Journal of Neural Transmission

Transcranial magnetic stimulation (TMS) was introduced as a non-invasive tool for the investigation of the motor cortex. The repetitive application (rTMS), causing longer lasting effects, was used to study the influence on a variety of cerebral functions. High-frequency (>1 Hz) rTMS is known to depolarize neurons under the stimulating coil and to indirectly affect areas being connected and related to emotion and behavior. Researchers found selective cognitive improvement after high-frequency (HF) stimulation specifically over the left dorsolateral prefrontal cortex (DLPFC). This article provides a systematic review of HF-rTMS studies (1999–2009) stimulating over the prefrontal cortex of patients suffering from psychiatric/neurological diseases or healthy volunteers, where the effects on cognitive functions were measured. The cognitive effect was analyzed with regard to the impact of clinical status (patients/healthy volunteers) and stimulation type (verum/sham). RTMS at 10, 15 or 20 Hz, applied over the left DLPFC, within a range of 10–15 successive sessions and an individual motor threshold of 80–110%, is most likely to cause significant cognitive improvement. In comparison, patients tend to reach a greater improvement than healthy participants. Limitations concern the absence of healthy groups in clinical studies and partly the absence of sham groups. Thus, future investigations are needed to assess cognitive rTMS effects in different psychiatric disorders versus healthy subjects using an extended standardized neuropsychological test battery. Since the pathophysiological and neurobiological basis of cognitive improvement with rTMS remains unclear, additional studies including genetics, experimental neurophysiology and functional brain imaging are necessary to explore stimulation-related functional changes in the brain.

The study of neurophysiological approaches together with rare and common risk factors for Autism Spectrum Disorder (ASD) allows elucidating the specific underlying neurobiology of ASD. Whereas most neurophysiologically based research in ASD to date has focussed on case–control differences based on the DSM- or ICD-based categorical ASD diagnosis, more recent studies have aimed at studying genetically and/or neurophysiologically defined homogeneous ASD subgroups for specific neuronal biomarkers. This review addresses the neurophysiological investigation of ASD by evoked and event-related potentials, by EEG/MEG connectivity measures such as coherence, and transcranial magnetic stimulation. As an example of classical neurophysiological studies in ASD, we report event-related potential studies which have illustrated which brain areas and processing stages are affected in the visual perception of socially relevant stimuli. However, a paradigm shift has taken place in recent years focussing on how these findings can be tracked down to basic neuronal functions such as deficits in cortico-cortical connectivity and the interaction between brain areas. Disconnectivity, for example, can again be related to genetically induced shifts in the excitation/inhibition balance. Genetic causes of ASD may be grouped by their effects on the brain’s system level to identify ASD subgroups which respond differentially to therapeutic interventions.

The purpose of this study was to assess the influence of age on thalamic deep brain stimulation (DBS) in essential tremor (ET). Tremor, cognition, mood and adverse events in patients with thalamic DBS for ET were evaluated in 26 consecutive patients with established standardized methods for tremor and cognition. Twelve patients <70 and 14 patients ≥70 years were included and followed for 2 years. Clinical outcomes did not differ significantly. DBS seems to be safe and effective for ET independent of age.

Recent large genome-wide association studies have found variants in TMEM106B (top SNP rs1990622) as a strong risk factor for frontotemporal lobar degeneration. Moreover, the TMEM106B risk variant is also implicated in the pathologic presentation of Alzheimer’s disease (AD). Here, we evaluated the association between TMEM106B rs1990622 polymorphism and late-onset AD (LOAD) in a Northern Han Chinese population consists of 1,133 LOAD patients and 1,159 controls. Our data demonstrate that TMEM106B and APOE interact to increase AD risk.

Recently a significant association of a missense mutation (Glu298Asp) of the endothelial nitric oxide synthase (NOS3) gene with late-onset Alzheimer's disease (LOAD) was reported. We tried to replicate this finding in a Japanese sample of 121 patients with LOAD, 51 with early-onset AD (EOAD), and 165 medical controls. However, the genotype and allelic distributions for the Glu298Asp polymorphism were similar for these three groups, suggesting that the Glu298Asp polymorphism of the NOS3 gene has no relevance to the development of AD in Japanese.

The brain is built with hemispheric asymmetries in structure and function to enable fast neuronal processing. In neuroimaging studies, several mental disorders have been associated with altered or attenuated hemispheric asymmetries. However, the exact mechanism linking asymmetries and disorders is not known. Here, studies in animal models of mental disorders render important insights into the etiology and neuronal alterations associated with both disorders and atypical asymmetry. In this review, the current literature of animal studies in rats and mice focusing on anxiety and fear, anhedonia and despair, addiction or substance misuse, neurodegenerative disorders as well as stress exposure, and atypical hemispheric asymmetries is summarized. Results indicate overall increased right-hemispheric neuronal activity and a left-sided behavioral bias associated with symptoms of anxiety, fear, anhedonia, behavioral despair as well as stress exposure. Addiction behavior is associated with right-sided bias and transgenic models of Alzheimer’s disease indicate an asymmetrical accumulation of fibrillar plaques. Most studies focused on changes in the bilateral amygdala and frontal cortex. Across studies, two crucial factors influencing atypical asymmetries arose independently of the disorder modeled: sex and developmental age. In conclusion, animal models of mental disorders demonstrate atypical hemispheric asymmetries similar to findings in patients. Particularly, increased left-sided behavior and greater right-hemispheric activity were found across models applying stress-based paradigms. However, sex- and age-dependent effects on atypical hemispheric asymmetries are present that require further investigation. Animal models enable the analysis of hemispheric changes on the molecular level which may be most effective to detect early alterations.

Effect of short (SP: 10 L: 14 D: Light: Dark) and long (LP: 14 L: 10 D) photoperiod was tested on pineal-thyroid axis in a tropical seasonally breeding rodentF. pennanti during sexually regressive phase of reproduction. SP reduced thyroid weight and plasma thyroxine (T4) as well as increased melatonin (aMT) while pinealectomy (Px) prevented such an effect of SP. LP and Px plus LP had no significant effect on thyroid activity when compared with their respective controls. These results suggest that SP stimulated pineal activity which increased the concentration of aMT, hence inhibited thyroid gland activity. However, the plasma aMT concentration under LP regime had no significant difference from controls, as the ambient photoperiodic length (13.6 hr) was almost similar to the experimental one (14.0 hr). It is suggested that being innervated from the same ganglion (SCG) which conveys photic stimuli to the pineal gland, the thyroid gland like the pineal is also under the influence of photoperiodic responses. Further pineal/melatonin also influences thyroid function indirectly.