Heteromodale Untersuchung der sprachlichen Perzeption mittels funktioneller Magnetresonanztomographie

Einleitung: Die Untersuchung sprachspezifischer Phänomene mit dem Ziel einer cerebralen Lokalisation hat seit dem 19. Jahrhundert tiefgreifende Modifikationen durchlaufen. Die bildgebenden Verfahren ermöglichten es, Vorgänge der Kognition in vivo zu studieren. Es resultierte eine Modifikation der traditionellen Sprachmodelle, wobei sich in der Vielzahl verschiedener Veröffentlichungen eine unvereinbare Heterogenität von einzelnen, speziellen Aspekten zeigt. Entgegen einer Suche nach Subfunktionen der Sprachverarbeitung soll Ziel dieser Studie daher sein, mittels funktioneller Magnetresonanztomographie die modalitätsunabhängigen cerebralen Repräsentationen der Sprachperzeption in einem globalen Sinn zu untersuchen.Methoden: Es wurden neunzehn gesunde Probanden in einem kombinierten visuellen und akustischen Paradigma untersucht. Der visuelle Teil bestand aus der Präsentation von Texten, die sich in randomisierter Folge mit fortlaufenden Pseudo-Worten (artikulierbare Folgen aus Vokalen und Konsonanten ohne Ähnlichkeit mit „realen“ Worten der Mutter- oder einer Fremdsprache) und Nicht-Worten (nicht artikulierbare Konsonantenreihen) im selben Format abwechselten. Im akustischen Teil hörten die Versuchspersonen die Lesung einer Geschichte. Als Gegenbedingung diente hier, entsprechend den Pseudo-Worten im visuellen Teil, rückwärts abgespielter Text. Ergebnisse: In der Konjunktion des visuellen und akustischen Paradigmas stellte sich im Kontrast der Haupt- mit den Ruhebedingungen ein linkshemisphärisch betontes fronto-temporales System dar. Neben inferofrontalen Clustern sowie einer Aktivierung des dorsolateralen präfrontalen Cortex fand sich das Maximum im Bereich des rostralen Gyrus temporalis medius. Im Kontrast mit den sprachähnlichen Reizen reduzierte sich dieses System auf den Schläfenlappen, in dem sich vom Temporalpol entlang des Sulcus temporalis superior bis zum Planum temporale ein Aktivierungs-Band zog. Diskussion: Als Kernstruktur der Repräsentation von modalitätsunabhängigen Aspekten der Sprachverarbeitung in einem engen Sinn – also befreit von den Charakteristika der Perzeption sprachähnlicher Reize – ist der linke Lobus temporalis im Bereich des Sulcus temporalis superior anzusehen. Dabei haben der Temporalpol und occipitale Anteile einschließlich des Planum temporale Schlüsselpositionen in der Prozessierung semantischer und syntaktischer Aspekte von Sprache inne

Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults

Recurrent mild traumatic brain injuries (mTBIs) are regarded as an independent risk factor for developing dementia in later life. We here aimed to evaluate associations between recurrent mTBIs, cognition, and gray matter volume and microstructure as revealed by structural magnetic resonance imaging (MRI) in the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to- middle-aged subjects, who reported two or more sports-related mTBIs, with the last mTBI > 6 months prior to study enrolment (mTBI group), and 21 age-, sex- and education matched controls with no history of mTBI (control group). All participants received comprehensive neuropsychological testing, and high resolution T1-weighted and diffusion tensor MRI in order to assess cortical thickness (CT) and microstructure, hippocampal volume, and ventricle size. Compared to the control group, subjects of the mTBI group presented with lower CT within the right temporal lobe and left insula using an a priori region of interest approach. Higher number of mTBIs was associated with lower CT in bilateral insula, right middle temporal gyrus and right entorhinal area. Our results suggest persistent detrimental effects of recurrent mTBIs on CT already in young-to-middle-aged adults. If additional structural deterioration occurs during aging, subtle neuropsychological decline may progress to clinically overt dementia earlier than in age-matched controls, a hypothesis to be assessed in future prospective trials

Anodal transcranial direct current stimulation temporarily reverses age-associated cognitive decline and functional brain activity changes

The rising proportion of elderly people worldwide will yield an increased incidence of age-associated cognitive impairments, imposing major burdens on societies. Consequently, growing interest emerged to evaluate new strategies to delay or counteract cognitive decline in aging. Here, we assessed immediate effects of anodal transcranial direct current stimulation (atDCS) on cognition and previously described detrimental changes in brain activity attributable to aging. Twenty healthy elderly adults were assessed in a crossover shamcontrolled design using functional magnetic resonance imaging (fMRI) and concurrent transcranial DCS administered to the left inferior frontal gyrus. Effects on performance and task-related brain activity were evaluated during overt semantic word generation, a task that is negatively affected by advanced age. Task-absent resting-state fMRI (RS-fMRI) assessed atDCS-induced changes at the network level independent of performance. Twenty matched younger adults served as controls. During sham stimulation, task-related fMRI demonstrated that enhanced bilateral prefrontal activity in older adults was associated with reduced performance. RS-fMRI revealed enhanced anterior and reduced posterior functional brain connectivity. atDCS significantly improved performance in older adults up to the level of younger controls; significantly reduced task-related hyperactivity in bilateral prefrontal cortices, the anterior cingulate gyrus, and the precuneus; and induced a more "youth-like" connectivity pattern during RS-fMRI. Our results provide converging evidence from behavioral analysis and two independent functional imaging paradigms that a single session of atDCS can temporarily reverse nonbeneficial effects of aging on cognition and brain activity and connectivity. These findings may translate into novel treatments to ameliorate cognitive decline in normal aging in the future

Differential effects of dual and unihemispheric motor cortex stimulation in older adults

Bihemispheric transcranial direct current stimulation (tDCS) is thought to upregulate excitability of the primary motor cortex (M1) using anodal stimulation while concurrently downregulating contralateral M1 using cathodal stimulation. This “dual” tDCS method enhances motor learning in healthy subjects and facilitates motor recovery after stroke. However, its impact on motor system activity and connectivity remains unknown. Therefore, we assessed neural correlates of dual and unihemispheric anodal tDCS effects in 20 healthy older subjects in a randomized, sham-controlled study using a cross-over design. Participants underwent tDCS and simultaneous functional magnetic resonance imaging during a choice reaction time task and at rest. Diffusion tensor imaging (DTI) allowed us to relate potential functional changes to structural parameters. The resting-state analysis demonstrated that, compared with sham, both dual and anodal tDCS decreased connectivity of right hippocampus and M1 (contralateral to the anode position) while increasing connectivity in the left prefrontal cortex. Notably, dual but not anodal tDCS enhanced connectivity of the left dorsal posterior cingulate cortex. Furthermore, dual tDCS yielded stronger activations in bilateral M1 compared with anodal tDCS when participants used either their left or right hand during the motor task. The corresponding tDCS-induced changes in laterality of activations were related to the microstructural status of transcallosal motor fibers. In conclusion, our results suggest that the impact of bihemispheric tDCS cannot be explained by mere add-on effects of anodal and concurrent cathodal stimulation, but rather by complex network modulations involving interhemispheric interactions and areas associated with motor control in the dorsal posterior cingulate cortex

Effects of transcranial direct current stimulation on neural networks in young and older adults

Transcranial direct current stimulation (tDCS) may be a viable tool to improve motor and cognitive function in advanced age. However, although a number of studies have demonstrated improved cognitive performance in older adults, other studies have failed to show restorative effects. The neural effects of beneficial stimulation response in both age groups is lacking. In the current study, tDCS was administered during simultaneous fMRI in 42 healthy young and older participants. Semantic word generation and motor speech baseline tasks were used to investigate behavioral and neural effects of uni-and bihemispheric motor cortex tDCS in a three-way, crossover, sham tDCS controlled design. Independent components analysis assessed differences in task-related activity between the two age groups and tDCS effects. at the network level. We also explored whether laterality of language network organization was effected by tDCS. Behaviorally, both active tDCS conditions significantly improved semantic word retrieval performance in young and older adults and were comparable between groups and stimulation conditions. Network-level tDCS effects were identified in the ventral and dorsal anterior cingulate networks in the combined sample during semantic fluency and motor speech tasks. In addition, a shift toward enhanced left laterality was identified in the older adults for both active stimulation conditions. Thus, tDCS results in common network-level modulations and behavioral improvements for both age groups, with an additional effect of increasing left laterality in older adults

Electrical Brain Stimulation Improves Cognitive Performance by Modulating Functional Connectivity and Task-Specific Activation

Excitatory anodal transcranial direct current stimulation (atDCS) can improve human cognitive functions, but neural underpinnings of its mode of action remain elusive. In a cross-over placebo ("sham") controlled study we used functional magnetic resonance imaging (fMRI) to investigate neurofunctional correlates of improved language functions induced by atDCS over a core language area, the left inferior frontal gyrus (IFG). Intrascanner transcranial direct current stimulation-induced changes in overt semantic word generation assessed behavioral modulation; task-related and task-independent (resting-state) fMRI characterized language network changes. Improved word-retrieval during atDCS was paralleled by selectively reduced task-related activation in the left ventral IFG, an area specifically implicated in semantic retrieval processes. Under atDCS, resting-state fMRI revealed increased connectivity of the left IFG and additional major hubs overlapping with the language network. In conclusion, atDCS modulates endogenous low-frequency oscillations in a distributed set of functionally connected brain areas, possibly inducing more efficient processing in critical task-relevant areas and improved behavioral performance

An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7

The 15q13.3 microdeletion copy number variation is strongly associated with schizophrenia and epilepsy. The CHRNA7 gene, encoding nicotinic acetylcholine alpha 7 receptors (nAChA7Rs), is hypothesized to be one of the main genes in this deletion causing the neuropsychiatric phenotype. Here we used a recently developed 15q13.3 microdeletion mouse model to explore whether an established schizophrenia-associated connectivity phenotype is replicated in a murine model, and whether positive modulation of nAChA7 receptor might pharmacologically normalize the connectivity patterns. Resting-state fMRI data were acquired from male mice carrying a hemizygous 15q13.3 microdeletion (N=9) and from wild-type mice (N=9). To study the connectivity profile of 15q13.3 mice and test the effect of nAChA7 positive allosteric modulation, the 15q13.3 mice underwent two imaging sessions, one week apart, receiving a single intraperitoneal injection of either 15 mg/kg Lu AF58801 or saline. The control group comprised wild-type mice treated with saline. We performed seed-based functional connectivity analysis to delineate aberrant connectivity patterns associated with the deletion (15q13.3 mice (saline treatment) versus wild-type mice (saline treatment)) and their modulation by Lu AF58801 (15q13.3 mice (Lu AF58801 treatment) versus 15q13.3 mice (saline treatment)). Compared to wild-type mice, 15q13.3 mice evidenced a predominant hyperconnectivity pattern. The main effect of Lu AF58801 was a normalization of elevated functional connectivity between prefrontal and frontal, hippocampal, striatal, thalamic and auditory regions. The strongest effects were observed in brain regions expressing nAChA7Rs, namely hippocampus, cerebral cortex and thalamus. These effects may underlie the antiepileptic, pro-cognitive and auditory gating deficit-reversal effects of nAChA7R stimulation

Transcranial direct current stimulation over multiple days improves learning and maintenance of a novel vocabulary

Introduction: Recently, growing interest emerged in the enhancement of human potential by means of non-invasive brain stimulation. In particular, anodal transcranial direct current stimulation (atDCS) has been shown to exert beneficial effects on motor and higher cognitive functions. However, the majority of transcranial direct current stimulation (tDCS) studies have assessed effects of single stimulation sessions that are mediated by transient neural modulation. Studies assessing the impact of multiple stimulation sessions on learning that may induce long-lasting behavioural and neural changes are scarce and have not yet been accomplished in the language domain in healthy individuals