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1.
Neuroscience ; 425: 194-216, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31786346

RESUMO

High gamma activity (HGA) of verbal-memory encoding using invasive-electroencephalogram has laid the foundation for numerous studies testing the integrity of memory in diseased populations. Yet, the functional connectivity characteristics of networks subserving these memory linkages remains uncertain. By integrating this electrophysiological biomarker of memory encoding from IEEG with resting-state BOLD fluctuations, we estimated the segregation and hubness of HGA-memory regions in drug-resistant epilepsy patients and matched healthy controls. HGA-memory regions express distinctly different hubness compared to neighboring regions in health and in epilepsy, and this hubness was more relevant than segregation in predicting verbal memory encoding. The HGA-memory network comprised regions from both the cognitive control and primary processing networks, validating that effective verbal-memory encoding requires integrating brain functions, and is not dominated by a central cognitive core. Our results demonstrate a tonic intrinsic set of functional connectivity, which provides the necessary conditions for effective, phasic, task-dependent memory encoding.

2.
Brain ; 143(1): 175-190, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860076

RESUMO

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia-thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of 'disconnection' simulations, we showed that these changes in interactive profiles of the basal ganglia-thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

3.
Netw Neurosci ; 3(3): 848-877, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410383

RESUMO

Chronically implantable neurostimulation devices are becoming a clinically viable option for treating patients with neurological disease and psychiatric disorders. Neurostimulation offers the ability to probe and manipulate distributed networks of interacting brain areas in dysfunctional circuits. Here, we use tools from network control theory to examine the dynamic reconfiguration of functionally interacting neuronal ensembles during targeted neurostimulation of cortical and subcortical brain structures. By integrating multimodal intracranial recordings and diffusion-weighted imaging from patients with drug-resistant epilepsy, we test hypothesized structural and functional rules that predict altered patterns of synchronized local field potentials. We demonstrate the ability to predictably reconfigure functional interactions depending on stimulation strength and location. Stimulation of areas with structurally weak connections largely modulates the functional hubness of downstream areas and concurrently propels the brain towards more difficult-to-reach dynamical states. By using focal perturbations to bridge large-scale structure, function, and markers of behavior, our findings suggest that stimulation may be tuned to influence different scales of network interactions driving cognition.

4.
Epilepsia ; 60(4): 593-604, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30889276

RESUMO

Epilepsy is among the most common chronic neurologic disorders, with 30%-40% of patients having seizures despite antiepileptic drug treatment. The advent of brain imaging and network analyses has greatly improved the understanding of this condition. In particular, developments in magnetic resonance imaging (MRI) have provided measures for the noninvasive characterization and detection of lesions causing epilepsy. MRI techniques can probe structural and functional connectivity, and network analyses have shaped our understanding of whole-brain anomalies associated with focal epilepsies. This review considers the progress made by neuroimaging and connectomics in the study of drug-resistant epilepsies due to focal substrates, particularly temporal lobe epilepsy related to mesiotemporal sclerosis and extratemporal lobe epilepsies associated with malformations of cortical development. In these disorders, there is evidence of widespread disturbances of structural and functional connectivity that may contribute to the clinical and cognitive prognosis of individual patients. It is hoped that studying the interplay between macroscale network anomalies and lesional profiles will improve our understanding of focal epilepsies and assist treatment choices.

5.
Neuroimage Clin ; 20: 398-406, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30128278

RESUMO

Background: Electrode contact locations are important when planning tailored brain surgeries to identify pathological tissue targeted for resection and conversely avoid eloquent tissue. Current methods employ trained experts to use neuroimaging scans that are manually co-registered and localize contacts within ~2 mm. Yet, the state of the art is limited by either the expertise needed for each type of intracranial electrode or the inter-modality co-registration which increases error, reducing accuracy. Patients often have a variety of strips, grids and depths implanted; therefore, it is cumbersome and time-consuming to apply separate localization methods for each type of electrode, requiring expertise across different approaches. New method: To overcome these limitations, a computational method was developed by separately registering an implant magnetic resonance image (MRI) and implant computed tomography image (CT) to the pre-implant MRI, then calculating an iterative closest point transformation using the contact locations extracted from the signal voids as ground truth. Results: The implant MRI is robustly co-registered to the pre-implant MRI with a boundary-based registration algorithm. By extracting and utilizing 'signal voids' (the metal induced artifacts from the implant MRI) as electrode fiducials, the novel method is an all-in-one approach for all types of intracranial electrodes while eliminating inter-modality co-registration errors. Comparison with existing methods: The distance between each electrode centroid and the brain's surface was measured, for the proposed method as well as the state of the art method using two available software packages, SPM 12 and FSL 4.1. The method presented here achieves the smallest distances to the brain's surface for all strip and grid type electrodes, i.e. contacts designed to rest directly on the brain surface. Conclusion: We use one of the largest reported sample sizes in localization studies to validate this novel method for localizing different kinds of intracranial electrodes including grids, strips and depth electrodes.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Eletrodos Implantados , Eletroencefalografia/métodos , Imagem por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrodos Implantados/normas , Eletroencefalografia/instrumentação , Eletroencefalografia/normas , Feminino , Humanos , Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/normas , Adulto Jovem
6.
Epilepsy Behav ; 81: 70-78, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29499551

RESUMO

OBJECTIVE: In epilepsy, asymmetries in the organization of mesial temporal lobe (MTL) functions help determine the cognitive risk associated with procedures such as anterior temporal lobectomy. Past studies have investigated the change/shift in a visual episodic memory laterality index (LI) in mesial temporal lobe structures through functional magnetic resonance imaging (fMRI) task activations. Here, we examine whether underlying task-related functional connectivity (FC) is concordant with such standard fMRI laterality measures. METHODS: A total of 56 patients with temporal lobe epilepsy (TLE) (Left TLE [LTLE]: 31; Right TLE [RTLE]: 25) and 34 matched healthy controls (HC) underwent fMRI scanning during performance of a scene encoding task (SET). We assessed an activation-based LI of the hippocampal gyrus (HG) and parahippocampal gyrus (PHG) during the SET and its correspondence with task-related FC measures. RESULTS: Analyses involving the HG and PHG showed that the patients with LTLE had a consistently higher LI (right-lateralized) than that of the HC and group with RTLE, indicating functional reorganization. The patients with RTLE did not display a reliable contralateral shift away from the pathology, with the mesial structures showing quite distinct laterality patterns (HG, no laterality bias; PHG, no evidence of LI shift). The FC data for the group with LTLE provided confirmation of reorganization effects, revealing that a rightward task LI may be based on underlying connections between several left-sided regions (middle/superior occipital and left medial frontal gyri) and the right PHG. The FCs between the right HG and left anterior cingulate/medial frontal gyri were also observed in LTLE. Importantly, the data demonstrate that the areas involved in the LTLE task activation shift to the right hemisphere showed a corresponding increase in task-related FCs between the hemispheres. SIGNIFICANCE: Altered laterality patterns based on mesial temporal lobe epilepsy (MTLE) pathology manifest as several different phenotypes, varying according to side of seizure onset and the specific mesial structures involved. There is good correspondence between task LI activation and FC patterns in the setting of LTLE, suggesting that reliable visual episodic memory reorganization may require both a shift in nodal activation and a change in nodal connectivity with mesial temporal structures involved in memory.


Assuntos
Mapeamento Encefálico/métodos , Epilepsia do Lobo Temporal/fisiopatologia , Lateralidade Funcional/fisiologia , Memória/fisiologia , Lobo Temporal/fisiopatologia , Adulto , Análise de Variância , Lobectomia Temporal Anterior , Estudos de Casos e Controles , Conectoma , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Memória Episódica , Pessoa de Meia-Idade , Córtex Pré-Frontal/patologia , Adulto Jovem
7.
Brain ; 141(5): 1375-1389, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29554279

RESUMO

Temporal lobe epilepsy tends to reshape the language system causing maladaptive reorganization that can be characterized by task-based functional MRI, and eventually can contribute to surgical decision making processes. However, the dynamic interacting nature of the brain as a complex system is often neglected, with many studies treating the language system as a static monolithic structure. Here, we demonstrate that as a specialized and integrated system, the language network is inherently dynamic, characterized by rich patterns of regional interactions, whose transient dynamics are disrupted in patients with temporal lobe epilepsy. Specifically, we applied tools from dynamic network neuroscience to functional MRI data collected from 50 temporal lobe epilepsy patients and 30 matched healthy controls during performance of a verbal fluency task, as well as during rest. By assigning 16 language-related regions into four subsystems (i.e. bilateral frontal and temporal), we observed regional specialization in both the probability of transient interactions and the frequency of such changes, in both healthy controls and patients during task performance but not rest. Furthermore, we found that both left and right temporal lobe epilepsy patients displayed reduced interactions within the left frontal 'core' subsystem compared to the healthy controls, while left temporal lobe epilepsy patients were unique in showing enhanced interactions between the left frontal 'core' and the right temporal subsystems. Also, both patient groups displayed reduced flexibility in the transient interactions of the left temporal and right frontal subsystems, which formed the 'periphery' of the language network. Importantly, such group differences were again evident only during task condition. Lastly, through random forest regression, we showed that dynamic reconfiguration of the language system tracks individual differences in verbal fluency with superior prediction accuracy compared to traditional activation-based static measures. Our results suggest dynamic network measures may be an effective biomarker for detecting the language dysfunction associated with neurological diseases such as temporal lobe epilepsy, specifying both the type of neuronal communications that are missing in these patients and those that are potentially added but maladaptive. Further advancements along these lines, transforming how we characterize and map language networks in the brain, have a high probability of altering clinical decision making in neurosurgical centres.10.1093/brain/awy042_video1awy042media15754656112001.


Assuntos
Mapeamento Encefálico , Epilepsia do Lobo Temporal/complicações , Transtornos da Linguagem/etiologia , Transtornos da Linguagem/patologia , Vias Neurais/fisiologia , Dinâmica não Linear , Adulto , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Vias Neurais/patologia , Testes Neuropsicológicos , Oxigênio/sangue , Estatísticas não Paramétricas , Comportamento Verbal/fisiologia
8.
Neurology ; 88(24): 2285-2293, 2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28515267

RESUMO

OBJECTIVE: To characterize the presurgical brain functional architecture presented in patients with temporal lobe epilepsy (TLE) using graph theoretical measures of resting-state fMRI data and to test its association with surgical outcome. METHODS: Fifty-six unilateral patients with TLE, who subsequently underwent anterior temporal lobectomy and were classified as obtaining a seizure-free (Engel class I, n = 35) vs not seizure-free (Engel classes II-IV, n = 21) outcome at 1 year after surgery, and 28 matched healthy controls were enrolled. On the basis of their presurgical resting-state functional connectivity, network properties, including nodal hubness (importance of a node to the network; degree, betweenness, and eigenvector centralities) and integration (global efficiency), were estimated and compared across our experimental groups. Cross-validations with support vector machine (SVM) were used to examine whether selective nodal hubness exceeded standard clinical characteristics in outcome prediction. RESULTS: Compared to the seizure-free patients and healthy controls, the not seizure-free patients displayed a specific increase in nodal hubness (degree and eigenvector centralities) involving both the ipsilateral and contralateral thalami, contributed by an increase in the number of connections to regions distributed mostly in the contralateral hemisphere. Simulating removal of thalamus reduced network integration more dramatically in not seizure-free patients. Lastly, SVM models built on these thalamic hubness measures produced 76% prediction accuracy, while models built with standard clinical variables yielded only 58% accuracy (both were cross-validated). CONCLUSIONS: A thalamic network associated with seizure recurrence may already be established presurgically. Thalamic hubness can serve as a potential biomarker of surgical outcome, outperforming the clinical characteristics commonly used in epilepsy surgery centers.


Assuntos
Mapeamento Encefálico , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Imagem por Ressonância Magnética , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia , Adulto , Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Cuidados Pré-Operatórios , Prognóstico , Descanso , Máquina de Vetores de Suporte , Resultado do Tratamento
9.
J Cancer Surviv ; 11(4): 438-446, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28181091

RESUMO

PURPOSE: The purpose of this study was to characterize the neurophysiological and clinical effects that may result from the neuro emotional technique (NET) in patients with traumatic stress symptoms associated with a cancer-related event. We hypothesized that self-regulatory processing of traumatic memories would be observable as physiological changes in key brain areas after undergoing the NET intervention and that these changes would be associated with improvement of traumatic stress symptoms. METHODS: We enrolled 23 participants with a prior cancer diagnosis who expressed a distressing cancer-related memory that was associated with traumatic stress symptoms of at least 6 months in duration. Participants were randomized to either the NET intervention or a waitlist control condition. To evaluate the primary outcome of neurophysiological effects, all participants received functional magnetic resonance imaging (fMRI) during the auditory presentation of both a neutral stimulus and a description of the specific traumatic event. Pre/post-comparisons were performed between the traumatic and neutral condition, within and between groups. Psychological measures included the Impact of Event Scale (IES), State Trait Anxiety Index (STAI), Brief Symptom Inventory (BSI)-18, and Posttraumatic Cognitions Inventory (PTCI). RESULTS: The initial fMRI scans in both groups showed significant increases in the bilateral parahippocampus and brainstem. After NET, reactivity in the parahippocampus, brainstem, anterior cingulate, and insula was significantly decreased during the traumatic stimulus. Likewise, participants receiving the NET intervention had significant reductions (p < 0.05) compared to the control group in distress as measured by the BSI-18 global severity index, anxiety as measured by the STAI, and traumatic stress as measured by the IES and PTCI. CONCLUSIONS: This study is an initial step towards understanding mechanistic features of the NET intervention. Specifically, brain regions involved with traumatic memories and distress such as the brainstem, insula, anterior cingulate gyrus, and parahippocampus had significantly reduced activity after the NET intervention and were associated with clinical improvement of symptoms associated with distressing recollections. IMPLICATIONS FOR CANCER SURVIVORS: This preliminary study suggests that the NET intervention may be effective at reducing emotional distress in patients who suffer from traumatic stress symptoms associated with a cancer-related event.


Assuntos
Encéfalo/fisiopatologia , Emoções/fisiologia , Neoplasias/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico/psicologia , Sobreviventes/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Hum Brain Mapp ; 38(5): 2540-2552, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28195438

RESUMO

Resting-state networks (RSNs) show spatial patterns generally consistent with networks revealed during cognitive tasks. However, the exact degree of overlap between these networks has not been clearly quantified. Such an investigation shows promise for decoding altered functional connectivity (FC) related to abnormal language functioning in clinical populations such as temporal lobe epilepsy (TLE). In this context, we investigated the network configurations during a language task and during resting state using FC. Twenty-four healthy controls, 24 right and 24 left TLE patients completed a verb generation (VG) task and a resting-state fMRI scan. We compared the language network revealed by the VG task with three FC-based networks (seeding the left inferior frontal cortex (IFC)/Broca): two from the task (ON, OFF blocks) and one from the resting state. We found that, for both left TLE patients and controls, the RSN recruited regions bilaterally, whereas both VG-on and VG-off conditions produced more left-lateralized FC networks, matching more closely with the activated language network. TLE brings with it variability in both task-dependent and task-independent networks, reflective of atypical language organization. Overall, our findings suggest that our RSN captured bilateral activity, reflecting a set of prepotent language regions. We propose that this relationship can be best understood by the notion of pruning or winnowing down of the larger language-ready RSN to carry out specific task demands. Our data suggest that multiple types of network analyses may be needed to decode the association between language deficits and the underlying functional mechanisms altered by disease. Hum Brain Mapp 38:2540-2552, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Mapeamento Encefálico , Epilepsia/patologia , Epilepsia/fisiopatologia , Linguagem , Rede Nervosa , Descanso/fisiologia , Adulto , Análise de Variância , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Tomografia por Emissão de Pósitrons , Adulto Jovem
11.
Hum Brain Mapp ; 38(1): 528-540, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27628031

RESUMO

OBJECTIVE: Focal epilepsies, such as temporal lobe epilepsy (TLE), are known to disrupt network activity in areas outside the epileptogenic zone [Tracy et al., 2015]. We devised a measure of temporal instability of resting state functional connectivity (FC), capturing temporal variations of BOLD correlations between brain regions that is less confounded than the "sliding window" approach common in the literature. METHODS: We investigated healthy controls and unilateral TLE patients (right and left seizure focus groups), utilizing group ICA to identify the default mode network (DMN), a network associated with episodic memory, a key cognitive deficit in TLE. Our instability analyses focused on: (1) connectivity between DMN region pairs, both within and between TLE patients and matched controls, (2) whole brain group differences between region pairs ipsilateral or contralateral to the epileptogenic temporal lobe. RESULTS: For both the whole brain and a more focused analysis of DMN region pairs, temporal stability appears to characterize the healthy brain. The TLE patients displayed more FC instability compared to controls, with this instability more pronounced for the right TLE patients. SIGNIFICANCE: Our findings challenge the view that the resting state signal is stable over time, providing a measure of signal coherence change that may generate insights into the temporal components of network organization. The precuneus was the region within the DMN consistently expressing this instability, suggesting this region plays a key role in large scale temporal dynamics of the DMN, with such dynamics disrupted in TLE, putting key cognitive functions at risk. Hum Brain Mapp 38:528-540, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Epilepsia Resistente a Medicamentos/patologia , Modelos Neurológicos , Vias Neurais/fisiopatologia , Descanso , Adulto , Encéfalo/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Feminino , Lateralidade Funcional , Humanos , Imagem Tridimensional , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem
12.
PLoS One ; 11(5): e0154660, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27171178

RESUMO

Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is necessary to produce reductions in episodic memory recall. The latter, in particular, demonstrates the complex structure/function interactions at work when trying to understand cognition in TLE, suggesting that subtle network effects can emerge bearing specific relationships to hemisphere and the type of pathology.


Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Substância Cinzenta/anormalidades , Substância Cinzenta/fisiopatologia , Memória Episódica , Rede Nervosa/fisiopatologia , Descanso , Adulto , Comportamento , Estudos de Casos e Controles , Cognição , Demografia , Epilepsia do Lobo Temporal/patologia , Feminino , Substância Cinzenta/patologia , Humanos , Masculino , Testes Neuropsicológicos , Tamanho do Órgão , Análise de Regressão
13.
J Neurosurg ; 124(4): 929-37, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26406797

RESUMO

OBJECTIVE: Predicting cognitive function following resective surgery remains an important clinical goal. Each MRI neuroimaging technique can potentially provide unique and distinct insight into changes that occur in the structural or functional organization of "at-risk" cognitive functions. The authors tested for the singular and combined power of 3 imaging techniques (functional MRI [fMRI], resting state fMRI, diffusion tensor imaging) to predict cognitive outcome following left (dominant) anterior temporal lobectomy for intractable epilepsy. METHODS; The authors calculated the degree of deviation from normal, determined the rate of change in this measure across the pre- and postsurgical imaging sessions, and then compared these measures for their ability to predict verbal fluency changes following surgery. RESULTS: The data show that the 3 neuroimaging techniques, in a combined model, can reliably predict cognitive outcome following anterior temporal lobectomy for medically intractable temporal lobe epilepsy. CONCLUSIONS: These findings suggest that these 3 imaging modalities can be used effectively, in an additive fashion, to predict functional reorganization and cognitive outcome following anterior temporal lobectomy.


Assuntos
Imagem de Tensor de Difusão/métodos , Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/cirurgia , Imagem por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Procedimentos Neurocirúrgicos/psicologia , Lobo Temporal/cirurgia , Comportamento Verbal , Adulto , Lobectomia Temporal Anterior/métodos , Cognição , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/psicologia , Valor Preditivo dos Testes , Descanso , Resultado do Tratamento , Substância Branca/cirurgia
14.
Neuroimage Clin ; 9: 458-66, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26594628

RESUMO

Developing more reliable predictors of seizure outcome following temporal lobe surgery for intractable epilepsy is an important clinical goal. In this context, we investigated patients with refractory temporal lobe epilepsy (TLE) before and after temporal resection. In detail, we explored gray matter (GM) volume change in relation with seizure outcome, using a voxel-based morphometry (VBM) approach. To do so, this study was divided into two parts. The first one involved group analysis of differences in regional GM volume between the groups (good outcome (GO), e.g., no seizures after surgery; poor outcome (PO), e.g., persistent postoperative seizures; and controls, N = 24 in each group), pre- and post-surgery. The second part of the study focused on pre-surgical data only (N = 61), determining whether the degree of GM abnormalities can predict surgical outcomes. For this second step, GM abnormalities were identified, within each lobe, in each patient when compared with an ad hoc sample of age-matched controls. For the first analysis, the results showed larger GM atrophy, mostly in the frontal lobe, in PO patients, relative to both GO patients and controls, pre-surgery. When comparing pre-to-post changes, we found relative GM gains in the GO but not in the PO patients, mostly in the non-resected hemisphere. For the second analysis, only the frontal lobe displayed reliable prediction of seizure outcome. 81% of the patients showing pre-surgical increased GM volume in the frontal lobe became seizure free, post-surgery; while 77% of the patients with pre-surgical reduced frontal GM volume had refractory seizures, post-surgery. A regression analysis revealed that the proportion of voxels with reduced frontal GM volume was a significant predictor of seizure outcome (p = 0.014). Importantly, having less than 1% of the frontal voxels with GM atrophy increased the likelihood of being seizure-free, post-surgery, by seven times. Overall, our results suggest that using pre-surgical GM abnormalities within the frontal lobe is a reliable predictor of seizure outcome post-surgery in TLE. We believe that this frontal GM atrophy captures seizure burden outside the pre-existing ictal temporal lobe, reflecting either the development of epileptogenesis or the loss of a protective, adaptive force helping to control or limit seizures. This study provides evidence of the potential of VBM-based approaches to predict surgical outcomes in refractory TLE candidates.


Assuntos
Encéfalo/patologia , Epilepsia do Lobo Temporal/cirurgia , Substância Cinzenta/patologia , Convulsões/patologia , Adulto , Epilepsia do Lobo Temporal/complicações , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Convulsões/etiologia
16.
Epilepsia ; 56(10): 1571-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26193910

RESUMO

OBJECTIVE: In temporal lobe epilepsy (TLE), the thalamus is well known for its role in the propagation and spread of epileptiform activity. However, the integrity of thalamocortical functional connectivity (FC) in TLE and its relation to specific seizure patterns have not yet been determined. We address these issues with resting-state functional magnetic resonance imaging (fMRI). METHODS: Resting-state fMRI was performed on two groups of unilateral TLE patients: those with focal seizures only (16 left TLE, 16 right TLE) and those with additional generalized seizures (16 left TLE, 10 right TLE), and 16 matched controls. A thalamic parcellation based on FC between five nonoverlapping cortical seeds (prefrontal, motor, somatosensory, parietal-occipital, and temporal) and the ipsilateral thalamus was carried out to parcel each thalamus into five corresponding segments. FCs between each segment and its ipsilateral cortical seed were extracted and compared across groups using analyses of variance (ANOVAs). RESULTS: Compared to healthy controls, patients with TLE displayed decreased thalamocortical FC in multiple posterior and ventromedial thalamic segments of both the ictal and nonictal hemispheres. Our parcellation analysis revealed that these thalamic regions were functionally connected to the parietal/occipital and temporal lobes. In patients with TLE with focal seizures these regional thalamocortical FC decreases were limited to the ictal hemisphere. In contrast, TLE patients with both focal and generalized epileptiform activity displayed FC decreases in both the ictal and nonictal thalamus involving the dorsolateral pulvinar, a region preferentially connected to the parietal and occipital lobes. SIGNIFICANCE: Our data provide the first evidence of regional specific thalamocortical FC decreases in patients with unilateral TLE. Furthermore, our results demonstrate that patients with different seizure types present different thalamoparietal/occipital FC decrease patterns. While patients with focal seizures present thalamocortical FC decreases in the ictal hemisphere only, patients with additional generalized seizure activity also show thalamocortical FC decreases involving the thalamus in the nonictal hemisphere.


Assuntos
Córtex Cerebral/patologia , Epilepsia do Lobo Temporal/patologia , Vias Neurais/patologia , Tálamo/patologia , Adulto , Córtex Cerebral/irrigação sanguínea , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Vias Neurais/irrigação sanguínea , Oxigênio/sangue , Descanso , Tálamo/irrigação sanguínea
17.
Curr Opin Neurol ; 28(2): 158-65, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25734954

RESUMO

PURPOSE OF REVIEW: Seizures produce dysfunctional, maladaptive networks, making functional connectivity an ideal technique for identifying complex brain effects of epilepsy. We review the current status of resting-state functional connectivity (rsFC) research, highlighting its potential added value to epilepsy surgery programs. RECENT FINDINGS: RsFC research has demonstrated that the brain impact of seizures goes beyond the epileptogenic zone, changing connectivity patterns in widespread cortical regions. There is evidence for abnormal connectivity, but the degree to which these represent adaptive or maladaptive plasticity responses is unclear. Empirical associations with cognitive performance and psychiatric symptoms have helped understand deleterious impacts of seizures outside the epileptogenic zone. Studies in the prediction of outcome suggest that there are identifiable presurgical patterns of functional connectivity associated with a greater likelihood of positive cognitive or seizure outcomes. SUMMARY: The role of rsFC remains limited in most clinical settings, but shows great promise for identifying epileptic circuits and foci, predicting outcomes following surgery, and explaining cognitive deficits and psychiatric symptoms of epilepsy. RsFC has demonstrated that even focal epilepsies constitute a network and brain systems disorder. By providing a tool to both identify and characterize the brain network impact of epileptiform activity, rsFC can make a strong contribution to presurgical algorithms in epilepsy.


Assuntos
Encéfalo/patologia , Tomada de Decisão Clínica , Epilepsia/diagnóstico , Epilepsia/patologia , Vias Neurais/fisiopatologia , Animais , Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos
18.
Epilepsia ; 56(4): 517-26, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25708625

RESUMO

OBJECTIVE: This study determined the ability of resting-state functional connectivity (rsFC) graph-theory measures to predict neurocognitive status postsurgery in patients with temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy (ATL). METHODS: A presurgical resting-state functional magnetic resonance imaging (fMRI) condition was collected in 16 left and 16 right TLE patients who underwent ATL. In addition, patients received neuropsychological testing pre- and postsurgery in verbal and nonverbal episodic memory, language, working memory, and attention domains. Regarding the functional data, we investigated three graph-theory properties (local efficiency, distance, and participation), measuring segregation, integration and centrality, respectively. These measures were only computed in regions of functional relevance to the ictal pathology, or the cognitive domain. Linear regression analyses were computed to predict the change in each neurocognitive domain. RESULTS: Our analyses revealed that cognitive outcome was successfully predicted with at least 68% of the variance explained in each model, for both TLE groups. The only model not significantly predictive involved nonverbal episodic memory outcome in right TLE. Measures involving the healthy hippocampus were the most common among the predictors, suggesting that enhanced integration of this structure with the rest of the brain may improve cognitive outcomes. Regardless of TLE group, left inferior frontal regions were the best predictors of language outcome. Working memory outcome was predicted mostly by right-sided regions, in both groups. Overall, the results indicated our integration measure was the most predictive of neurocognitive outcome. In contrast, our segregation measure was the least predictive. SIGNIFICANCE: This study provides evidence that presurgery rsFC measures may help determine neurocognitive outcomes following ATL. The results have implications for refining our understanding of compensatory reorganization and predicting cognitive outcome after ATL. The results are encouraging with regard to the clinical relevance of using graph-theory measures in presurgical algorithms in the setting of TLE.


Assuntos
Cognição/fisiologia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Imagem por Ressonância Magnética/métodos , Cuidados Pré-Operatórios/métodos , Descanso/fisiologia , Adulto , Epilepsia do Lobo Temporal/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Resultado do Tratamento
19.
Hum Brain Mapp ; 36(1): 288-303, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25187327

RESUMO

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post-surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting-state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting-state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left-hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations.


Assuntos
Encéfalo/patologia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/patologia , Lateralidade Funcional/fisiologia , Transtornos da Linguagem/etiologia , Descanso , Adulto , Encéfalo/irrigação sanguínea , Mapeamento Encefálico , Eletroencefalografia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Análise de Regressão
20.
Brain Topogr ; 28(1): 113-26, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24881003

RESUMO

Temporal lobe epilepsy (TLE) is associated with abnormalities which extend into the entire brain. While the age of seizure onset (SO) has a large impact on brain plasticity, its effect on brain connectivity at rest remains unclear, especially, in interaction with factors such as the presence of mesial temporal sclerosis (MTS). In this context, we investigated whole-brain and regional functional connectivity (FC) organization in 50 TLE patients who underwent a resting-state fMRI scan, in comparison to healthy controls, using graph-theory measures. We first classified TLE patients according to the presence of MTS or not. Then, we categorized the patients based on their age of SO into two subgroups (early or late age of SO). Results revealed whole-brain differences with both reduced functional segregation and increased integration in the patients, regardless of the age of SO and MTS, relative to the controls. At a local level, we revealed that the connectivity of the ictal hippocampus remains the most impaired for an early SO, even in the absence of MTS. Importantly, we showed that the impact of age of SO on whole-brain and regional resting-state FC depends on the presence of MTS. Overall, our results highlight the importance of investigating the effect of age of SO when examining resting-state activity in TLE, as this factor leads different perturbations of network modularity and connectivity at the global and local level, with different implications for regional plasticity and adaptive organization.


Assuntos
Encéfalo/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Convulsões/fisiopatologia , Adulto , Idade de Início , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Mapeamento Encefálico , Epilepsia do Lobo Temporal/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/crescimento & desenvolvimento , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Descanso , Esclerose/patologia , Esclerose/fisiopatologia , Convulsões/patologia , Processamento de Sinais Assistido por Computador
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