Agnes Flöel

In patients in the chronic phase after recurrent mild traumatic brain injury (mTBI), alterations in gamma-aminobutyric acid (GABA) concentration and receptor activity have been reported, possibly mediating subtle but persistent cognitive deficits and increased rate of dementia in older age. We evaluated whether anodal transcranial direct current stimulation (atDCS) over the primary motor cortex reduces GABA concentration and GABA _B receptor activity in patients with recurrent mTBI. Seventeen patients (mean age 25, two women) in the chronic phase after recurrent mTBI and 22 healthy control subjects (mean age 26, two women) were included. All participants received comprehensive cognitive testing and detailed questionnaires on post-concussive symptoms at baseline. Subsequently, they participated in four experimental sessions, consisting of either magnetic resonance spectroscopy (MRS)/atDCS/MRS, transcranial magnetic stimulation (TMS)/atDCS/TMS, MRS/sham/MRS, or TMS/sham/TMS to determine GABA concentration (from MRS) and GABA _B receptor activity (from TMS) after atDCS and after sham stimulation. Patients with mTBI scored significantly lower on verbal fluency tasks compared with healthy control subjects. GABA concentration at baseline was associated with the number of mTBI, although no group differences in GABA concentration and GABA _B receptor activity were found. Moreover, no effects of atDCS on GABA concentration and receptor activity were seen in patients with mTBI or healthy control subjects. GABA concentration may increase with the number of mTBI, but atDCS did not modulate GABA concentration and receptor activity, as has been reported previously. Specifics of experimental design and analysis, but also characteristics of the respective samples, may account for these differential findings, and should be addressed in future larger studies.

Alzheimer’s disease (AD) not only involves loss of memory functions but also prominent deterioration of sleep physiology, already evident in the stage of mild cognitive impairment (MCI). Cortical slow oscillations (SO, 0.5-1 Hz) and thalamo-cortical spindle activity (12-15 Hz) during sleep, and their temporal coordination, are considered critical for memory formation. We investigated the potential of slow oscillatory transcranial direct current stimulation (so-tDCS), applied during a daytime nap in a sleep state-dependent manner, to modulate these activity patterns and sleep-related memory consolidation in 16 patients with MCI. Stimulation significantly increased overall SO and spindle power, amplified spindle power during SO up-phases, and led to stronger synchronization between SO and spindle power fluctuations in electroencephalographic recordings. Moreover, visual declarative memory was improved by so-tDCS compared to sham stimulation, associated with stronger synchronization. These findings indicate a well-tolerated therapeutic approach for disordered sleep physiology and deficits in memory consolidation in MCI patients.

Sprachtherapie ist ein unverzichtbarer Baustein in der Rehabilitation aphasischer Störungen nach einem Schlaganfall. Vor dem Hintergrund der prognostizierten Zunahme von Aphasien und den limitierten Ressourcen des Gesundheitssystems ist die Entwicklung effizienter und nachhaltiger Behandlungsmethoden von herausragender Bedeutung. Die konsensbasierten Behandlungskonzepte sollten dabei ebenso wie innovative Verfahren im Sinne der evidenzbasierten Medizin hinsichtlich ihrer Wirksamkeit überprüft werden. Für die Rehabilitation subakuter und chronischer Aphasien konnte die Wirksamkeit hochfrequenter klassischer Sprachübungstherapie auf hoher Evidenzstufe nachgewiesen werden. Darüber hinausgehende neu entwickelte Therapiekonzepte beruhen meist auf kleineren Studien mit geringerer Evidenzstufe. Beispielhaft zu nennen sind hier das computerbasierte hochfrequente Benenntraining, videobasierte Übungen zur Verbalisierung komplexer Inhalte und die Therapie nach der „Forced-use“-Methode mit standardisierten Inhalten. Gleichzeitig werden Sprachtrainingsadjuvanzien zur Verstärkung der Therapieeffekte evaluiert; hier sind insbesondere die nichtinvasive Hirnstimulation und die pharmakologische Modulation zu nennen. Transkranielle Gleichstromstimulation zeigt in mehreren randomisierten kontrollierten Studien einen positiven Effekt bei Aphasien, aber die Auswahl der Patienten und die jeweils optimalen Stimulationsprotokolle bedürfen weiterer Erforschung. Auch für die Wirksamkeit medikamentöser Unterstützung des Sprachlernens gibt es Hinweise, doch auch hier sind vor einem breiten Einsatz weitere randomisierte und kontrollierte Studien mit größeren Fallzahlen notwendig.

Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology, publishing the highest quality original research and advancing our understanding of the brain and behavior.

Metabolic changes have been suggested to contribute to dementia and its precursor mild cognitive impairment (MCI), yet previous results particularly for the “satiety hormone” leptin are mixed. Therefore, we aimed to determine if MCI patients show systematic differences in leptin, independent of sex, adipose mass, age, and glucose and lipid metabolism, and whether leptin levels correlated with memory performance and hippocampal integrity. Forty MCI patients (20 females, aged 67 years ± 7 SD) were compared to 40 healthy controls (HC) that were pair‐wise matched for sex, age, and body fat. Memory performance was assessed using the auditory verbal learning test. Volume and microstructure of the hippocampus were determined using 3T‐neuroimaging. Fasting serum markers of leptin, glucose and lipid metabolism, and other confounding factors were assayed. MCI patients, compared with HC, showed lower serum leptin, independent of sex, age, and body fat (P < 0.001). Glucose and lipid markers did not attenuate these results. Moreover, MCI patients exhibited poorer memory and lower volume and microstructural integrity within hippocampal subfields. While leptin and memory were not significantly correlated, mediation analyses indicated that lower leptin contributed to poorer memory through its negative effect on right hippocampus volume and left hippocampus microstructure. We demonstrated that MCI is associated with lower serum leptin independent of sex, age, body fat, glucose, and lipid metabolism. Our data further suggest that inefficient leptin signaling could partly contribute to decreases in memory performance through changes in hippocampus structure, a hypothesis that should now be verified in longitudinal studies. Hum Brain Mapp 37:4539–4549, 2016. © 2016 Wiley Periodicals, Inc.

The corticomotor silent period (CSP), as assessed noninvasively by transcranial magnetic stimulation (TMS) in the primary motor cortex, has been found to reflect intracortical inhibitory mechanisms. Analysis of CSP is mostly conducted manually. However, this approach is time-consuming, and comparison of results from different laboratories may be compromised by inter-rater variability in analysis. No open source program for automated analysis is currently available. Here, we describe cross-validation with the manual analysis of an in-house written automated tool to assess CSP (cSPider). Results from automated routine were compared with results of the manual evaluation. We found high inter-method reliability between automated and manual analysis (pcSPider can be downloaded free of charge. cSPider allows automated analysis of CSP in a reliable and time-efficient manner. Use of this open-source tool may help to improve comparison of data from different laboratories.