Insights around the function and dynamics of brain networks.

The brain processes sensory input, controls our body, stores information and shapes our consciousness. Using state-of-the-art technical and digital methods, researchers can now localize areas that are responsible for specific abilities. However, it is still not known exactly which path neuronal impulses take in the highly complex dynamic network of around 100 billion nerve cells and how the different brain areas cooperate spatially and temporally.

Almost all sensorimotor and cognitive processes rely on the activity of large networks in our brain. To exchange and integrate information, different brain regions must dynamically couple with each other. The existence of such couplings was discovered more than 30 years ago, but it is still not clear exactly what their functional significance is. Dynamic coupling of signals in the cortex seems to play a key role in the development of perception, attention, memory, language, thinking, and problem-solving abilities. In everyday life, the process of multisensory integration is also of great importance. This enables the exchange of information between the respective sensory systems involved. In diseases, the simultaneous processing of sensory impressions may be altered. Using the processing of visual and auditory signals as an example, Berlin researchers have used EEG measurements of brain activity to find that multisensory integration can help compensate for attentional deficits that exist in processing in single sensory channels in individuals with schizophrenia.

Reorganize networks after stroke

Stroke and the brain’s ability to overcome these limitations was the subject of further consideration. Stroke is one of the most common causes of acquired disability worldwide. Late effects include speech disorders or hemiplegia. New and increasingly better treatment options such as thrombolysis and thrombectomy have revolutionized the treatment of acute stroke in recent years. Beyond the acute phase, however, the therapeutic repertoire is largely limited to special training measures – with moderate success. To improve the limited therapeutic options for recovery, the use of noninvasive brain stimulation via transcranial magnetic stimulation (TMS) is currently being investigated in stroke patients. This has the potential to modulate affected brain networks after stroke and mitigate their neurological dysfunction beyond the effect of training methods. The most important factor for functional recovery after stroke is neuronal reorganization. This is dependent on factors at both the cellular and network levels. To date, the best results to support reorganization of neural networks have been provided by a combination of neuroimaging techniques and neurostimulation techniques such as TMS. In addition, the use of artificial intelligence could also make a significant contribution to improving treatment outcomes after a stroke in the future. The strategic use of an ever-increasing amount of patient-related data can help to calculate algorithm-based outcome predictions on the individual course in individual stroke patients, both in the acute and chronic stages. AI approaches are becoming more precise and are revealing factors that may favor rapid recovery or a complicated course. In this way, therapies can be individually adapted.

Neurostimulation without surgery?

Whether Parkinson’s, Alzheimer’s, stroke, epilepsy or chronic pain – scientists hope that stimulating the brain with electrical or magnetic stimuli will lead to new therapeutic approaches for neurological and psychiatric diseases. Deep brain stimulation is already established in the treatment of Parkinson’s disease. For this purpose, electrodes are implanted into the brain. Non-invasive brain stimulation offers new possibilities where traditional therapies reach their limits or surgery is too risky. To date, the best studied with a rapidly growing body of data from human studies is low-intensity focused transcranial ultrasound (fTUS) stimulation. Special transducers and ultrasound frequencies in the range of 0.5 MHz can be used to modulate both superficial and deep focal brain regions. The technique has been studied in patients with chronic pain, dementia, epilepsy, traumatic brain injury, and depression. The short-term stimulation effects varied depending on the ultrasound parameters and positively affected excitability, brain connectivity, plasticity, and behavior. The side effect profile was characterized by mild symptoms such as headache, mood worsening, scalp warming, cognitive problems, neck pain, muscle twitching, anxiety, and drowsiness. fTUS can be used to modulate even deep brain areas with great spatial precision while remaining non-invasive. This sets this method apart from other technologies.

Another form of neurostimulation currently being researched is temporal interference stimulation (TIS). It uses two transcranial alternating current stimulators ( tACS) that can induce temporal interference in deep brain regions. While no biological effects are to be expected at the brain surface due to the high frequencies prevailing there (2 kHz), in the depth of the brain the electrical interference field (10 Hz) can lead to a modulation of neuronal activity. This has been demonstrated experimentally in mice.

Recognize faces

The most basic aspect of face perception is the detection of the presence of a face, which requires the extraction of features it has in common with other faces. This presumably occurs through the matching of high-dimensional sensory information with internal face templates, which is achieved through top-down mediated coupling between prefrontal regions and brain areas in occipito-temporal cortex. Illusory face recognition tasks can be used to investigate these top-down influences. One study investigated the mechanisms involved in face recognition using functional magnetic resonance imaging (fMRI).

An illusory face recognition paradigm was used in which subjects were shown noise-only images. However, they were told that half contained a face. The main goal was to investigate how the interaction of the prefrontal cortex with the nuclear system leads to the illusory perception of faces. The fMRI data analysis was divided into five steps. Analyses 1-3 examined the pattern of brain activity during illusory face recognition by comparing trials in which a face was recognized with those in which no face was recognized. In Analysis 4, the pattern of functional connectivity between the core system and the prefrontal cortex was examined using a psychophysiological interaction (PPI) analysis. Analysis 5 examined how and which regions in the prefrontal cortex upregulate brain activity in the nuclear system during illusory face recognition.

It has been shown that the perception of illusory faces activates the core system in the same way as real faces, albeit with atypical left lateralization of the occipital face area. The core system was coupled with two different brain regions in the IFG and the OFC. DCM analysis revealed that activity in the nuclear system during mock face recognition was upregulated by a modulating face-specific influence of the IFG and not by the OFC, as previously hypothesized.

Transcranial stimulation for dichotic hearing

In dichotic listening (DL), two different sounds are presented simultaneously to both ears. Participants with left hemispheric dominance report more sounds from the right ear, representing a right ear advantage (REA). For left ear reports, auditory information must be transferred from the right to the left (dominant) hemisphere. Accordingly, electroencephalography (EEG) showed increased functional connectivity between both auditory cortices during left ear reports. In one study, this connectivity between the two auditory cortices was modulated during DL using transcranial gamma alternating current stimulation (tACS). The background was the hypothesis that synchronization and de-synchronization of the activity of both auditory cortexes by tACS would interact with brain activity and thus, influence behavioral performance during DL.

Twenty-nine right-handed participants were recruited for five sessions over five weeks (one week apart). In each session, they performed two DL blocks with simultaneous EEG recording and tACS. Each session included 20 minutes of bilateral 40-Hz stimulation of the temporal areas with an amplitude of 1 mA (peak-to-peak). Five different stimulation conditions were applied (one per session): sham stimulation and 4 verum stimulations with 4 different phase shifts (of 0°, 45°, 90°, and 180°) between the left and right tACS stimulation sites.

At the behavioral level, participants showed the typical right ear advantage during the sham stimulation condition. Consistent with a similar previous study, the other conditions did not show significant changes at the behavioral level. Calculation of the phase shift between the two auditory cortices showed a significant difference between the reports for the left and right ear in the time window 84-108 ms after stimulus presentation. The individual phase delays within this time window were circularly correlated with behavioral level changes only during the 180° stimulation condition. A personalized post hoc analysis showed that the stimulation condition that was close to the individual (endogenous) phase delay resulted in a lower REA.

The results suggest that it is not stimulation per se that affects interhemispheric connectivity, but rather the interaction between the phase delay of stimulation and the endogenous phase delay. In this sense, the stimulation condition with the smallest phase delay to the endogenous phase delay may improve interhemispheric communication between both auditory cortices and thus decrease FGD. Clinically, this study may help identify potential brain targets for neurostimulation for the treatment of auditory hallucinations in schizophrenia associated with greater interhemispheric interhemispheric connectivity and thus abnormally reduced REA.

Congress: German Society for Clinical Neurophysiology and Functional Imaging (DGKN)