present recent findings and developments in PET radiopharmaceuticals. Second, we present novel image analysis techniques and new software in the last decade for EZ localization. Finally, we summarize the overall findings and discuss future perspectives in the field of PET and SPECT in epilepsy.ConclusionCombining new radiopharmaceutical development, new indications, new techniques, and software improves EZ localization and provides a better understanding of epilepsy. These have proven not to only predict prognosis but also to improve the outcome of epilepsy surgery

Imaging functional and structural networks in the human epileptic brain

Epileptic activity in the brain arises from dysfunctional neuronal networks involving cortical and subcortical grey matter as well as their connections via white matter fibres. Physiological brain networks can be affected by the structural abnormalities causing the epileptic activity, or by the epileptic activity itself. A better knowledge of physiological and pathological brain networks in patients with epilepsy is critical for a better understanding the patterns of seizure generation, propagation and termination as well as the alteration of physiological brain networks by a chronic neurological disorder. Moreover, the identification of pathological and physiological networks in an individual subject is critical for the planning of epilepsy surgery aiming at resection or at least interruption of the epileptic network while sparing physiological networks which have potentially been remodelled by the disease. This work describes the combination of neuroimaging methods to study the functional epileptic networks in the brain, structural connectivity changes of the motor networks in patients with localisation-related or generalised epilepsy and finally structural connectivity of the epileptic network. The combination between EEG source imaging and simultaneous EEG-fMRI recordings allowed to distinguish between regions of onset and propagation of interictal epileptic activity and to better map the epileptic network using the continuous activity of the epileptic source. These results are complemented by the first recordings of simultaneous intracranial EEG and fMRI in human. This whole-brain imaging technique revealed regional as well as distant haemodynamic changes related to very focal epileptic activity. The combination of fMRI and DTI tractography showed subtle changes in the structural connectivity of patients with Juvenile Myoclonic Epilepsy, a form of idiopathic generalised epilepsy. Finally, a combination of intracranial EEG and tractography was used to explore the structural connectivity of epileptic networks. Clinical relevance, methodological issues and future perspectives are discussed

A study of Clinico-Neuroradiologic Correlation in Patients with Dementia

INTRODUCTION: Dementia is characterized by decline in the cognitive functioning of an individual that significantly affects the quality of life and intrudes into the activity of daily living. The prevalence of dementia is increasing and is on the rise. This is due to the increased longevity that has resulted in increasing proportions of elderly population in whom the prevalence of dementia is higher. Dementia is defined by the DSM 5 criteria as decline from previously established baseline in the at least one of the cognitive domains: Memory and learning, executive function, language, complex attention, social cognition and perceptual motor function and it affects the activities of daily living. The symptoms in these patients do not occur exclusively during delirium and are not explainable by psychiatric disorder. AIM OF THE STUDY: To study the association between clinical deficits in cognitive domains of attention, memory and language in subjects with dementia and the neuroimaging correlates of the corresponding networks. OBJECTIVES: 1. To evaluate clinical deficits in cognitive domains of attention, memory and language in subjects with dementia. 2. To study the neuroimaging findings in subjects of Dementia on MR voxel based morphometry, MR diffusion tensor imaging and 18-Fluorodeoxyglucose Positron Emission Tomography in corresponding networks of attention, language and memory respectively. 3. To determine neuroimaging correlates of deficits in attention, language and memory in subjects with dementia in corresponding networks of attention, language and memory respectively. MATERIALS AND METHODS: Subjects attending dementia and cognitive neurosciences clinic at Rajiv Gandhi Government General Hospital, Chennai (RGGGH) were enrolled in the study. A total of 60 patients and 30 controls were recruited for the study. All the subjects were well informed about the study and the consent forms were obtained prior to the assessments. All the patients in the study underwent clinical examination for establishing the diagnosis of dementia. After the clinical assessment the subjects under investigation underwent four different types of assessments. The assessments include neuropsychological assessments, Voxel based Morphometry, Diffusion Tensor Imaging (for both controls and cases), and FDG-PET (for cases alone). METHODOLOGY: A random sample of 60 patients and 30 age-gender matched controls were selected from dementia and cognitive neurosciences clinic at Rajiv Gandhi Government General Hospital(RGGGH), Chennai during Dec. 2014 – Feb. 2018. The study was approved by Institutional Ethical Committee of Rajiv Gandhi Government General Hospital, Chennai. Neuropsychological tests were performed after obtaining consents from the subjects or caretakers. Patients were selected on the basis of MoCA scores where a case with a MoCA score of below 27 and satisfying the inclusion/exclusion criteria has been treated as a patient and included in the present study. The following clinical assessments were made on each patient: Addenbrooke‘s Cognitive Examination III (ACE III), Wechsler‘s Memory Scale (WMS), Trail Making Test A & B (TMT), Auditory Verbal Learning Test (AVLT) and scores were assessed accordingly. Neuropsychological aspects of both patients and controls were assessed by a single trained clinical psychologist. RESULTS: Before carrying out the major study, a pilot study was conducted taking a random sample of 10 patients and 10 controls. Reliability and validity of the protocols used for carrying out the major study were computed using appropriate statistical tools such as Cronbach‘s alpha for reliability and expert opinion on the validity of the protocols. Reliability analysis was carried out using split half method and the Cronbach alpha for part 1 of the protocol was obtained as 0.913 and for part 2 it was 0.993. The overall reliability of the protocol was 0.937 indicating high reliability of the test schedule used in the present study. CONCLUSIONS: Patients and controls were well differentiated in all the neuro-psychological parameters, MoCA, Addenbrook‘s Cognitive Score, WMS, AVLT, Digit Span, Story Recall, and Complex figure. Patients are found to have low scores in all these aspects compared to controls. Stepwise regression analysis indicates scores in only five parameters, namely attention, memory, AVLT, Digit span, and complex figure are enough to classify a person as having dementia or a normal person with a prediction accuracy of nearly 99 per cent. All these neuro psychological parameters are interrelated to one another. Inter correlations of neuro psychological parameters are very high among patients compared to controls in the present study. Analysis of Diffusion Tensor Imaging indicates that the white matter tract, Superior Longitudinal Fasciculus does not play any major role in attention and language domain. In contrast, Fornix has a major role to play in the memory domain. All the metrics of DTI show significant difference between patients and controls in the white matter tract Fornix on either side of the brain. As far as the DTI metrics are concerned, all the metrics have the same levels on both sides of brain of patients and controls. In most of the white matter tracts, the metrics, RD, MD, and AD are found to be high among patients compared to controls. FA is found to be low among patients in white matter tracts like IFO and Fornix. The analysis of diffusion metrics suggests the varying involvement of the white matter fasciculi of the respective domains. Analysis of FDG PET data indicates that about 70 per cent to 93 per cent of patients have hypometabolism in all the five cortical areas of attention domain- frontal association, posterior cingulate, parietal association, anterior cingulate, and caudate regions on either side of brain. Similarly 77 to 91 per cent of patients have hypometabolism in cortical areas of language domain, frontal association, temporal association and parietal association regions on either side of brain. About 85 to 89 per cent of patients have hypometabolism on either side of anterior cingulate regions. Voxel based Morphometry analysis clearly indicated that the patients and controls are significantly different in the following gray matter hubs of Attention Network : Dorsolateral Prefrontal Cortex, Frontal Eye Field, Occipital Eye Field, Cingulate Cortex and Superior Parietal Lobule. Similar scenario is seen in gray matter hubs of language Network: Broca's Area, Wernicke's Area, and Geschwind‘s Area (Inferior Parietal Lobule). In gray matter hubs of Memory Network: Uncus, Hippocampus, and Nucleus Accumbens areas, patients are found to be significantly different from the controls

Left ear advantage in speech-related dichotic listening is not specific to auditory processing disorder in children: A machine-learning fMRI and DTI study

AbstractDichotic listening (DL) tests are among the most frequently included in batteries for the diagnosis of auditory processing disorders (APD) in children. A finding of atypical left ear advantage (LEA) for speech-related stimuli is often taken by clinical audiologists as an indicator for APD. However, the precise etiology of ear advantage in DL tests has been a source of debate for decades. It is uncertain whether a finding of LEA is truly indicative of a sensory processing deficit such as APD, or whether attentional or other supramodal factors may also influence ear advantage. Multivariate machine learning was used on diffusion tensor imaging (DTI) and functional MRI (fMRI) data from a cohort of children ages 7–14 referred for APD testing with LEA, and typical controls with right-ear advantage (REA). LEA was predicted by: increased axial diffusivity in the left internal capsule (sublenticular region), and decreased functional activation in the left frontal eye fields (BA 8) during words presented diotically as compared to words presented dichotically, compared to children with right-ear advantage (REA). These results indicate that both sensory and attentional deficits may be predictive of LEA, and thus a finding of LEA, while possibly due to sensory factors, is not a specific indicator of APD as it may stem from a supramodal etiology