Distinct Neurophysiological Mechanisms Support the Online Formation of Individual and Across-Episode Memory Representations.

Individual experiences often overlap in their content, presenting opportunities for rapid generalization across them. In this study, we show in 2 independent experiments that integrative encoding-the ability to form individual and across memory representations during online encoding-is supported by 2 distinct neurophysiological responses. Brain potential is increased gradually during encoding and fit to a trial level memory measure for individual episodes, whereas neural oscillations in the theta range (4-6 Hz) emerge later during learning and predict participants' generalization performance in a subsequent test. These results suggest that integrative encoding requires the recruitment of 2 separate neural mechanisms that, despite their co-occurrence in time, differ in their underlying neural dynamics, reflect different brain learning rates and are supportive of the formation of opposed memory representations, individual versus across-event episodes.

Music supported therapy promotes motor plasticity in individuals with chronic stroke.

Novel rehabilitation interventions have improved motor recovery by induction of neural plasticity in individuals with stroke. Of these, Music-supported therapy (MST) is based on music training designed to restore motor deficits. Music training requires multimodal processing, involving the integration and co-operation of visual, motor, auditory, affective and cognitive systems. The main objective of this study was to assess, in a group of 20 individuals suffering from chronic stroke, the motor, cognitive, emotional and neuroplastic effects of MST. Using functional magnetic resonance imaging (fMRI) we observed a clear restitution of both activity and connectivity among auditory-motor regions of the affected hemisphere. Importantly, no differences were observed in this functional network in a healthy control group, ruling out possible confounds such as repeated imaging testing. Moreover, this increase in activity and connectivity between auditory and motor regions was accompanied by a functional improvement of the paretic hand. The present results confirm MST as a viable intervention to improve motor function in chronic stroke individuals.

Tracking post-error adaptation in the motor system by transcranial magnetic stimulation.

The commission of an error triggers cognitive control processes dedicated to error correction and prevention. Post-error adjustments leading to response slowing following an error ("post-error slowing"; PES) might be driven by changes in excitability of the motor regions and the corticospinal tract (CST). The time-course of such excitability modulations of the CST leading to PES is largely unknown. To track these presumed excitability changes after an error, single pulse transcranial magnetic stimulation (TMS) was applied to the motor cortex ipsilateral to the responding hand, while participants were performing an Eriksen flanker task. A robotic arm with a movement compensation system was used to maintain the TMS coil in the correct position during the experiment. Magnetic pulses were delivered over the primary motor cortex ipsilateral to the active hand at different intervals (150, 300, 450 ms) after correct and erroneous responses, and the motor-evoked potentials (MEP) of the first dorsal interosseous muscle (FDI) contralateral to the stimulated hemisphere were recorded. MEP amplitude was increased 450 ms after the error. Two additional experiments showed that this increase was neither associated to the correction of the erroneous responses nor to the characteristics of the motor command. To the extent to which the excitability of the motor cortex ipsi- and contralateral to the response hand are inversely related, these results suggest a decrease in the excitability of the active motor cortex after an erroneous response. This modulation of the activity of the CST serves to prevent further premature and erroneous responses. At a more general level, the study shows the power of the TMS technique for the exploration of the temporal evolution of post-error adjustments within the motor system.

Analysis of automated methods for spatial normalization of lesioned brains.

Normalization of brain images is a crucial step in MRI data analysis, especially when dealing with abnormal brains. Although cost function masking (CFM) appears to successfully solve this problem and seems to be necessary for patients with chronic stroke lesions, this procedure is very time consuming. The present study sought to find viable, fully automated alternatives to cost function masking, such as Automatic Lesion Identification (ALI) and Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). It also sought to quantitatively assess, for the first time, Symmetrical Normalization (SyN) with constrained cost function masking. The second aim of this study was to investigate the normalization process in a group of drug-resistant epileptic patients with large resected regions (temporal lobe and amygdala) and in a group of stroke patients. A dataset of 500 artificially generated lesions was created using ten patients with brain-resected regions (temporal lobectomy), ten stroke patients and twenty five-healthy subjects. The results indicated that although a fully automated method such as DARTEL using New Segment with an extra prior (the mean of the white matter and cerebro-spinal fluid) obtained the most accurate normalization in both patient groups, it produced a shrinkage in lesion volume when compared to Unified Segmentation with CFM. Taken together, these findings suggest that further research is needed in order to improve automatic normalization processes in brains with large lesions and to completely abandon manual, time consuming normalization methods.

Human hypothalamus shows differential responses to basic motivational stimuli--an invasive electrophysiology study.

The hypothalamus supports basic motivational behaviours such as mating and feeding. Recording directly from the posterior inferior hypothalamus in a male patient receiving a deep brain stimulation (DBS) electrode for the alleviation of cluster headache, we tested the hypothalamic response to different classes of motivational stimuli (sexually relevant: pictures of dressed and undressed women; pictures of food) and pictures of common objects as control. Averaged local field potentials (LFP) to sexually relevant stimuli were characterized by a biphasic significantly enhanced response (relative to objects; bootstrapping statistics) with a first phase starting at around 200 ms and a second phase peaking at around 600 ms. Sexually relevant stimuli also showed a greatly enhanced positivity relative to other stimulus classes in surface event-related potentials in a group of 11 male control participants. It is suggested that the hypothalamus is involved in the recruitment of attentional resources by sexually relevant stimuli reflected in this surface positivity. In a second session, the response to food stimuli relative to objects was tested in two states: after fasting for 14 h, LFPs to food and object stimuli showed significant differences in between 300 and 850 ms, which disappeared after a full high-calorie meal, thus replicating classic studies in monkeys [Rolls et al., Brain Res (1976) 111:53-66]. The current data are the first to demonstrate hypothalamic responses to the sight of motivational stimuli in man and thus shows that recording from DBS electrodes might provide important information about the cognitive functions of subcortical structures.

Neural reorganization underlies improvement in stroke-induced motor dysfunction by music-supported therapy.

Motor impairments are common after stroke, but efficacious therapies for these dysfunctions are scarce. By extending an earlier study on the effects of music-supported therapy, behavioral indices of motor function as well as electrophysiological measures were obtained before and after a series of therapy sessions to assess whether this new treatment leads to neural reorganization and motor recovery in patients after stroke. The study group comprised 32 stroke patients in a large rehabilitation hospital; they had moderately impaired motor function and no previous musical experience. Over a period of 3 weeks, these patients received 15 sessions of music-supported therapy using a manualized step-by-step approach. For comparison 30 additional patients received standard rehabilitation procedures. Fine as well as gross motor skills were trained by using either a MIDI-piano or electronic drum pads programmed to emit piano tones. Motor functions were assessed by an extensive test battery. In addition, we studied event-related desynchronization/synchronization and coherences from all 62 patients performing self-paced movements of the index finger (MIDI-piano) and of the whole arm (drum pads). Results showed that music-supported therapy yielded significant improvement in fine as well as gross motor skills with respect to speed, precision, and smoothness of movements. Neurophysiological data showed a more pronounced event-related desynchronization before movement onset and a more pronounced coherence in the music-supported therapy group in the post-training assessment, whereas almost no differences were observed in the control group. Thus we see that music-supported therapy leads to marked improvements of motor function after stroke and that these are accompanied by electrophysiological changes indicative of a better cortical connectivity and improved activation of the motor cortex.

Theta EEG oscillatory activity and auditory change detection.

The mismatch negativity is an electrophysiological marker of auditory change detection in the event-related brain potential and has been proposed to reflect an automatic comparison process between an incoming stimulus and the representation of prior items in a sequence. There is evidence for two main functional subcomponents comprising the MMN, generated by temporal and frontal brain areas, respectively. Using data obtained in an MMN paradigm, we performed time-frequency analysis to reveal the changes in oscillatory neural activity in the theta band. The results suggest that the frontal component of the MMN is brought about by an increase in theta power for the deviant trials and, possibly, by an additional contribution of theta phase alignment. By contrast, the temporal component of the MMN, best seen in recordings from mastoid electrodes, is generated by phase resetting of theta rhythm with no concomitant power modulation. Thus, frontal and temporal MMN components do not only differ with regard to their functional significance but also appear to be generated by distinct neurophysiological mechanisms.

Functional neural dynamics underlying auditory event-related N1 and N1 suppression response.

Presenting tone triplets of identical stimuli preceded by silent intervals of 30 s produces a series of three N1 averaged event-related potentials (ERPs), the first being of greater amplitude (non-suppressed N1) than the second and third ones (suppressed N1). Maximal statistically independent components (ICs) of single-trial multi-electrode scalp EEG responses to triplets were obtained by ICA algorithm, and then each IC was searched for underlying brain structures by LORETA inverse solution, and for oscillatory contributions by time-frequency analysis. Non-suppressed N1 cortical mechanisms were broken down into five ICs, grouped in two time-windows (early-onset and late-onset) involving the participation of temporal, frontal and parietal structures, and sub-serving EEG oscillatory contributions of power enhancement and putative phase concentration of mainly theta, alpha and low beta bands. Suppressed N1 was due to the modulation of two above-mentioned early-onset ICs, involving temporal structures only, and mainly sub-serving oscillatory contributions of phase concentration of theta and alpha. Present results, showing quantifiable changes of IC descriptors - i.e. time window of activation, implied structures and oscillatory contributions - extracted from two distinct brain functional situations (non-suppressed versus suppressed N1), give support to the view that ICA is not merely a statistical "latent variables" model when applied to ERPs, but could help to capture underlying specific function subunits of brain dynamics.

Mismatch negativity impairment associated with alcohol consumption in chronic alcoholics: a scalp current density study.

Previous studies, based on amplitude and latency measurements of auditory event-related brain potentials, yielded inconclusive results about the status of mismatch negativity (MMN) in chronic alcoholics. The present study explores scalp current density (SCD) dynamics during MMN latency range in alcoholics, and correlates electrical SCD results with clinical data of the patients. SCD was computed from 30 electrodes in 16 abstinent chronic alcoholics and 16 healthy control volunteers in a paradigm on MMN elicited by duration changes. Reduced activity was observed in left frontal and right anterior and posterior temporal areas during MMN in alcoholics. Alcohol consumption correlated negatively with SCD intensity in these regions. Delayed activation was observed in the left posterior temporal area in the patients. Alcohol abstinence duration correlated positively with SCD intensity in this region. These results point to an impairment of automatic brain processing mechanisms associated with auditory change detection in chronic alcoholism. The present results suggest a reorganization of the computational neurodynamics of automatic auditory change detection linked to the amount of alcohol consumed in abstinent chronic alcoholics.

Location of brain rhythms and their modulation by preparatory attention estimated by current density.

To test the hypothesis that there is a functional modulation of conventional EEG bands associated with preparatory attention, putative changes in the spontaneous brain rhythms and their associated cerebral sources were addressed. The goals of the present report were, first, to find the brain areas with maximal rhythmic activity before warning and imperative stimuli in a classic contingent negative variation (CNV) paradigm, and, second, to study the modulation of the EEG rhythms of these areas during the preparatory attention interval which precedes the S2 (imperative) stimulus. Trial by trial LORETA analysis found similar brain rhythm generators during both pre-S1 and pre-S2 intervals. Each theta, alpha and beta traditional EEG rhythm originates in several anatomically distinct brain structures. Preparatory attention is associated with a decrease in power in alpha (right and left occipital and temporal areas) and low-beta (left frontal, bilateral occipital and middle frontal areas) EEG bands. In these structures power changes associated with preparatory attention modulated either a dominant or a non-dominant oscillatory band, suggesting that non-dominant rhythms of a cerebral area have some functional relevance. Our results imply distributed regional sources for brain rhythms and support the view that during preparatory attention there is a modulation of the brain sources generating alpha and beta brain rhythms. Moreover, the proposed combined approach makes it possible to explore the definition of a given brain area not only anatomically, but also by the frequency content and the functional reactivity of the electrical rhythms that it generates.

Modulation of spectral power and of phase resetting of EEG contributes differentially to the generation of auditory event-related potentials.

Nowadays, the mechanisms involved in the genesis of event-related potentials (ERPs) are a matter of debate among neuroscientists. Specifically, the debate lies in whether ERPs arise due to the contribution of a fixed-polarity and fixed-latency superimposed neuronal activity to background electroencephalographic oscillations (evoked model) and/or due to a partial phase synchronization of the ongoing EEG (oscillatory model). The participation of the two mechanisms can be explored by the spectral power modulation and phase coherence of scalp EEG rhythms, respectively. However, an important limitation underlies their measurement: the fact that an added neural activity will be relatively phase-locked to stimulus, thus enhancing both spectral power and phase synchrony measures and making the contribution of each mechanism less clear-cut. This would not be relevant in the case that an increase in phase concentration was not accompanied by any concurrent spectral power modulation, thus opening the way to an oscillatory-based explanation. We computed event-related spectral power modulations and phase coherence to an auditory repeated-stimulus presentation paradigm with tone intensity far from threshold (90 dB SPL), in which N1 decreases its amplitude (N1 gating) as an attenuation brain process. Our data indicate that evoked and oscillatory activity could contribute together to the non-attenuated N1, while N1 to repeated stimuli could be explained by partial phase concentration of scalp EEG activity without concurrent power increase. Therefore, our results show that both increased spectral power and partial phase resetting contribute differentially to different ERPs. Moreover, they show that certain ERPs could arise through reorganization of the phase of ongoing scalp EEG activity only.

Combined ICA-LORETA analysis of mismatch negativity.

A major challenge for neuroscience is to map accurately the spatiotemporal patterns of activity of the large neuronal populations that are believed to underlie computing in the human brain. To study a specific example, we selected the mismatch negativity (MMN) brain wave (an event-related potential, ERP) because it gives an electrophysiological index of a "primitive intelligence" capable of detecting changes, even abstract ones, in a regular auditory pattern. ERPs have a temporal resolution of milliseconds but appear to result from mixed neuronal contributions whose spatial location is not fully understood. Thus, it is important to separate these sources in space and time. To tackle this problem, a two-step approach was designed combining the independent component analysis (ICA) and low-resolution tomography (LORETA) algorithms. Here we implement this approach to analyze the subsecond spatiotemporal dynamics of MMN cerebral sources using trial-by-trial experimental data. We show evidence that a cerebral computation mechanism underlies MMN. This mechanism is mediated by the orchestrated activity of several spatially distributed brain sources located in the temporal, frontal, and parietal areas, which activate at distinct time intervals and are grouped in six main statistically independent components.