Between neurons and networks: investigating mesoscale brain connectivity in neurological and psychiatric disorders.

The study of brain connectivity has been a cornerstone in understanding the complexities of neurological and psychiatric disorders. It has provided invaluable insights into the functional architecture of the brain and how it is perturbed in disorders. However, a persistent challenge has been achieving the proper spatial resolution, and developing computational algorithms to address biological questions at the multi-cellular level, a scale often referred to as the mesoscale. Historically, neuroimaging studies of brain connectivity have predominantly focused on the macroscale, providing insights into inter-regional brain connections but often falling short of resolving the intricacies of neural circuitry at the cellular or mesoscale level. This limitation has hindered our ability to fully comprehend the underlying mechanisms of neurological and psychiatric disorders and to develop targeted interventions. In light of this issue, our review manuscript seeks to bridge this critical gap by delving into the domain of mesoscale neuroimaging. We aim to provide a comprehensive overview of conditions affected by aberrant neural connections, image acquisition techniques, feature extraction, and data analysis methods that are specifically tailored to the mesoscale. We further delineate the potential of brain connectivity research to elucidate complex biological questions, with a particular focus on schizophrenia and epilepsy. This review encompasses topics such as dendritic spine quantification, single neuron morphology, and brain region connectivity. We aim to showcase the applicability and significance of mesoscale neuroimaging techniques in the field of neuroscience, highlighting their potential for gaining insights into the complexities of neurological and psychiatric disorders.

Assessing clinical progression from subjective cognitive decline to mild cognitive impairment with incomplete multi-modal neuroimages.

Accurately assessing clinical progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) is crucial for early intervention of pathological cognitive decline. Multi-modal neuroimaging data such as T1-weighted magnetic resonance imaging (MRI) and positron emission tomography (PET), help provide objective and supplementary disease biomarkers for computer-aided diagnosis of MCI. However, there are few studies dedicated to SCD progression prediction since subjects usually lack one or more imaging modalities. Besides, one usually has a limited number (e.g., tens) of SCD subjects, negatively affecting model robustness. To this end, we propose a Joint neuroimage Synthesis and Representation Learning (JSRL) framework for SCD conversion prediction using incomplete multi-modal neuroimages. The JSRL contains two components: 1) a generative adversarial network to synthesize missing images and generate multi-modal features, and 2) a classification network to fuse multi-modal features for SCD conversion prediction. The two components are incorporated into a joint learning framework by sharing the same features, encouraging effective fusion of multi-modal features for accurate prediction. A transfer learning strategy is employed in the proposed framework by leveraging model trained on the Alzheimer's Disease Neuroimaging Initiative (ADNI) with MRI and fluorodeoxyglucose PET from 863 subjects to both the Chinese Longitudinal Aging Study (CLAS) with only MRI from 76 SCD subjects and the Australian Imaging, Biomarkers and Lifestyle (AIBL) with MRI from 235 subjects. Experimental results suggest that the proposed JSRL yields superior performance in SCD and MCI conversion prediction and cross-database neuroimage synthesis, compared with several state-of-the-art methods.

Patterns of default mode network in temporal lobe epilepsy with and without hippocampal sclerosis.

The default mode network (DMN) consists of the deactivation of specific regions during the performance of cognitive tasks and activation during resting or mind wandering. Several pieces of evidence indicate the impairment of DMN in patients with mesial temporal lobe epilepsy (MTLE). However, most of these studies combined different underlying etiologies, failing to disentangle the influence of seizures and presence and side of hippocampal sclerosis (HS). We included 119 patients with MTLE divided into right-HS (n = 42), left-HS (n = 46), and magnetic resonance imaging (MRI)-negative MTLE (n = 31) and controls (n = 59). All underwent resting-state seed-based functional connectivity (FC), with a seed placed at the posterior cingulate cortex (PCC), an essential node for the DMN. To access group inferences, we used an SPM (Statistical Parametric Mapping) full-factorial model to compare patterns of activation using pairwise comparisons among all groups. Our results indicate a different pattern of DMN FC when controlling for side and presence of HS. The group with right-HS had increased FC in the left angular gyrus and the left middle occipital gyrus, when compared to controls, and increased FC of the left hippocampus when compared to the group with left-HS. The MRI-negative group had increased FC of the left hippocampus, left ventral diencephalon, and left fusiform gyrus as compared to left-HS, but did not show any areas of reduced FC compared to controls. By contrast, the group with left-HS did not show areas of increased FC compared to controls or the right-HS and had reduced FC in the left hippocampus compared to controls. Hence, the right-HS presented increased FC in areas related to the DMN in the left hemisphere; the MRI-negative group also showed increased FC in left-sided structures close to temporal lobe when compared to left-HS, probably indicating engagement in a compensatory system. In a subanalysis considering only the MRI-negative with left-sided EEG (electroencephalogram) subgroup, we found differences against controls, with left angular gyrus more connected in the first group, but no significant differences when compared to the group with left-HS. We conclude that the origin of seizures on the left hemisphere seems to engender a less prominent capacity of recruiting other neighbor areas related to DMN as compared to right-HS and controls. Considering recent studies that have revealed the importance of DMN for cognitive skills and memory, our findings may indicate that deficiencies exhibited by patients with left-HS temporal lobe epilepsy (TLE) in connecting to the DMN could be a surrogate marker of their known worse neuropsychological performance. Further studies with direct comparisons between cognitive tests and FC within the DMN are needed to validate these findings, especially for MRI-negative patients. This article is part of the Special Issue "NEWroscience 2018".

Testing the Stability and Validity of an Executive Dysfunction Classification Using Task-Based Assessment in Children and Adolescents.

OBJECTIVE: It is unclear if pediatric executive dysfunction assessed only with cognitive tasks predicts clinically relevant outcomes independently of psychiatric diagnoses. This study tested the stability and validity of a task-based classification of executive function. METHOD: A total of 2,207 individuals (6-17 years old) from the Brazilian High-Risk Cohort Study participated in this study (1,930 at baseline, 1,532 at follow-up). Executive function was measured using tests of working memory and inhibitory control. Dichotomized age- and sex-standardized performances were used as input in latent class analysis and receiver operating curves to create an executive dysfunction classification (EDC). The study tested EDC's stability over time, association with symptoms, functional impairment, a polymorphism in the CADM2 gene, polygenic risk scores (PRS), and brain structure. Analyses covaried for age, sex, social class, IQ, and psychiatric diagnoses. RESULTS: EDC at baseline predicted itself at follow-up (odds ratio [OR] = 5.11; 95% CI 3.41-7.64). Participants in the EDC reported symptoms spanning several domains of psychopathology and exhibited impairment in multiple settings, including more adverse school events (OR = 2.530; 95% CI 1.838-3.483). Children in the EDC presented higher attention-deficit/hyperactivity disorder and lower educational attainment PRS at baseline; higher schizophrenia PRS at follow-up; and lower chances of presenting a polymorphism in a gene previously linked to high performance in executive function (CADM2 gene). They also exhibited smaller intracranial volumes and smaller bilateral cortical surface areas in several brain regions. CONCLUSION: Task-based executive dysfunction is associated with several validators, independently of psychiatric diagnoses and intelligence. Further refinement of task-based assessments might generate clinically useful tools.

Effects of computerized cognitive training as add-on treatment to stimulants in ADHD: a pilot fMRI study.

The neurofunctional effects of Cognitive training (CT) are poorly understood. Our main objective was to assess fMRI brain activation patterns in children with ADHD who received CT as an add-on treatment to stimulant medication. We included twenty children with ADHD from a clinical trial of stimulant medication and CT (10 in medication + CT and 10 in medication + non-active training). Between-group differences were assessed in performance and in brain activation during 3 fMRI paradigms of working memory (N-back: 0-back, 1-back, 2-back, 3-back), sustained attention (Sustained Attention Task - SAT: 2 s, 5 s and 8 s delays) and inhibitory control (Go/No-Go). We found significant group x time x condition interactions in working memory (WM) and sustained attention on brain activation. In N-back, decreases were observed in the BOLD signal change from baseline to endpoint with increasing WM load in the right insula, right putamen, left thalamus and left pallidum in the CT compared to the non-active group; in SAT - increases in the BOLD signal change from baseline to endpoint with increasing delays were observed in bilateral precuneus, right insula, bilateral associative visual cortex and angular gyrus, right middle temporal, precentral, postcentral, superior frontal and middle frontal gyri in the CT compared to the non-active group. CT in ADHD was associated with changes in activation in task-relevant parietal and striato-limbic regions of sustained attention and working memory. Changes in brain activity may precede behavioral performance modifications in working memory and sustained attention, but not in inhibitory control.

Dislexia y discalculia: una revisión sistemática actual desde la neurogenética / Dyslexia and Dyscalculia: a Current Systematic Revision from a Neurogenetics Perspective

Resumen Los Trastornos Específicos del Aprendizaje constituyen un grupo heterogéneo de alteraciones frecuentes que pueden generar problemas importantes no solo durante la etapa escolar, sino a lo largo de toda la vida. Las dificultades persistentes en lectura (dislexia) y en matemáticas (discalculia) son, por su relevancia y prevalencia, los dos Trastornos de Aprendizaje más importantes en la práctica educativa y clínica. El objetivo del estudio es realizar una síntesis de los descubrimientos científicos de los últimos diez años sobre las bases neuroanatómicas y genéticas de la dislexia y la discalculia. Se realizó un análisis exhaustivo bibliográfico desde 2006 hasta enero de 2017 en inglés y español centrados en neuroimagen y genética de dislexia y discalculia mediante las bases de datos Medline, PsyInfo, Scopus, Web of Science y Dialnet. Se incluyeron 38 artículos de los cuales se extrajeronn las aportaciones desde la neuroimagen y la genética tanto para la dislexia como de discalculia. Estos datos facilitaron herramientas para orientar al contexto psicológico y educativo, a su vez proporcionando respuestas definitivas.

Abstract The Specific Learning Disorders represent a heterogeneous group of common conditions that can generate important problems not only during schooling but also throughout life. The persistent difficulties in reading (dyslexia) and maths (dyscalculia) are, due to their significance and prevalence, the two most important learning disorders in both educational and clinical practice. The objective of this study is to make a synthesis of the scientific findings of the past ten years about neuroanatomical and genetic basis of dyslexia and dyscalculia. To this aim a comprehensive bibliographic analysis is conducted from 2006 until January, 2017 in English and Spanish from databases Medline, PsyInfo, Scopus, Web of Science y Dialnet. There were included 43 articles with contributions so much about dyslexia as dyscalculia from the neuroimagen and the genetics. This information will provide tools to guide psychological and educational environments and to provide definitive answers.

Depression comorbidity in epileptic rats is related to brain glucose hypometabolism and hypersynchronicity in the metabolic network architecture.

OBJECTIVE: Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy syndromes in the world. Depression is an important comorbidity of epilepsy, which has been reported in patients with TLE and in different experimental models of epilepsy. However, there is no established consensus on which brain regions are associated with the manifestation of depression in epilepsy. Here, we investigated the alterations in cerebral glucose metabolism and the metabolic network in the pilocarpine-induced rat model of epilepsy and correlated it with depressive behavior during the chronic phase of epilepsy. METHODS: Fluorodeoxyglucose (18 F-FDG) was used to investigate the cerebral metabolism, and a cross-correlation matrix was used to examine the metabolic network in chronically epileptic rats using micro-positron emission tomography (microPET) imaging. An experimental model of epilepsy was induced by pilocarpine injection (320 mg/kg, ip). Forced swim test (FST), sucrose preference test (SPT), and eating-related depression test (ERDT) were used to evaluate depression-like behavior. RESULTS: Our results show an association between epilepsy and depression comorbidity based on changes in both cerebral glucose metabolism and the functional metabolic network. In addition, we have identified a significant correlation between brain glucose hypometabolism and depressive-like behavior in chronically epileptic rats. Furthermore, we found that the epileptic depressed group presents a hypersynchronous brain metabolic network in relation to the epileptic nondepressed group. SIGNIFICANCE: This study revealed relevant alterations in glucose metabolism and the metabolic network among the brain regions of interest for both epilepsy and depression pathologies. Thus it seems that depression in epileptic animals is associated with a more diffuse hypometabolism and altered metabolic network architecture and plays an important role in chronic epilepsy.

The neural basis of kinesthetic and visual imagery in sports: an ALE meta - analysis.

Imagery is a widely spread technique in the sport sciences that entails the mental rehearsal of a given situation to improve an athlete's learning, performance and motivation. Two modalities of imagery are reported to tap into distinct brain structures, but sharing common components: kinesthetic and visual imagery. This study aimed to investigate the neural basis of those types of imagery with Activation Likelihood Estimation algorithm to perform a meta - analysis. A systematic search was used to retrieve only experimental studies with athletes or sportspersons. Altogether, nine studies were selected and an ALE meta - analysis was performed. Results indicated significant activation of the premotor, somatosensory cortex, supplementary motor areas, inferior and superior parietal lobule, caudate, cingulate and cerebellum in both imagery tasks. It was concluded that visual and kinesthetic imagery share similar neural networks which suggests that combined interventions are beneficial to athletes whereas separate use of those two modalities of imagery may seem less efficient from a neuropsychological approach.

Clinical variables related to the diagnostic stability of demential syndromes.

BACKGROUND: Assigning a diagnosis to a patient with dementia is important for the present treatment of the patient and caregivers, and scientific research. Nowadays, the dementia diagnostic criteria are based on clinical information regarding medical, history, physical examination, neuropsychological tests, and supplementary exams and, therefore, subject to variability through time. METHODS: A retrospective observational study to evaluate variables related to clinical diagnostic stability in dementia syndromes in at least one year follow up. From a sample of 432 patients, from a single university center, data were collected regarding sociodemographic aspects, Clinical Dementia Rating, physical examination, neuropsychological tests, and supplementary exams including a depression triage scale. RESULTS: From this sample, 113 (26.6%) patients have their diagnosis changed, most of them adding a vascular component to initial diagnosis or depression as comorbidity or main disease. Our findings show that many factors influence the diagnostic stability including the presence of symmetric Parkinsonism, initial diagnosis of vascular dementia, presence of diabetes and hypertension, the presence of long term memory deficit in the neuropsychological evaluation, and normal neuroimaging. We discuss our findings with previous findings in the literature. CONCLUSION: Every step of the clinical diagnosis including history, vascular comorbidities and depression, physical examination, neuropsychological battery, and neuroimaging were relevant to diagnosis accuracy.

Demências rapidamente progressivas. Importância da neuroimagem nas etapas diagnósticas. / Rapidly progressive dementias. Importance of neuroimage in the diagnostic steps.

As demências rapidamente progressivas constituem um grupo heterogêneo de condições clínicas (neurodegenerativas, vasculares, infecciosas, imunomediadas, tóxicas, metabólicas, tumorais, psicogênicas) e cirúrgicas. Avaliação detalhada é imprescindível, devendo ser seguido protocolo extenso constituído por diversas etapas diagnósticas, que compreendem anamnese detalhada, exames clínico e neurológico, e avaliação complementar. É ressaltada a importância da neuroimagem (RM estrutural do cérebro), sendo apresentadas imagens ilustrativas características das principais condições.

Rapidly progressive dementias constitute a heterogeneous group of clinical (neurodegenerative, vascular, infectious, immunomediated, toxic, metabolic, tumoral, psychogenic) and surgical conditions. Detailed evaluation is essential, and an extensive protocol constituted by several diagnostic steps must be followed, which include detailed anamnesis, clinical and neurological examination, and complementary assessment. The importance of neuroimage (structural MRI of the brain) is highlighted, and illustrative images characteristic of the main conditions are presented.

Hippocampal volume and CDR-SB can predict conversion to dementia in MCI patients / O volume do hipocampo e a soma dos subitens da escala CDR podem predizer a conversão para a demência nos pacientes com comprometimento cognitivo leve

OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

OBJETIVO: Avaliar a combinação de dois fatores: clinical dementia rating sum of boxes scores (CDR-SB) e volume hipocampal (VH) como preditores de conversão de ditúrbio cognitivo leve (DCL) em demência. MÉTODO: Vinte e oito indivíduos (9 normais e 19 com DCL) foram classificados de acordo com a soma dos escores CDR-SB em 3 grupos. RESULTADOS: O volume do hipocampo foi significativamente menor no grupo de alto risco e naqueles que desenvolveram demência depois de dois anos. A taxa de conversão foi crescente entre os três grupos. CONCLUSÃO: Propusemos uma medição adicional do volume do hipocampo que pode ser útil no prognóstico. No entanto, notou-se que a CDR-SB é um método tão eficiente quanto neuroimagem para prever demência com a vantagem de ser um processo de baixo custo e de fácil implementação, mais consistente com a política pública.

Caracterización etiológica del síndrome de Lennox-Gastaut sintomático / Etiological characterization of the symptomatic Lennox-Gastaut syndrome

Introducción: el síndrome de Lennox-Gastaut es una encefalopatía epiléptica dependiente de la edad, de gran severidad, por su farmacorresistencia y las discapacidades asociadas. Objetivos: caracterizar el síndrome de Lennox-Gastaut sintomático según sexo, edad de inicio y diagnóstico, tipo de crisis predominantes, hallazgos en neuroimagen y etiología. Métodos: estudio descriptivo, retrospectivo con una muestra de 36 pacientes egresados del servicio de neuropediatría del Hospital Pediátrico "Juan M. Márquez", con diagnóstico de síndrome de Lennox-Gastaut sintomático y que tuvieran estudios de neuroimagen (tomografía axial computarizada y resonancia magnética nuclear). Las variables cualitativas se describieron estadísticamente mediante frecuencias absolutas y cifras porcentuales. Para los porcentajes de interés, se calculó su intervalo de confianza con el 95 % de confiabilidad (IC 95 %). Resultados y conclusiones: el síndrome de Lennox-Gastaut sintomático fue más frecuente en varones, que comenzaron con epilepsia antes del año de edad, el 33 % presentó síndrome de West. Más del 60 % se diagnosticó antes de los 4 años de edad. Las crisis más frecuentes fueron las tónicas y atónicas de cuello. La tomografía axial computarizada permite localizar zonas de atrofia y pocas lesiones estructurales, que se precisan por resonancia magnética nuclear como alteraciones de la migración neuronal. Después de las malformaciones del sistema nervioso central, la causa más frecuente fue la hipoxia perinatal.

Introduction: the Lennox-Gastaut syndrome is an age-dependent epileptic encephalopathy very severe due to its drug-resistance and the associated inabilities. Objectives: to characterize the symptomatic Lennox-Gastaut syndrome, according to sex, onset age and diagnosis, type of predominant crises, findings in neuroimage and etiology. Methods: a retrospective and descriptive study was conducted in 36 patients discharged from the neuropediatric service of the "Juan Manuel Márquez" Children Hospital diagnosed with symptomatic Lennox-Gastaut syndrome and underwent neuroimage studies (computerized axial tomography and nuclear magnetic resonance). Qualitative variables were statistically described by means of absolute frequencies and percentage figures. For interesting percentages, its 95 % confidence interval (CI) was estimated (95 % CI). Results and conclusions: the symptomatic Lennox-Gastaut syndrome was more frequent in males starting with epilepsy before one year old. The 33 % had West's syndrome. More than 60 % was diagnosed before the four years old. The more frequent crises were the tonic and atonic ones of neck. The CAT allows locating zones of atrophy and few structural lesions signaled b y nuclear magnetic resonance (NMR) as alterations of neuronal migration. After the central nervous system (CNS) malformations, the more frequent cause was the perinatal hypoxia.

A ultrassonografia transcraniana como método diagnóstico em neurologia. Parte II: revisão da literatura / Transcranial Ultrasonography as diagnostic method in neurology. Part II: Literature review

A ultrassonografia transcraniana (USTC) é um método de neuroimagem baseado na física acústica. Nos indivíduos com janela acústica temporal adequada, o exame permite a visualização de estruturas encefálicas, principalmente o mesencéfalo, núcleos da base, tálamos e segmentos do sistema ventricular. A técnica já foi utilizada em pesquisas de diversas doenças neuropsiquiátricas. Em cerca de 90% dos portadores da doença de Parkinson, observa-se um aumento da área ecogênica da substância negra visualizada à USTC. O presente artigo é a segunda parte de uma revisão bibliográfica sobre o tema.

Transcranial sonography (TCS) is a neuroimaging technique that uses physical acoustic principles. A good acoustic temporal bone window allows sonographic depiction of encephalic structures as the mesencephalon, basal ganglia, thalami and fragments of the ventricular system. The technique has been used in researches of different neuropsychiatric diseases. In 90% of Parkinsonïs disease patients an enlargement of the substantia nigra echogenic area is found by TCS. This paper is a review on the subject.