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Tesfaye S.,Sheffield Teaching Hospitals | Boulton A.J.M.,University of Manchester | Dyck P.J.,Mayo Medical School | Freeman R.,Beth Israel Deaconess Medical Center | And 38 more authors.
Diabetes Care | Year: 2010

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs. © 2010 by the American Diabetes Association.


Avena-Koenigsberger A.,Indiana University Bloomington | Goni J.,Indiana University Bloomington | Betzel R.F.,Indiana University Bloomington | van den Heuvel M.P.,Rudolf Magnus Institute | And 4 more authors.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2014

Graph theory has provided a key mathematical framework to analyse the architecture of human brain networks. This architecture embodies an inherently complex relationship between connection topology, the spatial arrangement of network elements, and the resulting network cost and functional performance. An exploration of these interacting factors and driving forces may reveal salient network features that are critically important for shaping and constraining the brain's topological organization and its evolvability. Several studies have pointed to an economic balance between network cost and network efficiency with networks organized in an 'economical' small-world favouring high communication efficiency at a low wiring cost. In this study, we define and explore a network morphospace in order to characterize different aspects of communication efficiency in human brain networks. Using a multi-objective evolutionary approach that approximates a Pareto-optimal set within the morphospace, we investigate the capacity of anatomical brain networks to evolve towards topologies that exhibit optimal information processing features while preserving network cost. This approach allows us to investigate network topologies that emerge under specific selection pressures, thus providing some insight into the selectional forces that may have shaped the network architecture of existing human brains.


Fitzsimons C.P.,Leiden University | Fitzsimons C.P.,University of Amsterdam | Van Hooijdonk L.W.A.,Leiden University | Schouten M.,University of Amsterdam | And 16 more authors.
Molecular Psychiatry | Year: 2013

Glucocorticoids (GCs) secreted after stress reduce adult hippocampal neurogenesis, a process that has been implicated in cognitive aspects of psychopathology, amongst others. Yet, the exact role of the GC receptor (GR), a key mediator of GC action, in regulating adult neurogenesis is largely unknown. Here, we show that GR knockdown, selectively in newborn cells of the hippocampal neurogenic niche, accelerates their neuronal differentiation and migration. Strikingly, GR knockdown induced ectopic positioning of a subset of the new granule cells, altered their dendritic complexity and increased their number of mature dendritic spines and mossy fiber boutons. Consistent with the increase in synaptic contacts, cells with GR knockdown exhibit increased basal excitability parallel to impaired contextual freezing during fear conditioning. Together, our data demonstrate a key role for the GR in newborn hippocampal cells in mediating their synaptic connectivity and structural as well as functional integration into mature hippocampal circuits involved in fear memory consolidation. © 2013 Macmillan Publishers Limited.


Avena-Koenigsberger A.,Indiana University Bloomington | Goni J.,Indiana University Bloomington | Betzel R.F.,Indiana University Bloomington | van den Heuvel M.P.,Rudolf Magnus Institute | And 7 more authors.
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

Graph theory has provided a key mathematical framework to analyse the architecture of human brain networks. This architecture embodies an inherently complex relationship between connection topology, the spatial arrangement of network elements, and the resulting network cost and functional performance. An exploration of these interacting factors and driving forces may reveal salient network features that are critically important for shaping and constraining the brain's topological organization and its evolvability. Several studies have pointed to an economic balance between network cost and network efficiency with networks organized in an 'economical' small-world favouring high communication efficiency at a low wiring cost. In this study, we define and explore a network morphospace in order to characterize different aspects of communication efficiency in human brain networks. Using a multi-objective evolutionary approach that approximates a Paretooptimal set within the morphospace, we investigate the capacity of anatomical brain networks to evolve towards topologies that exhibit optimal information processing features while preserving network cost. This approach allows us to investigate network topologies that emerge under specific selection pressures, thus providing some insight into the selectional forces that may have shaped the network architecture of existing human brains. © 2014 The Authors.


Smeets T.,Maastricht University | Cornelisse S.,Rudolf Magnus Institute | Quaedflieg C.W.E.M.,Maastricht University | Meyer T.,Maastricht University | And 2 more authors.
Psychoneuroendocrinology | Year: 2012

Stress-related research has employed several procedures to activate the human stress system. Two of the most commonly used laboratory paradigms are the Trier Social Stress Test (TSST) and the Cold Pressor Test (CPT). We combined their most stressful features to create a simple laboratory stress test capable of eliciting strong autonomic and glucocorticoid stress responses. In comparison with the CPT and its variations, our stress tool (labeled the Maastricht Acute Stress Test; MAST) was found to yield superior salivary cortisol responses, while being equally effective in eliciting subjective stress reactions and (systolic and diastolic) blood pressure increases (study 1; N= 80). In study 2 (N= 20), we directly compared the effectiveness of the MAST and TSST and found that both methods elicited similar subjective, salivary alpha-amylase, and salivary cortisol stress responses. Finally, we developed and evaluated an appropriate no-stress control version of the MAST that was similar to the stress version, although it did not comprise stressful components (study 3; N= 40). Collectively, our results confirm the effectiveness of the MAST in terms of subjective, autonomic, and - most importantly - glucocorticoid stress responses. Thus, as a brief and simple stress protocol, the MAST holds considerable promise for future research. © 2012 Elsevier Ltd.


PubMed | University of Lausanne, Rudolf Magnus Institute and Indiana University Bloomington
Type: Journal Article | Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2014

Graph theory has provided a key mathematical framework to analyse the architecture of human brain networks. This architecture embodies an inherently complex relationship between connection topology, the spatial arrangement of network elements, and the resulting network cost and functional performance. An exploration of these interacting factors and driving forces may reveal salient network features that are critically important for shaping and constraining the brains topological organization and its evolvability. Several studies have pointed to an economic balance between network cost and network efficiency with networks organized in an economical small-world favouring high communication efficiency at a low wiring cost. In this study, we define and explore a network morphospace in order to characterize different aspects of communication efficiency in human brain networks. Using a multi-objective evolutionary approach that approximates a Pareto-optimal set within the morphospace, we investigate the capacity of anatomical brain networks to evolve towards topologies that exhibit optimal information processing features while preserving network cost. This approach allows us to investigate network topologies that emerge under specific selection pressures, thus providing some insight into the selectional forces that may have shaped the network architecture of existing human brains.


Dyck P.J.,Mayo Medical School | Albers J.W.,University of Michigan | Andersen H.,Aarhus University Hospital | Arezzo J.C.,Yeshiva University | And 6 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2011

Prior to a joint meeting of the Neurodiab Association and International Symposium on Diabetic Neuropathy held in Toronto, Ofntario, Canada, 13-18 October 2009, Solomon Tesfaye, Sheffield, UK, convened a panel of neuromuscular experts to provide an update on polyneuropathies associated with diabetes (Toronto Consensus Panels on DPNs, 2009). Herein, we provide definitions of typical and atypical diabetic polyneuropathies (DPNs), diagnostic criteria, and approaches to diagnose sensorimotor polyneuropathy as well as to estimate severity. Diabetic sensorimotor polyneuropathy (DSPN), or typical DPN, usually develops on long-standing hyperglycaemia, consequent metabolic derangements and microvessel alterations. It is frequently associated with microvessel retinal and kidney disease-but other causes must be excluded. By contrast, atypical DPNs are intercurrent painful and autonomic small-fibre polyneuropathies. Recognizing that there is a need to detect and estimate severity of DSPN validly and reproducibly, we define subclinical DSPN using nerve conduction criteria and define possible, probable, and confirmed clinical levels of DSPN. For conduct of epidemiologic surveys and randomized controlled trials, it is necessary to pre-specify which attributes of nerve conduction are to be used, the criterion for diagnosis, reference values, correction for applicable variables, and the specific criterion for DSPN. Herein, we provide the performance characteristics of several criteria for the diagnosis of sensorimotor polyneuropathy in healthy subject- and diabetic subject cohorts. Also outlined here are staged and continuous approaches to estimate severity of DSPN. © 2011 John Wiley & Sons, Ltd.


Donahue M.J.,University of Oxford | Donahue M.J.,Vanderbilt University | Hoogduin H.,University Utrecht | Hoogduin H.,Rudolf Magnus Institute | And 8 more authors.
Human Brain Mapping | Year: 2012

Synchrony measurements of spontaneous low-frequency blood oxygenation level-dependent (BOLD) fluctuations are increasingly being used to investigate spatial regions of functional connectivity. Although information regarding BOLD-BOLD synchrony between different regions is frequently reported, the relationship between spontaneous activity and behavioral state, and the association of spontaneous signal synchrony and evoked response, are less well characterized. The purpose of this study is to exploit the higher signal-to-noise ratio and in turn available spatial resolution at 7.0 T to understand the relationship between synchrony, measured as Pearson's R value, and amplitude, measured as signal standard deviation over time, in sensorimotor cortex for four separate behavioral states: eyes closed resting (EC), eyes open fixation (EO), EO with constant right hand fist clench (EO-F) and EO with 6 s off/6 s on (0.083 Hz) right hand finger tapping (EO-T). BOLD (TE/TR = 25/3,000 ms; 100 time points) scans were performed in healthy volunteers (7.0 T; 4 M/3 F; right-handed) at high spatial resolution = 1.6 × 1.6 × 1.6 mm 3. Results (z > 5; P < 0.05; low-pass filtering <0.067 Hz) reveal that synchrony is highest in the EC state (R = 0.35 ± 0.07) and reduces for EO (R = 0.26 ± 0.07), EO-F (R = 0.23 ± 0.07; P < 0.05), and EO-T (R = 0.12 ± 0.04; P < 0.05) conditions. Amplitude was highest in the EC condition and only reduced significantly (P < 0.05) for the EO-T condition. Synchrony within sensorimotor cortex correlated with evoked finger-tapping response magnitude (R = 0.81; P = 0.03), suggesting that spontaneous signal synchrony may be a predictor of evoked BOLD response magnitude and may account for intersubject variability in sensorimotor cortex. © 2011 Wiley Periodicals, Inc.


Houwink A.,Radboud University Nijmegen | Nijland R.H.,VU University Amsterdam | Geurts A.C.,Radboud University Nijmegen | Kwakkel G.,VU University Amsterdam | Kwakkel G.,Rudolf Magnus Institute
Archives of Physical Medicine and Rehabilitation | Year: 2013

Objective: To describe recovery of upper limb capacity after stroke during inpatient rehabilitation based on the Stroke Upper Limb Capacity Scale (SULCS). Design: Prospective observational study. Setting: Inpatient department of a rehabilitation center. Participants: Patients with stroke (N=299) admitted to a specialized stroke rehabilitation center. Intervention: Not applicable. Main Outcome Measures: Upper limb capacity was assessed at the start and end of the rehabilitation phase with the SULCS (range, 0-10). The following demographic and clinical characteristics were registered: age, sex, side of stroke, stroke type, time since stroke, and length of stay in the rehabilitation center. Results: On admission, 125 patients had no hand capacity (SULCS score, 0-3), 58 had basic hand capacity (SULCS score, 4-7), and 116 had advanced hand capacity (SULCS score, 8-10). Of the patients without initial hand capacity, 41% regained some hand capacity (SULCS score, ≥4) at discharge. Of these, patients with SULCS scores of 2 and 3 had 29 and 97 times greater chance of regaining some hand capacity compared with patients with an initial SULCS score of 0, respectively. Of the patients with initial basic hand capacity, 78% regained advanced hand capacity at discharge. The SULCS score on admission explained 51% of the SULCS score variance at discharge, while time since stroke was negatively associated with upper limb recovery, explaining an additional 7% of the SULCS score variance at discharge. Conclusions: Even patients with minimal proximal shoulder and elbow control of the upper paretic limb on admission in a rehabilitation center have a fair chance of regaining some hand capacity in the long-term after stroke, whereas patients without such proximal arm control have a much poorer prognosis for regaining hand capacity.


van Hasselt F.N.,University of Amsterdam | de Visser L.,Rudolf Magnus Institute | Tieskens J.M.,University of Amsterdam | Cornelisse S.,Rudolf Magnus Institute | And 5 more authors.
PLoS ONE | Year: 2012

Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology-e.g. depression, anxiety and schizophrenia- later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures. © 2012 van Hasselt et al.

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