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      Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma


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          Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown.


          To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP.


          A cross-sectional study with a median follow-up time of 22 (6–49) years after operation.


          The South Medical Region of Sweden (2.5 million inhabitants).


          Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958–2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients.

          Main outcome measures

          Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry.


          Right uncinate fasciculus was significantly altered ( P ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26–38% of the variation, and with visuospatial ability and executive function, explaining 19–29%. Patients who had smaller hippocampal volume had worse general knowledge ( P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory.


          A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.

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          Most cited references24

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          Interplay of hippocampus and prefrontal cortex in memory.

          Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Multiple anatomical systems embedded within the primate medial temporal lobe: implications for hippocampal function.

            A review of medial temporal lobe connections reveals three distinct groupings of hippocampal efferents. These efferent systems and their putative memory functions are: (1) The 'extended-hippocampal system' for episodic memory, which involves the anterior thalamic nuclei, mammillary bodies and retrosplenial cortex, originates in the subicular cortices, and has a largely laminar organisation; (2) The 'rostral hippocampal system' for affective and social learning, which involves prefrontal cortex, amygdala and nucleus accumbens, has a columnar organisation, and originates from rostral CA1 and subiculum; (3) The 'reciprocal hippocampal-parahippocampal system' for sensory processing and integration, which originates from the length of CA1 and the subiculum, and is characterised by columnar, connections with reciprocal topographies. A fourth system, the 'parahippocampal-prefrontal system' that supports familiarity signalling and retrieval processing, has more widespread prefrontal connections than those of the hippocampus, along with different thalamic inputs. Despite many interactions between these four systems, they may retain different roles in memory which when combined explain the importance of the medial temporal lobe for the formation of declarative memories. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Frontotemporal connections in episodic memory and aging: a diffusion MRI tractography study.

              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.

                Author and article information

                Eur J Endocrinol
                Eur. J. Endocrinol
                European Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                June 2018
                16 March 2018
                : 178
                : 6
                : 577-587
                [1 ]Department of Endocrinology Skåne University Hospital, Lund, Sweden
                [2 ]Department of Diagnostic Radiology Clinical Sciences
                [3 ]Division of Occupational and Environmental Medicine Department of Experimental Medical Science, Lund University, Lund, Sweden
                [4 ]Translational Neuroendocrine Research Unit Department of Experimental Medical Science, Lund University, Lund, Sweden
                [5 ]Department of Medical Imaging and Physiology Skåne University Hospital, Lund, Sweden
                [6 ]Department of Endocrinology and Medical and Health Sciences Linköping University, Linköping, Sweden
                [7 ]Department of Psychology and Psychiatry Skåne University Hospital, Lund, Sweden
                Author notes
                Correspondence should be addressed to E M Erfurth; Email: Eva_Marie.Erfurth@ 123456med.lu.se
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                : 30 January 2018
                : 28 March 2018
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes


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