Specific Subcortical Structures Research Articles

Levels of Physical Activity at Age 10 Years and Brain Morphology Changes From Ages 10 to 14 Years

Physical activity may promote healthy brain development in children, but previous research was predominantly cross-sectional and included small samples, providing limited knowledge. To investigate the longitudinal associations of physical activity with brain morphology changes. A 4-year longitudinal population-based cohort study in Rotterdam, the Netherlands, embedded in Generation R, a cohort from fetal life onward. From the women enrolled during pregnancy, children who had repeated measures of brain structure at ages 10 (range 8 to 12) years and 14 (range 13 to 15) years were included. Data were collected from March 2013 to November 2015 (baseline) and from October 2016 to January 2020 (follow-up). Data were analyzed from April to December 2022. At age 10 years, both the child and their primary caregiver reported the child's levels of physical activity with regard to sport participation, outdoor play, and total physical activity. Primary analyses were based on an average multi-informant report. Brain morphology was quantified by magnetic resonance imaging. Hypothesized regions of interest were the bilateral amygdala and hippocampal volumes. Global brain measures were studied to test the specificity of the hypothesis. Data were available for 1088 children (566 girls [52%]; 693 [64%] Dutch). Their mean (SD) age at baseline was 10.1 (0.6) years. For amygdala volume change, positive associations with multi-informant reports of total physical activity (β = 2.6; 95% CI, 0.3-4.9) were found. Total physical activity was associated with hippocampal volume increases only when reported by the child (β = 3.1; 95% CI, 0.4-5.8). No robust associations with global brain measures were found. In this cohort study of 1088 children, more physical activity at 10 years was consistently associated with an increase in amygdala volume in children aged 10 to 14 years. Physical activity and increases in hippocampal volume were found using child reports of physical activity only. These findings suggest physical activity in late childhood was prospectively associated with volumetric changes in specific subcortical structures, but not to global brain development, from late childhood to early adolescence. These findings may inform the design of future public health interventions to best facilitate neurodevelopment with physical activity.

Exposing distinct subcortical components of the auditory brainstem response evoked by continuous naturalistic speech.

Speech processing is built upon encoding by the auditory nerve and brainstem, yet we know very little about how these processes unfold in specific subcortical structures. These structures are deep and respond quickly, making them difficult to study during ongoing speech. Recent techniques have begun to address this problem, but yield temporally broad responses with consequently ambiguous neural origins. Here, we describe a method that pairs re-synthesized 'peaky' speech with deconvolution analysis of electroencephalography recordings. We show that in adults with normal hearing the method quickly yields robust responses whose component waves reflect activity from distinct subcortical structures spanning auditory nerve to rostral brainstem. We further demonstrate the versatility of peaky speech by simultaneously measuring bilateral and ear-specific responses across different frequency bands and discuss the important practical considerations such as talker choice. The peaky speech method holds promise as a tool for investigating speech encoding and processing, and for clinical applications.

Volumetric changes in subcortical structures following repeated ketamine treatment in patients with major depressive disorder: a longitudinal analysis

Abnormal subcortical structures have been associated with major depressive disorder (MDD) and could be reversed by antidepressant treatment. To date no study has examined the relationship between subcortical volumes and repeated ketamine treatment. The current study investigated volume changes in specific subcortical structures and hippocampal subfields after six ketamine infusions. Forty-four patients with MDD received six subanesthetic dose infusions of ketamine. Depressive symptoms were assessed and magnetic resonance imaging scans were performed before and after six ketamine infusions. FreeSurfer software was used to process the T1 images and analyze the volumes of the subcortical regions and hippocampal subfields. After six ketamine infusions, increases were observed in the volumes of the left amygdala; the right hippocampus; the cornu ammonis 4 body, granule cell and molecular layer of the dentate gyrus body in the left hippocampus; and the cornu ammonis 4 head and molecular layer head in the right hippocampus. Positive correlations were found between symptom improvement and the pretreatment volumes of the right thalamus (r = 0.501; P = 0.001) and left subiculum head of the hippocampus (r = 0.471; P = 0.002), and changes in the volumes of the left amygdala (r = −0.452; P = 0.003) and the left cornu ammonis 4 body (r = −0.537; P < 0.001). Our findings provided evidence for critical roles of the amygdala and specific hippocampal subfields in the antidepressant effect of repeated ketamine treatment. Relatively larger volumes in right thalamus and left subiculum head in the hippocampus can predict a superior clinical outcome of ketamine treatment in MDD patients.

Neural activity in the periaqueductal gray and other specific subcortical structures is enhanced when a selective serotonin reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected death in epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is a critical issue in epilepsy, and DBA/1 mice are a useful animal model of this devastating epilepsy sequela. The serotonin hypothesis for SUDEP proposes that modifying serotonergic function significantly alters susceptibility to seizure-induced respiratory arrest (S-IRA). Agents that enhance serotonergic function, including a selective serotonin reuptake inhibitor, fluoxetine, selectively prevent S-IRA in DBA/1 mice. This study examined fluoxetine-induced changes in brain activity using manganese-enhanced magnetic resonance imaging (MEMRI) to reveal sites in the DBA/1 mouse brain where fluoxetine acts to prevent S-IRA. DBA/1 mice were subjected to audiogenic seizures (Sz) after saline or fluoxetine (45mg/kg, intraperitoneal) administration. Control DBA/1 mice received fluoxetine or saline, but Sz were not evoked. A previous MEMRI study established the regions of interest (ROIs) for Sz in the DBA/1 mouse brain, and the present study examined MEMRI differences in the ROIs of these mouse groups. The neural activity in several ROIs was significantly increased in fluoxetine-treated DBA/1 mice that exhibited Sz but not S-IRA when compared to the saline-treated mice that exhibited both Sz and respiratory arrest. These structures included the periaqueductal gray (PAG), amygdala, reticular formation (sensorimotor-limbic network), Kölliker-Fuse nucleus, facial-parafacial group (respiratory network), and pontine raphe. Of these ROIs, only the PAG showed significantly decreased neural activity with saline pretreatment when seizure-induced respiratory arrest occurred as compared to saline treatment without seizure. The PAG is known to play an important compensatory role for respiratory distress caused by numerous exigent situations in normal animals. The pattern of fluoxetine-induced activity changes in the present study suggests that PAG may be the most critical target for fluoxetine's action to prevent seizure-induced sudden death. These findings have potential clinical importance, because there is evidence of anomalous serotonergic function and PAG imaging abnormalities in human SUDEP.

Linking Inter-Individual Variability in Functional Brain Connectivity to Cognitive Ability in Elderly Individuals.

Increasing evidence suggests that functional brain connectivity is an important determinant of cognitive aging. However, the fundamental concept of inter-individual variations in functional connectivity in older individuals is not yet completely understood. It is essential to evaluate the extent to which inter-individual variability in connectivity impacts cognitive performance at an older age. In the current study, we aimed to characterize individual variability of functional connectivity in the elderly and to examine its significance to individual cognition. We mapped inter-individual variability of functional connectivity by analyzing whole-brain functional connectivity magnetic resonance imaging data obtained from a large sample of cognitively normal older adults. Our results demonstrated a gradual increase in variability in primary regions of the visual, sensorimotor, and auditory networks to specific subcortical structures, particularly the hippocampal formation, and the prefrontal and parietal cortices, which largely constitute the default mode and fronto-parietal networks, to the cerebellum. Further, the inter-individual variability of the functional connectivity correlated significantly with the degree of cognitive relevance. Regions with greater connectivity variability demonstrated more connections that correlated with cognitive performance. These results also underscored the crucial function of the long-range and inter-network connections in individual cognition. Thus, individual connectivity–cognition variability mapping findings may provide important information for future research on cognitive aging and neurocognitive diseases.

Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to improved approaches directed at prevention of human SUDEP.

Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Eighteen de novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD-NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine were tremor dominant and nine were postural instability gait disorder (PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD-NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD-MCI with right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided symptom dominance. When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures.

Subcortical atrophy and cognition

Gray matter (GM) atrophy is common in multiple sclerosis (MS), as is cognitive dysfunction. Understanding the exact relationship between atrophy and cognition requires further investigation. The aim of this study was to investigate the relationship between subcortical GM atrophy and cognition in early relapsing onset MS. Structural MRI and neuropsychological evaluations were performed in 120 patients (80 women) and 50 controls (30 women), part of an early inception cohort, 6 years postdiagnosis. Deep GM volumes were segmented automatically. Cognition was assessed in 7 domains. Stepwise linear regression was used to predict average cognition in the patient group. Most deep GM volumes were reduced in patients, with larger effects on average in men (-11%) than in women (-6.3%). Only the bilateral hippocampus, amygdala, and right nucleus accumbens in men, and right hippocampus and nucleus accumbens, bilateral amygdala, and putamen in women, showed no atrophy compared to controls. All cognitive domains except visuospatial memory were affected in men; none were significantly affected in women. In the MS group, average cognition was best predicted by thalamic volume, sex, and education (adjusted R(2) = 0.31), while lesion volume was not a significant predictor in the model. Six years postdiagnosis, almost all subcortical structures were affected by MS, especially in men. Cognition was most severely affected in male patients. Thalamic volume, sex, and education best predicted average cognition. These results underline the relevance of specific subcortical structures to cognition, as well as the relevance of (sex-specific) atrophy in MS.

Functional mapping–guided resection of low-grade gliomas in eloquent areas of the brain: improvement of long-term survival

Low-grade gliomas (LGGs) frequently infiltrate highly functional or "eloquent" brain areas. Given the lack of long-term survival data, the prognostic significance of eloquent brain tumor location and the role of functional mapping during resective surgery in presumed eloquent brain regions are unknown. We performed a retrospective analysis of 281 cases involving adults who underwent resection of a supratentorial LGG at a brain tumor referral center. Preoperative MR images were evaluated blindly for involvement of eloquent brain areas, including the sensorimotor and language cortices, and specific subcortical structures. For high-risk tumors located in presumed eloquent brain areas, long-term survival estimates were evaluated for patients who underwent intraoperative functional mapping with electrocortical stimulation and for those who did not. One hundred and seventy-four patients (62%) had high-risk LGGs that were located in presumed eloquent areas. Adjusting for other known prognostic factors, patients with tumors in areas presumed to be eloquent had worse overall and progression-free survival (OS, hazard ratio [HR] 6.1, 95% CI 2.6-14.1; PFS, HR 1.9, 95% CI 1.2-2.9; Cox proportional hazards). Confirmation of tumor overlapping functional areas during intraoperative mapping was strongly associated with shorter survival (OS, HR 9.6, 95% CI 3.6-25.9). In contrast, when mapping revealed that tumor spared true eloquent areas, patients had significantly longer survival, nearly comparable to patients with tumors that clearly involved only noneloquent areas, as demonstrated by preoperative imaging (OS, HR 2.9, 95% CI 1.0-8.5). Presumed eloquent location of LGGs is an important but modifiable risk factor predicting disease progression and death. Delineation of true functional and nonfunctional areas by intraoperative mapping in high-risk patients to maximize tumor resection can dramatically improve long-term survival.

Sub‐millimeter isotropic MRI for segmentation of subcortical brain regions and brain visualization

To evaluate a rapid sub-millimeter isotropic spoiled gradient-echo (nonselective SPGR) to facilitate the brain subcortical segmentation and the visualization of brain volume compared with the commonly accepted inversion recovery-prepared SPGR (SPGR-IR) technique. The feasibility of the nonselective SPGR was evaluated for two segmentation algorithms. FAST was used to segment the brain into constituent tissue classes (white matter, gray matter, cerebrospinal fluid) and FreeSurfer was used to segment specific subcortical structures (hippocampus, caudate, putamen, and thalamus). Localized apparent signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values for nonselective SPGR and the SPGR-IR were compared for the studied subcortical regions. The three-dimensional volume rendering was generated to evaluate the nonselective SPGR and the SPGR-IR for brain visualization. In basal ganglia regions, nonselective SPGR allows for consistent segmentation results for both FAST and FreeSurfer. This sequence also better differentiated gray/white matter compared with SPGR-IR. An approximate two-fold improvement of image quality in apparent SNR and CNR was indicated for subcortical brain anatomical structures with nonselective SPGR versus SPGR-IR. The nonselective SPGR improved clarity and yielded a more realistic depiction of the brain surface for visualization compared with SPGR-IR. Compared with SPGR-IR, nonselective SPGR allows for consistent segmentation results for basal ganglia regions and improved clarity for visualization of the brain.

MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer's disease.

Causes of cognitive impairment in subcortical ischemic vascular disease (SIVD) are less well understood than in AD, but have been thought to result from direct effects of subcortical lacunes and white matter lesions, perhaps related to disruption of important cortical-subcortical pathways. To examine the relation between cognitive abilities and quantitative MRI measures of subcortical cerebrovascular disease and cortical and hippocampal atrophy. Subjects were 157 participants in a multicenter study of SIVD and AD who included cognitively normal, cognitively impaired, and demented individuals with and without subcortical lacunar infarcts. Dependent variables were neuropsychological tests of global cognitive function, memory, language, and executive function. Independent variables were quantitative MRI measures of volume of lacunar infarcts in specific subcortical structures, volume of white matter lesion (WML), volume of cortical gray matter (cGM), and total hippocampal volume (HV). Multiple regression analyses were used to identify MRI predictors of cognition. Subcortical lacunes were not related to cognitive measures independent of effects of other MRI variables. WML was independently related to selected, timed measures. HV and cGM were strong and independent predictors of cognitive variables, with effects that did not differ in subjects with and without subcortical lacunes. Results suggest that cognitive impairment associated with subcortical ischemic vascular disease is primarily a result of associated hippocampal and cortical changes.

Structural analysis in the treatment of sexual disturbances

Physiological conception of the constituents of the copulative cycle shows that normal intercourse is based on the interaction of several independent innervation systems which join one another in the increasing dynamic integwity throughout the copulative cycle. This physiological conception defines four determinants, characterized by a) anatomo-physiological structure b) the final effect. These determinants are: 1) The neuro-humoral determinant. It includes some specific subcortical structures of the diencephalo-hypophyseal area and the entire system of the endocrine glands. This complex provides for the necessary quantitative level of sexual pressure (libido) and corresponding excitability of the nerve centres that participate in sexual performance. 2) The psychological determinant. It consists of the cortical structures and, most important, the combination of conditioned reflexes in the sexual sphere. It ensures qualitative direction of libido, effects erection before immissiorl and fulfills other minor tasks, mainly to effect the overt manifestations of sexual behavior specific for the human race, conforming more or less with the requirements of certain ethnic and social strata of society and with the needs of a particular situation with regard to place and time. 3) The erection determinant. It is based on purely functional anatomo-physiological structures of the lower level, consisting of the spinal and extra-spinal erection centers and the peripheral vascular function of cavernous bodies in the penis. This erection determinant serves mainly the mechanical function of intercourse. 4) The ejaculatory determinant. It is the most complicated and widely dispersed component and includes ejaculatory and orgastic effects. It is located on several levels, from the prostate with its own intra- and extra-mural anatomic ganglia up to the paracentral lobuli of the cortex. This determinant is responsible for the biologically most important function of the entire copulative cycle: the discharge of the sperm.

EXPERIMENTAL "PETIT MAL" IN KITTENS.

The experimental production of epileptogenic cortical foci in monkeys by means of local application of alumina cream to the cortex was initially described by Kopeloff, Barrera, and Kopeloff¹in 1942. The technique does not readily lend itself, however, to the creation of focal deep lesions, since the fluid irritative agent backs up through the needle tract and often spreads through the ventricles or subarachnoid spaces. In our laboratories a method was introduced to produce epileptogenic foci in deep structures of the brain.²Crystalline aluminum oxide was stereotaxically introduced into specific subcortical structures of the brain. A primary epileptogenic focus developed at the site of the alumina, and, subsequently, secondary discharge developed in the homotopic structure of the contralateral hemisphere. This report is concerned with the induction of petit mal-like patterns after the introduction of crystalline aluminum oxide into deep structures of the brains of kittens. Reports in the