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Older individuals typically display stronger regional brain activity than younger subjects during motor performance. However, knowledge regarding age-related changes of motor network interactions between brain regions remains scarce. We here investigated the impact of ageing on the interaction of cortical areas during movement selection and initiation using dynamic causal modelling (DCM). We found that age-related psychomotor slowing was accompanied by increases in both regional activity and effective connectivity, especially for ‘core’ motor coupling targeting primary motor cortex (M1). Interestingly, younger participants within the older group showed strongest connectivity targeting M1, which steadily decreased with advancing age. Conversely, prefrontal influences on the motor system increased with advancing age, and were inversely correlated with reduced parietal influences and core motor coupling. Interestingly, higher net coupling within the prefrontal-premotor-M1 axis predicted faster psychomotor speed in ageing. Hence, as opposed to a uniform age-related decline, our findings are compatible with the idea of different age-related compensatory mechanisms, with an important role of the prefrontal cortex compensating for reduced coupling within the core motor network. Keywords: fMRI, Ageing, Motor control, Effective connectivity

In recent years, changes in resting-state networks (RSN), identified by functional magnetic resonance imaging (fMRI), have gained increasing attention as potential biomarkers and trackers of neurological disorders such as Alzheimer's disease (AD). Intersession reliability of RSN is fundamental to this approach.In this study, we investigated the test-retest reliability of three memory related RSN (i.e., the default mode, salience, and executive control network) in 15 young, 15 healthy seniors (HS), and 15 subjects affected by mild cognitive impairment (MCI) with positive biomarkers suggestive of incipient AD (6 females each). FMRI was conducted on three separate occasions. Independent Component Analysis decomposed the resting-state data into RSNs. Comparisons of variation in functional connectivity between groups were made applying different thresholds in an explorative approach. Intersession test-retest reliability was evaluated by intraclass correlation coefficient (ICC) comparisons. To assess the effect of gray matter volume loss, motion, cerebrospinal fluid based biomarkers and the time gap between sessions on intersession variation, the former four were correlated separately with the latter.Data showed that i) young subjects ICCs (relative to HS/MCI-subjects) had higher intersession reliability, ii) stringent statistical thresholds need to be applied to prevent false-positives, iii) both HS and MCI-subjects (relative to young) showed significantly more clusters of intersession variation in all three RSN, iv) while intersession variation was highly correlated with head motion, it was also correlated with biomarkers (especially phospho-tau), the time gap between sessions and local GMV. Results indicate that time gaps between sessions should be kept constant and that head motion must be taken into account when using RSN to assess aging and neurodegeneration. In patients with prodromal AD, re-test reliability may be increased by accouting for overall disease burden by including biomarkers of neuronal injury (especially phospho-tau) in statistical analyses. Local atrophy however, does not seem to play a major role in regards to reliability, but should be used as covariate depending on the research question. Keywords: ICA, MCI, fMRI, DMN

Behavioral research has revealed deficits in the development of joint attention (JA) as one of the earliest signs of autism. While the neural basis of JA has been studied predominantly in adults, we recently demonstrated a protracted development of the brain networks supporting JA in typically developing children and adolescents. The present eye-tracking/fMRI study now extends these findings to adolescents with autism. Our results show that in adolescents with autism JA is subserved by abnormal activation patterns in brain areas related to social cognition abnormalities which are at the core of ASD including the STS and TPJ, despite behavioral maturation with no behavioral differences. Furthermore, in the autism group we observed increased neural activity in a network of social and emotional processing areas during interactions with their mother. Moreover, data indicated that less severely affected individuals with autism showed higher frontal activation associated with self-initiated interactions. Taken together, this study provides first-time data of JA in children/adolescents with autism incorporating the interactive character of JA, its reciprocity and motivational aspects. The observed functional differences in adolescents ASD suggest that persistent developmental differences in the neural processes underlying JA contribute to social interaction difficulties in ASD.

After stroke, movements of the paretic hand rely on altered motor network dynamics typically including additional activation of the contralesional primary motor cortex (M1). The functional implications of contralesional M1 recruitment to date remain a matter of debate.We here assessed the role of contralesional M1 in 12 patients recovering from a first-ever stroke using online transcranial magnetic stimulation (TMS): Short bursts of TMS were administered over contralesional M1 or a control site (occipital vertex) while patients performed different motor tasks with their stroke-affected hand.In the early subacute phase (1–2weeks post-stroke), we observed significant improvements in maximum finger tapping frequency when interfering with contralesional M1, while maximum grip strength and speeded movement initiation remained unaffected. After >3months of motor recovery, disruption of contralesional M1 activity did not interfere with performance in any of the three tasks, similar to what we observed in healthy controls.In patients with mild to moderate motor deficits, contralesional M1 has a task- and time-specific negative influence on motor performance of the stroke-affected hand. Our results help to explain previous contradicting findings on the role of contralesional M1 in recovery of function. Keywords: Motor reorganization, Cortical plasticity, Brain stimulation, Motor control

Apraxia, a disorder of higher motor cognition, is a frequent and outcome-relevant sequel of left hemispheric stroke. Deficient pantomiming of object use constitutes a key symptom of apraxia and is assessed when testing for apraxia. To date the neural basis of pantomime remains controversial. We here review the literature and perform a meta-analysis of the relevant structural and functional imaging (fMRI/PET) studies. Based on a systematic literature search, 10 structural and 12 functional imaging studies were selected. Structural lesion studies associated pantomiming deficits with left frontal, parietal and temporal lesions. In contrast, functional imaging studies associate pantomimes with left parietal activations, with or without concurrent frontal or temporal activations. Functional imaging studies that selectively activated parietal cortex adopted the most stringent controls. In contrast to previous suggestions, current analyses show that both lesion and functional studies support the notion of a left-hemispheric fronto-(temporal)-parietal network underlying pantomiming object use. Furthermore, our review demonstrates that the left parietal cortex plays a key role in pantomime-related processes. More specifically, stringently controlled fMRI-studies suggest that in addition to storing motor schemas, left parietal cortex is also involved in activating these motor schemas in the context of pantomiming object use. In addition to inherent differences between structural and functional imaging studies and consistent with the dedifferentiation hypothesis, the age difference between young healthy subjects (typically included in functional imaging studies) and elderly neurological patients (typically included in structural lesion studies) may well contribute to the finding of a more distributed representation of pantomiming within the motor-dominant left hemisphere in the elderly.