RESUMEN
Long-term aluminum (Al) exposure increases the risk of mild cognitive impairment (MCI). The aim of the present study was to investigate the neural mechanisms of Al-induced MCI. In our study, a total of 52 individuals with occupational Al exposure >10â years were enrolled and divided into two groups: MCI (Al-MCI) and healthy controls (Al-HC). Plasma Al concentrations and Montreal Cognitive Assessment (MoCA) score were collected for all participants. And diffusion tensor imaging and resting-state functional magnetic resonance imaging were used to examine changes of white matter (WM) and functional connectivity (FC). There was a negative correlation between MoCA score and plasma Al concentration. Compared with the Al-HC, fractional anisotropy value for the right fornix (cres)/stria terminalis (FX/ST) was higher in the Al-MCI. Furthermore, there was a difference in FC between participants with and without MCI under Al exposure. We defined the regions with differing FC as a "pathway," specifically the connectivity from the right temporal pole to the right FX/ST, then to the right sagittal stratum, and further to the right anterior cingulate and paracingulate gyri and right inferior frontal gyrus, orbital part. In summary, we believe that the observed differences in WM integrity and FC in the right FX/ST between participants with and without MCI under long-term Al exposure may represent the neural mechanisms underlying MCI induced by Al exposure.
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Aluminio , Disfunción Cognitiva , Imagen de Difusión Tensora , Fórnix , Imagen por Resonancia Magnética , Exposición Profesional , Sustancia Blanca , Humanos , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Masculino , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Femenino , Persona de Mediana Edad , Anciano , Aluminio/toxicidad , Fórnix/patología , Fórnix/diagnóstico por imagen , Fórnix/efectos de los fármacos , Exposición Profesional/efectos adversos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Vías Nerviosas/patologíaRESUMEN
INTRODUCTION: The limbic system is critical for memory function and degenerates early in the Alzheimer's disease continuum. Whether obstructive sleep apnea (OSA) is associated with alterations in the limbic white matter tracts remains understudied. METHODS: Polysomnography, neurocognitive assessment, and brain magnetic resonance imaging (MRI) were performed in 126 individuals aged 55-86 years, including 70 cognitively unimpaired participants and 56 participants with mild cognitive impairment (MCI). OSA measures of interest were the apnea-hypopnea index and composite variables of sleep fragmentation and hypoxemia. Microstructural properties of the cingulum, fornix, and uncinate fasciculus were estimated using free water-corrected diffusion tensor imaging. RESULTS: Higher levels of OSA-related hypoxemia were associated with higher left fornix diffusivities only in participants with MCI. Microstructure of the other white matter tracts was not associated with OSA measures. Higher left fornix diffusivities correlated with poorer episodic verbal memory. DISCUSSION: OSA may contribute to fornix damage and memory dysfunction in MCI. HIGHLIGHTS: Sleep apnea-related hypoxemia was associated with altered fornix integrity in MCI. Altered fornix integrity correlated with poorer memory function. Sleep apnea may contribute to fornix damage and memory dysfunction in MCI.
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Disfunción Cognitiva , Imagen de Difusión Tensora , Fórnix , Hipoxia , Humanos , Masculino , Femenino , Disfunción Cognitiva/etiología , Anciano , Fórnix/diagnóstico por imagen , Fórnix/patología , Persona de Mediana Edad , Anciano de 80 o más Años , Hipoxia/complicaciones , Polisomnografía , Pruebas Neuropsicológicas/estadística & datos numéricos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Imagen por Resonancia Magnética , Síndromes de la Apnea del Sueño/complicaciones , Apnea Obstructiva del Sueño/complicacionesRESUMEN
OBJECTIVE: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of â¼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. METHODS: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n = 7 lesions) was compared to a craniectomy approach (n = 22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histologic methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. RESULTS: Comparing a motorized adjustment system (â¼1 mm precision, n = 17 lesions) to the motorized system with an added micromanipulator (â¼0.1 mm precision, n = 14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. CONCLUSIONS: The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.
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Fórnix , Ultrasonido Enfocado de Alta Intensidad de Ablación , Animales , Ratas , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Fórnix/diagnóstico por imagen , Fórnix/cirugía , Ratas Sprague-Dawley , Transductores , Cirugía Asistida por Computador/métodos , Masculino , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética Intervencional/métodosRESUMEN
In March 2020, C.T., a kind, bright, and friendly young woman underwent surgery for a midline tumor involving her septum pellucidum and extending down into her fornices bilaterally. Following tumor diagnosis and surgery, C.T. experienced significant memory deficits: C.T.'s family reported that she could remember things throughout the day, but when she woke up in the morning or following a nap, she would expect to be in the hospital, forgetting all the information that she had learned before sleep. The current study aimed to empirically validate C.T.'s pattern of memory loss and explore its neurological underpinnings. On two successive days, C.T. and age-matched controls watched an episode of a TV show and took a nap or stayed awake before completing a memory test. Although C.T. performed numerically worse than controls in both conditions, sleep profoundly exacerbated her memory impairment, such that she could not recall any details following a nap. This effect was replicated in a second testing session. High-resolution MRI scans showed evidence of the trans-callosal surgical approach's impact on the mid-anterior corpus callosum, indicated that C.T. had perturbed white matter particularly in the right fornix column, and demonstrated that C.T.'s hippocampal volumes did not differ from controls. These findings suggest that the fornix is important for processing episodic memories during sleep. As a key output pathway of the hippocampus, the fornix may ensure that specific memories are replayed during sleep, maintain the balance of sleep stages, or allow for the retrieval of memories following sleep.
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Recuerdo Mental , Sueño , Humanos , Femenino , Fórnix/diagnóstico por imagen , Aprendizaje , Hipocampo/diagnóstico por imagen , Trastornos de la Memoria/etiologíaRESUMEN
The fornix, the limbic system's white matter tract connecting the extended hippocampal system to subcortical structures of the medial diencephalon, is strongly associated with learning and memory in humans and nonhuman primates (NHPs). Here, we sought to investigate alterations in structural connectivity across key cortical and subcortical regions after fornix transection in NHPs. We collected diffusion-weighted MRI (dMRI) data from three macaque monkeys that underwent bilateral fornix transection during neurosurgery and from four age- and cohort-matched control macaques that underwent surgery to implant a head-post but remained neurologically intact. dMRI data were collected from both groups at two time points, before and after the surgeries, and scans took place at around the same time for the two groups. We used probabilistic tractography and employed the number of tracking streamlines to quantify connectivity across our regions of interest (ROIs), in all dMRI sessions. In the neurologically intact monkeys, we observed high connectivity across certain ROIs, including the CA3 hippocampal subfield with the retrosplenial cortex (RSC), the anterior thalamus with the RSC, and the RSC with the anterior cingulate cortex (ACC). However, we found that, compared to the control group, the fornix-transected monkeys showed marked, significant, connectivity changes including increases between the anterior thalamus and the ACC and between the CA3 and the ACC, as well as decreases between the CA3 and the RSC. Our results highlight cortical and subcortical network changes after fornix transection and identify candidate indirect connectivity routes that may support memory functions after damage and/or neurodegeneration.
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Imagen de Difusión Tensora , Fórnix , Animales , Humanos , Fórnix/diagnóstico por imagen , Fórnix/cirugía , Hipocampo/diagnóstico por imagen , Hipocampo/cirugía , Giro del Cíngulo , Macaca mulatta , Vías Nerviosas/diagnóstico por imagenRESUMEN
Converging evidence from studies of human and nonhuman animals suggests that the hippocampus contributes to sequence learning by using temporal context to bind sequentially occurring items. The fornix is a white matter pathway containing the major input and output pathways of the hippocampus, including projections from medial septum and to diencephalon, striatum, lateral septum and prefrontal cortex. If the fornix meaningfully contributes to hippocampal function, then individual differences in fornix microstructure might predict sequence memory. Here, we tested this prediction by performing tractography in 51 healthy adults who had undertaken a sequence memory task. Microstructure properties of the fornix were compared with those of tracts connecting medial temporal lobe regions but not predominantly the hippocampus: the Parahippocampal Cingulum bundle (PHC) (conveying retrosplenial projections to parahippocampal cortex) and the Inferior Longitudinal Fasciculus (ILF) (conveying occipital projections to perirhinal cortex). Using principal components analysis, we combined Free-Water Elimination Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging measures obtained from multi-shell diffusion MRI into two informative indices: the first (PC1) capturing axonal packing/myelin and the second (PC2) capturing microstructural complexity. We found a significant correlation between fornix PC2 and implicit reaction-time indices of sequence memory, indicating that greater fornix microstructural complexity is associated with better sequence memory. No such relationship was found with measures from the PHC and ILF. This study highlights the importance of the fornix in aiding memory for objects within a temporal context, potentially reflecting a role in mediating inter-regional communication within an extended hippocampal system.
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Imagen de Difusión Tensora , Sustancia Blanca , Adulto , Humanos , Imagen de Difusión Tensora/métodos , Fórnix/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Lóbulo Temporal/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Sustancia Blanca/diagnóstico por imagenRESUMEN
Isolated fornix anterior column infarction has rarely been described and is difficult to assess accurately using conventional magnetic resonance imaging (MRI). We report the case of a 75-year-old female who experienced acute anterograde amnesia. MRI performed within 24 h after amnesia onset showed an isolated infarction of the bilateral anterior columns of the fornix on diffusion-weighted imaging (DWI). Her symptoms persisted for up to 50 days, and diffusion tensor imaging (DTI) showed disruption of the fiber tracts of the fornix. when acute amnesia syndrome onset, fornix anterior column infarction should be considered, and optimized DWI and DTI methods are needed to study the fornix in vivo in future research.
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Imagen de Difusión Tensora , Fórnix , Humanos , Femenino , Fórnix/diagnóstico por imagen , Fórnix/patología , Anciano , Imagen de Difusión por Resonancia Magnética , Amnesia Anterógrada/etiología , Amnesia/etiología , Amnesia/diagnóstico por imagen , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/complicacionesRESUMEN
Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer's Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.
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Enfermedad de Alzheimer , Estimulación Encefálica Profunda , Humanos , Enfermedad de Alzheimer/terapia , Encéfalo/diagnóstico por imagen , Fórnix/diagnóstico por imagen , Fórnix/fisiología , Tálamo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and clinical entity that occurs independently and with co-existent Alzheimer's disease (AD) and small vessel disease. We compared diffusion tensor imaging (DTI) metrics of the fornix, the primary efferent tract of the hippocampus between CAA, AD and Mild Cognitive Impairment (MCI) and healthy controls. METHODS: Sixty-eight healthy controls, 32 CAA, 21 AD, and 26 MCI patients were recruited at two centers. Diffusion tensor images were acquired at 3 T with high spatial resolution and fluid-attenuated inversion recovery (FLAIR) to suppress cerebrospinal fluid (CSF) and minimize partial volume effects on the fornix. The fornix was delineated with deterministic tractography to yield mean diffusivity (MD), axial diffusivity (AXD), radial diffusivity (RD), fractional anisotropy (FA) and tract volume. Volumetric measurements of the hippocampus, thalamus, and lateral ventricles were obtained using T1-weighted MRI. RESULTS: Diffusivity (MD, AXD, and RD) of the fornix was highest in AD followed by CAA compared to controls; the MCI group was not significantly different from controls. FA was similar between groups. Fornix tract volume was â¼ 30% lower for all three patient groups compared to controls, but not significantly different between the patient groups. Thalamic and hippocampal volumes were preserved in CAA, but lower in AD and MCI compared to controls. Lateral ventricular volumes were increased in CAA, AD and MCI. Global cognition, memory, and executive function all correlated negatively with fornix diffusivity across the combined clinical group. CONCLUSION: There were significant diffusion changes of the fornix in CAA, AD and MCI compared to controls, despite relatively intact thalamic and hippocampal volumes in CAA, suggesting the mechanisms for fornix diffusion abnormalities may differ in CAA compared to AD and MCI.
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Enfermedad de Alzheimer , Angiopatía Amiloide Cerebral , Disfunción Cognitiva , Enfermedad de Alzheimer/patología , Anisotropía , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Fórnix/diagnóstico por imagen , Fórnix/patología , HumanosRESUMEN
BACKGROUND AND PURPOSE: The fornix-fimbria complex is mainly involved in emotions and memory. In brain MR imaging studies of young children, we have occasionally noted DWI hyperintensity in this region. The significance of this finding remains unclear. This study evaluated the DWI signal in the fornix-fimbria complex of children 0-2 years of age, including the frequency of signal hyperintensity and clinical context. MATERIALS AND METHODS: Brain MR imaging of 714 children 0-2 years of age (mean, 11 months), performed between September 2018 and May 2021, was reviewed and evaluated for DWI signal changes in the fornix-fimbria. All children with available MR imaging studies including DWI were included. Children with poor image quality, poor visualization of the fornix-fimbria region, and missing medical data were excluded. Additional imaging findings were also evaluated. Demographic data were retrieved from the medical files. We compared the ADC values of the fimbria and fornix between children with and without signal changes. The unpaired 2-tailed Student t test and χ2 test were used for statistical analysis. RESULTS: DWI signal hyperintensity of the Fornix-fimbria complex was noted in 53 (7.4%) children (mean age, 10 months). Their mean ADC values were significantly lower than those of the children with normal DWI findings (P < .05). About half of the children had otherwise normal MR imaging findings. When detected, the most common abnormality was parenchymal volume loss (15%). The most common indication for imaging was seizures (26.5%). CONCLUSIONS: DWI hyperintensity in the fornix-fimbria complex was detected in 7.4% of children 0-2 years of age. The etiology is not entirely clear, possibly reflecting a transient phenomenon.
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Fórnix , Imagen por Resonancia Magnética , Encéfalo , Niño , Preescolar , Imagen de Difusión por Resonancia Magnética/métodos , Fórnix/diagnóstico por imagen , Humanos , LactanteRESUMEN
Episodic memory relies on the coordination of widespread brain regions that reconstruct spatiotemporal details of an episode. These topologically dispersed brain regions can rapidly communicate through structural pathways. Research in animal and human lesion studies implicate the fornix-the major output pathway of the hippocampus-in supporting various aspects of episodic memory. Because episodic memory undergoes marked changes in early childhood, we tested the link between the fornix and episodic memory in an age window of robust memory development (ages 4-8 years). Children were tested on the stories subtest from the Children's Memory Scale, a temporal order memory task, and a source memory task. Fornix streamlines were reconstructed using probabilistic tractography to estimate fornix microstructure. In addition, we measured fornix macrostructure and computed free water. To assess selectivity of our findings, we also reconstructed the uncinate fasciculus. Findings show that children's memory increases from ages 4 to 8 and that fornix micro- and macrostructure increases between ages 4 and 8. Children's memory performance across nearly every memory task correlated with individual differences in fornix, but not uncinate fasciculus, white matter. These findings suggest that the fornix plays an important role in supporting the development of episodic memory, and potentially semantic memory, in early childhood.
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Memoria Episódica , Sustancia Blanca , Niño , Humanos , Preescolar , Fórnix/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Red Nerviosa , EncéfaloRESUMEN
Acute episodes of amnestic syndrome can be a challenging diagnostic problem. Except for nonvascular etiology, thalamic strokes or infarction involving several temporal lobe structures has been reported in earlier cases. The authors report a patient who suddenly developed memory loss without any other focal neurologic deficits. Brain magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) performed 1 day after onset revealed acute infarction involving the bilateral fornix column and the genu of corpus callosum. Because simple fornix infarcts often have no obvious positive neurological signs, most of the related manifestations were provided by family members, are easy to be diagnosed falsely, and missed in clinical areas, we suggest that bilateral fornix infarction should be considered in the diagnosis of an acute onset amnestic syndrome.
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Amnesia , Fórnix , Amnesia/diagnóstico por imagen , Amnesia/etiología , Amnesia/patología , Fórnix/irrigación sanguínea , Fórnix/diagnóstico por imagen , Fórnix/patología , Humanos , Infarto/complicaciones , Infarto/patología , Imagen por Resonancia Magnética , Trastornos de la MemoriaRESUMEN
Social interaction complexity makes humans unique. But in times of social deprivation, this strength risks exposure of important vulnerabilities. Human social neuroscience studies have placed a premium on the default network (DN). In contrast, hippocampus (HC) subfields have been intensely studied in rodents and monkeys. To bridge these two literatures, we here quantified how DN subregions systematically covary with specific HC subfields in the context of subjective social isolation (i.e., loneliness). By codecomposition using structural brain scans of â¼40,000 UK Biobank participants, loneliness was specially linked to midline subregions in the uncovered DN patterns. These association cortex patterns coincided with concomitant HC patterns implicating especially CA1 and molecular layer. These patterns also showed a strong affiliation with the fornix white matter tract and the nucleus accumbens. In addition, separable signatures of structural HC-DN covariation had distinct associations with the genetic predisposition for loneliness at the population level.NEW & NOTEWORTHY The hippocampus and default network have been implicated in rich social interaction. Yet, these allocortical and neocortical neural systems have been interrogated in mostly separate literatures. Here, we conjointly investigate the hippocampus and default network at a subregion level, by capitalizing structural brain scans from â¼40,000 participants. We thus reveal unique insights on the nature of the "lonely brain" by estimating the regimes of covariation between the hippocampus and default network at population scale.
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Red en Modo Predeterminado/anatomía & histología , Predisposición Genética a la Enfermedad , Hipocampo/anatomía & histología , Soledad , Adulto , Anciano , Bases de Datos Factuales , Femenino , Fórnix/anatomía & histología , Fórnix/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Herencia Multifactorial , Núcleo Accumbens/anatomía & histología , Núcleo Accumbens/diagnóstico por imagen , Sustancia Blanca/anatomía & histología , Sustancia Blanca/diagnóstico por imagenRESUMEN
A tool was developed to automatically segment several subcortical limbic structures (nucleus accumbens, basal forebrain, septal nuclei, hypothalamus without mammillary bodies, the mammillary bodies, and fornix) using only a T1-weighted MRI as input. This tool fills an unmet need as there are few, if any, publicly available tools to segment these clinically relevant structures. A U-Net with spatial, intensity, contrast, and noise augmentation was trained using 39 manually labeled MRI data sets. In general, the Dice scores, true positive rates, false discovery rates, and manual-automatic volume correlation were very good relative to comparable tools for other structures. A diverse data set of 698 subjects were segmented using the tool; evaluation of the resulting labelings showed that the tool failed in less than 1% of cases. Test-retest reliability of the tool was excellent. The automatically segmented volume of all structures except mammillary bodies showed effectiveness at detecting either clinical AD effects, age effects, or both. This tool will be publicly released with FreeSurfer (surfer.nmr.mgh.harvard.edu/fswiki/ScLimbic). Together with the other cortical and subcortical limbic segmentations, this tool will allow FreeSurfer to provide a comprehensive view of the limbic system in an automated way.
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Aprendizaje Profundo , Sistema Límbico/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Prosencéfalo Basal/diagnóstico por imagen , Femenino , Fórnix/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Núcleo Accumbens/diagnóstico por imagen , Reproducibilidad de los Resultados , Núcleos Septales/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Although the interforniceal approach with the preservation of the fornix is useful during the endoscopic approach for retroforaminal colloid cysts, it carries a significant risk of memory and cognitive difficulties. Because most reports have reported the endoscopic approach to colloid cysts through the foramen with little emphasis on retroforaminal cysts, the aim of this study was to investigate colloid cysts as a special entity with regard to their different characteristics and surgical approaches and outcomes. METHODS: In this retrospective study, 12 patients with third ventricular colloid cysts with retroforaminal extensions were included. All patients underwent endoscopic transseptal interforniceal approach with tumor resection. The surgical technique was briefly described, and preoperative and postoperative data were evaluated. RESULTS: Among the 12 patients included in this study, most of our patients were males. Average diameter of the colloid cyst was relatively large (average 22 mm). Gross total resection was achieved in 10 cases (83.3%). The stable images showed no local recurrence in the long-term follow-up period except in 1 case at the 28-month follow-up period. CONCLUSIONS: Retroforaminal colloid cyst represents a unique entity that requires special attention to its mode of growth. The endoscopic approach for retroforaminal colloid cysts is nearly the same as that for foraminal cysts. It has a lower incidence rate of postoperative memory changes, lower chances of total resection, and lower incidence rate of hard contents. Moreover, sufficient knowledge on morbid anatomy is important to avoid fornix injury.
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Quiste Coloide/cirugía , Fórnix/cirugía , Neuroendoscopía/métodos , Tabique del Cerebro/cirugía , Adolescente , Adulto , Quiste Coloide/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Fórnix/diagnóstico por imagen , Humanos , Masculino , Estudios Retrospectivos , Tabique del Cerebro/diagnóstico por imagen , Adulto JovenRESUMEN
While stress may be a potential mechanism by which childhood threat and deprivation influence mental health, few studies have considered specific stress-related white matter pathways, such as the stria terminalis (ST) and medial forebrain bundle (MFB). Our goal was to examine the relationships between childhood adversity and ST and MFB structural integrity and whether these pathways may provide a link between childhood adversity and affective symptoms and disorders. Participants were young adults (n = 100) with a full distribution of maltreatment history and affective symptom severity. Threat was determined by measures of childhood abuse and repeated traumatic events. Socioeconomic deprivation (SED) was determined by a measure of childhood socioeconomic status (parental education). Participants underwent diffusion spectrum imaging. Human Connectome Project data was used to perform ST and MFB tractography; these tracts were used as ROIs to extract generalized fractional anisotropy (gFA) from each participant. Childhood threat was associated with ST gFA, such that greater threat was associated with less ST gFA. SED was also associated with ST gFA, however, conversely to threat, greater SED was associated with greater ST gFA. Additionally, threat was negatively associated with MFB gFA, and MFB gFA was negatively associated with post-traumatic stress symptoms. Our results suggest that childhood threat and deprivation have opposing influences on ST structural integrity, providing new evidence that the context of childhood adversity may have an important influence on its neurobiological effects, even on the same structure. Further, the MFB may provide a novel link between childhood threat and affective symptoms.
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Experiencias Adversas de la Infancia , Síntomas Afectivos/patología , Haz Prosencefálico Medial/patología , Estrés Psicológico/patología , Sustancia Blanca/patología , Adulto , Adultos Sobrevivientes del Maltrato a los Niños , Síntomas Afectivos/diagnóstico por imagen , Imagen de Difusión Tensora , Femenino , Fórnix/diagnóstico por imagen , Fórnix/patología , Humanos , Masculino , Haz Prosencefálico Medial/diagnóstico por imagen , Carencia Psicosocial , Núcleos Septales/diagnóstico por imagen , Núcleos Septales/patología , Factores Socioeconómicos , Estrés Psicológico/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
PURPOSES: The recently developed myelin imaging method, inhomogeneous magnetization transfer (ihMT), is a surrogate measure of myelin content. The goal of the current study was to investigate alterations in myelin integrity in patients with recurrent major depressive disorder (rMDD). METHODS: Fifty-two patients with rMDD (36 female and 16 male) and 42 healthy controls (HC, 29 female and 13 male) were included. Two ihMT indices, quantitative ihMT (qihMT) and quantitative MT (qMT), were estimated from the ihMT data. A 50 white matter atlas was used to extract the regional quantitative values for each subject. The differences in qihMT and qMT values between the rMDD and HC groups were compared by a general linear model. Pearson correlation analyses were conducted to investigate associations between the significantly altered ihMT indices and clinical measures (Hamilton Depression Rating Scale scores and disease duration) in rMDD group. RESULTS: The rMDD group showed significantly lower qihMT values in the fornix, left anterior limb of internal capsule, and left sagittal stratum, and lower qMT values in the fornix and left anterior limb of internal capsule than those of the HC group (p < 0.05, false discovery rate corrected). Both the qihMT and qMT values in the fornix of patients with rMDD were negatively correlated with disease duration (qihMT: r = -0.478, p < 0.001, Bonferroni corrected; qMT: r = -0.433, p = 0.001, Bonferroni corrected). CONCLUSION: Our findings suggested that rMDD is associated with myelin impairment in the fornix, left anterior limb of internal capsule, and left sagittal stratum. In addition, this disruption of myelin integrity in the fornix could be cumulative as the disease progresses.
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Trastorno Depresivo Mayor/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Vaina de Mielina/metabolismo , Adulto , Trastorno Depresivo Mayor/metabolismo , Femenino , Fórnix/diagnóstico por imagen , Fórnix/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The fornix is the primary efferent pathway of the hippocampus and plays a central role in memory circuitry. Diffusion tensor imaging has shown changes in the fornix with typical development and aging. Here, the fornix was investigated in 903 healthy young adult participants aged 22-36 years old from the high-spatial resolution 1.25 mm isotropic Human Connectome Project (HCP) diffusion dataset. Manual deterministic tractography was used to assess relationships between fornix diffusion parameters and age, sex, laterality, hippocampus volume, memory scores, and genetic effects in a subgroup of mono- and dizygotic twins. Fornix diffusion metrics were weakly correlated with age over the given age span. While significant hemispheric and sex differences were observed (greater fractional anisotropy (FA) and volume in the right hemisphere; greater FA and volume in females), there was great overlap between the groups. Hippocampus volume measurements showed greater volume in the right hemisphere, were found to be larger in males, and were weakly correlated with fornix FA and volume. Interestingly, all fornix diffusion measurements correlated strongly with fornix volume, suggesting the presence of partial volume effects despite the high-spatial resolution of the data. Both fornix diffusion parameters and hippocampal volumes were able to explain some variance (0.6-5.5%) in the memory tests evaluated. The fornix diffusion parameters were influenced by both genetic and shared environmental factors, displaying greater variability in dizygotic than in monozygotic twins. These findings provide a comprehensive depiction of the fornix in healthy, young individuals, upon which future typical development/aging and pathological studies could anchor.
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Fórnix/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Adulto , Conectoma , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Factores Sexuales , Gemelos , Adulto JovenRESUMEN
Novelty facilitates memory formation and is detected by both the dorsal and ventral hippocampus. Although dentate granule cells (GCs) in the dorsal hippocampus are known to mediate the formation of novelty-induced contextual memories, the required pathways and mechanisms remain unclear. Here we demonstrate that a powerful excitatory pathway from mossy cells (MCs) in the ventral hippocampus to dorsal GCs is necessary and sufficient for driving dorsal GC activation in novel environment exploration. In vivo Ca2+ imaging in freely moving mice indicated that this pathway relays environmental novelty. Furthermore, manipulation of ventral MC activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MC activity gates contextual memory formation through an intra-hippocampal interaction activated by environmental novelty.