The causal role of the subthalamic nucleus in the inhibitory network.

The neural network mediating successful response inhibition mainly includes right hemisphere activation of the pre-supplementary motor area, inferior frontal gyrus (IFG), subthalamic nucleus (STN), and caudate nucleus. However, the causal role of these regions in the inhibitory network is undefined. Five patients with Parkinson's disease were assessed prior to and after therapeutic thermal ablation of the right STN in two separate functional magnetic resonance imaging (fMRI) sessions while performing a stop-signal task. Initiation times were faster but motor inhibition with the left hand (contralateral to the lesion) was significantly impaired as evident in prolonged stop-signal reaction times. Reduced inhibition after right subthalamotomy was associated (during successful inhibition) with the recruitment of basal ganglia regions outside the established inhibitory network. They included the putamen and caudate together with the anterior cingulate cortex and IFG of the left hemisphere. Subsequent network connectivity analysis (with the seed over the nonlesioned left STN) revealed a new inhibitory network after right subthalamotomies. Our results highlight the causal role of the right STN in the neural network for motor inhibition and the possible basal ganglia mechanisms for compensation upon losing a key node of the inhibition network.

Functional asymmetries in early learning during right, left, and bimanual performance in right-handed subjects.

PURPOSE: To elucidate differences in activity and connectivity during early learning due to the performing hand. MATERIALS AND METHODS: Twenty right-handed subjects were recruited. The neural correlates of explicit visuospatial learning executed with the right, the left hand, and bimanually were investigated using functional magnetic resonance imaging. Connectivity analyses were carried out using the psychophysiological interactions model, considering right and left anterior putamen as index regions. RESULTS: A common neural network was found for the three tasks during learning. Main activity increases were located in posterior cingulate cortex, supplementary motor area, parietal cortex, anterior putamen, and cerebellum (IV-V), whereas activity decrements were observed in prefrontal regions. However, the left hand task showed a greater recruitment of left hippocampal areas when compared with the other tasks. In addition, enhanced connectivity between the right anterior putamen and motor cortical and cerebellar regions was found for the left hand when compared with the right hand task. CONCLUSION: An additional recruitment of brain regions and increased striato-cortical and striato-cerebellar functional connections is needed when early learning is performed with the nondominant hand. In addition, access to brain resources during learning may be directed by the dominant hand in the bimanual task.

Cortical hypoperfusion in Parkinson's disease assessed using arterial spin labeled perfusion MRI.

Alterations in cerebral perfusion and metabolism in Parkinson's disease have been assessed in several studies, using nuclear imaging techniques and more recently magnetic resonance imaging. However, to date there is no consensus in the literature regarding the extent and the magnitude of these alterations. In this work, arterial spin labeled perfusion MRI was employed to quantify absolute cerebral blood flow in a group of early-to-moderate Parkinson's disease patients and age-matched healthy controls. Perfusion comparisons between the two groups showed that Parkinson's disease is characterized by wide-spread cortical hypoperfusion. Subcortically, hypoperfusion was also found in the caudate nucleus. This pattern of hypoperfusion could be related to cognitive dysfunctions that have been previously observed even at the disease early stages. The present results were obtained by means of whole brain voxel-wise comparisons of absolute perfusion values, using statistical parametric mapping, thus avoiding the potentially biased global mean normalization procedure. In addition, this work demonstrates that between-group comparison of relative perfusion values after global mean normalization, introduced artifactual relative perfusion increases, where absolute perfusion was in fact preserved. This has implications for perfusion studies of other brain disorders.

The motor inhibitory network in patients with asymmetrical Parkinson's disease: An fMRI study.

Recent imaging studies with the stop-signal task in healthy individuals indicate that the subthalamic nucleus, the pre-supplementary motor area and the inferior frontal gyrus are key components of the right hemisphere "inhibitory network". Limited information is available regarding neural substrates of inhibitory processing in patients with asymmetric Parkinson's disease. The aim of the current fMRI study was to identify the neural changes underlying deficient inhibitory processing on the stop-signal task in patients with predominantly left-sided Parkinson's disease. Fourteen patients and 23 healthy controls performed a stop-signal task with the left and right hands. Behaviorally, patients showed delayed response inhibition with either hand compared to controls. We found small imaging differences for the right hand, however for the more affected left hand when behavior was successfully inhibited we found reduced activation of the inferior frontal gyrus bilaterally and the insula. Using the stop-signal delay as regressor, contralateral underactivation in the right dorsolateral prefrontal cortex, inferior frontal and anterior putamen were found in patients. This finding indicates dysfunction of the right inhibitory network in left-sided Parkinson's disease. Functional connectivity analysis of the left subthalamic nucleus showed a significant increase of connectivity with bilateral insula. In contrast, the right subthalamic nucleus showed increased connectivity with visuomotor and sensorimotor regions of the cerebellum. We conclude that altered inhibitory control in left-sided Parkinson's disease is associated with reduced activation in regions dedicated to inhibition in healthy controls, which requires engagement of additional regions, not observed in controls, to successfully stop ongoing actions.

Brain Activity and Functional Connectivity Patterns Associated With Fast and Slow Motor Sequence Learning in Late Middle Adulthood.

The human brain undergoes structural and functional changes across the lifespan. The study of motor sequence learning in elderly subjects is of particularly interest since previous findings in young adults might not replicate during later stages of adulthood. The present functional magnetic resonance imaging (fMRI) study assessed the performance, brain activity and functional connectivity patterns associated with motor sequence learning in late middle adulthood. For this purpose, a total of 25 subjects were evaluated during early stages of learning [i.e., fast learning (FL)]. A subset of these subjects (n = 11) was evaluated after extensive practice of a motor sequence [i.e., slow learning (SL) phase]. As expected, late middle adults improved motor performance from FL to SL. Learning-related brain activity patterns replicated most of the findings reported previously in young subjects except for the lack of hippocampal activity during FL and the involvement of cerebellum during SL. Regarding functional connectivity, precuneus and sensorimotor lobule VI of the cerebellum showed a central role during improvement of novel motor performance. In the sample of subjects evaluated, connectivity between the posterior putamen and parietal and frontal regions was significantly decreased with aging during SL. This age-related connectivity pattern may reflect losses in network efficiency when approaching late adulthood. Altogether, these results may have important applications, for instance, in motor rehabilitation programs.

Continuous performance of a novel motor sequence leads to highly correlated striatal and hippocampal perfusion increases.

The time course of changes in regional cerebral perfusion during a continuous motor learning task performed with the right hand was monitored using the arterial spin labeling (ASL) technique at high field (3 T). ASL allowed measuring explicit learning related effects in neural activity elicited throughout a 6 minute task period. During this time learning took place as demonstrated by performance improvement. Comparing the initial and final learning phases, perfusion decreases were detected in most of the cortical regions recruited during early learning. More interestingly however perfusion increases were observed in a few cortical and subcortical regions of the contralateral hemisphere: the supplementary motor area, the primary somatosensory area, the posterior insula and posterior putamen, the hippocampus and bilaterally the retrosplenial cortex. Moreover, perfusion increases in the posterior putamen and hippocampus were highly correlated during the learning period. These results support the hypothesis that the striatum and hippocampus form interactive memory systems with parallel processing.

Functional and anatomical basis for brain plasticity in facial palsy rehabilitation using the masseteric nerve.

Several techniques have been described for smile restoration after facial nerve paralysis. When a nerve other than the contralateral facial nerve is used to restore the smile, some controversy appears because of the nonphysiological mechanism of smile recovering. Different authors have reported natural results with the masseter nerve. The physiological pathways which determine whether this is achieved continue to remain unclear. Using functional magnetic resonance imaging, brain activation pattern measuring blood-oxygen-level-dependent (BOLD) signal during smiling and jaw clenching was recorded in a group of 24 healthy subjects (11 females). Effective connectivity of premotor regions was also compared in both tasks. The brain activation pattern was similar for smile and jaw-clenching tasks. Smile activations showed topographic overlap though more extended for smile than clenching. Gender comparisons during facial movements, according to kinematics and BOLD signal, did not reveal significant differences. Effective connectivity results of psychophysiological interaction (PPI) from the same seeds located in bilateral facial premotor regions showed significant task and gender differences (p < 0.001). The hypothesis of brain plasticity between the facial nerve and masseter nerve areas is supported by the broad cortical overlap in the representation of facial and masseter muscles.

Dopaminergic modulation of the trade-off between probability and time in economic decision-making.

Studies on animals and humans have demonstrated the importance of dopamine in modulating decision-making processes. In this work, we have tested dopaminergic modulation of economic decision-making and its neural correlates by administering either placebo or metoclopramide, a dopamine D2-receptor antagonist, to healthy subjects, during a functional MRI study. The decision-making task combined probability and time delay with a fixed monetary reward. For individual behavioral characterization, we used the Probability Time Trade-off (PTT) economic model, which integrates the traditional trade-offs of reward magnitude-time and reward magnitude-probability into a single measurement, thereby quantifying the subjective value of a delayed and probabilistic outcome. A regression analysis between BOLD signal and the PTT model index permitted to identify the neural substrate encoding the subjective reward-value. Behaviorally, medication reduced the rate of temporal discounting over probability, reflected in medicated subjects being more prone to postpone the reward in order to increase the outcome probability. In addition, medicated subjects showed less activity during the task in the postcentral gyrus as well as frontomedian areas, whereas there were no differences in the ventromedial orbitofrontal cortex (VMOFC) between groups when coding the subjective value. The present study demonstrates by means of behavior and imaging that dopamine modulation alters the probability-time trade-off in human economic decision-making.

The neural substrate and functional integration of uncertainty in decision making: an information theory approach.

Decision making can be regarded as the outcome of cognitive processes leading to the selection of a course of action among several alternatives. Borrowing a central measurement from information theory, Shannon entropy, we quantified the uncertainties produced by decisions of participants within an economic decision task under different configurations of reward probability and time. These descriptors were used to obtain blood oxygen level-dependent (BOLD) signal correlates of uncertainty and two clusters codifying the Shannon entropy of task configurations were identified: a large cluster including parts of the right middle cingulate cortex (MCC) and left and right pre-supplementary motor areas (pre-SMA) and a small cluster at the left anterior thalamus. Subsequent functional connectivity analyses using the psycho-physiological interactions model identified areas involved in the functional integration of uncertainty. Results indicate that clusters mostly located at frontal and temporal cortices experienced an increased connectivity with the right MCC and left and right pre-SMA as the uncertainty was higher. Furthermore, pre-SMA was also functionally connected to a rich set of areas, most of them associative areas located at occipital and parietal lobes. This study provides a map of the human brain segregation and integration (i.e., neural substrate and functional connectivity respectively) of the uncertainty associated to an economic decision making paradigm.