Dynamics of the human structural connectome underlying working memory training

Brain region-specific changes have been demonstrated with a variety of cognitive training interventions. The effect of cognitive training on brain subnetworks in humans, however, remains largely unknown, with studies limited to functional networks. Here, we used a well-established working memory training program and state-of-the art neuroimaging methods in 40 healthy adults (21 females, mean age 26.5 years). Near and far-transfer training effects were assessed using computerized working memory and executive function tasks. Adaptive working memory training led to improvement on (non)trained working memory tasks and generalization to tasks of reasoning and inhibition. Graph theoretical analysis of the structural (white matter) network connectivity (“connectome”) revealed increased global integration within a frontoparietal attention network following adaptive working memory training compared with the nonadaptive group. Furthermore, the impact on the outcome of graph theoretical analyses of different white matter metrics to infer “connection strength” was evaluated. Increased efficiency of the frontoparietal network was best captured when using connection strengths derived from MR metrics that are thought to be more sensitive to differences in myelination (putatively indexed by the [quantitative] longitudinal relaxation rate, R1) than previously used diffusion MRI metrics (fractional anisotropy or fiber-tracking recovered streamlines). Our findings emphasize the critical role of specific microstructural markers in providing important hints toward the mechanisms underpinning training-induced plasticity that may drive working memory improvement in clinical populations

Longitudinal data on cortical thickness before and after working memory training

The data and supplementary information provided in this article relate to our research article “Task complexity and location specific changes of cortical thickness in executive and salience networks after working memory training.” [1]. We provide cortical thickness and subcortical volume data derived from parieto-frontal cortical regions and the basal ganglia with the FreeSurfer longitudinal analyses stream (http://surfer.nmr.mgh.harvard.edu [2]) before and after working memory training, “Cogmed and Cogmed Working Memory Training” [3]. This article also provides supplementary information to the research article, i.e., within-group comparisons between baseline and outcome cortical thickness and subcortical volume measures, between-group tests of performance changes in cognitive benchmark tests (www.cambridgebrainsciences.com[4]), correlation analyses between performance changes in benchmark tests and training-related structural changes, correlation analyses between the time spent training and structural changes, a scatterplot of the relationship between cortical thickness measures derived from the occipital lobe as control region and the chronological order of the MRI sessions to assess potential scanner drift effects and a post-hoc vertex-wise whole brain analysis with FreeSurfer Qdec (https://surfer.nmr.mgh.harvard.edu/fswiki/Qdec [5])

The effects of musical instrument training on fluid intelligence and executive functions in healthy older adults: A systematic review and meta-analysis

Intervention studies combining cognitive and motor demands have reported far-transfer cognitive benefits in healthy ageing. This systematic review and meta-analysis evaluated the effects of music and rhythm intervention on cognition in older adulthood. Inclusion criteria specified: 1) musical instrument training; 2) healthy, musically-naïve adults (≥60 years); 3) control group; 4) measure of executive function. Ovid, PubMed, Scopus and the Cochrane Library online databases were searched in August 2023. Data from thirteen studies were analysed (N = 502 participants). Study quality was assessed using the Cochrane Risk of Bias tool (RoB 2; Sterne et al., 2019). Random effects models revealed: a low effect on inhibition (d = 0.27, p = .0335); a low-moderate effect on switching (d = -0.39, p = .0021); a low-moderate effect on verbal category switching (d = 0.39, p = .0166); and a moderate effect on processing speed (d = 0.47, p < .0001). No effect was found for selective visual attention, working memory, or verbal memory. With regards to overall bias, three studies were rated as “high”, nine studies were rated as having “some concerns” and one was rated “low”. The meta-analysis suggests that learning to play a musical instrument enhances attention inhibition, switching and processing speed in ageing

Age-related fornix decline predicts conservative response strategy-based slowing in perceptual decision-making

Aging leads to response slowing but the underpinning cognitive and neural mechanisms remain elusive. We modelled older and younger adults’ response times (RT) from a flanker task with a diffusion drift model (DDM) and employed diffusion-weighted magnetic resonance imaging and spectroscopy to study neurobiological predictors of DDM components (drift-rate, boundary separation, non-decision time). Microstructural indices were derived from white matter pathways involved in visuo-perceptual and attention processing [optic radiation, inferior and superior longitudinal fasciculi (ILF, SLF), fornix]. Estimates of metabolite concentrations [N-acetyl aspartate (NAA), glutamate (Glx), and γ-aminobutyric acid (GABA), creatine (Cr), choline (Cho), myoinositol (mI)] were measured from occipital (OCC), anterior cingulate (ACC) and posterior parietal cortices (PPC). Age-related increases in RT, boundary separation, and non-decision time were observed with response conservatism acounting for RT slowing. Aging was associated with reductions in white matter microstructure (lower fractional anisotropy and restricted signal fraction, larger diffusivities) and in metabolites (NAA in ACC and PPC, Glx in ACC). Regression analyses identified brain regions involved in top-down (fornix, SLF, ACC, PPC) and bottom-up (ILF, optic radiation OCC) processing as predictors for DDM parameters and RT. Fornix FA was the strongest predictor for increases in boundary separation (beta = −0.8) and mediated the effects of age on RT. These findings demonstrate that response slowing in visual discrimination is driven by the adoption of a more conservative response strategy. Age-related fornix decline may result in noisier communication of contextual information from the hippocampus to anterior decision-making regions and thus contribute to the conservative response strategy shift

Age-related fornix decline predicts conservative response strategy-based slowing in perceptual decision-making

Aging leads to increased response latencies but the underpinning cognitive and neural mechanisms remain elusive. We modelled older and younger adults’ response time (RT) data from a 2-choice flanker task with a diffusion drift model (DDM) and employed multi-shell diffusion weighted magnetic resonance imaging and spectroscopy to study neurobiological predictors of DDM components thought to govern RTs: drift rate, boundary separation and non-decision time. Microstructural indices of fractional anisotropy (FA), diffusivities and the restricted signal fraction (FR) from the Composite Hindered and Restricted Model of Diffusion (CHARMED) were derived from white matter pathways of visuo-perceptual and attention networks (optic radiation, inferior and superior longitudinal fasciculi, fornix) and estimates of metabolite concentrations [N-acetyl aspartate (NAA), glutamate (Glx), γ-aminobutyric acid (GABA), creatine (Cr), choline (Cho) and myoinositol (mI)] were measured from occipital (OCC), anteri- or and posterior cingulate cortices (ACC, PPC). Ageing was associated with increased RT, boundary separation, and non-decision time. Differences in boundary separation but not non-decision time mediated age-related response slowing. Regression analyses revealed a network of brain regions involved in top-down (fornix FA, diffusivities in right SLF) and bottom-up processing (mI in OCC, AD in left optic radiation) and verbal intelligence as significant predictors of RTs and non-decision time (NAA in ACC, AD in the right ILF, creatine in the OCC) while fornix FA was the only predictor for boundary separation. Fornix FA mediated the effects of age on RTs but not vice versa. These results provide novel insights into the cognitive and neural underpinnings of age-related slowing

Association of imaging abnormalities of the subcallosal septal area with Alzheimer's disease and mild cognitive impairment

Aim: To evaluate the use the distance between the adjacent septal nuclei as a surrogate marker of septal area atrophy seen in Alzheimer's disease (AD). Materials & Methods: Interseptal distance (ISD) was measured, blind to clinical details, in 250 patients who underwent computed tomography (CT) of the brain at University Hospital of Wales. Clinical details including memory problem history were retrieved. An ISD cut-off value that discriminated those with and without memory symptoms was sought. ISD measurements were also made in 20 AD patients. To test both the method and the defined cut-off, measurements were then made in an independent cohort of 21 mild cognitive impairment (MCI) patients and 45 age-matched healthy controls, in a randomised and blinded fashion. Results: ISD measurement was achieved in all patients. In 28 patients with memory symptoms, the mean ISD was 5.9 mm compared with 2.3 mm in those without overt symptoms (p=0.001). The optimum ISD cut-off value was 4 mm (sensitivity 85.7% and specificity 85.8%). All AD patients had an ISD of >4 mm (mean ISD= 6.1 mm). The mean ISD for MCI patients was 3.84 mm compared with 2.18 mm in age-matched healthy controls (p=0.001). Using a 4 mm cut-off correctly categorised 10 mild cognitive impairment patients (47.6%) and 38 healthy controls (84.4%). Conclusion: ISD is a simple and reliable surrogate measurement for septal area atrophy, applicable to CT and magnetic resonance imaging (MRI). It can be used to help select patients for further investigation

A critical review of white matter changes in Huntington’s disease

Huntington’s disease is a genetic neurodegenerative disorder. White matter alterations have recently been identified as a relevant pathophysiological feature of Huntington’s disease, but their etiology and role in disease pathogenesis and progression remain unclear. Increasing evidence suggests that white matter changes in this disorder are due to alterations in myelin-associated biological processes. This review first discusses evidence from neurochemical studies lending support to the ‘De-myelination hypothesis’ of Huntington’s disease, and demonstrating aberrant myelination and changes in oligodendrocytes in the Huntington’s brain. Next, evidence from neuroimaging studies is reviewed, the limitations of the described methodologies are discussed, and suggested interpretations of findings from published studies are challenged. Although our understanding of Huntington’s associated pathological changes in the brain will increasingly rely on neuroimaging techniques, the shortcomings of these methodologies must not be forgotten. Advances in MRI techniques and tissue modeling will enable a better in vivo, longitudinal characterization of the biological properties of white matter microstructure. This, in turn, will facilitate identification of disease-related biomarkers and the specification of outcome measures in clinical trials

The cingulum bundle: anatomy, function, and dysfunction

The cingulum bundle is a prominent white matter tract that interconnects frontal, parietal, and medial temporal sites, while also linking subcortical nuclei to the cingulate gyrus. Despite its apparent continuity, the cingulum’s composition continually changes as fibres join and leave the bundle. To help understand its complex structure, this review begins with detailed, comparative descriptions of the multiple connections comprising the cingulum bundle. Next, the impact of cingulum bundle damage in rats, monkeys, and humans is analysed. Despite causing extensive anatomical disconnections, cingulum bundle lesions typically produce only mild deficits, highlighting the importance of parallel pathways and the distributed nature of its various functions. Meanwhile, non-invasive brain imaging implicates the cingulum bundle in executive control, emotion, pain (dorsal cingulum), and episodic memory (parahippocampal cingulum), while clinical studies reveal cingulum abnormalities in numerous conditions, including schizophrenia, depression, post-traumatic stress disorder, obsessive compulsive disorder, autism spectrum disorder, Mild Cognitive Impairment, and Alzheimer’s disease. Understanding the seemingly diverse contributions of the cingulum will require better ways of isolating pathways within this highly complex tract

Precommissural and postcommissural fornix microstructure in healthy aging and cognition

The fornix is a key tract of the hippocampal formation, whose status is presumed to contribute to age-related cognitive decline. The precommissural and postcommissural fornix subdivisions form respective basal forebrain/frontal and diencephalic networks that may differentially affect aging and cognition. We employed multi-parametric magnetic resonance imaging (MRI) including neurite orientation density and dispersion imaging, quantitative magnetization transfer (qMT), and T1-relaxometry MRI to investigate the microstructural properties of these fornix subdivisions and their relationship with aging and cognition in 149 asymptomatic participants (38–71 years). Aging was associated with increased free water signal and reductions in myelin-sensitive R1 and qMT indices but no apparent axon density differences in both precommissural and postcommissural fibers. Precommissural relative to postcommissural fibers showed a distinct microstructural pattern characterised by larger free water signal and axon orientation dispersion, with lower apparent myelin and axon density. Furthermore, differences in postcommissural microstructure were related to performance differences in object-location paired-associate learning. These results provide novel in vivo neuroimaging evidence for distinct microstructural properties of precommissural and postcommissural fibers that are consistent with their anatomy as found in axonal tracer studies, as well as for a contribution of postcommissural fibers to the learning of spatial configurations