Search

Understanding cerebellar alterations due to healthy aging provides a reference point against which pathological findings in late-onset disease, for example spinocerebellar ataxia type 6 (SCA6), can be contrasted. In the present study, we investigated the impact of aging on the cerebellar nuclei and cerebellar cortex in 109 healthy controls (age range: 16 – 78 years) using 3 Tesla magnetic resonance imaging (MRI). Findings were compared with 25 SCA6 patients (age range: 38 – 78 years). A subset of 16 SCA6 (included: 14) patients and 50 controls (included: 45) received an additional MRI scan at 7 Tesla and were re-scanned after one year. MRI included T1-weighted, T2-weighted FLAIR, and multi-echo T2*-weighted imaging. The T2*-weighted phase images were converted to quantitative susceptibility maps (QSM). Since the cerebellar nuclei are characterized by elevated iron content with respect to their surroundings, two independent raters manually outlined them on the susceptibility maps. T1-weighted images acquired at 3T were utilized to automatically identify the cerebellar gray matter (GM) volume. Linear correlations revealed significant atrophy of the cerebellum due to tissue loss of cerebellar cortical GM in healthy controls with increasing age. Reduction of the cerebellar GM was substantially stronger in SCA6 patients. The volume of the dentate nuclei did not exhibit a significant relationship with age, at least in the age range between 18 and 78 years, whereas mean susceptibilities of the dentate nuclei increased with age. As previously shown, the dentate nuclei volumes were smaller and magnetic susceptibilities were lower in SCA6 patients compared to age- and sex-matched controls. The significant dentate volume loss in SCA6 patients could also be confirmed with 7T MRI. Linear mixed effects models and individual paired t-tests accounting for multiple comparisons revealed no statistical significant change in volume and susceptibility of the dentate nuclei after one year in neither patients nor controls. Importantly, dentate volumes were more sensitive to differentiate between SCA6 (Cohen's d = 3.02) and matched controls than the cerebellar cortex volume (d = 2.04). In addition to age-related decline of the cerebellar cortex and atrophy in SCA6 patients, age-related increase of susceptibility of the dentate nuclei was found in controls, whereas dentate volume and susceptibility was significantly decreased in SCA6 patients. Because no significant changes of any of these parameters was found at follow-up, these measures do not allow to monitor disease progression at short intervals.

Multiple studies have reported a significant dependence of the effective transverse relaxation rate constant (R2*) and the phase of gradient-echo based (GRE) signal on the orientation of white matter fibres in the human brain. It has also been hypothesized that magnetic susceptibility, as obtained by single-orientation quantitative susceptibility mapping (QSM), exhibits such a dependence. In this study, we investigated this hypothesized relationship in a cohort of healthy volunteers. We show that R2* follows the predicted orientation dependence consistently across white matter regions, whereas the apparent magnetic susceptibility is related differently to fibre orientation across the brain and often in a complex non-monotonic manner. In addition, we explored the effect of fractional anisotropy measured by diffusion-weighted MRI on the strength of the orientation dependence and observed only a limited influence in many regions. However, with careful consideration of such an impact and the limitations imposed by the ill-posed nature of the dipole inversion process, it is possible to study magnetic susceptibility anisotropy in specific brain regions with a single orientation acquisition.

Transcranial alternating current stimulation (tACS) can non-invasively modulate neuronal activity in the cerebral cortex, in particular at the frequency of the applied stimulation. Such modulation can matter for speech processing, since the latter involves the tracking of slow amplitude fluctuations in speech by cortical activity. tACS with a current signal that follows the envelope of a speech stimulus has indeed been found to influence the cortical tracking and to modulate the comprehension of the speech in background noise. However, how exactly tACS influences the speech-related cortical activity, and how it causes the observed effects on speech comprehension, remains poorly understood. A computational model for cortical speech processing in a biophysically plausible spiking neural network has recently been proposed. Here we extended the model to investigate the effects of different types of stimulation waveforms, similar to those previously applied in experimental studies, on the processing of speech in noise. We assessed in particular how well speech could be decoded from the neural network activity when paired with the exogenous stimulation. We found that, in the absence of current stimulation, the speech-in-noise decoding accuracy was comparable to the comprehension of speech in background noise of human listeners. We further found that current stimulation could alter the speech decoding accuracy by a few percent, comparable to the effects of tACS on speech-in-noise comprehension. Our simulations further allowed us to identify the parameters for the stimulation waveforms that yielded the largest enhancement of speech-in-noise encoding. Our model thereby provides insight into the potential neural mechanisms by which weak alternating current stimulation may influence speech comprehension and allows to screen a large range of stimulation waveforms for their effect on speech processing.

Volumetric magnetic resonance imaging studies have shown that intense learning can be associated with grey matter volume increases in the adult brain. The underlying mechanisms are poorly understood. Here we used monocular deprivation in rats to analyze the mechanisms underlying use-dependent grey matter increases. Optometry for quantification of visual acuity was combined with volumetric magnetic resonance imaging and microscopic techniques in longitudinal and cross-sectional studies. We found an increased spatial vision of the open eye which was associated with a transient increase in the volumes of the contralateral visual and lateral entorhinal cortex. In these brain areas dendrites of neurons elongated, and there was a strong increase in the number of spines, the targets of synapses, which was followed by spine maturation and partial pruning. Astrocytes displayed a transient pronounced swelling and underwent a reorganization of their processes. The use-dependent increase in grey matter corresponded predominantly to the swelling of the astrocytes. Experience-dependent increase in brain grey matter volume indicates a gain of structure plasticity with both synaptic and astrocyte remodeling.

Auditory cortical activity entrains to speech rhythms and has been proposed as a mechanism for online speech processing. In particular, neural activity in the theta frequency band (4–8 ​Hz) tracks the onset of syllables which may aid the parsing of a speech stream. Similarly, cortical activity in the delta band (1–4 ​Hz) entrains to the onset of words in natural speech and has been found to encode both syntactic as well as semantic information. Such neural entrainment to speech rhythms is not merely an epiphenomenon of other neural processes, but plays a functional role in speech processing: modulating the neural entrainment through transcranial alternating current stimulation influences the speech-related neural activity and modulates the comprehension of degraded speech. However, the distinct functional contributions of the delta- and of the theta-band entrainment to the modulation of speech comprehension have not yet been investigated. Here we use transcranial alternating current stimulation with waveforms derived from the speech envelope and filtered in the delta and theta frequency bands to alter cortical entrainment in both bands separately. We find that transcranial alternating current stimulation in the theta band but not in the delta band impacts speech comprehension. Moreover, we find that transcranial alternating current stimulation with the theta-band portion of the speech envelope can improve speech-in-noise comprehension beyond sham stimulation. Our results show a distinct contribution of the theta- but not of the delta-band stimulation to the modulation of speech comprehension. In addition, our findings open up a potential avenue of enhancing the comprehension of speech in noise.