Kirstin Heise

Brain Oscillatory Substrates of Visual Short-Term Memory Capacity

The amount of information that can be stored in visual short-term memory is strictly limited to about four items. Therefore, memory capacity relies not only on the successful retention of relevant information but also on efficient suppression of distracting information, visual attention, and executive functions. However, completely separable neural signatures for these memory capacity-limiting factors remain to be identified. Because of its functional diversity, oscillatory brain activity may offer a utile solution. In the present study, we show that capacity-determining mechanisms, namely retention of relevant information and suppression of distracting information, are based on neural substrates independent of each other: the successful maintenance of relevant material in short-term memory is associated with cross-frequency phase synchronization between theta (rhythmical neural activity around 5 Hz) and gamma (> 50 Hz) oscillations at posterior parietal recording sites. On the other hand, electroencephalographic alpha activity (around 10 Hz) predicts memory capacity based on efficient suppression of irrelevant information in short-term memory. Moreover, repetitive transcranial magnetic stimulation at alpha frequency can modulate short-term memory capacity by influencing the ability to suppress distracting information. Taken together, the current study provides evidence for a double dissociation of brain oscillatory correlates of visual short-term memory capacity.

Modulation of Training by Single-Session Transcranial Direct Current Stimulation to the Intact Motor Cortex Enhances Motor Skill Acquisition of the Paretic Hand

Background and Purpose— Mechanisms of skill learning are paramount components for stroke recovery. Recent noninvasive brain stimulation studies demonstrated that decreasing activity in the contralesional motor cortex might be beneficial, providing transient functional improvements after stroke. The more crucial question, however, is whether this intervention can also enhance the acquisition of complex motor tasks, yielding longer-lasting functional improvements. In the present study, we tested the capacity of cathodal transcranial direct current stimulation (tDCS) applied over the contralesional motor cortex during training to enhance the acquisition and retention of complex sequential finger movements of the paretic hand. Method— Twelve well-recovered chronic patients with subcortical stroke attended 2 training sessions during which either cathodal tDCS or a sham intervention were applied to the contralesional motor cortex in a double-blind, crossover design. Two different motor sequences, matched for their degree of complexity, were tested in a counterbalanced order during as well as 90 minutes and 24 hours after the intervention. Potential underlying mechanisms were evaluated with transcranial magnetic stimulation. Results— tDCS facilitated the acquisition of a new motor skill compared with sham stimulation (P=0.04) yielding better task retention results. A significant correlation was observed between the tDCS-induced improvement during training and the tDCS-induced changes of intracortical inhibition (R2=0.63). Conclusions— These results indicate that tDCS is a promising tool to improve not only motor behavior, but also procedural learning. They further underline the potential of noninvasive brain stimulation as an adjuvant treatment for long-term recovery, at least in patients with mild functional impairment after stroke.

Facilitating skilled right hand motor function in older subjects by anodal polarization over the left primary motor cortex.

Healthy ageing is accompanied by limitations in performance of activities of daily living and personal independence. Recent reports demonstrated improvements in motor function induced by noninvasive anodal direct current stimulation (tDCS) of the primary motor cortex (M1) in young healthy adults. Here we tested the hypothesis that a single session of anodal tDCS over left M1 could facilitate performance of right upper extremity tasks required for activities of daily living (Jebsen-Taylor hand function test, JTT) in older subjects relative to Sham in a double-blind cross-over study design. We found (a) significant improvement in JTT function with tDCS relative to Sham that outlasted the stimulation period by at least 30 min, (b) that the older the subjects the more prominent this improvement appeared and (c) that consistent with previous results in younger subjects, these effects were not accompanied by any overt undesired side effect. We conclude that anodal tDCS applied over M1 can facilitate performance of skilled hand functions required for activities of daily living in older subjects.

Deficient intracortical inhibition (SICI) during movement preparation after chronic stroke

Background: In healthy subjects, preparation to move is accompanied by motor cortical disinhibition. Poor control of intracortical inhibitory function in the primary motor cortex (M1) might contribute to persistent abnormal motor behavior in the paretic hand after chronic stroke. Methods: Here, we studied GABAergic short intracortical inhibition (SICI) in the ipsilesional M1 in well-recovered chronic stroke patients (n = 14; 63.8 ± 3.0 years) engaged in preparation to move the impaired hand in a reaction time paradigm. Results: The main finding was an abnormal persistence of SICI in the ipsilesional M1 during movement preparation that was absent in age-matched controls (n = 14). Additionally, resting SICI was reduced in the patient group relative to controls. Conclusions: Our findings document a deficit of dynamic premovement modulation of intracortical inhibition in the ipsilesional primary motor cortex of patients with chronic stroke. This abnormality might contribute to deficits in motor control of the paretic hand, presenting a possible target for correction in the framework of developing novel therapeutic interventions after chronic stroke.

Distinct Temporospatial Interhemispheric Interactions in the Human Primary and Premotor Cortex during Movement Preparation

The preparation of a voluntary unimanual action requires sequential processing in bihemispheric motor areas. In both animals and humans, activity in the dorsal premotor cortex (PMd) ipsilateral to the moving hand has been demonstrated to precede ipsilateral primary motor cortex (M1) activity. We investigated with double-pulse transcranial magnetic stimulation how right-hemispheric motor areas (rM1, rPMd) modulate left M1 (lM1) during the preparatory period of a finger movement with the dominant right hand. We tested the hypothesis that the influence of higher order motor areas such as rPMd on lM1 (rPMd-lM1) precedes interhemispheric interactions between homologue primary motor areas (rM1-lM1). rPMd-lM1 showed modulation in the early and late phase of movement preparation, whereas the intrinsic state of inhibition between rM1-lM1 was only modulated in the late phase. The present results complement existing hierarchical models of cortical movement control by demonstrating temporospatially distinct involvement of interhemispheric interactions from PMd and M1 during movement preparation.

Enhancing Consolidation of a New Temporal Motor Skill by Cerebellar Noninvasive Stimulation

Cerebellar transcranial direct current stimulation (tDCS) has the potential to modulate cerebellar outputs and visuomotor adaptation. The cerebellum plays a pivotal role in the acquisition and control of skilled hand movements, especially its temporal aspects. We applied cerebellar anodal tDCS concurrently with training of a synchronization-continuation motor task. We hypothesized that anodal cerebellar tDCS will enhance motor skill acquisition. Cerebellar tDCS was applied to the right cerebellum in 31 healthy subjects in a double-blind, sham-controlled, parallel design. During synchronization, the subjects tapped the sequence in line with auditory cues. Subsequently, in continuation, the learned sequence was reproduced without auditory cuing. Motor task performance was evaluated before, during, 90 min, and 24 h after training. Anodal cerebellar tDCS, compared with sham, improved the task performance in the follow-up tests (F1,28 = 5.107, P = 0.032) of the synchronization part. This effect on retention of the skill was most likely mediated by enhanced motor consolidation. We provided first evidence that cerebellar tDCS can enhance the retention of a fine motor skill. This finding supports the promising approach of using noninvasive brain stimulation techniques to restore impaired motor functions in neurological patients, such after a stroke.

Development of movement-related intracortical inhibition in acute to chronic subcortical stroke

Objective: A prospective longitudinal cohort study in stroke patients was performed to better understand the role of γ-aminobutyric acid–dependent intracortical inhibition (ICI) for recovery after stroke. Methods: Patients with acute first-ever subcortical stroke and hand paresis were recruited, and motor function as well as ICI were measured up to 1 year after stroke. Motor recovery was defined as the change in hand motor function from the acute to the chronic stage (Δ = recovery over 1 year). Primary outcome measures for hand motor function were the recovery of grip strength (ΔGS) and finger-tapping speed (ΔFT). Using double-pulse transcranial magnetic stimulation, we studied ICI in the ipsilesional primary motor cortex during the preparation of a movement with the paretic hand at different time points during recovery (first week, 7 weeks, 3 months, and 1 year after stroke). Results: Eleven patients were enrolled (mean age 62.9 ± 3.8 years). The results of a multiple regression analysis showed a significant association of movement-related ICI in the acute stage only (first week) with motor recovery over 1 year (ΔGS: R2 = 0.75, F = 17.6, p = 0.006; ΔFT: R2 = 0.55, F = 7.3, p = 0.035). More disinhibition of ICI in the acute phase of stroke predicted more improvement in ΔGS (β = −0.86, p = 0.006) and ΔFT (β = −0.74, p = 0.035), independent of the initial motor deficit. Conclusions: Movement-related ICI one week after a subcortical stroke is associated with better outcome of hand motor function. Disinhibition in the ipsilesional primary motor cortex could be a mechanism of how the brain attempts to promote motor recovery after stroke.

The control of complex finger movements by directional information flow between mesial frontocentral areas and the primary motor cortex

Complex movements require the interplay of local activation and interareal communication of sensorimotor brain regions. This is reflected in a decrease of task‐related spectral power over the sensorimotor cortices and an increase in functional connectivity predominantly in the upper alpha band in the electroencephalogram (EEG). In the present study, directionality of information flow was investigated using EEG recordings to gain better understanding about the network architecture underlying the performance of complex sequential finger movements. This was assessed by means of Granger causality‐derived directed transfer function (DTF). As DTF measures the influence one signal exerts on another based on a time lag between them, it allows implications to be drawn on causal relationships. To reveal causal connections between brain regions that are specifically modulated by task complexity, we contrasted the performance of right‐handed sequential finger movements of different complexities (simple, scale, complex) that were either pre‐learned (memorized) or novel instructed. A complexity‐dependent increase in information flow from mesial frontocentral to the left motor cortex and, less pronounced, also to the right motor cortex specifically in the upper alpha range was found. Effective coupling during sequences of high complexity was larger for memorized sequences compared with novel sequences (P = 0.0037). These findings further support the role of mesial frontocentral areas in directing the primary motor cortex in the process of orchestrating complex movements and in particular learned sequences.

Task-related modulation of SICI underlies effects of sex and hemisphere

Background: Cortical excitability is modulated before movement onset in the contralateral primary motor cortex (M1). It underlies changes across lifespan and has been shown to be deficient in several neurological diseases. Influences of sex and hemisphere on cortical excitability at rest have been described previously. Here, a meta-analysis of previously analyzed healthy subpopulations was conducted regarding the main effects of sex, hemisphere, and age on modulation of M1 excitability during movement preparation. Methods: Single and paired-pulse TMS was used to examine modulation of cortical excitability, i.e. unconditioned motor evoked potentials (SP), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF) in a sample of 46 healthy right-handed subjects (44.24±20.06 years, range 20–88, 26 females). The participants were instructed to perform a visually triggered simple reaction time task (abduction of the index finger). Measures of cortical excitability were assessed in the contralateral M1 (30 left, 16 right hemisphere) during rest and task performance. Results: Multiple regression conducted on the rest data revealed that predictor variables SEX, HEMISPHERE, and AGE did not account for the variability of rest SICI (p=0.071), SP (p=0.977), or ICF (p=0.723). Separate t-tests did not produce significant differences between groups (male – female, right – left hemisphere) at rest, the same applied when the data was stratified for old and young subjects. During movement preparation, separate RM-ANOVA with factor TIME, HEMISPHERE, and SEX with AGE as covariant were conducted for SP, SICI, and ICF. No significant main effects or interactions were evident for SP or ICF data. For SICI RM-ANOVA revealed significant effects of TIME (F=9.522, p=0.000), SEX (F=4.432, p=0.042), HEMISPHERE (F=5.265, p=0.027), and significant TIME x AGE interaction (F=4.097, p=0.024). Discussion: The results show that the non-dominant hemisphere is more disinhibited than the dominant hemisphere and women show less inhibition during movement preparation than men. Overall, SICI modulation diminishes with increasing age. However, lateralization effects of SICI modulation have been discussed controversially so far. Our results extend previous findings, which suggest an impact of sex (ovarian hormones) on GABAergic modulated motor cortical excitability at rest and during preparation of a voluntary movement.

131. Modulation of SICI in preparation of movement in elder compared to young healthy subjects

auditory processing in severely depressed patients: A combined MRS and MEG study—M. Tollkötter , P. Sörös , N. Michael , B. Pfleiderer 4 ( Knappschaftskrankenhaus Recklinghausen, Neurologie, Recklinghausen, Germany, 2 University of Western Ontario, School of Communications Sciences and Disorders, Ontario, Canada, 3 Ev. Stiftung Tannenhof, Psychiatrie, Remscheid, Germany, 4 UKM, Klinische Radiologie, Münster, Germany)