Neural Encoding of the Reliability of Directional Information During the Preparation of Targeted Movements.

Visual information about the location of an upcoming target can be used to prepare an appropriate motor response and reduce its reaction time. Here, we investigated the brain mechanisms associated with the reliability of directional information used for motor preparation. We recorded brain activity using magnetoencephalography (MEG) during a delayed reaching task in which a visual cue provided valid information about the location of the upcoming target with 50, 75, or 100% reliability. We found that reaction time increased as cue reliability decreased and that trials with invalid cues had longer reaction times than trials with valid cues. MEG channel analysis showed that during the late cue period the power of the beta-band from left mid-anterior channels, contralateral to the responding hand, correlated with the reliability of the cue. This effect was source localized over a large motor-related cortical and subcortical network. In addition, during invalid-cue trials there was a phasic increase of theta-band power following target onset from left posterior channels, localized to the left occipito-parietal cortex. Furthermore, the theta-beta cross-frequency coupling between left mid-occipital and motor cortex transiently increased before responses to invalid-cue trials. In conclusion, beta-band power in motor-related areas reflected the reliability of directional information used during motor preparation, whereas phasic theta-band activity may have signaled whether the target was at the expected location or not. These results elucidate mechanisms of interaction between attentional and motor processes.

The Degree of Modulation of Beta Band Activity During Motor Planning Is Related to Trait Impulsivity.

Impulsivity is a prominent personality trait, and a key modulating component of neurologic and psychiatric disorders. How impulsivity is related to the brain mechanisms associated with action planning is poorly understood. Here, we investigated the relation between impulsivity and the modulation of beta band oscillatory activity associated with action planning and execution. Given that beta power decreases during action planning and decreases further during action execution, we hypothesized that during planning the level of beta band power of more impulsive individuals would be closer to the level reached during execution than that of less impulsive individuals. This could explain the tendency to "jump the gun" (commission errors) in high impulsivity. To test this hypothesis, we recruited healthy volunteers (50 participants analyzed) and used the Barratt Impulsiveness Scale questionnaire to evaluate their impulsivity as high or low. We then recorded their brain neuromagnetic signals while they performed an instructed-delay task that induced different levels of action planning by varying the number of spatial cues, hence the uncertainty, about the location of the upcoming target. During the early cue period of the task, we found a posterior (source localized in the occipito-parietal areas) and a left fronto-central group of channels (source localized in the left sensorimotor areas) where beta power was modulated by number of cues, whereas during the late cue period only the left fronto-central group was modulated. We found that the decrease of relative beta band power during action planning in the left fronto-central group of channels was more pronounced in the high impulsivity group than in the low impulsivity group. In addition, we found that the beta band-mediated functional connectivity between the posterior and the left fronto-central groups of channels was weaker in the high impulsivity group than in the low impulsivity group during the early cue period. Furthermore, high impulsives made more commission and movement errors in the task than low impulsives. These results reveal neural mechanisms through which impulsivity affects action planning and open the way for further study of the role of beta band activity in impulsivity, especially in the context of disease and therapeutics.

Brain oscillatory activity during motor preparation: effect of directional uncertainty on beta, but not alpha, frequency band.

In time-constraint activities, such as sports, it is advantageous to be prepared to act even before knowing precisely what action will be needed. Here, we studied the relation between neural oscillations during motor preparation and amount of uncertainty about the direction of the upcoming target. Ten right-handed volunteers participated in a cued center-out task. A brief visual cue identified the region of space in which the target would appear. Three cue sizes were used to vary the amount of information about the direction of the upcoming target. The target appeared at a random location within the region indicated by the cue, and the participants moved a joystick-controlled cursor toward it. Time-frequency analyses showed phasic increases of power in low (delta/theta: <7 Hz) and high (gamma: >30 Hz) frequency-bands in relation to the onset of visual stimuli and of the motor response. More importantly in regard to motor preparation, there was a tonic reduction of power in the alpha (8-12 Hz) and beta (14-30 Hz) bands during the period between cue presentation and target onset. During motor preparation, the main source of change of power of the alpha band was localized over the contralateral sensorimotor region and both parietal cortices, whereas for the beta-band the main source was the contralateral sensorimotor region. During cue presentation, the reduction of power of the alpha-band in the occipital lobe showed a brief differentiation of condition: the wider the visual cue, the more the power of the alpha-band decreased. However, during motor preparation, only the power of the beta-band was dependent on directional uncertainty: the less the directional uncertainty, the more the power of the beta-band decreased. In conclusion, the results indicate that the power in the alpha-band is associated briefly with cue size, but is otherwise an undifferentiated indication of neural activation, whereas the power of the beta-band reflects the level of motor preparation.

Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype.

Elevated lifetime prevalence rates of alcohol use disorders (AUDs) are a feature of bipolar disorder (BD). Individuals at-risk for AUDs exhibit blunted subjective responses to alcohol (low levels of response), which may represent a biomarker for AUDs. Thus, individuals at-risk for BD may exhibit low responses to alcohol. Participants were 20 unmedicated adult males who reported high rates of hypomanic experiences (bipolar phenotype participants; BPPs), aged 18 to 21 years, and 20 healthy controls matched on age, gender, IQ, BMI, and weekly alcohol intake. Subjective and pharmacokinetic responses to acute alcohol (0.8 g/kg) vs placebo administration were collected in a randomized, double-blind, cross-over, placebo-controlled, within-subjects design. BPP participants reported significantly lower subjective intoxication effects ('feel high': F=14.2, p=0.001; 'feel effects': F=8.1, p=0.008) across time, but did not differ in their pharmacokinetic, stimulant, or sedative responses. Paradoxically, however, the BPP participants reported significantly higher expectations of the positive effects of alcohol than controls. Our results suggest that unmedicated young males with previous hypomanic experiences exhibit diminished subjective responses to alcohol. These blunted alcohol responses are not attributable to differences in weekly alcohol intake, pharmacokinetic effects (eg, absorption rates), or familial risk of AUDs. These observations suggest that the dampened intoxication may contribute to the increased rates of alcohol misuse in young people at-risk for BD, and suggest possible shared etiological factors in the development of AUDs and BD.

Beta-band activity during motor planning reflects response uncertainty.

It has been known for many years that the power of beta-band oscillatory activity in motor-related brain regions decreases during the preparation and execution of voluntary movements. However, it is not clear yet whether the amplitude of this desynchronization is modulated by any parameter of the motor task. Here, we examined whether the degree of uncertainty about the upcoming movement direction modulated beta-band desynchronization during motor preparation. To this end, we recorded whole-head neuromagnetic signals while human subjects performed an instructed-delay reaching task with one, two, or three possible target directions. We found that the reduction of power of beta-band activity (16-28 Hz) during motor preparation was scaled relative to directional uncertainty. Furthermore, we show that the change of beta-band power correlates with the change of latency of response associated with response uncertainty. Finally, we show that the main source of beta-band desynchronization was located in the peri-Rolandic region. The results establish directional uncertainty as an important determinant of beta-band power during motor preparation and indicate that neural activity in the sensorimotor cortex during motor preparation covaries with directional uncertainty.

Cerebral cortical mechanisms of copying geometrical shapes: a multidimensional scaling analysis of fMRI patterns of activation.

We used multidimensional scaling (MDS) to characterize the integrative neural mechanisms during viewing and subsequently copying nine geometrical shapes. Human subjects initially looked at a central fixation point ("rest" period), then looked at a geometrical shape ("visual" period) which they copied without visual feedback ("copying" period). BOLD signal was recorded from voxels in 28 cortical areas (14 from each hemisphere) using a 4 Tesla magnet. For each voxel, signal ratios of "Visual versus Rest" (VR), and "Copy versus Visual" (CV) were calculated and used to construct two sets of Euclidean distance dissimilarity matrices for the nine shapes, with separate matrices defined for each region of interest (ROI) across subjects. The relations of perceptual and motor aspects of the shapes to MDS dimensions and specific ROIs were assessed using stepwise multiple regressions. The optimal individually scaled (INDSCAL) solutions were 2-dimensional. For the VR condition, MDS dimensions were significantly associated with the presence of crossing in a shape (Dimension 1), and with perimeter, height, cycles, peak segment speed, and horizontal symmetry (Dimension 2). ROIs most prominently associated with these dimensions essentially comprised the medial frontal lobe bilaterally, the inferior frontal gyrus bilaterally, and the left intraparietal sulcus (Dimension 1), and visual areas, including the calcarine sulcus and cuneus bilaterally (Dimension 2). These results document the expected involvement of visual areas and support the hypothesis advanced on the basis of previous findings (Lewis et al. 2003a) that a motor rehearsal of the upcoming shape copying is occurring during this visual presentation period. For the CV condition, practically one motor feature (number of segments drawn) dominated both dimensions, with a secondary engagement of horizontal symmetry in Dimension 1. The right postcentral gyrus, right intraparietal sulcus, right superior parietal lobule and right inferior parietal lobule contributed mostly to Dimension 1; the superior frontal gyrus bilaterally, right middle frontal gyrus, left postcentral gyrus, left inferior parietal lobule contributed mostly to Dimension 2; and the left superior parietal lobule and left intraparietal sulcus contributed to both dimensions approximately equally. CV BOLD activation of ROIs contributing to Dimension 1 (or to both dimensions) was significantly associated with the number of shape segments drawn. Since the direction of movement differs in successively drawn shape segments, the number of segments (minus one) equals the number of changes in the direction of movement. We conclude that this fundamental spatial motor aspect of drawing geometrical shapes is the critical variable, independent of the particular shape drawn, that dominates cortical activation during copying.

Ultra-high field parallel imaging of the superior parietal lobule during mental maze solving.

We used ultra-high field (7 T) fMRI and parallel imaging to scan the superior parietal lobule (SPL) of human subjects as they mentally traversed a maze path in one of four directions (up, down, left, right). A counterbalanced design for maze presentation and a quasi-isotropic voxel (1.46 x 1.46 x 2 mm thick) collection were implemented. Fifty-one percent of single voxels in the SPL were tuned to the direction of the maze path. Tuned voxels were distributed throughout the SPL, bilaterally. A nearest neighbor analysis revealed a "honeycomb" arrangement such that voxels tuned to a particular direction tended to occur in clusters. Three-dimensional (3D) directional clusters were identified in SPL as oriented centroids traversing the cortical depth. There were 13 same-direction clusters per hemisphere containing 22 voxels per cluster, on the average; the mean nearest-neighbor, same-direction intercluster distance was 9.4 mm. These results provide a much finer detail of the directional tuning in SPL, as compared to those obtained previously at 4 T (Gourtzelidis et al. Exp Brain Res 165:273-282, 2005). The more accurate estimates of quantitative clustering parameters in 3D brain space in this study were made possible by the higher signal-to-noise and contrast-to-noise ratios afforded by the higher magnetic field of 7 T as well as the quasi-isotropic design of voxel data collection.

Logarithmic transformation for high-field BOLD fMRI data.

Parametric statistical analyses of BOLD fMRI data often assume that the data are normally distributed, the variance is independent of the mean, and the effects are additive. We evaluated the fulfilment of these conditions on BOLD fMRI data acquired at 4 T from the whole brain while 15 subjects fixated a spot, looked at a geometrical shape, and copied it using a joystick. We performed a detailed analysis of the data to assess (a) their frequency distribution (i.e. how close it was to a normal distribution), (b) the dependence of the standard deviation (SD) on the mean, and (c) the dependence of the response on the preceding baseline. The data showed a strong departure from normality (being skewed to the right and hyperkurtotic), a strong linear dependence of the SD on the mean, and a proportional response over the baseline. These results suggest the need for a logarithmic transformation. Indeed, the log transformation reduced the skewness and kurtosis of the distribution, stabilized the variance, and made the effect additive, i.e. independent of the baseline. We conclude that high-field BOLD fMRI data need to be log-transformed before parametric statistical analyses are applied.

Mental maze solving: directional fMRI tuning and population coding in the superior parietal lobule.

The superior parietal lobule (SPL) of six human subjects was imaged at 4 T during mental traversing of a directed maze path. Here we demonstrate the orderly involvement of the SPL in this function, as follows. Forty-two percent of the voxels were tuned with respect to the direction of the maze path. This suggests a coherent tuning of local neuronal populations contributing to the change of the single-voxel BOLD signal. Preferred directions ranged throughout the directional continuum of 360 degrees. Voxels with similar preferred directions tended to cluster together: on average there were seven same-direction clusters per slice, with an average cluster membership of five voxels/cluster and an average nearest-neighbor same-direction intercluster distance of 13.1 mm. On the other hand, the average nearest-neighbor intercluster distance between a given direction and all other directions was 3.1 mm. This suggests a patchy arrangement such that patches of directionally tuned voxels, containing voxels with different preferred directions, alternate with patches of non-tuned voxels. Finally, the population vector predicted accurately the direction of the maze path (with an error of 12.7 degrees), and provided good estimates (with an error of 29 degrees) when calculated within parts of the SPL. Altogether, these findings document a new, orderly functional organization of the SPL with respect to mental tracing.

Cerebellar activation during copying geometrical shapes.

We studied functional MRI activation in the cerebellum during copying 9 geometrical shapes (equilateral triangle, isosceles triangle, square, diamond, vertical trapezoid, pentagon, hexagon, circle, and vertical lemniscate). Twenty subjects were imaged during 3 consecutive 45-s periods (rest, visual presentation, and copying). First, there was a positive relation between cerebellar activation and the peak speed of individual movements. This effect was strongest in the lateral and posterior ipsilateral cerebellum but it was also present in the paramedian zones of both cerebellar hemispheres and in the vermis. A finer grain analysis of the relations between the time course of the blood oxygenation level-dependent activation and movement parameters revealed a significant relation to hand position and speed but not to acceleration. Second, there was a significant relation between the intensity of voxel activation during visual presentation and the speed of the upcoming movement. The spatial distribution of these voxels was very similar to that of the voxels activated during copying, indicating that the cerebellum might be involved in motor rehearsal, in addition to its role during movement execution. Finally, a factor analysis of the intensity of activated voxels in the ipsilateral cerebellum during copying (adjusted for the speed effect) extracted 3 shape factors. Factor 1 reflected "roundness," factor 2 "upward pointing," and factor 3 "pointing (up or down) and elongation." These results link cerebellar activation to more global, spatial aspects of copying.