Daniel G. Woolley

Homologous involvement of striatum and prefrontal cortex in rodent and human water maze learning

The multiple memory systems hypothesis posits that dorsal striatum and hippocampus are central nodes in independent memory systems, supporting response-based and place-based learning, respectively. Although our understanding of the function of hippocampus within this framework is relatively well established, the contribution of dorsal striatum is less clear. This in part seems to be due to the heterogeneous nature of dorsal striatum, which receives extensive topographically organized projections from higher cortical areas. Here we quantified neural activity in the intact brain while mice and humans acquired analogous versions of the Morris water maze. We found that dorsomedial striatum and medial prefrontal cortex support the initial acquisition of what is typically considered a hippocampus-dependent spatial learning task. We suggest that the circuit involving dorsomedial striatum and medial prefrontal cortex identified here plays a more task-independent role in early learning than currently thought. Furthermore, our results demonstrate that dorsomedial and dorsolateral striatum serve fundamentally different roles during place learning. The remarkably high degree of anatomical overlap in brain function between mouse and human observed in our study emphasizes the extent of convergence achievable with a well-matched multilevel approach.

Sex differences in human virtual water maze performance: novel measures reveal the relative contribution of directional responding and spatial knowledge.

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.

Underconnectivity of the superior temporal sulcus predicts emotion recognition deficits in autism

Neurodevelopmental disconnections have been assumed to cause behavioral alterations in autism spectrum disorders (ASDs). Here, we combined measurements of intrinsic functional connectivity (iFC) from resting-state functional magnetic resonance imaging (fMRI) with task-based fMRI to explore whether altered activity and/or iFC of the right posterior superior temporal sulcus (pSTS) mediates deficits in emotion recognition in ASD. Fifteen adults with ASD and 15 matched-controls underwent resting-state and task-based fMRI, during which participants discriminated emotional states from point light displays (PLDs). Intrinsic FC of the right pSTS was further examined using 584 (278 ASD/306 controls) resting-state data of the Autism Brain Imaging Data Exchange (ABIDE). Participants with ASD were less accurate than controls in recognizing emotional states from PLDs. Analyses revealed pronounced ASD-related reductions both in task-based activity and resting-state iFC of the right pSTS with fronto-parietal areas typically encompassing the action observation network (AON). Notably, pSTS-hypo-activity was related to pSTS-hypo-connectivity, and both measures were predictive of emotion recognition performance with each measure explaining a unique part of the variance. Analyses with the large independent ABIDE dataset replicated reductions in pSTS-iFC to fronto-parietal regions. These findings provide novel evidence that pSTS hypo-activity and hypo-connectivity with the fronto-parietal AON are linked to the social deficits characteristic of ASD.

Gone for 60 seconds: Reactivation length determines motor memory degradation during reconsolidation

When a stable memory is reactivated it becomes transiently labile and requires restabilization, a process known as reconsolidation. Animal studies have convincingly demonstrated that during reconsolidation memories are modifiable and can be erased when reactivation is followed by an interfering intervention. Few studies have been conducted in humans, however, and results are inconsistent regarding the extent to which a memory can be degraded. We used a motor sequence learning paradigm to show that the length of reactivation constitutes a crucial boundary condition determining whether human motor memories can be degraded. In our first experiment, we found that a short reactivation (less than 60xa0sec) renders the memory labile and susceptible to degradation through interference, while a longer reactivation does not. In our second experiment, we reproduce these results and show a significant linear relationship between the length of memory reactivation and the detrimental effect of the interfering task performed afterwards, i.e., the longer the reactivation, the smaller the memory loss due to interference. Our data suggest that reactivation via motor execution activates a time-dependent process that initially destabilizes the memory, which is then followed by restabilization during further practice.

Aging effects on the resting state motor network and interlimb coordination.

Both increases and decreases in resting state functional connectivity have been previously observed within the motor network during aging. Moreover, the relationship between altered functional connectivity and age‐related declines in bimanual coordination remains unclear. Here, we explored the developmental dynamics of the resting brain within a task‐specific motor network in a sample of 128 healthy participants, aged 18–80 years. We found that age‐related increases in functional connectivity between interhemispheric dorsal and ventral premotor areas were associated with poorer performance on a novel bimanual visuomotor task. Additionally, a control analysis performed on the default mode network confirmed that our age‐related increases in functional connectivity were specific to the motor system. Our findings suggest that increases in functional connectivity within the resting state motor network with aging reflect a loss of functional specialization that may not only occur in the active brain but also in the resting brain. Hum Brain Mapp 35:3945–3961, 2014.

Visual guidance modulates hemispheric asymmetries during an interlimb coordination task.

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.

Movement Observation Improves Early Consolidation of Motor Memory

Practicing a motor task can induce neuroplastic changes in the human primary motor cortex (M1) that are subsequently consolidated, leading to a stable memory trace. Currently, little is known whether early consolidation, tested several minutes after skill acquisition, can be improved by behavioral interventions. Here we test whether movement observation, known to evoke similar neural responses in M1 as movement execution, can benefit the early consolidation of new motor memories. We show that observing the same type of movement as that previously practiced (congruent movement stimuli) substantially improves performance on a retention test 30 min after training compared with observing either an incongruent movement type or control stimuli not showing biological motion. Differences in retention following observation of congruent, incongruent, and control stimuli were not found when observed 24 h after initial training and neural evidence further confirmed that, unlike motor practice, movement observation alone did not induce plastic changes in the motor cortex. This time-specific effect is critical to conclude that movement observation of congruent stimuli interacts with training-induced neuroplasticity and enhances early consolidation of motor memories. Our findings are not only of theoretical relevance for memory research, but also have great potential for application in clinical settings when neuroplasticity needs to be maximized.

Virtual water maze learning in human increases functional connectivity between posterior hippocampus and dorsal caudate

Recent work has demonstrated that functional connectivity between remote brain regions can be modulated by task learning or the performance of an already well‐learned task. Here, we investigated the extent to which initial learning and stable performance of a spatial navigation task modulates functional connectivity between subregions of hippocampus and striatum. Subjects actively navigated through a virtual water maze environment and used visual cues to learn the position of a fixed spatial location. Resting‐state functional magnetic resonance imaging scans were collected before and after virtual water maze navigation in two scan sessions conducted 1 week apart, with a behavior‐only training session in between. There was a large significant reduction in the time taken to intercept the target location during scan session 1 and a small significant reduction during the behavior‐only training session. No further reduction was observed during scan session 2. This indicates that scan session 1 represented initial learning and scan session 2 represented stable performance. We observed an increase in functional connectivity between left posterior hippocampus and left dorsal caudate that was specific to scan session 1. Importantly, the magnitude of the increase in functional connectivity was correlated with offline gains in task performance. Our findings suggest cooperative interaction occurs between posterior hippocampus and dorsal caudate during awake rest following the initial phase of spatial navigation learning. Furthermore, we speculate that the increase in functional connectivity observed during awake rest after initial learning might reflect consolidation‐related processing. Hum Brain Mapp 36:1265–1277, 2015.

Structural and functional cortical connectivity mediating cross education of motor function

Cross-education (CE) is the process whereby training with one limb leads to subsequent improvement in performance by the opposite untrained limb. We used multimodal neuroimaging in humans to investigate the mediating neural mechanisms by relating quantitative estimates of functional and structural cortical connectivity to individual levels of interlimb transfer. Resting-state (rs)-fMRI and diffusion weighted imaging (DWI) scans were undertaken before unilateral ballistic wrist flexion training. The rs-fMRI sequence was repeated immediately afterward. The increase in performance of the untrained limb was 83.6% of that observed for the trained limb and significantly greater than that of a control group who undertook no training. Functional connectivity in the resting motor network between right and left supplementary motor areas (SMA) was elevated after training. These changes were not, however, correlated with individual levels of transfer. Analysis of the DWI data using constrained spherical deconvolution-based tractography indicated that fractional anisotropy and apparent fiber density in tracts connecting bilateral SMA were negatively correlated with and predictive of transfer. The findings suggest that interhemispheric interactions between bilateral SMA play an instrumental role in CE and that the structural integrity of the connecting white matter pathways influences the level of transfer. SIGNIFICANCE STATEMENT Strength or skill training with one limb also brings about improvements in the performance of the opposite, untrained limb. This phenomenon, termed cross-education (CE), has obvious potential for the rehabilitation of functional capacity that has been lost through brain insult or musculoskeletal injury. The neural mechanisms that give rise to CE are, however, poorly understood. We used a combination of neuroimaging methods to investigate the pathways in the human brain that mediate CE. We determined that the supplementary motor area (SMA) plays an important role in the interlimb transfer of performance gains and demonstrate that the quality of the white matter fibers connecting right and left SMA predicts the benefit that an individual derives from CE.

Changes in Corticomotor Excitability and Intracortical Inhibition of the Primary Motor Cortex Forearm Area Induced by Anodal tDCS

Objective Previous studies have investigated how tDCS over the primary motor cortex modulates excitability in the intrinsic hand muscles. Here, we tested if tDCS changes corticomotor excitability and/or cortical inhibition when measured in the extensor carpi radialis (ECR) and if these aftereffects can be successfully assessed during controlled muscle contraction. Methods We implemented a double blind cross-over design in which participants (nu200a=u200a16) completed two sessions where the aftereffects of 20 min of 1 mA (0.04 mA/cm2) anodal vs sham tDCS were tested in a resting muscle, and two more sessions where the aftereffects of anodal vs sham tDCS were tested in an active muscle. Results Anodal tDCS increased corticomotor excitability in ECR when aftereffects were measured with a low-level controlled muscle contraction. Furthermore, anodal tDCS decreased short interval intracortical inhibition but only when measured at rest and after non-responders (nu200a=u200a2) were removed. We found no changes in the cortical silent period. Conclusion These findings suggest that targeting more proximal muscles in the upper limb with anodal tDCS is achievable and corticomotor excitability can be assessed in the presence of a low-level controlled contraction of the target muscle.