Using pulse oximetry to account for high and low frequency physiological artifacts in the BOLD signal.

The BOLD signal not only reflects changes in local neural activity, but also exhibits variability from physiological processes like cardiac rhythms and breathing. We investigated how both of these physiological sources are reflected in the pulse oximetry (PO) signal, a direct measure of blood oxygenation, and how this information can be used to account for different types of noise in the BOLD response. Measures of heart rate, respiration and PO were simultaneously recorded while neurologically healthy participants performed an eye-movement task in a 3T MRI. PO exhibited power in frequencies that matched those found in the independently recorded cardiac and respiration signals. Using the phasic and aphasic properties of these signals as nuisance regressors, we found that the different frequency components of the PO signal could be used to identify different types of physiological artifacts in the BOLD response. A comparison of different physiological noise models found that a simple, down-sampled version of the PO signal improves the estimation of task-relevant statistics nearly as well as more established noise models that may run the risk of over-parameterization. These findings suggest that the PO signal captures multiple sources of physiological noise in the BOLD response and provides a simple and efficient way of modeling these noise sources in subsequent analysis.</p

Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum.

<p>Modification of spatial attention via reinforcement learning (Lee and Shomstein, 2013) requires the integration of reward, attention, and executive processes. Corticostriatal pathways are an ideal neural substrate for this integration because these projections exhibit a globally parallel (Alexander et al., 1986), but locally overlapping (Haber, 2003), topographical organization. Here we explore whether there are unique striatal regions that exhibit convergent anatomical connections from orbitofrontal cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. Deterministic fiber tractography on diffusion spectrum imaging data from neurologically healthy adults (N = 60) was used to map frontostriatal and parietostriatal projections. In general, projections from cortex were organized according to both a medial-lateral and a rostral-caudal gradient along the striatal nuclei. Within rostral aspects of the striatum, we identified two bilateral convergence zones (one in the caudate nucleus and another in the putamen) that consisted of voxels with unique projections from orbitofrontal cortex, dorsolateral prefrontal cortex, and parietal regions. The distributed cortical connectivity of these striatal convergence zones was confirmed with follow-up functional connectivity analysis from resting state fMRI data, in which a high percentage of structurally connected voxels also showed significant functional connectivity. The specificity of this convergent architecture to these regions of the rostral striatum was validated against control analysis of connectivity within the motor putamen. These results delineate a neurologically plausible network of converging corticostriatal projections that may support the integration of reward, executive control, and spatial attention that occurs during spatial reinforcement learning.</p

Early life environment modulates 'handedness' in rats.

Right handedness is one of the most prominent markers of human functional brain asymmetry. Deviation from this norm appears to be associated with certain developmental disorders. While many studies have dealt with the genetic contribution to the determination of handedness, few have examined whether environmental factors that are subtler than forced hand switching can modulate the development of handedness. In this study, we exposed rats to a novel environment for 3 min daily during their first 3 weeks of life and found that their paw preferences during both infancy and adulthood showed a leftward shift compared with the controls. This result suggests that 'handedness' can be modified by rather subtle early environmental manipulation. Since exposure to a novel environment does not involve a direct asymmetric activation of the sensory--motor system underlying paw-use, mechanisms beyond this paw-specific system must exist to mediate the observed modulation of 'handedness'.</p

Network dynamics mediating ipsilateral motor cortex activity during unimanual actions.

Executing difficult actions with the left hand results in bilateral activity of motor areas along the precentral gyrus. Using TMS and fMRI, we explored the functional relationship between primary (M1) and premotor areas during unimanual actions, focusing on M1 activity in the ipsilateral hemisphere. Single-pulse TMS revealed that the amplitude of motor-evoked potentials (MEPs), elicited in the stationary right-hand muscles following left M1 stimulation, fluctuated with the state of homologous muscles in the moving left hand. This ipsilateral excitability was pronounced when the left-hand movements were more complex. We used fMRI to visualize the cortical dynamics during unimanual actions. Trial-by-trial fluctuations in ipsilateral M1 activity were correlated with contralateral M1 responses and this correlation increased with movement complexity. Consistent with previous studies, the left caudal precentral premotor area (pcPM) was engaged during movements of either hand. Following low-frequency rTMS over left pcPM, the correlation between the activity level in the two M1s increased. This finding indicates that left pcPM may regulate the unintentional mirroring of motor commands in M1 during unilateral movement.</p

In vivo quantification of global connectivity in the human corpus callosum.

<p>Histological studies on nonhuman primates have shown a rich topography of homotopic (i.e., going to the same regions) or heterotopic (i.e., going to different regions) callosal projections. Unfortunately, a complete within-subject mapping of commissural projections in humans has been limited due to the inability of typical imaging methods to detect lateral projections in posterior cortical regions. Here, we set out to map callosal projection connectivity, at the single subject level (N=6), by combining high angular resolution diffusion weighted imaging and a novel multi-stage, region-of-interest (ROI) based fiber tracking approach. With these methods we were able to obtain a consistent increase in coverage of lateral projections to posterior cortical regions. Using 70 automatically segmented ROIs in each hemisphere and permutation statistics, we characterized significant interhemispheric connectivity patterns within each subject and observed: (1) consistent projections to frontal, parietal and occipital, but not temporal, areas, (2) a greater relative proportion of homotopic than heterotopic connections, and (3) commissural projections to the basal ganglia and thalamus that are consistent with human and nonhuman primate neuroanatomical literature. These results illustrate the first full connectivity analysis of the human corpus callosum, revealing several patterns consistent with histological findings in the nonhuman primate.</p

Two types of TMS-induced movement variability after stimulation of the primary motor cortex.

Using transcranial magnetic stimulation, we studied the role of the primary motor cortex (M1) in repetitive movements, examining whether the functional contribution of this region is associated with controlling response timing, response implementation, or both. In two experiments, participants performed a rhythmic tapping task, attempting to produce isochronous intervals (range of 350-550 ms) while stimulation was applied over M1 or a control site. M1 stimulation was associated with increased variability of the inter-tap intervals (ITI), and, by manipulating stimulation intensity, we identified two distinct changes in performance: a generalized increase in ITI variability and a delay in the subsequent response when the pulse fell within a restricted window prior to movement onset. Using a series of simulations, we demonstrate that the general increase in variability and the temporally specific delay reflect disruption of response implementation processes rather than an increase in noise associated with response timing.</p

In vivo mapping of microstructural somatotopies in the human corticospinal pathways.

The human corticospinal pathway is organized in a body-centric (i.e., somatotopic) manner that begins in cortical cell bodies and is maintained in the axons as they project through the midbrain on their way to spinal motor neurons. The subcortical segment of this somatotopy has been described using histological methods on non-human primates but only coarsely validated from lesion studies in human patient populations. Using high definition fiber tracking (HDFT) techniques, we set out to provide the first in vivo quantitative description of the midbrain somatotopy of corticospinal fibers in humans. Multi-shell diffusion imaging and deterministic fiber tracking were used to map white matter bundles that originate in the neocortex, navigate complex fiber crossings, and project through the midbrain. These fiber bundles were segmented into premotor (dorsal premotor, ventral premotor, and supplementary motor area) and primary motor sections based on the cortical origin of each fiber streamline. With HDFT, we were able to reveal several unique corticospinal patterns, including the cortical origins of ventral premotor fibers and small (∼ 1-2 mm) shifts in the midbrain location of premotor versus primary motor cortex fibers. More importantly, within the relatively small diameter of the pyramidal tracts (∼ 5 mm), we were able to map and quantify the direction of the corticospinal somatotopy. These results show how an HDFT approach to white matter mapping provides the first in vivo, quantitative mapping of subcortical corticospinal topographies at resolutions previously only available with postmortem histological techniques.</p

Microstructural organizational patterns in the human corticostriatal system.

The axons that project into the striatum are known to segregate according to macroscopic cortical systems; however, the within-region organization of these fibers has yet to be described in humans. We used in vivo fiber tractography, in neurologically healthy adults, to map white matter bundles that originate in different neocortical areas, navigate complex fiber crossings, and project into the striatum. As expected, these fibers were generally segregated according to cortical origin. Within a subset of pathways, a patched pattern of inputs was observed, consistent with previous ex vivo histological studies. In projections from the prefrontal cortex, we detected a topography in which fibers from rostral prefrontal areas projected mostly to rostral parts of the striatum and vice versa for inputs originating in caudal cortical areas. Importantly, within this prefrontal system there was also an asymmetry in the subset of divergent projections, with more fibers projecting in a posterior direction than anterior. This asymmetry of information projecting into the basal ganglia was predicted by previous network-level computational models. A rostral-caudal topography was also present at the local level in otherwise somatotopically organized fibers projecting from the motor cortex. This provides clear evidence that the longitudinal organization of input fields, observed at the macroscopic level across cortical systems, is also found at the microstructural scale at which information is segregated as it enters the human basal ganglia.</p

Competing basal ganglia pathways determine the difference between stopping and deciding not to go.

<p>The architecture of corticobasal ganglia pathways allows for many routes to inhibit a planned action: the hyperdirect pathway performs fast action cancellation and the indirect pathway competitively constrains execution signals from the direct pathway. We present a novel model, principled off of basal ganglia circuitry, that differentiates control dynamics of reactive stopping from intrinsic no-go decisions. Using a nested diffusion model, we show how reactive braking depends on the state of an execution process. In contrast, no-go decisions are best captured by a failure of the execution process to reach the decision threshold due to increasing constraints on the drift rate. This model accounts for both behavioral and functional MRI (fMRI) responses during inhibitory control tasks better than alternative models. The advantage of this framework is that it allows for incorporating the effects of context in reactive and proactive control into a single unifying parameter, while distinguishing action cancellation from no-go decisions.</p

Neonatal novelty exposure modulates hippocampal volumetric asymmetry in the rat.

Early life environmental manipulations have been shown to affect hippocampal-dependent learning, hippocampal volume and cerebral lateralization. In this study, we investigated the effects of neonatal stimulation on hippocampal volumetric asymmetry. Long-Evans hooded rats were exposed to a novel non-home environment 3 min daily for the first 3 weeks of life. Histological measures of the left and right hippocampus were made at 8 months of age. We found that neonatal novelty exposure resulted in a long-lasting change in hippocampal volumetric asymmetry. Specifically, this brief and transient early life stimulation increased the right hippocampal volumetric dominance at mid-adulthood.</p