Prefrontal stimulation prior to motor sequence learning alters multivoxel patterns in the striatum and the hippocampus

© The Author(s) 2021. Motor sequence learning (MSL) is supported by dynamical interactions between hippocampal and striatal networks that are thought to be orchestrated by the prefrontal cortex. In the present study, we tested whether individually-tailored theta-burst stimulation of the dorsolateral prefrontal cortex (DLPFC) prior to MSL can modulate multivoxel response patterns in the stimulated cortical area, the hippocampus and the striatum. Response patterns were assessed with multivoxel correlation structure analyses of functional magnetic resonance imaging data acquired during task practice and during resting-state scans before and after learning/stimulation. Results revealed that, across stimulation conditions, MSL induced greater modulation of task-related DLPFC multivoxel patterns than random practice. A similar learning-related modulatory effect was observed on sensorimotor putamen patterns under inhibitory stimulation. Furthermore, MSL as well as inhibitory stimulation affected (posterior) hippocampal multivoxel patterns at post-intervention rest. Exploratory analyses showed that MSL-related brain patterns in the posterior hippocampus persisted into post-learning rest preferentially after inhibitory stimulation. These results collectively show that prefrontal stimulation can alter multivoxel brain patterns in deep brain regions that are critical for the MSL process. They also suggest that stimulation influenced early offline consolidation processes as evidenced by a stimulation-induced modulation of the reinstatement of task pattern into post-learning wakeful rest.Belgian Research Foundation Flanders (FWO; G099516N); KU Leuven; FWO (G0D7918N, G0B1419N, 1524218N); Excellence of Science (EOS, 30446199, MEMODYN); European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (703490); FWO (132635) postdoctoral fellowship; Air Force Office of Scientific Research (AFOSR, Virginia, USA; FA9550-16-1-0191)

Protocol for mapping of the supplementary motor area using repetitive navigated transcranial magnetic stimulation

BackgroundDamage to the supplementary motor area (SMA) can lead to impairments of motor and language function. A detailed preoperative mapping of functional boarders of the SMA could therefore aid preoperative diagnostics in these patients.ObjectiveThe aim of this study was the development of a repetitive nTMS protocol for non-invasive functional mapping of the SMA while assuring effects are caused by SMA rather than M1 activation.MethodsThe SMA in the dominant hemisphere of 12 healthy subjects (28.2 ± 7.7 years, 6 females) was mapped using repetitive nTMS at 20 Hz (120% RMT), while subjects performed a finger tapping task. Reductions in finger taps were classified in three error categories (≤15% = no errors, 15–30% = mild, >30% significant). The location and category of induced errors was marked in each subject’s individual MRI. Effects of SMA stimulation were then directly compared to effects of M1 stimulation in four different tasks (finger tapping, writing, line tracing, targeting circles).ResultsMapping of the SMA was possible for all subjects, yet effect sizes varied. Stimulation of the SMA led to a significant reduction of finger taps compared to baseline (BL: 45taps, SMA: 35.5taps; p < 0.01). Line tracing, writing and targeting of circles was less accurate during SMA compared to M1 stimulation.ConclusionMapping of the SMA using repetitive nTMS is feasible. While errors induced in the SMA are not entirely independent of M1, disruption of the SMA induces functionally distinct errors. These error maps can aid preoperative diagnostics in patients with SMA related lesions

How the brain controls hand actions: TMS, fMRI and behavioural studies

This thesis focused on testing the predictions made in Milner and Goodale’s model and reports finding from experiments investigating how inputs from both the dorsal and the ventral streams are required when we perform hand actions with objects (Chapter 2) and tools (Chapter 3 & 4) using different paradigms such as real and pantomimed grasping and techniques such as transcranial magnetic stimulation, motion-tracking of hand movements and cutting-edge fMRI multivoxel pattern analysis. The primary aim was to gain a new insight on the role of the dorsal and the ventral visual streams in real grasping and pantomiming and to understand what specific aspects of objects and movements associated with them are represented within the two streams. The first experiment (Chapter 2) examined the causal role of the anterior intraparietal and the lateral occipital in object’s real and pantomimed grasping using TMS. The results showed that real object grasping and pantomime actions without the objects in hand require the left dorsal stream but that information from the ventral stream is additionally required for pantomiming. The experiments in Chapter 3 and 4 investigated how tools and tool related actions are represented within the dorsal and the ventral stream (Chapter 3) and whether different action end-goals affected early grasping kinematics (Chapter 4). Using MVPA we showed that both dorsal and ventral stream regions represent information about functional and structural manipulation knowledge of tools. Moreover, we showed that both streams represent tool identity, which seems in line with our behavioural findings that tool identity affects grasping kinematics. The current work provided a detailed understanding of how the dorsal and the ventral streams interact in tool processing and propose a more sophisticated view of the distributed representations across the two streams. These findings open up a number of research avenues as well as help understanding how actions are disrupted in brain-damaged patients and advance the development of neural prosthetics

cTBS disruption of the supplementary motor area perturbs cortical sequence representation but not behavioural performance.

Neuroimaging studies have repeatedly emphasized the role of the supplementary motor area (SMA) in motor sequence learning, but interferential approaches have led to inconsistent findings. Here, we aimed to test the role of the SMA in motor skill learning by combining interferential and neuroimaging techniques. Sixteen subjects were trained on simple finger movement sequences for 4 days. Afterwards, they underwent two neuroimaging sessions, in which they executed both trained and novel sequences. Prior to entering the scanner, the subjects received inhibitory transcranial magnetic stimulation (TMS) over the SMA or a control site. Using multivariate fMRI analysis, we confirmed that motor training enhances the neural representation of motor sequences in the SMA, in accordance with previous findings. However, although SMA inhibition altered sequence representation (i.e. between-sequence decoding accuracy) in this area, behavioural performance remained unimpaired. Our findings question the causal link between the neuroimaging correlate of elementary motor sequence representation in the SMA and sequence generation, calling for a more thorough investigation of the role of this region in performance of learned motor sequences

Cognitive Assessment and Rehabilitation of subjects with Traumatic Brain Injury

This thesis regards the study and the development of new cognitive assessment and rehabilitation techniques of subjects with traumatic brain injury (TBI). In particular, this thesis i) provides an overview about the state of art of this new assessment and rehabilitation technologies, ii) suggests new methods for the assessment and rehabilitation and iii) contributes to the explanation of the neurophysiological mechanism that is involved in a rehabilitation treatment. Some chapters provide useful information to contextualize TBI and its outcome; they describe the methods used for its assessment/rehabilitation. The other chapters illustrate a series of experimental studies conducted in healthy subjects and TBI patients that suggest new approaches to assessment and rehabilitation. The new proposed approaches have in common the use of electroencefalografy (EEG). EEG was used in all the experimental studies with a different purpose, such as diagnostic tool, signal to command a BCI-system, outcome measure to evaluate the effects of a treatment, etc. The main achieved results are about: i) the study and the development of a system for the communication with patients with disorders of consciousness. It was possible to identify a paradigm of reliable activation during two imagery task using EEG signal or EEG and NIRS signal; ii) the study of the effects of a neuromodulation technique (tDCS) on EEG pattern. This topic is of great importance and interest. The emerged founding showed that the tDCS can manipulate the cortical network activity and through the research of optimal stimulation parameters, it is possible move the working point of a neural network and bring it in a condition of maximum learning. In this way could be possible improved the performance of a BCI system or to improve the efficacy of a rehabilitation treatment, like neurofeedback