Left Basal Forebrain Research Articles

Low bone mineral density is associated with gray matter volume decrease in UK Biobank.

Previous research has found an association of low bone mineral density (BMD) and regional gray matter (GM) volume loss in Alzheimer's disease (AD). We were interested whether BMD is associated with GM volume decrease in brains of a healthy elderly population from the UK Biobank. T1-weighted images from 5,518 women (MAge = 70.20, SD = 3.54; age range: 65-82 years) and 7,595 men (MAge = 70.84, SD = 3.68; age range: 65-82 years) without neurological or psychiatric impairments were included in voxel-based morphometry (VBM) analysis in CAT12 with threshold-free-cluster-enhancement (TFCE) across the whole brain. We found a significant decrease of GM volume in women in the superior frontal gyri, middle temporal gyri, fusiform gyri, temporal poles, cingulate gyri, precunei, right parahippocampal gyrus and right hippocampus, right ventral diencephalon, and right pre- and postcentral gyrus. Only small effects were found in men in subcallosal area, left basal forebrain and entorhinal area. BMD is associated with low GM volume in women but less in men in regions afflicted in the early-stages of AD even in a sample without neurodegenerative diseases.

Cerebral gray matter volume correlates with fatigue and varies between desk workers and non-desk workers.

Chronic fatigue syndrome (CFS), a clinical entity of chronic fatigue, has been associated with a decrease in regional gray matter volume (rGMV). In this study targeting a large number of healthy middle-aged individuals without CFS, the relationship between fatigue perception and rGMV was investigated. Considering that the work setting is an environmental factor that influences fatigue perception among healthy individuals, the differences between desk workers and non-desk workers were investigated. Chalder Fatigue Questionnaire (CFQ) scores were used for perceptional evaluation of fatigue, and rGMV of 110 brain regions was adapted with Statistical Parametric Mapping (SPM) 8 on 1.5 T magnetic resonance imaging (MRI) results for the volumetric calculation of gray matter. The CFQ scores were negatively correlated with the right supplementary motor area (SMC) and positively correlated with the right superior parietal lobule (SPL) and left basal forebrain in all participants (n = 1,618). In desk workers and non-desk workers, the CFQ scores correlated with different regions and yielded different mechanisms of fatigue perception in the brain. Identifying the gray matter regions correlated with fatigue perception in healthy individuals may help understand the early stage of fatigue progression and establish future preventive measures.

SVM-Based Normal Pressure Hydrocephalus Detection

Background and PurposeAs magnetic resonance imaging (MRI) signs of normal pressure hydrocephalus (NPH) may precede clinical symptoms we sought to evaluate an algorithm that automatically detects this pattern.MethodsA support vector machine (SVM) was trained in 30 NPH patients treated with ventriculoperitoneal shunts and 30 healthy controls. For comparison, four neuroradiologists visually assessed sagittal MPRAGE images and graded them as no NPH pattern, possible NPH pattern, or definite NPH pattern.ResultsHuman accuracy to visually detect a NPH was between 0.85 and 0.97. Interobserver agreement was substantial (κ = 0.656). Accuracy of the SVM algorithm was 0.93 and AUROC 0.99. Among 272 prespecified regions, gray matter and CSF volumes of both caudate, the right parietal operculum, the left basal forebrain, and the 4th ventricle showed the highest discriminative power to separate a NPH and a no NPH pattern.ConclusionA NPH pattern can be reliably detected using a support vector machine (SVM). Its role in the work-up of asymptomatic patients or neurodegenerative disease has to be evaluated.

Segregated Co-activation Patterns in the Emergence of Decision Confidence During Visual Perception.

Visual metacognition—the introspection and evaluation of one’s own visual perceptual processes—is measured through both decision confidence and “metacognitive efficiency.” Metacognitive efficiency refers to an individual’s ability to accurately judge incorrect and correct decisions through confidence ratings given their task performance. Previous imaging studies in humans and nonhuman primates reported widely distributed brain regions being involved in decision confidence and metacognition. However, the neural correlates of metacognition are remarkably inconsistent across studies concerning spatial outline. Therefore, this study investigates the neural correlates of visual metacognition by examining co-activation across regions that scale with visual decision confidence. We hypothesized that interacting processes of perceptual and metacognitive performance contribute to the arising decision confidence in distributed, but segregable co-activating brain regions. To test this hypothesis, we performed task-fMRI in healthy humans during a visual backward masking task with four-scale, post-decision confidence ratings. We measured blood oxygenation covariation patterns, which served as a physiological proxy for co-activation across brain regions. Decision confidence ratings and an individual’s metacognitive efficiency served as behavioral measures for metacognition. We found three distinct co-activation clusters involved in decision confidence: the first included right-centered fronto-temporal-parietal regions, the second included left temporal and parietal regions, and the left basal forebrain (BF), and the third included cerebellar regions. The right fronto-temporal-parietal cluster including the supplementary eye field and the right basal forebrain showed stronger co-activation in subjects with higher metacognitive efficiency. Our results provide novel evidence for co-activation of widely distributed fronto-parieto-temporal regions involved in visual confidence. The supplementary eye field was the only region that activated for both decision confidence and metacognitive efficiency, suggesting the supplementary eye field plays a key role in visual metacognition. Our results link findings in electrophysiology studies and human fMRI studies and provide evidence that confidence estimates arise from the integration of multiple information processing pathways.

Regional volume changes of the brain in migraine chronification.

The pathophysiology of migraine is complex. Neuroimaging studies reveal functional and structural changes in the brains of migraine patients. We sought to explore regional volume differences in intracranial structures in patients with episodic and chronic migraine. Sixteen episodic migraine patients, 16 chronic migraine patients, and 24 normal controls were recruited and underwent 3.0 T MRI scanning. The volumes of 142 brain regions were calculated by an automatic volumetric algorithm and compared with clinical variables. Results demonstrated that the volumes of specific regions in the frontal and occipital lobes, and the right putamen, were increased and the volume of the fourth ventricle was decreased in the episodic migraine patients compared with controls. The volumes of the left basal forebrain, optic chiasm, and, the fourth ventricle were decreased in the chronic migraine patients, while the occipital cortex and the right putamen were larger. Compared to episodic migraine patiants, chronic migraine patients displayed larger left thalamus and smaller frontal regions. Correlation analysis showed that headache frequency was negatively correlated with the volume of the right frontal pole, right lateral orbital gyrus, and medial frontal lobes and positively correlated with the volume of the left thalamus. The sleep disturbance score was negatively correlated with the volume of the left basal forebrain. This suggests that migraine patients have structural changes in regions associated with pain processing and modulation, affective and cognitive processing, and visual perception. The remodeling of selective intracranial structures may be involved in migraine attacks. This study was approved by the Ethics Committee of Chinese PLA General Hospital (approval No. S2018-027-02) on May 31, 2018.

Anosognosia predicts default mode network hypometabolism and clinical progression to dementia.

ObjectiveTo identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild cognitive impairment.MethodsWe stratified 468 patients with amnestic mild cognitive impairment into intact and impaired awareness groups, determined by the discrepancy between the patient and the informant score on the Everyday Cognition questionnaire. Voxel-based linear regression models evaluated the associations between self-awareness status and baseline β-amyloid load, measured by [18F]florbetapir, and the relationships between awareness status and regional brain glucose metabolism measured by [18F]fluorodeoxyglucose at baseline and at 24-month follow-up. Multivariate logistic regression tested the association of awareness status with conversion from amnestic mild cognitive impairment to dementia.ResultsWe found that participants with impaired awareness had lower [18F]fluorodeoxyglucose uptake and increased [18F]florbetapir uptake in the posterior cingulate cortex at baseline. In addition, impaired awareness in mild cognitive impairment predicted [18F]fluorodeoxyglucose hypometabolism in the posterior cingulate cortex, left basal forebrain, bilateral medial temporal lobes, and right lateral temporal lobe over 24 months. Furthermore, participants with impaired awareness had a nearly 3-fold increase in likelihood of conversion to dementia within a 2-year time frame.ConclusionsOur results suggest that anosognosia is linked to Alzheimer disease pathophysiology in vulnerable structures, and predicts subsequent hypometabolism in the default mode network, accompanied by an increased risk of progression to dementia. This highlights the importance of assessing awareness of cognitive decline in the clinical evaluation and management of individuals with amnestic mild cognitive impairment.

Recovery of injured cingulum in a patient with traumatic brain injury.

Recovery of injured cingulum in a patient with traumatic brain injury.

Case 35-2008

A 65-year-old right-handed man was transferred to this hospital because of the recent onset of confusion and memory loss. MRI scans of the brain showed symmetric abnormalities involving the temporal lobes, left basal forebrain, and insular regions. A CT scan of the chest disclosed an anterior mediastinal mass. A diagnostic procedure was performed.

Single stroke dementia: Insights from 12 cases in Singapore

Background: Vascular dementia (VaD) is occasionally caused by a single, strategically located stroke. In this report, we describe the clinical and anatomical features of 12 cases of strategic single infarct dementia (SSID) from Singapore. Methods: Each patient completed a standardized diagnostic evaluation including history, neurological and neuropsychological examination, laboratory testing, and brain imaging. Dementia was diagnosed using the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-III-R) criteria, and VaD was diagnosed using the National Institute of Neurologic Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS–AIREN) criteria. VaD patients whose brain imaging study revealed a single cerebrovascular event were diagnosed with SSID. Results: We identified 12 cases of SSID among 125 VaD patients (9.6%). Stroke mechanism was lacunar infarction in five cases, embolism in four cases, large vessel thrombosis in two cases, and parenchymal hemorrhage in one case. The most commonly impaired cognitive domains on neuropsychological testing were visual memory, visuoconstruction, and language. In 11 of the 12 SSID cases, the stroke was located in the left hemisphere. The thalamus, either alone or as the proximal portion of a posterior cerebral artery infarction, was involved in 8 of the 12 cases. Stroke locations in the nonthalamic SSID cases included left angular gyrus, subcortical left frontal lobe including minor forceps, left basal forebrain and medial frontal lobe plus anterior corpus callosum (proximal anterior cerebral artery infarction), and anterior corpus callosum alone. Conclusions: Various stroke mechanisms may produce SSID. In our SSID cases, vascular damage almost always involved the left hemisphere and frequently involved the thalamus and major interhemispheric or intrahemispheric white matter pathways.

Basal forebrain control of cortical cerebral blood flow is independent of local cortical neurons

To determine whether intrinsic cortical neurons participate in mediating increases in cortical cerebral blood flow (CBF) in response to electrical stimulation of the basal forebrain (BF), cortical CBF was assessed by laser-DOppler flowmetry in rats before and after unilaterally removing local cortical neurons with the excitotoxin ibotenic acid (IBO). On the first day of testing, CBF responses to right and left BF stimulation were nearly identical in right and left frontal cortices, corresponding to the frequency of stimulation, up to a maximum at 25 Hz (+180%). Subsequently, animals received a unilateral microinjection of IBO and a contralateral microinjection of phosphate-buffered saline (PBS) into the responsive cortical sites. After five days, responses in lesioned cortices were remarkably intact both in comparison to the contralateral PBS-injected site and to the same site tested prior to lesioning on day 1. IBO lesions of the response sites were histologically confirmed to extend through the entire depth of the frontal cortex and to encompass a large surface area ( 7.7 ± 0.5mm 2 ). These results indicate that local cortical neurons are not critical to the mediation of increases in cortical CBF as elicited by BF stimulation. This study further supports the role of the BF as a distinct intracerebral neurogenic regulator of cortical CBF.

Effects of some cholinergic agonists on neocortical slow wave activity in rats with basal forebrain lesions

Chronic rats, prepared with unilateral injections of kainic acid in the left basal forebrain, displayed prominent large amplitude slow wave activity in the neocortex ipsilateral to the injection. Oxotremorine and pilocarpine, given systemically following pretreatment with methyl scopolamine to block peripheral muscarinic effects, restored low voltage fast activity (LVFA) in a dose-related manner. Oxotremorine was more potent than pilocarpine. Arecoline was not consistently effective. Tetrahydroaminoacridine abolished abnormal 4–6 Hz rhythmical slow waves in the left neocortex but had little effect on large amplitude irregular slow waves. Direct-acting cholinergic agonists can restore near-normal neocortical activity after extensive cholinergic deafferentation of the neocortex.