The occipital and frontal lobes are anatomically distant yet functionally highly integrated to generate some of the most complex behaviour. A series of long associative fibres, such as the ...fronto-occipital networks, mediate this integration via rapid feed-forward propagation of visual input to anterior frontal regions and direct top–down modulation of early visual processing.
Despite the vast number of anatomical investigations a general consensus on the anatomy of fronto-occipital connections is not forthcoming. For example, in the monkey the existence of a human equivalent of the ‘inferior fronto-occipital fasciculus’ (iFOF) has not been demonstrated. Conversely, a ‘superior fronto-occipital fasciculus’ (sFOF), also referred to as ‘subcallosal bundle’ by some authors, is reported in monkey axonal tracing studies but not in human dissections.
In this study our aim is twofold. First, we use diffusion tractography to delineate the in vivo anatomy of the sFOF and the iFOF in 30 healthy subjects and three acallosal brains. Second, we provide a comprehensive review of the post-mortem and neuroimaging studies of the fronto-occipital connections published over the last two centuries, together with the first integral translation of Onufrowicz's original description of a human fronto-occipital fasciculus (1887) and Muratoff's report of the ‘subcallosal bundle’ in animals (1893).
Our tractography dissections suggest that in the human brain (i) the iFOF is a bilateral association pathway connecting ventro-medial occipital cortex to orbital and polar frontal cortex, (ii) the sFOF overlaps with branches of the superior longitudinal fasciculus (SLF) and probably represents an ‘occipital extension’ of the SLF, (iii) the subcallosal bundle of Muratoff is probably a complex tract encompassing ascending thalamo-frontal and descending fronto-caudate connections and is therefore a projection rather than an associative tract.
In conclusion, our experimental findings and review of the literature suggest that a ventral pathway in humans, namely the iFOF, mediates a direct communication between occipital and frontal lobes. Whether the iFOF represents a unique human pathway awaits further ad hoc investigations in animals.
OBJECTIVEThe purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia.
...METHODSThirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed.
RESULTSProcessing speed index (PSI) was lower in patients than controls by 9.34 points (95% confidence interval4.635–14.855, p = 0.0003). Full Scale IQ was lower by 4.14 scaled points (95% confidence interval−1.066 to 9.551, p = 0.1), but this difference was abolished when PSI was included as a covariate (p = 0.18). There were no differences in cognition between patients with and without silent cerebral infarction, and both groups had lower PSI than controls (both p < 0.001). In patients, arterial oxygen content, socioeconomic status, age, and male sex were identified as predictors of PSI, and correlations were found between PSI and DTI scalars (fractional anisotropy r = 0.614, p < 0.00001; r = −0.457, p < 0.00001; mean diffusivity r = −0.341, p = 0.0016; radial diffusivity r = −0.457, p < 0.00001) and NODDI parameters (intracellular volume fraction r = 0.364, p = 0.0007) in widespread regions.
CONCLUSIONOur results extend previous reports of impairment that is independent of presence of infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI.
Aim
Sickle cell disease (SCD) is the commonest cause of childhood stroke worldwide. Magnetic resonance imaging (MRI) is routinely used to detect additional silent cerebral infarction (SCI), as IQ is ...lower in SCI as well as stroke. This review assesses the effect of infarction on IQ, and specifically whether, compared to healthy controls, IQ differences are seen in children with SCI with no apparent MRI abnormality.
Method
A systematic review was conducted to include articles with an SCD paediatric population, MRI information, and Wechsler IQ. A meta‐analysis of 19 articles was performed to compare IQ in three groups: stroke vs SCI; SCI vs no SCI; and no SCI vs healthy controls.
Results
Mean differences in IQ between all three groups were significant: stroke patients had lower IQ than patients with SCI by 10 points (six studies); patients with SCI had lower IQ than no patients with SCI by 6 points (17 studies); and no patients with SCI had lower IQ than healthy controls by 7 points (seven studies).
Interpretation
Children with SCD and no apparent MRI abnormality have significantly lower IQ than healthy controls. In this chronic condition, other biological, socioeconomic, and environmental factors must play a significant role in cognition.
What this paper adds
Systematic review of all IQ studies using Wechsler scales in patients with silent cerebral infarction (SCI) with magnetic resonance imaging (MRI).
Meta‐analysis shows hierarchy for IQ by MRI status.
Critical appraisal of SCI lesion size quantification studies.
Critical appraisal of appropriate control comparison group.
Discussion of non‐radiological biological, socioeconomic, or environmental factors associated with lowered IQ.
Silent cerebral infarction (SCI) is the most commonly reported radiological abnormality in patients with sickle cell anemia (SCA) and is associated with future clinical stroke risk. To date, there ...have been few histological and quantitative MRI studies of SCI and multiple radiological definitions exist. As a result, the tissue characteristics and composition of SCI remain elusive. The objective of this work was therefore to investigate the composition of segmented SCI lesions using quantitative MRI for R
2
*
and quantitative magnetic susceptibility mapping (QSM). 211 SCI lesions were segmented from 32 participants with SCA and 6 controls. SCI were segmented according to two definitions (FLAIR+/–T1w-based threshold) using a semi-automated pipeline. Magnetic susceptibility (χ) and R
2
*
maps were calculated from a multi-echo gradient echo sequence and mean SCI values were compared to an equivalent region of interest in normal appearing white matter (NAWM). SCI χ and R
2
*
were investigated as a function of SCI definition, patient demographics, anatomical location, and cognition. Compared to NAWM, SCI were significantly less diamagnetic (χ = –0.0067 ppm vs. –0.0153 ppm,
p
< 0.001) and had significantly lower R
2
*
(16.7 s
−1
vs. 19.2 s
−1
,
p
< 0.001). SCI definition had a significant effect on the mean SCI χ and R
2
*
, with lesions becoming significantly less diamagnetic and having significantly lower R
2
*
after the application of a more stringent T1w-based threshold. SCI-NAWM R
2
*
decrease was significantly greater in patients with SCA compared with controls (–2.84 s
−1
vs. –0.64 s
−1
,
p
< 0.0001). No significant association was observed between mean SCI–NAWM χ or R2
*
differences and subject age, lesion anatomical location, or cognition. The increased χ and decreased R
2
*
in SCI relative to NAWM observed in both patients and controls is indicative of lower myelin or increased water content within the segmented lesions. The significant SCI–NAWM R
2
*
differences observed between SCI in patients with SCA and controls suggests there may be differences in tissue composition relative to NAWM in SCI in the two populations. Quantitative MRI techniques such as QSM and R
2
*
mapping can be used to enhance our understanding of the pathophysiology and composition of SCI in patients with SCA as well as controls.
University students in the United Kingdom are experiencing increasing levels of anxiety. A program designed to increase awareness of one's present levels of well-being and suggest personalized health ...behaviors may reduce anxiety and improve mental well-being in students. The efficacy of a digital version of such a program, providing biofeedback and therapeutic content based on personalized well-being metrics, is reported here.
The aim of this study was to test the efficacy and sustained effects of using a mobile app (BioBase) and paired wearable device (BioBeam), compared with a waitlist control group, on anxiety and well-being in university students with elevated levels of anxiety and stress.
The study employed a randomized, waitlist-controlled trial with assessments at baseline, 2 weeks, postintervention (4 weeks), and follow-up (6 weeks). Participants were eligible if they were current full-time undergraduate students and (1) at least 18 years of age, (2) scored >14 points on the Depression, Anxiety, and Stress Scale-21 items (DASS-21) stress subscale or >7 points on the DASS-21 anxiety subscale, (3) owned an iOS mobile phone, (4) did not have any previous psychiatric or neurological conditions, (6) were not pregnant at the time of testing, and (7) were able to read and understand English. Participants were encouraged to use BioBase daily and complete at least one course of therapeutic content. A P value ≤.05 was considered statistically significant.
We found that a 4-week intervention with the BioBase program significantly reduced anxiety and increased perceived well-being, with sustained effects at a 2-week follow-up. Furthermore, a significant reduction in depression levels was found following the 4-week usage of BioBase.
This study shows the efficacy of a biofeedback digital intervention in reducing self-reported anxiety and increasing perceived well-being in UK university students. Results suggest that digital mental health interventions could constitute a novel approach to treat stress and anxiety in students, which could be combined or integrated with existing therapeutic pathways.
Open Science Framework (OSF.io) 2zd45; https://osf.io/2zd45/.
It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive ...difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.
In recent years, interest has grown in the potential for magnetic resonance imaging (MRI) measures of venous oxygen saturation (Y
v
) to improve neurological risk prediction. T
2
...-relaxation-under-spin-tagging (TRUST) is an MRI technique which has revealed changes in Y
v
in patients with sickle cell anemia (SCA). However, prior studies comparing Y
v
in patients with SCA relative to healthy controls have reported opposing results depending on whether the calibration model, developed to convert blood T
2
to Y
v
, is based on healthy human hemoglobin (HbA), bovine hemoglobin (HbBV) or sickle hemoglobin (HbS). MRI Quantitative Susceptibility Mapping (QSM) is an alternative technique that may hold promise for estimating Y
v
in SCA as blood magnetic susceptibility is linearly dependent upon Y
v
, and no significant difference has been found between the magnetic susceptibility of HbA and HbS. Therefore, the aim of this study was to compare estimates of Y
v
using QSM and TRUST with five published calibration models in healthy controls and patients with SCA. 17 patients with SCA and 13 healthy controls underwent MRI. Susceptibility maps were calculated from a multi-parametric mapping acquisition and Y
v
was calculated from the mean susceptibility in a region of interest in the superior sagittal sinus. TRUST estimates of T
2,
within a similar but much smaller region, were converted to Y
v
using five different calibration models. Correlation and Bland-Altman analyses were performed to compare estimates of Y
v
between TRUST and QSM methods. For each method, t-tests were also used to explore group-wise differences between patients with SCA and healthy controls. In healthy controls, significant correlations were observed between QSM and TRUST measures of Y
v,
while in SCA, there were no such correlations. The magnitude and direction of group-wise differences in Y
v
varied with method. The TRUST-HbBV and QSM methods suggested decreased Y
v
in SCA relative to healthy controls, while the TRUST-HbS (
p
< 0.01) and TRUST-HbA models suggested increased Y
v
in SCA as in previous studies. Further validation of all MRI measures of Y
v
, relative to ground truth measures such as O
15
PET and jugular vein catheterization, is required in SCA before QSM or TRUST methods can be considered for neurological risk prediction.
Previous studies have pointed to a role for regional cerebral hemodynamic stress in neurological complications in patients with sickle cell anemia (SCA), with watershed regions identified as ...particularly at risk of ischemic tissue injury. Using single- and multi-inflow time (TI) arterial spin labeling sequences (ASL) in 94 patients with SCA and 42 controls, the present study sought to investigate cerebral blood flow (CBF) and bolus arrival times (BAT) across gray matter, white matter with early arrival times, and in individual watershed areas (iWSAs). In iWSAs, associations between hemodynamic parameters, lesion burden, white matter integrity, and general cognitive performance were also explored. In patients, increases in CBF and reductions in BAT were observed in association with reduced arterial oxygen content across gray matter and white matter with early arrival times using both sequences (all
< 0.001, d = -1.55--2.21). Across iWSAs, there was a discrepancy between sequences, with estimates based on the single-TI sequence indicating higher CBF in association with reduced arterial oxygen content in SCA patients, and estimates based on the multi-TI sequence indicating no significant between-group differences or associations with arterial oxygen content. Lesion burden was similar between white matter with early arrival times and iWSAs in both patients and controls, and using both sequences, only trend-level associations between iWSA CBF and iWSA lesion burden were observed in patients. Further, using the multi-TI sequence in patients, increased iWSA CBF was associated with reduced iWSA microstructural tissue integrity and slower processing speed. Taken together, the results highlight the need for researchers to consider BAT when estimating CBF using single-TI sequences. Moreover, the findings demonstrate the feasibility of multi-TI ASL for objective delineation of iWSAs and for detection of regional hemodynamic stress that is associated with reduced microstructural tissue integrity and slower processing speed. This technique may hold promise for future studies and treatment trials.
Summary
Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. ...This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n = 144; aged 5–20 years; 74 male) and sibling controls (n = 53; aged 5–17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n = 37), vasculopathy (n = 15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non‐SCA children may be vulnerable to contemporaneous anaemia.
The human brain changes structurally and functionally during adolescence, with associated alterations in cerebral perfusion. We performed dynamic arterial spin labeling (ASL) magnetic resonance ...imaging in healthy subjects between 8 and 32 years of age, to investigate changes in cerebral hemodynamics during normal development. In addition, an inversion recovery sequence allowed quantification of changes in longitudinal relaxation time (T1) and equilibrium longitudinal magnetization (M0). We present mean and reference ranges for normal values of T1, M0, cerebral blood flow (CBF), bolus arrival time, and bolus duration in cortical gray matter, to provide a tool for identifying age-matched perfusion abnormalities in this age range in clinical studies. Cerebral blood flow and T1 relaxation times were negatively correlated with age, without gender or hemisphere differences. The same was true for M0 anteriorly, but posteriorly, males but not females showed a significant decline in M0 with increasing age. Two examples of the clinical utility of these data in identifying age-matched perfusion abnormalities, in Sturge–Weber syndrome and sickle cell anemia, are illustrated.
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