Accelerated long-term forgetting in patients with acquired brain injury.

OBJECTIVE: Recent research suggests that patients with neurological disorders without overt seizures may also experience accelerated long-term forgetting (ALF). This term describes unimpaired learning and memory performance after standard retention intervals, but an excessive rate of forgetting over delays of days or weeks. The objective of this retrospective study was to investigate ALF in patients with an acquired brain injury (ABI) and to associate memory performance with executive functions. METHODS: Verbal memory performance (short-term recall, 30-min recall, 1-week recall) was assessed in 34 adult patients with ABI and compared to a healthy control group (n = 54) using an auditory word learning and memory test. RESULTS: Repeated measure analysis showed significant effects of time and group as well as interaction effects between time and group regarding recall and recognition performance. Patients with ABI had a significantly impaired 1-week recall and recognition performance compared to the healthy control group. Correlations between recall performance and executive functions were nonsignificant. DISCUSSION: Our results demonstrate that non-epileptic patients with ABI, especially patients with frontal and fronto-temporal lesions, are prone to ALF. Additionally, our data support the assumption that ALF results from a consolidation impairment since verbal recall and recognition were impaired in patients with ABI.

Multi-focal Stimulation of the Cortico-cerebellar Loop During the Acquisition of a Novel Hand Motor Skill in Chronic Stroke Survivors.

Impairment of hand motor function is a frequent consequence after a stroke and strongly determines the ability to regain a self-determined life. An influential research strategy for improving motor deficits is the combined application of behavioral training and non-invasive brain stimulation of the motor cortex (M1). However, a convincing clinical translation of the present stimulation strategies has not been achieved yet. One alternative and innovative approach is to target the functionally relevant brain network-based architecture, e.g., the dynamic interactions within the cortico-cerebellar system during learning. Here, we tested a sequential multifocal stimulation strategy targeting the cortico-cerebellar loop. Anodal transcranial direct current stimulation (tDCS) was applied simultaneously to a hand-based motor training in N = 11 chronic stroke survivors during four training sessions on two consecutive days. The tested conditions were: sequential multifocal (M1-cerebellum (CB)-M1-CB) vs. monofocal control stimulation (M1-sham-M1-sham). Additionally, skill retention was assessed 1 and 10 days after the training phase. Paired-pulse transcranial magnetic stimulation data were recorded to characterize stimulation response determining features. The application of CB-tDCS boosted motor behavior in the early training phase in comparison to the control condition. No faciliatory effects on the late training phase or skill retention were detected. Stimulation response variability was related to the magnitude of baseline motor ability and short intracortical inhibition (SICI). The present findings suggest a learning phase-specific role of the cerebellar cortex during the acquisition of a motor skill in stroke and that personalized stimulation strategies encompassing several nodes of the underlying brain network should be considered.

Brain-actuated functional electrical stimulation elicits lasting arm motor recovery after stroke.

Brain-computer interfaces (BCI) are used in stroke rehabilitation to translate brain signals into intended movements of the paralyzed limb. However, the efficacy and mechanisms of BCI-based therapies remain unclear. Here we show that BCI coupled to functional electrical stimulation (FES) elicits significant, clinically relevant, and lasting motor recovery in chronic stroke survivors more effectively than sham FES. Such recovery is associated to quantitative signatures of functional neuroplasticity. BCI patients exhibit a significant functional recovery after the intervention, which remains 6-12 months after the end of therapy. Electroencephalography analysis pinpoints significant differences in favor of the BCI group, mainly consisting in an increase in functional connectivity between motor areas in the affected hemisphere. This increase is significantly correlated with functional improvement. Results illustrate how a BCI-FES therapy can drive significant functional recovery and purposeful plasticity thanks to contingent activation of body natural efferent and afferent pathways.

Principles of proportional recovery after stroke generalize to neglect and aphasia.

BACKGROUND AND PURPOSE: Motor recovery after stroke can be characterized into two different patterns. A majority of patients recover about 70% of initial impairment, whereas some patients with severe initial deficits show little or no improvement. Here, we investigated whether recovery from visuospatial neglect and aphasia is also separated into two different groups and whether similar proportions of recovery can be expected for the two cognitive functions. METHODS: We assessed 35 patients with neglect and 14 patients with aphasia at 3 weeks and 3 months after stroke using standardized tests. Recovery patterns were classified with hierarchical clustering and the proportion of recovery was estimated from initial impairment using a linear regression analysis. RESULTS: Patients were reliably clustered into two different groups. For patients in the first cluster (n = 40), recovery followed a linear model where improvement was proportional to initial impairment and achieved 71% of maximal possible recovery for both cognitive deficits. Patients in the second cluster (n = 9) exhibited poor recovery (<25% of initial impairment). CONCLUSIONS: Our findings indicate that improvement from neglect or aphasia after stroke shows the same dichotomy and proportionality as observed in motor recovery. This is suggestive of common underlying principles of plasticity, which apply to motor and cognitive functions.

Memory in time: electrophysiological comparison between reality filtering and temporal order judgment.

Orbitofrontal reality filtering (ORF) denotes a little known but vital memory control mechanism, expressed at 200-300ms after stimulus presentation, that allows one to sense whether evoked memories (thoughts) refer to present reality and can be acted upon, or not. Its failure induces reality confusion evident in confabulations that patients act upon and disorientation. In what way ORF differs from temporal order judgment (TOJ), that is, the conscious knowledge about when something happened in the past, has never been explored. Here we used evoked potential analysis to compare ORF and TOJ within a combined experimental task and within a comparable time frame, close to the experienced present. Seventeen healthy human subjects performed an experiment using continuous recognition tasks that combined the challenges of ORF and TOJ. We found that the two mechanisms dissociated behaviorally: subjects were markedly slower and less accurate in TOJ than ORF. Both mechanisms evoked similar potentials at 240-280ms, when ORF normally occurs. However, they rapidly dissociated in terms of amplitude differences and electrical source from 310 to 360ms and again from 530 to 560ms. We conclude that the task of consciously ordering memories in the immediate past (TOJ) is effortful and slow in contrast to sensing memories' relation with the present (ORF). Both functions invoke similar early electrocortical processes which then rapidly dissociate and engage different brain areas. The results are consistent with the different consequences of the two mechanisms' dysfunction: while failure of ORF has a known clinical manifestation (reality confusion as evident in confabulation and disorientation), the failure of TOJ, as tested here, has no such known clinical correlate.

Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation.

BACKGROUND: Reliable recording of motor evoked potentials (MEPs) of the masseter muscle by transcranial magnetic stimulation (TMS) has proved more difficult than from facial or intrinsic hand muscles. Up to now it was unclear whether this difficulty was due to methodological and/or anatomical reasons. METHODS: The mechanism of pyramidal cell activation in masseter MEPs was investigated by using magnetic and electric transcranial stimulation. Analysing the effect of magnetic coil positioning and orientation over the scalp, and scrutinizing the masseter recording technique to avoid compound motor action potential (CMAP) contamination from facial muscles, an optimized method of masseter MEPs was developed. RESULTS: In particular, an antero-lateral inducing current orientation in the stimulating coil, approximately paralleling the central sulcus, proved clearly more effective for the masseter muscles than the postero-lateral orientation (P=0.005) found optimal for intrinsic hand muscles. The thus evoked masseter MEPs by transcranial magnetic stimulation (TMS) were found to be identical in shape, amplitude and latency as those evoked by transcranial electric stimulation (TES), evidencing a direct rather than trans-synaptic activation of the pyramidal cells. CONCLUSIONS: We conclude that in TMS evoked MEPs of masseter muscles, the direct stimulation of the pyramidal tract is more easily achieved than the trans-synaptic activation, which is in contrast to the intrinsic hand muscles. We hypothesize that the presynaptic projections to pyramidal cells of the masticatory muscles are less abundant than in hand muscles, and are therefore less accessible to trans-synaptic stimulation.