Sex differences in humans on virtual water maze navigation are well established when overall performance is measured, e.g., by the total time taken to find the hidden platform, total path length, or quadrant dwell time during probe trials. Currently, it is unknown whether males are better spatial learners than females, or if overall performance differences reflect other aspects of the task unrelated to spatial memory. Here, males and females were tested on a virtual analogue of the Morris water maze. We devised a novel method of analysis in which each trial was divided into an initial trajectory phase and search phase. We also implemented a new measure of spatial learning during early and late training, by including trials in which subjects were only required to indicate where they thought the hidden target zone was located. Consistent with previous reports, males outperformed females on overall measures of task performance. Males also performed significantly better on all initial trajectory phase variables. Interestingly, only small (non-significant) differences were observed during the search phase and when spatial learning was tested without the constraints of a typical water maze trial. Our results suggest that spatial knowledge regarding the location of the hidden target zone is not the main factor responsible for overall sex differences in virtual water maze performance. Instead, the largest sex differences were observed during the initial trajectory phase of the trial, which is thought to depend on effective processing of distal features of the environment.

The cerebral hemispheres of humans exhibit functional asymmetries. It is generally thought that the left hemisphere contributes to higher order planning of demanding motor tasks, while the right hemisphere plays an important role in processing visual or proprioceptive stimuli and controls spatial attention. Few studies have directly investigated which aspects of motor control increase the involvement of right-lateralized areas. We used fMRI to examine hemispheric lateralization during unilateral motor coordination of the wrist and ankle performed either with the left or right body side, and either with or without visual guidance. Visual guidance was provided such that the spatial position of a cursor directly informed subjects about the mode and quality of the coordination pattern. Activation was only considered lateralized for a specific condition if it was significantly stronger in one hemisphere than the other, independent of which body side performed the task. We found that task performance with visual guidance mainly engaged a right-lateralized occipital-temporoparietal network and the inferior frontal gyrus, a circuit known to integrate visual and proprioceptive information to guide movements in space. Importantly, this lateralized activation was only observed when visual guidance was provided, but not when movements were performed without visual guidance or when subjects passively watched a similar visual stimulus without moving their limbs. We argue that the functional lateralization of right visuomotor areas was a direct consequence of performing this motor task in the presence of visual guidance, i.e., visuospatial information was integrated with somatosensory guidance to produce well coordinated hand-foot movements.

Complex behavior typically relies upon many different processes which are related to activity in multiple brain regions. In contrast, neuroimaging analyses typically focus upon isolated processes. Here we present a new approach, combinatorial brain decoding, in which we decode complex behavior by combining the information which we can retrieve from the neural signals about the many different sub-processes. The case in point is visuospatial navigation. We explore the extent to which the route travelled by human subjects (N = 3) in a complex virtual maze can be decoded from activity patterns as measured with functional magnetic resonance imaging. Preliminary analyses suggest that it is difficult to directly decode spatial position from regions known to contain an explicit cognitive map of the environment, such as the hippocampus. Instead, we were able to indirectly derive spatial position from the pattern of activity in visual and motor cortex. The non-spatial representations in these regions reflect processes which are inherent to navigation, such as which stimuli are perceived at which point in time and which motor movement is executed when (e.g., turning left at a crossroad). Highly successful decoding of routes followed through the maze was possible by combining information about multiple aspects of navigation events across time and across multiple cortical regions. This "proof of principle" study highlights how visuospatial navigation is related to the combined activity of multiple brain regions, and establishes combinatorial brain decoding as a means to study complex mental events that involve a dynamic interplay of many cognitive processes.

Recent work in young adults has demonstrated that motor learning can modulate resting state functional connectivity. However, evidence for older adults is scarce. Here, we investigated whether learning a bimanual tracking task modulates resting state functional connectivity of both inter- and intra-hemispheric regions differentially in young and older individuals, and whether this has behavioral relevance. Both age groups learned a set of complex bimanual tracking task variants over a 2-week training period. Resting-state and task-related functional magnetic resonance imaging scans were collected before and after training. Our analyses revealed that both young and older adults reached considerable performance gains. Older adults even obtained larger training-induced improvements relative to baseline, but their overall performance levels were lower than in young adults. Short-term practice resulted in a modulation of resting state functional connectivity, leading to connectivity increases in young adults, but connectivity decreases in older adults. This pattern of age differences occurred for both inter- and intra-hemispheric connections related to the motor network. Additionally, long-term training-induced increases were observed in intra-hemispheric connectivity in the right hemisphere across both age groups. Overall, at the individual level, the long-term changes in inter-hemispheric connectivity correlated with training-induced motor improvement. Our findings confirm that short-term task practice shapes spontaneous brain activity differentially in young and older individuals. Importantly, the association between changes in resting state functional connectivity and improvements in motor performance at the individual level may be indicative of how training shapes the short-term functional reorganization of the resting state motor network for improvement of behavioral performance.

The human brain's ability to store information and remember past events is thought to be orchestrated by the synchronization of neuronal oscillations in various frequency bands. A vast amount of research has found that neural oscillations in the theta (∼4-7 Hz) and alpha (∼8-12 Hz) bands play an important role in memory formation. More specifically, it has been suggested that memory performance benefits if the same oscillatory pattern is present during encoding and retrieval. However, the causal relevance of these oscillations is not well understood. Rhythmic sensory stimulation is thought to entrain ongoing brain oscillations and modulate associated functions (e.g., memory formation). In the present study, we used rhythmic visual stimulation at 6 and 10 Hz to experimentally modulate the memory encoding process in a recognition memory task. In addition, we reinstated oscillatory activity from the encoding episode during retrieval, which has been hypothesized to result in memory performance improvements compared to non-reinstated conditions and incongruent reinstatement. Contrary to our hypothesis, we find no effect of neural entrainment during encoding on subsequent memory performance. Likewise, memory retrieval does not benefit from neural reinstatement. The results are discussed with respect to methodological challenges of rhythmic sensory stimulation as a means to alter cognitive processes and induce context-dependent memory effects.