Ovidiu Lungu

Brain plasticity related to the consolidation of motor sequence learning and motor adaptation

This study aimed to investigate, through functional MRI (fMRI), the neuronal substrates associated with the consolidation process of two motor skills: motor sequence learning (MSL) and motor adaptation (MA). Four groups of young healthy individuals were assigned to either (i) a night/sleep condition, in which they were scanned while practicing a finger sequence learning task or an eight-target adaptation pointing task in the evening (test) and were scanned again 12 h later in the morning (retest) or (ii) a day/awake condition, in which they were scanned on the MSL or the MA tasks in the morning and were rescanned 12 h later in the evening. As expected and consistent with the behavioral results, the functional data revealed increased test–retest changes of activity in the striatum for the night/sleep group compared with the day/awake group in the MSL task. By contrast, the results of the MA task did not show any difference in test–retest activity between the night/sleep and day/awake groups. When the two MA task groups were combined, however, increased test–retest activity was found in lobule VI of the cerebellar cortex. Together, these findings highlight the presence of both functional and structural dissociations reflecting the off-line consolidation processes of MSL and MA. They suggest that MSL consolidation is sleep dependent and reflected by a differential increase of neural activity within the corticostriatal system, whereas MA consolidation necessitates either a period of daytime or sleep and is associated with increased neuronal activity within the corticocerebellar system.

Cortical control of motor sequences

The neural substrate of sequence learning is well known. However, we lack a clear understanding of the detailed functional properties of many of the areas involved. The reason for this discrepancy lies, in part, in the fact that two types of processes, implicit and explicit, subserve motor sequence learning, and these often interact with each other. The most significant recent advances have been the elucidation of the very complex relationships between medial motor areas and the temporal and ordinal control of sequences, and the demonstration that motor cortex is an important site for sequence storage and production. The challenge for the future will be to develop a coherent and internally consistent theory of sequence control.

Differential Effect of Reward and Punishment on Procedural Learning

Reward and punishment are potent modulators of associative learning in instrumental and classical conditioning. However, the effect of reward and punishment on procedural learning is not known. The striatum is known to be an important locus of reward-related neural signals and part of the neural substrate of procedural learning. Here, using an implicit motor learning task, we show that reward leads to enhancement of learning in human subjects, whereas punishment is associated only with improvement in motor performance. Furthermore, these behavioral effects have distinct neural substrates with the learning effect of reward being mediated through the dorsal striatum and the performance effect of punishment through the insula. Our results suggest that reward and punishment engage separate motivational systems with distinctive behavioral effects and neural substrates.

The impact of aging on gray matter structural covariance networks

Previous anatomical volumetric studies have shown that healthy aging is associated with gray matter tissue loss in specific cerebral regions. However, these studies may have potentially missed critical elements of age-related brain changes, which largely exist within interrelationships among brain regions. This magnetic resonance imaging research aims to assess the effects of aging on the organization of gray matter structural covariance networks. Here, we used voxel-based morphometry on high-definition brain scans to compare the patterns of gray matter structural covariance networks that sustain different sensorimotor and high-order cognitive functions among young (n=88, mean age=23.5±3.1 years, female/male=55/33) and older (n=88, mean age=67.3±5.9 years, female/male=55/33) participants. This approach relies on the assumption that functionally correlated brain regions show correlations in gray matter volume as a result of mutually trophic influences or common experience-related plasticity. We found reduced structural association in older adults compared with younger adults, specifically in high-order cognitive networks. Major differences were observed in the structural covariance networks that subserve the following: a) the language-related semantic network, b) the executive control network, and c) the default-mode network. Moreover, these cognitive functions are typically altered in the older population. Our results indicate that healthy aging alters the structural organization of cognitive networks, shifting from a more distributed (in young adulthood) to a more localized topological organization in older individuals.

Predictive motor timing performance dissociates between early diseases of the cerebellum and Parkinson's disease.

There is evidence that both the basal ganglia and the cerebellum play a role in the neural representation of time in a variety of behaviours, but whether one of them is more important is not yet clear. To address this question in the context of predictive motor timing, we tested patients with various movement disorders implicating these two structures in a motor-timing task. Specifically, we investigated four different groups: (1) patients with early Parkinsons disease (PD); (2) patients with sporadic spinocerebellar ataxia (SCA); (3) patients with familial essential tremor (ET); and (4) matched healthy controls. We used a predictive motor-timing task that involved mediated interception of a moving target, and we assessed the effect of movement type (acceleration, deceleration and constant), speed (slow, medium and fast) and angle (0°, 15° and 30°) on performance (hit, early error and late error). The main results showed that PD group and arm ET subgroup did not significantly differ from the control group. SCA and head ET subjects (severe and mild cerebellar damage, respectively) were significantly worse at interception than the other two groups. Our findings support the idea that the basal ganglia play a less significant role in predictive motor timing than the cerebellum. The fact that SCA and ET subjects seemed to have a fundamental problem with predictive motor timing suggests that the cerebellum plays an essential role in integrating incoming visual information with the motor output in a timely manner, and that ET is a heterogeneous entity that deserves increased attention from clinicians.

Daytime sleep enhances consolidation of the spatial but not motoric representation of motor sequence memory.

Motor sequence learning is known to rely on more than a single process. As the skill develops with practice, two different representations of the sequence are formed: a goal representation built under spatial allocentric coordinates and a movement representation mediated through egocentric motor coordinates. This study aimed to explore the influence of daytime sleep (nap) on consolidation of these two representations. Through the manipulation of an explicit finger sequence learning task and a transfer protocol, we show that both allocentric (spatial) and egocentric (motor) representations of the sequence can be isolated after initial training. Our results also demonstrate that nap favors the emergence of offline gains in performance for the allocentric, but not the egocentric representation, even after accounting for fatigue effects. Furthermore, sleep-dependent gains in performance observed for the allocentric representation are correlated with spindle density during non-rapid eye movement (NREM) sleep of the post-training nap. In contrast, performance on the egocentric representation is only maintained, but not improved, regardless of the sleep/wake condition. These results suggest that motor sequence memory acquisition and consolidation involve distinct mechanisms that rely on sleep (and specifically, spindle) or simple passage of time, depending respectively on whether the sequence is performed under allocentric or egocentric coordinates.

Impaired predictive motor timing in patients with cerebellar disorders.

The ability to precisely time events is essential for both perception and action. There is evidence that the cerebellum is important for the neural representation of time in a variety of behaviors including time perception, the tapping of specific time intervals, and eye-blink conditioning. It has been difficult to assess the contribution of the cerebellum to timing during more dynamic motor behavior because the component movements themselves may be abnormal or any motor deficit may be due to an inability to combine the component movements into a complete action rather than timing per se. Here we investigated the performance of subjects with cerebellar disease in predictive motor timing using a task that involved mediated interception of a moving target, and we tested the effect of movement type (acceleration, deceleration, constant), speed (slow, medium, fast), and angle (0°, 15° and 30°) on performance. The subjects with cerebellar damage were significantly worse at interception than healthy controls even when we controlled for basic motor impairments such as response time. Our data suggest that subjects with damage to the cerebellum have a fundamental problem with predictive motor timing and indicate that the cerebellum plays an essential role in integrating incoming visual information with motor output when making predictions about upcoming actions. The findings demonstrate that the cerebellum may have properties that would facilitate the processing or storage of internal models of motor behavior.

Sleep spindles predict neural and behavioral changes in motor sequence consolidation

The purpose of this study was to investigate the predictive function of sleep spindles in motor sequence consolidation. BOLD responses were acquired in 10 young healthy subjects who were trained on an explicitly known 5‐item sequence using their left nondominant hand, scanned at 9:00 pm while performing that same task and then were retested and scanned 12 h later after a night of sleep during which polysomnographic measures were recorded. An automatic algorithm was used to detect sleep spindles and to quantify their characteristics (i.e., density, amplitude, and duration). Analyses revealed significant positive correlations between gains in performance and the amplitude of spindles. Moreover, significant increases in BOLD signal were observed in several motor‐related areas, most of which were localized in the right hemisphere, particularly in the right cortico‐striatal system. Such increases in BOLD signal also correlated positively with the amplitude of spindles at several derivations. Taken together, our results show that sleep spindles predict neural and behavioral changes in overnight motor sequence consolidation. Hum Brain Mapp 34:2918–2928, 2013.

Agenesis of corpus callosum and emotional information processing in schizophrenia.

Corpus callosum (CC) is essential in providing the integration of information related to perception and action within a subcortico-cortical network, thus supporting the generation of a unified experience about and reaction to changes in the environment. Its role in schizophrenia is yet to be fully elucidated, but there is accumulating evidence that there could be differences between patients and healthy controls regarding the morphology and function of CC, especially when individuals face emotionally laden information. Here, we report a case study of a patient with partial agenesis of corpus callosum (agCC patient with agenesis of the anterior aspect, above the genu) and we provide a direct comparison with a group of patients with no apparent callosal damage (CC group) regarding the brain activity during the processing of emotionally laden information. We found that although the visual cortex activation in response to visual stimuli regardless of their emotional content was comparable in agCC patient and CC group both in terms of localization and intensity of activation, we observed a very large, non-specific and non-lateralized cerebral activation in the agCC patient, in contrast with the CC group, which showed a more lateralized and spatially localized activation, when the emotional content of the stimuli was considered. Further analysis of brain activity in the regions obtained in the CC group revealed that the agCC patient actually had an opposite activation pattern relative to most participants with no CC agenesis, indicating a dysfunctional response to these kind of stimuli, consistent with the clinical presentation of this particular patient. Our results seem to give support to the disconnection hypothesis which posits that the core symptoms of schizophrenia are related to aberrant connectivity between distinct brain areas, especially when faced with emotional stimuli, a fact consistent with the clinical tableau of this particular patient.

Primary Motor Area Activation during Precision-Demanding versus Simple Finger Movement

The authors used functional magnetic resonance imaging to explore whether the primary motor area (M1) serves a processing role in a finger-movement tracking task, emphasizing attention to accuracy, beyond its execution role of simple movements, with no attention to accuracy. Twenty healthy subjects performed alternating conditions: Rest, involving no finger movement; Track, involving careful control of a cursor along a target pathway with finger extension/flexion movements; and Move, involving finger extension/flexion movements without careful control. The authors compared volume of activated voxels in the M1, blood-oxygen-level-dependent (BOLD) signal intensity of activated voxels in the M1, and BOLD signal intensity of all voxels in the M1 between the Track and Move conditions. The results showed greater volume and signal intensity in both the contralateral and ipsilateral M1 during Track than during Move. Overall, the results suggest that the M1 is engaged not only in the execution of movements but also in spatial and temporal processing to produce accurately controlled movements. These findings invite further work exploring whether precision-demanding movements, such as tracking, form a more potent stimulus for promoting helpful brain reorganization in the M1 during the recovery from stroke than simple repetitive movements.