HighlightsDetailed descriptions of connections comprising the cingulum bundle.Impact of cingulum bundle damage in rats, monkeys, and humans.Imaging evidence of cingulum abnormalities in multiple psychiatric conditions.Analyses of changing functions along the length of the cingulum.Contrasting effects of fornix and cingulum bundle damage on cognition.

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Human episodic memory is supported by networks of white matter tracts that connect frontal, temporal, and parietal regions. Degradation of white matter microstructure is increasingly recognized as a general mechanism of cognitive deterioration with aging. However, atrophy of gray matter regions also occurs and, to date, the potential role of specific white matter connections has been largely ignored. Changes to frontotemporal tracts may be important for the decline of episodic memory; while frontotemporal cooperation is known to be critical, the precise pathways of interaction are unknown. Diffusion-weighted MRI tractography was used to reconstruct three candidate fasciculi known to link components of memory networks: the fornix, the parahippocampal cingulum, and the uncinate fasciculus. Age-related changes in the microstructure of these tracts were investigated in 40 healthy older adults between the ages of 53 and 93 years. The relationships between aging, microstructure, and episodic memory were assessed for each individual tract. Age-related reductions of mean fractional anisotropy and/or increased mean diffusivity were found in all three tracts. However, age-related decline in recall was specifically associated with degradation of fornix microstructure, consistent with the view that this tract is important for episodic memory. In contrast, a decline in uncinate fasciculus microstructure was linked to impaired error monitoring in a visual object-location association task, echoing the effects of uncinate transection in monkeys. These results suggest that degradation of microstructure in the fornix and the uncinate fasciculus make critical but differential contributions to the mechanisms underlying age-related cognitive decline and subserve distinct components of memory.

Cognitive control, an important facet of human cognition, provides flexibility in response to varying behavioral demands. Previous work has focused on the role of prefrontal cortex, notably the anterior cingulate cortex. However, it is now clear that this is one node of a distributed cognitive network. In this emerging network view, structural connections are inherent elements, but their role has not been emphasized. Furthermore, lesion and functional imaging studies have contributed little knowledge about anatomical segregation, functional specialization, and behavioral importance of white matter connections. The relationship between cognitive control and microstructure of connections within the cingulum, a major white matter tract and conduit of projections to prefrontal sites, was probed in vivo in humans with diffusion MRI. Twenty healthy controls and 25 individuals with amnestic mild cognitive impairment (MCI), an early stage of age-associated cognitive deterioration, underwent cognitive testing, including several measures of cognitive control. For each individual, the anterior, middle, posterior, and parahippocampal portions of the cingulum bundle were reconstructed separately using deterministic tractography and anatomical landmarks. Microstructural variation in the left anterior cingulum was closely related to interindividual control based on verbal or symbolic rules. Errors in a task that involved maintenance of spatial rules were largely restricted to patients with MCI and were related, additionally, to right anterior cingulum microstructure. Cognitive control in MCI was also independently related to posterior parahippocampal connections. These results show how specific subpopulations of connections are critical in cognitive control and illustrate fine-grained anatomical specializations in the white matter infrastructure of this network.

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Objective: To examine the pattern of association between microstructure of temporal lobe connections and the breakdown of episodic memory that is a core feature of mild cognitive impairment (MCI).Methods: Twenty-five individuals with MCI and 20 matched controls underwent diffusion MRI and cognitive assessment. Three temporal pathways were reconstructed by tractography: fornix, parahippocampal cingulum (PHC), and uncinate fasciculus. Tissue volume fraction-a tract-specific measure of atrophy-and microstructural measures were derived for each tract. To test specificity of associations, a comparison tract (corticospinal tract) and control cognitive domains were also examined.Results: In MCI, tissue volume fraction was reduced in the fornix. Axial and radial diffusivity were increased in uncinate and PHC implying more subtle microstructural change. In controls, tissue volume fraction in the fornix was the predominant correlate of free recall. In contrast, in MCI, the strongest relationship was with left PHC. Microstructure of uncinate and PHC also correlated with recognition memory, and recognition confidence, in MCI.Conclusions: Episodic memory in MCI is related to the structure of multiple temporal association pathways. These associations are not confined to the fornix, as they are in healthy young and older adults. In MCI, because of a compromised fornix, alternative pathways may contribute disproportionally to episodic memory performance. Breakdown of episodic memory is a core feature of mild cognitive impairment (MCI).1 Previous studies of MCI have focused on changes in the medial temporal lobe (MTL). However, the MTL is one node of wider networks for memory that include frontal and parietal lobes.2 The "extended hippocampal system" 3 incorporates the fornix-a large fiber tract composed mostly of connections associated with the hippocampal formation. 4 Alternatively, MTL-cortical interactions can be mediated by parahippocampal tracts including the uncinate fasciculus and the temporal portion of the cingulum bundle (parahippocampal cingulum [PHC]).In healthy older adults, the microstructure of the fornix is an established correlate of episodic memory performance. Fornix microstructure accounts for both age-related and age-independent variations in free recall.5 Recent diffusion MRI studies have found that fornix microstructure is compromised in MCI and Alzheimer disease. 6,7 Early damage might lead to engagement of alternative interactions, 8 so that episodic memory becomes disproportionately associated with microstructure of tracts other than the fornix. To test this hypothesis, diffusion MRI tractography was used to reconstruct the fornix, PHC, and uncinate in MCI and controls. Intrinsic microstructure and subtle atrophy were quantified separately 9,10 dealing with an important confound in MCI and aging.

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, R 1 ) 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.

ObjectiveTo determine the differences in motor pathways and selected non-motor pathways of the basal ganglia in Parkinson’s disease (PD) patients compared to healthy controls (HCs).MethodsWe analysed diffusion weighted imaging data of 24 PD patients and 26 HCs. We performed deterministic tractography analysis using the spherical deconvolution-based damped Richardson-Lucy algorithm and subcortical volume analysis.ResultsWe found significantly increased fractional anisotropy (FA) in the motor pathways of PD patients: the bilateral corticospinal tract (right; corrected p = 0.0003, left; corrected p = 0.03), bilateral thalamus-motor cortex tract (right; corrected p = 0.02, left; corrected p = 0.004) and the right supplementary area-putamen tract (corrected p = 0.001). We also found significantly decreased FA in the right uncinate fasiculus (corrected p = 0.01) and no differences of FA in the bilateral supero-lateral medial forebrain bundles (p > 0.05) of PD patients compared to HCs. There were no subcortical volume differences (p > 0.05) between the PD patients and HCs.ConclusionThese results can inform biological models of neurodegeneration and neuroplasticity in PD. We suggest that increased FA values in the motor tracts in PD may reflect compensatory reorganization of neural circuits indicative of adaptive or extended neuroplasticity.Key points• Fractional anisotropy was higher in motor pathways of PD patients compared to healthy controls.• Fractional anisotropy was lower in the uncinate fasciculus of PD patients compared to healthy controls.• Increased fractional anisotropy could suggest adaptive neuroplasticity or selective neurodegeneration.Electronic supplementary materialThe online version of this article (doi:10.1007/s00330-015-4178-1) contains supplementary material, which is available to authorized users.