Feed-Forward-Only Training of Neural Networks

While artificial neural networks have reached immense advances over the last decade, the underlying approach to training neural networks, that is, solving the credit assignment problem by computing gradients with back-propagation, has remained largely the same. Nonetheless, back-propagation has long been criticized for being biologically implausible as it relies on concepts that are not viable in the brain. With delayed error forward projection (DEFP), I introduce a feed-forward-only training algorithm that solves two core issues for biological plausibility: the weight transport and the update locking problem. It is based on the similarly plausible direct random target projection algorithm but improves the approximated gradients by using delayed error information as a sample-wise scaling factor in place of the targets. By evaluating delayed error forward projection on image classification with fully-connected and convolutional neural networks, I find that it can achieve higher accuracy than direct random target projection, especially for fully- connected networks. Interestingly, scaling the updates with the error yields significantly better results than scaling with the gradient of the loss for all networks and datasets. In total, delayed error forward projection demonstrates the applicability of feed-forward-only training algorithms. This offers exciting new possibilities for both in-the-loop training on neuromorphic devices and pipelined parallelization

Begegnung mit dem Schönen – Die Sammlung Groß: Eine Ausstellungsbeschreibung

Im April 2006 ist die „Begegnung mit dem Schönen - Die Sammlung Groß“ als Teil der neuen Dauerausstellung auf Burg Gnandstein in Räumen des Südflügels eröffnet worden. Sie zeigt ausgewählte Stücke aus dem Kunstbesitz der Erlanger Familie Groß. Als „Sammlung Groß“ ist dieser 2004 im Rahmen einer Schenkung in die Bestände der Burg Gnandstein übereignet worden

Feed-Forward Optimization With Delayed Feedback for Neural Networks

Backpropagation has long been criticized for being biologically implausible, relying on concepts that are not viable in natural learning processes. This paper proposes an alternative approach to solve two core issues, i.e., weight transport and update locking, for biological plausibility and computational efficiency. We introduce Feed-Forward with delayed Feedback (F$^3$), which improves upon prior work by utilizing delayed error information as a sample-wise scaling factor to approximate gradients more accurately. We find that F$^3$ reduces the gap in predictive performance between biologically plausible training algorithms and backpropagation by up to 96%. This demonstrates the applicability of biologically plausible training and opens up promising new avenues for low-energy training and parallelization

Acute Beneficial Hemodynamic Effects of a Novel 3D-Echocardiographic Optimization Protocol in Cardiac Resynchronization Therapy

Post-implantation therapies to optimize cardiac resynchronization therapy (CRT) focus on adjustments of the atrio-ventricular (AV) delay and ventricular-to-ventricular (VV) interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized optimization of device based AV delays and VV intervals compared to empiric programming.25 recipients of CRT (male: 56%, mean age: 67 years) were included in this study. Ejection fraction (EF), the primary outcome parameter, and left ventricular (LV) dimensions were evaluated by 3DE before CRT (baseline), after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming) and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI) was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI), calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation), and the VV interval with the lowest SDI was programmed (individualized optimization).EF increased from baseline 23±7% to 30±8 (p<0.001) after AV delay optimization and to 32±8% (p<0.05) after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001). Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001).Compared with empiric programming of biventricular pacemakers, individualized echocardiographic optimization with the integration of 3-dimensional indices into the optimization protocol acutely improved LV systolic function and decreased ESV and can be used to select the optimal AV delay and VV interval in CRT

Begegnung mit dem Schönen – Die Sammlung Groß: Eine Ausstellungsbeschreibung

Im April 2006 ist die „Begegnung mit dem Schönen - Die Sammlung Groß“ als Teil der neuen Dauerausstellung auf Burg Gnandstein in Räumen des Südflügels eröffnet worden. Sie zeigt ausgewählte Stücke aus dem Kunstbesitz der Erlanger Familie Groß. Als „Sammlung Groß“ ist dieser 2004 im Rahmen einer Schenkung in die Bestände der Burg Gnandstein übereignet worden

Begegnung mit dem Schönen – Die Sammlung Groß: Eine Ausstellungsbeschreibung

Im April 2006 ist die „Begegnung mit dem Schönen - Die Sammlung Groß“ als Teil der neuen Dauerausstellung auf Burg Gnandstein in Räumen des Südflügels eröffnet worden. Sie zeigt ausgewählte Stücke aus dem Kunstbesitz der Erlanger Familie Groß. Als „Sammlung Groß“ ist dieser 2004 im Rahmen einer Schenkung in die Bestände der Burg Gnandstein übereignet worden

Correlation of ventricular diameter and cognitive dysfunction in patients with idiopathic Parkinson´s Disease – comparison of transcranial sonography and MRI

Hintergrund: Im Verlauf der Parkinson-Krankheit (IPS) entwickeln ca. 30% der Patienten eine Demenz, was neue Herausforderungen an Diagnostik und Therapie stellt. In mehreren Studien konnte bereits bei Multipler Sklerose oder HIV-Patienten ein Zusammenhang zwischen Ventrikelweite als Marker der Hirnatrophie und kognitiven Parametern gezeigt werden. Zielsetzung: Das Ziel dieser Studie war es zu ermitteln, ob der Ventrikeldurchmesser gemessen durch TCS und MR-Bildgebung einen Marker für Hirnatrophie bei IPS darstellt und ob eine Korrelation zur Erkrankungsschwere und kognitiver Funktion besteht. Methodik: In dieser Studie wurden 108 IPS Patienten (64% männlich, 36% weiblich, durchschnittliches Alter: 63,64 (± 8.24 Jahre (J)) und 39 Kontrollprobanden (36% männlich, 64% weiblich; durchschnittliches Alter: 51,7 (± 15.6 J) einer transkraniellen Ultraschalldiagnostik sowie einer MRT-Untersuchung (T1,T2) unterzogen. Mit beiden Methoden wurde der transversale Durchmesser des 3. Ventrikels (3V) sowie des linken und rechten Seitenventrikels (liSV, reSV) vermessen. Zudem wurden neurologische Untersuchung, standardisierte motorische (UPDRS, Webster) sowie kognitive Funktionstests (MMST, PANDA, ZVT) durchgeführt. In einem 5-Jahres-Follow-Up wurden insgesamt 30 Probanden erneut untersucht. Resultate: Die B-Bild-sonographische Ventrikelmessung korrelierten mit der MRT Messung (Spearman rank Korrelation, 3V r= 0.8, liSV r= 0.4; p< .01, reSV r= 0.2; p<0.05). Die Interobserver-Realibilität war signifikant. In der IPS-Gruppe betrug die Weite des 3. Ventrikels 0.54 (± 0,02 cm), die des Seitenventrikelvorderhorns 1.49 ± 0.36 cm. Ein signifikanter Unterschied zwischen Ventrikelweite der IPS-Gruppe und der Kontrollgruppe zeigte sich nicht (F (1.12)= 5.5; p< .05). Eine wichtige Einflußgröße auf die Ventrikelweite war das Alter (3V: r= 0.49; p< 0.01; reSV: r= 0.389; p< 0.01; liSV: r=0.421; p< 0.01). TCS- und MRT-Daten korrelierten überwiegend mit kognitiven Parametern: MMST (3V: r= -0.3; p= n.s.; liSV: r= -0.5; p< 0,01; reSV: r= -0.5; p< .05), PANDA-Test (3V: Spearman-Rho -0.457; p< .05; liSV: Spearman-Rho -0.417; p< 0,05; reSV: Spearman-Rho -0.261; p= n.s.). Zwischen motorisch-funktionellen Testparametern und der Ventrikelweite ergab sich kein Zusammenhang. Im Follow-Up nach 5 Jahren zeigten beide Gruppen eine signifikante Zunahme der Seitenventrikeldurchmesser (re+liSV p< 0.0005), in der IPS-Gruppe betont (reSV: p= 0.28; liSV: p= 0.01). Beim IPS zeigte sich vergleichbar mit den Daten bei MS oder HIV eine Korrelation zwischen kognitiver Funktion und der Ventrikelweite. Schlussfolgerung: Zusammenfassend steht mit der TCS eine schnelle, kostengünstige und reliable Methodik zur Messung der Ventrikelweite als Surrogatmarker der Hirnatrophie zur Verfügung, die beim IPS vor allem eine Assoziation mit Alter und Kognitionsparametern aufweist. Welchen Stellenwert die TCS in der Beurteilung einer kognitiven Dysfunktion bei IPS einnehmen kann, bleibt weiterführenden Studien überlassen.Background: During idiopathic Parkinson´s disease (IPD) 30% of these patients are developing a dementia and represents new challenges in medical diagnosis and therapy. In several studies there was shown a correlation of ventricular diameter as a marker of brain atrophy and cognitive parameter in multiple sclerosis or in HIV-patients. Objective: The aim of this study was to evaluate if ventricular diameter measured by TCS and MR-imaging is a marker of brain atrophy and if it is correlated with severity of disease and cognitive dysfunction. Methods: In this study 108 PD patients (64% male, 36% female; mean age: 63,64 (± 8,24 years (yrs)) and 39 controls (36% male, 64% female; mean age: 51.7 (± 15,6yrs)) underwent a T1/T2-weighted MR Imaging and TCS. The transverse diameter of the third ventricle (3v) and the frontal horns of right (rv) and left (lv) lateral ventricles were measured. Furthermore, neurological examinations, standardized motor functional (UPDRS, Webster) and cognitive (MMST, PANDA, ZVT) testings were performed. 30 probands were followed up after 5 yrs. Results: The transcranial sonographic measurement of ventricular diameter showed a significant correlation with the MRI measurement (Spearman rank correlation, 3v r=0.8, lv r= 0.4; p< .01, rv r= 0.2; p< .05). The interobserver reliability was significant. In the PD-group the diameter of the third ventricle was 0.54 (± 0.02 cm) and of the lateral ventricles 1.49 (± 0.36 cm). Neither the IPD patients nor the control group influenced the ventricular diameter for the transcranial sonographic or MR measurement, except for the left ventricle in TCS (F (1.12)= 5.5; p< .05). Another important influencing factor of the ventricular diameter was age (3v: r 0.49; p< 0.01; rv: r 0.389; p< 0.01; lv: r 0.421; p< 0.01). Above all, MRI and TCS data were correlated significantly with cognitive tests: MMST (3v: r -0.3; p= n.s.; lv: r -0.5; p< 0.01; rv: r -0.5; p< 0.05), PANDA-Test (3v: Spearman-Rho -0.457; p< 0.05; lv: Spearman-Rho -0.417; p< 0.05; re SV: Spearman-Rho -0.261; p= n.s.). For testing of motor function and ventricular diameter there was no significant correlation. The 5-years-Follow-up both groups showed a significant increase of the lateral ventricular diameter (rv+lv p< 0.0005) especially the PD-group (rv: p= 0.28; lv: p= 0.01). To sum it up, PD-data are comparable with MS and HIV-data concerning the correlation of cognitive function and ventricular diameter. Conclusions: Our results suggest that the measurements of ventricular diameters are a quick, low priced and simple method that should be used in routine clinical practise and indicates a marker of brain atrophy. Especially in Parkinson´s disease there was found an association between age and cognitive parameters. As ventricular diameter is related to cognitive dysfunction it is indicated for follow-up examinations in patients with IPD

Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation

Background: MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome. Case presentation: We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.Gly225Aspfs*56 in exon 4 of the MEN1 gene. Diagnosis and clinical phenotyping of MEN1 was established by laboratory tests, ultrasound, biopsy, MRI imaging and endosonography. The clinical course of the disease was followed in the index patient and her family members for eight years. The mutation was associated with distinct clinical phenotypes in the index patient and three family members harboring p.Gly225Aspfs*56. Family members affected showed primary hyperparathyroidism but variable patterns of associated endocrine tumors, adrenal cortical adenomas, prolactinoma, multifocal pancreatic neuroendocrine tumors, insulinoma and nonsecretory neuroendocrine tumors of the pancreas. The mutation c.674delG; p.Gly225Aspfs*56 leads to a frameshift from codon 225 with early truncation of the menin protein. In silico analysis predicts loss of multiple protein-menin interactions in p.Gly225Aspfs*56, potentially rendering menin insufficient to control cell division and replication. However, no aggressive neuroendocrine tumors were observed in the follow-up of this family. Conclusions: We report a novel heterozygous MEN1 frameshift mutation, potentially causing (at least partial) inactivation of menin tumor suppression potential but lacking a genotype–phenotype correlation. Our study highlights the importance of personalized care with appropriate testing and counseling in MEN1 families