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Background: The P3 event-related potential (ERP) is presumably partly generated by the basal ganglia. Because degeneration of these brain structures starts many years before clinical disease onset in Huntington's disease (HD), studying the interplay between P3 characteristics and basal ganglia volumes in 'premanifest' carriers might lead to new insights into the disease process. Methods: Fourteen premanifest HD mutation carriers and twelve non-mutation carriers underwent clinical, MRI and P3-ERP investigations. The P3 was measured during the Sustained Attention to Response Task. Results: P3 amplitude and latency did not differ between groups. In carriers, longer P3 latency during Go-trials was strongly associated with smaller caudate, putamen and globus pallidus volumes (r values up to )0.827, P ≤ 0.001). Conclusion: The exceptionally strong relations of P3 latency with basal ganglia volumes in carriers suggest that the P3 may provide a marker for disease progression in HD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Tumor necrosis factor alpha was recently implicated as an important mediator of communication between the peripheral and cerebral immune systems in an animal model of chronic inflammation. The purpose of this study was to examine by proton magnetic resonance spectroscopy ((1)H-MRS) the influence of inflammation on cerebral metabolism in patients with rheumatoid arthritis (RA). METHODS: Single-voxel (1)H-MRS of the centrum semiovale was performed on 35 RA patients (6 men and 29 women; mean +/- SD age 51.8 +/- 14.6 years) and 28 healthy age- and sex-matched control subjects (9 men and 19 women; mean +/- SD age 50.2 +/- 10.4 years). None of the study subjects had any neurologic signs or symptoms. Clinical markers of disease activity were correlated with the (1)H-MRS findings. RESULTS: Patients with active RA, as reflected by an elevated erythrocyte sedimentation rate (ESR), had a significantly higher ratio of choline to creatine and a significantly lower ratio of N-acetylaspartate to choline than did patients with inactive RA, as reflected by a normal ESR. Moreover, the ratios of choline to creatine and NAA to choline were significantly correlated with the ESR after correction for age, sex, smoking status, handedness, alcohol consumption, medication use, and disease duration. Medication use had no additional effect on these associations. CONCLUSION: Our data show that systemic inflammation in RA is associated with metabolic changes in the brain. [ABSTRACT FROM AUTHOR]

Objective Normal pressure hydrocephalus is characterized by gait impairment, cognitive impairment, and urinary incontinence, and is associated with disproportionate ventricular dilation. Here we report the distribution of ventricular volume relative to sulcal cerebrospinal fluid (CSF) volume, and the association of increasing ventricular volume relative to sulcal CSF volume with a cluster of gait impairment, cognitive impairment, and urinary incontinence in a stroke-free cohort of elderly persons from the general population. Methods Data are based on 858 persons (35.4% men; age range, 66-92 years) who participated in the Age, Gene/Environment Susceptibility-Reykjavik Study. Gait was evaluated with an assessment of gait speed. Composite scores representing speed of processing, memory, and executive function were constructed from a neuropsychological battery. Bladder function was assessed with a questionnaire. Magnetic resonance brain imaging was followed by semiautomated segmentation of intracranial CSF volume. White matter hyperintensity (WMH) volume was assessed with a semiquantitative scale. For the analysis of ventricular dilation relative to the sulcal spaces, ventricular volume was divided by sulcal CSF volume (VV/SV). Results Disproportion between ventricular and sulcal CSF volume, defined as the highest quartile of the VV/SV z score, was associated with gait impairment (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3) and cognitive impairment (OR, 1.8; 95% CI, 1.1-3.0). We did not find an association between the VV/SV z score and bladder dysfunction. Interpretation The prevalence and severity of gait impairment and cognitive impairment increases with ventricular dilation in persons without stroke from the general population, independent of WMH volume. Ann Neurol 2009;66:485-493 [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate whether, in neuropsychiatric systemic lupus erythematosus (NPSLE) patients, magnetization transfer ratio (MTR) histogram parameters are related to neurochemical findings obtained using proton magnetic resonance spectroscopy (1H-MRS) and to determine whether MTR histogram changes are linked to specific SLE and NPSLE characteristics. METHODS: Eighteen SLE patients (15 female, 3 male; mean +/- SD age 42.8 +/- 12.8 years), 34 NPSLE patients (32 female, 2 male; mean +/- SD age 35.9 +/- 12.2 years), and 15 healthy controls (14 female, 1 male; mean +/- SD age 44.7 +/- 9.6 years) underwent magnetization transfer imaging and 1H-MRS. Whole-brain MTR histogram parameters were associated with 1H-MRS metabolite ratios, certain SLE criteria, and neuropsychiatric syndromes. RESULTS: No differences were found in the MTR histogram parameters between SLE patients and NPSLE patients. NPSLE patients had a lower MTR histogram peak height than did the healthy controls. The MTR histogram peak height and the mean height were significantly associated with the N-acetylaspartate to creatinine ratio, suggesting neuronal dysfunction. Of all SLE criteria, renal dysfunction and arthritis were associated with MTR histogram parameters. After corrections for age, sex, and these SLE criteria, of the various neuropsychiatric syndromes only cognitive dysfunction was associated with the MTR histogram peak height. CONCLUSION: The MTR peak height is lower in NPSLE patients than in healthy controls. MTR peak height reflects neuronal dysfunction, as detected by 1H-MRS. Furthermore, the MTR peak height is associated with cognitive dysfunction but not with the other neuropsychiatric syndromes evaluated in our study. [ABSTRACT FROM AUTHOR]

Purpose To assess whether magnetization transfer imaging (MTI) parameters change in correspondence with clinical changes in NPSLE patients. Materials and Methods Nineteen female patients (mean age = 37.5 years, range = 19-64) underwent MTI on at least two separate occasions (mean time between scans = 25.4 months, range = 5.4-52.3 months). Twenty-four pairs of scans of 19 patients were available. Each patient's clinical course was classified as improved, stable, or deteriorated. Whole-brain magnetization transfer ratio (MTR) histograms were generated. The peak height of these histograms was used as an estimate of parenchymal integrity. Based on the change in clinical status, paired examinations were grouped and tested for significant differences between the first and second examinations using paired-samples t-tests. Results Four patients clinically deteriorated, all patients showed a significant peak height decrease (mean decrease = 8.6%, P = 0.02), and in 14 patients with stable disease the peak height did not change significantly (mean increase = 0.4%). Six patients clinically improved, and all showed a significant relative peak height increase (mean increase = 12.0%, P = 0.02). Conclusion The peak height of whole-brain MTR histograms corresponds to changes in the clinical status of individual NPSLE patients. This suggests that MTI can be a valuable tool in the clinical assessment of such patients. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Unlabelled: During venoarterial extracorporeal membrane oxygenation the right carotid artery is ligated in a hypoxic neonate. The aim of the present study was to compare the morphology and metabolism of the left and right basal ganglia in 10 neonates after extracorporeal membrane oxygenation, using proton magnetic resonance imaging and spectroscopy. Data could be obtained in 9 neonates. No significant metabolic differences were found between either the left or right basal ganglia, despite a small right-sided thalamic infarct in one child. Metabolism was normal in all cases. All the infants showed symmetrical neurodevelopment.Conclusion: Ligation of the right carotid artery for venoarterial extracorporeal membrane oxygenation did not produce persistent changes in brain metabolism in the basal ganglia in this small group of patients. [ABSTRACT FROM AUTHOR]

Aims: Dysfunction of nitric oxide-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate signalling is implicated in the pathophysiology of cognitive impairment. Zagociguat is a central nervous system (CNS) penetrant sGC stimulator designed to amplify nitric oxide-cyclic guanosine monophosphate signalling in the CNS. This article describes a phase 1b study evaluating the safety and pharmacodynamic effects of zagociguat., Methods: In this randomized crossover study, 24 healthy participants aged ≥65 years were planned to receive 15 mg zagociguat or placebo once daily for 2 15-day periods separated by a 27-day washout. Adverse events, vital signs, electrocardiograms and laboratory tests were conducted to assess safety. Pharmacokinetics of zagociguat were evaluated in blood and cerebrospinal fluid (CSF). Pharmacodynamic assessments included evaluation of cerebral blood flow, CNS tests, pharmaco-electroencephalography, passive leg movement and biomarkers in blood, CSF and brain., Results: Twenty-four participants were enrolled; 12 participants completed both treatment periods, while the other 12 participants completed only 1 treatment period. Zagociguat was well-tolerated and penetrated the blood-brain barrier, with a CSF/free plasma concentration ratio of 0.45 (standard deviation 0.092) measured 5 h after the last dose of zagociguat on Day 15. Zagociguat induced modest decreases in blood pressure. No consistent effects of zagociguat on other pharmacodynamic parameters were detected., Conclusion: Zagociguat was well-tolerated and induced modest blood pressure reductions consistent with other sGC stimulators. No clear pharmacodynamic effects of zagociguat were detected. Studies in participants with proven reduced cerebral blood flow or CNS function may be an avenue for further evaluation of the compound., (© 2023 British Pharmacological Society.)

The hypothalamus has been suggested to be important in the initiation cascade of migraine attacks based on clinical and biochemical observations. Previous imaging studies could not disentangle the changes due to the attack and those due to the trigger compound. With a novel approach, we assessed hypothalamic neuronal activity in early premonitory phases of glyceryl-trinitrate (GTN)-induced and spontaneous migraine attacks. We measured the hypothalamic blood oxygen level-dependent (BOLD) response to oral glucose ingestion with 3T-functional magnetic resonance imaging (MRI) in 27 women, 16 with migraine without aura and 11 controls group matched for age and body mass index (BMI), on 1 day without prior GTN administration and on a second day after GTN administration (to coincide with the premonitory phase of an induced attack). Interestingly, subgroups of patients with and without GTN-triggered attacks could be compared. Additionally, five migraineurs were investigated in a spontaneous premonitory phase. Linear mixed models were used to study between- and within-group effects. Without prior GTN infusion, the BOLD response to glucose was similar in migraine participants and controls (P = .41). After prior GTN infusion, recovery occurred steeper and faster in migraineurs (versus Day 1; P < .0001) and in those who developed an attack versus those who did not (P < .0001). Prior GTN infusion did not alter the glucose-induced response in controls (versus baseline; P = .71). Just before spontaneous attacks, the BOLD-response recovery was also faster (P < .0001). In this study, we found new and direct evidence of altered hypothalamic neuronal function in the immediate preclinical phase of both GTN-provoked and spontaneous migraine attacks., (© 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Structural covariance networks are able to identify functionally organized brain regions by gray matter volume covariance across a population. We examined the transcriptomic signature of such anatomical networks in the healthy brain using postmortem microarray data from the Allen Human Brain Atlas. A previous study revealed that a posterior cingulate network and anterior cingulate network showed decreased gray matter in brains of Parkinson's disease patients. Therefore, we examined these two anatomical networks to understand the underlying molecular processes that may be involved in Parkinson's disease. Whole brain transcriptomics from the healthy brain revealed upregulation of genes associated with serotonin, GPCR, GABA, glutamate, and RAS-signaling pathways. Our results also suggest involvement of the cholinergic circuit, in which genes NPPA, SOSTDC1, and TYRP1 may play a functional role. Finally, both networks were enriched for genes associated with neuropsychiatric disorders that overlap with Parkinson's disease symptoms. The identified genes and pathways contribute to healthy functions of the posterior and anterior cingulate networks and disruptions to these functions may in turn contribute to the pathological and clinical events observed in Parkinson's disease., (© 2021 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Aims: Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. Toxic accumulation of misfolded mutant huntingtin protein induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. We evaluated the safety, pharmacokinetics and pharmacodynamics of SBT-020, a novel compound to improve mitochondrial function, in a 2-part study in early stage HD patients., Methods: Part 1 consisted of 7-day multiple ascending dose study to select the highest tolerable dose for Part 2, a 28-day multiple dose study. Mitochondrial function was measured in the visual cortex and calf muscle, using phosphorous magnetic resonance spectroscopy, and in circulating peripheral blood mononuclear cells., Results: Treatment-emergent adverse events were mild and more present in the SBT-020 group. Injection site reactions occurred in 91% in Part 1 and 97% in Part 2. Mitochondrial function in calf muscle, peripheral blood mononuclear cells or visual cortex was not changed overall due to treatment with SBT-020. In a posthoc analysis, patients with a higher degree of mitochondrial dysfunction (below the median [∆Ψ m < 3412 and τPCr > 42.5 s]) showed more improvement than patients with a relatively lower level of mitochondrial dysfunction., Conclusion: SBT-020 was safe at all doses, but no significant differences in any of the pharmacodynamic measurements between the treatment groups and placebo group could be demonstrated. The data suggest that the better than expected mitochondrial function in our patient population at baseline might explain the lack of effect of SBT-020., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background Cerebral amyloid angiopathy ( CAA ) is a major cause of lobar intracerebral hemorrhage in elderly adults; however, presymptomatic diagnosis of CAA is difficult. Hereditary cerebral hemorrhage with amyloidosis-Dutch type ( HCHWA -D) is a rare autosomal-dominant disease that leads to pathology similar to sporadic CAA . Presymptomatic HCHWA -D mutation carriers provide a unique opportunity to study CAA -related changes before any symptoms have occurred. In this study we investigated early CAA -related alterations in the white matter. Methods and Results We investigated diffusion magnetic resonance imaging ( dMRI ) data for 15 symptomatic and 11 presymptomatic HCHWA -D mutation carriers and 30 noncarrier control participants using 4 different approaches. We looked at (1) the relation between age and global dMRI measures for mutation carriers versus controls, (2) voxel-wise d MRI , (3) independent component-clustered dMRI measures, and (4) structural connectomics between presymptomatic or symptomatic carriers and controls. Fractional anisotropy decreased, and mean diffusivity and peak width of the skeletonized mean diffusivity increased significantly over age for mutation carriers compared with controls. In addition, voxel-wise and independent component-wise fractional anisotropy, and mean diffusivity, and structural connectomics were significantly different between HCHWA -D patients and control participants, mainly in the periventricular frontal and occipital regions and in the occipital lobe. We found no significant differences between presymptomatic carriers and control participants. Conclusions The d MRI technique is sensitive in detecting alterations in symptomatic HCHWA -d carriers but did not show alterations in presymptomatic carriers. This result indicates that d MRI may be less suitable for identifying early white matter changes in CAA .

Aging is associated with cognitive decline, diminished brain function, regional brain atrophy, and disrupted structural and functional brain connectivity. Understanding brain networks in aging is essential, as brain function depends on large-scale distributed networks. Little is known of structural covariance networks to study inter-regional gray matter anatomical associations in aging. Here, we investigate anatomical brain networks based on structural covariance of gray matter volume among 370 middle-aged to older adults of 45-85 years. For each of 370 subjects, we acquired a T1-weighted anatomical MRI scan. After segmentation of structural MRI scans, nine anatomical networks were defined based on structural covariance of gray matter volume among subjects. We analyzed associations between age and gray matter volume in anatomical networks using linear regression analyses. Age was negatively associated with gray matter volume in four anatomical networks (P < 0.001, corrected): a subcortical network, sensorimotor network, posterior cingulate network, and an anterior cingulate network. Age was not significantly associated with gray matter volume in five networks: temporal network, auditory network, and three cerebellar networks. These results were independent of gender and white matter hyperintensities. Gray matter volume decreases with age in networks containing subcortical structures, sensorimotor structures, posterior, and anterior cingulate cortices. Gray matter volume in temporal, auditory, and cerebellar networks remains relatively unaffected with advancing age., (© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Atrophy is one of the major age-related changes in the brain. The absence of brain atrophy in elderly individuals reflects deceleration in the process of biological aging. Moreover, results from human twin studies suggest a large genetic influence on the variance of human brain tissue volumes. To investigate the association of brain volumes with exceptional longevity, we tested whether middle-aged to elderly offspring of nonagenarian siblings have larger brain volumes than their spouses using magnetic resonance imaging. No differences in whole brain, gray matter and white matter volume were found. These brain volumes were associated with chronological age in offspring and control subjects (all P < 0.001). Left amygdalar volume of the offspring was larger (P = 0.03) compared with control subjects [mean volume offspring (cm3) (95% confidence interval, CI) = 1.39 (1.36-1.42), mean volume control subjects (cm3) (95% CI) = 1.32 (1.29-1.35)]. Association of left amygdalar volume with familial longevity was particularly pronounced when offspring with the oldest long-lived parent were compared with control subjects (P = 0.01). Amygdalar volumes were not associated with chronological age in both groups. Our findings suggest that the observed association of a larger left amygdalar volume with familial longevity is not caused by a relative preservation of the left amygdala during the course of aging but most likely a result of early development caused by a genetic familial trait., (© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)

Objective: The clinical manifestations of nervous system involvement in systemic lupus erythematosus (neuropsychiatric SLE [NPSLE]) are highly diverse, and their etiology is incompletely understood. The aim of this study was to provide an inventory of abnormalities on conventional brain magnetic resonance imaging (MRI) in NPSLE and to interpret the findings in relation to possible underlying pathogenetic mechanisms., Methods: MR images of the first episode of active NPSLE in 74 patients were retrospectively reviewed. All patients fulfilled the American College of Rheumatology (ACR) 1982 revised criteria for the classification of SLE and were classified according to the 1999 ACR case definitions for NPSLE syndromes. We excluded patients with a history of brain disease and patients in whom other mechanisms unrelated to SLE caused the neuropsychiatric symptoms., Results: The principal findings were: 1) focal hyperintensities in white matter (WM) (49% of all patients) or both WM and gray matter (GM) (5% of all patients), suggestive of vasculopathy or vasculitis; 2) more widespread, confluent hyperintensities in the WM, suggestive of chronic hypoperfusion due to the same mechanisms; 3) diffuse cortical GM lesions (12% of all patients), compatible with an immune response to neuronal components or postseizure changes; and 4) absence of MRI abnormalities, despite signs and symptoms of active disease (42% of all patients)., Conclusion: Several distinct brain MRI patterns were observed in patients with active NPSLE, suggestive of different pathogenetic mechanisms. To advance our understanding of the various processes leading to NPSLE, the radiographic manifestations may be a good starting point and useful for categorization of patients in further research., (Copyright © 2011 by the American College of Rheumatology.)

Objective: The aim of this study was to determine whether there are differences in white matter integrity between systemic lupus erythematosus (SLE) patients and healthy controls, as determined using tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging data., Methods: Twelve patients with SLE (mean age 42 years [range 15-61 years]) diagnosed according to the American College of Rheumatology 1982 revised criteria for SLE and 28 healthy controls (mean age 46 years [range 21-61 years]) were included in the study. Magnetic resonance imaging was performed on a 3.0T scanner. Fractional anisotropy (FA) maps were calculated for each patient. TBSS analysis was used to compare the FA maps. The TBSS technique projects the FA data into a common space through the use of an initial approximate nonlinear registration, followed by projection onto an alignment-invariant tract representation (mean FA skeleton). The cluster results were corrected for multiple comparisons across space, and a threshold of significance of 0.05 was used., Results: The white matter of tracts in the inferior fronto-occipital fasciculus, the fasciculus uncinatus, as well as the fornix, the posterior limb of the internal capsule (corticospinal tract), and the anterior limb of the internal capsule (anterior thalamic radiation) of patients with SLE showed reduced integrity as compared with normal subjects., Conclusion: In this preliminary study, the integrity of white matter tracts in areas around limbic structures and in the internal capsule was found to be reduced. Larger studies could improve our understanding of the pathologic mechanisms behind the reduced white matter tract integrity in SLE., (Copyright © 2010 by the American College of Rheumatology.)

Background and Methods: In six hydrocephalic foetuses (gestational age 29-38 wk), proton MR spectroscopy (1H-MRS) was performed in the basal ganglia for detection of lactate in vivo., Results: Lactate was present in two foetal brains, absent in two and not detectable because of movement in two., Conclusion: With adequate immobilization of the foetus, 1H-MRS can be used for detection of foetal brain lactate.