Effective connectivity in a duration selective cortico-cerebellar network.

How the human brain represents millisecond unit of time is far from clear. A recent neuroimaging study revealed the existence in the human premotor cortex of a topographic representation of time i.e., neuronal units selectively responsive to specific durations and topographically organized on the cortical surface. By using high resolution functional Magnetic Resonance Images here, we go beyond this previous work, showing duration preferences across a wide network of cortical and subcortical brain areas: from cerebellum to primary visual, parietal, premotor and prefrontal cortices. Most importantly, we identify the effective connectivity structure between these different brain areas and their duration selective neural units. The results highlight the role of the cerebellum as the network hub and that of medial premotor cortex as the final stage of duration recognition. Interestingly, when a specific duration is presented, only the communication strength between the units selective to that specific duration and to the neighboring durations is affected. These findings link for the first time, duration preferences within single brain region with connectivity dynamics between regions, suggesting a communication mode that is partially duration specific.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Chronotopic maps in human supplementary motor area.

Time is a fundamental dimension of everyday experiences. We can unmistakably sense its passage and adjust our behavior accordingly. Despite its ubiquity, the neuronal mechanisms underlying the capacity to perceive time remains unclear. Here, in two experiments using ultrahigh-field 7-Tesla (7T) functional magnetic resonance imaging (fMRI), we show that in the medial premotor cortex (supplementary motor area [SMA]) of the human brain, neural units tuned to different durations are orderly mapped in contiguous portions of the cortical surface so as to form chronomaps. The response of each portion in a chronomap is enhanced by neighboring durations and suppressed by nonpreferred durations represented in distant portions of the map. These findings suggest duration-sensitive tuning as a possible neural mechanism underlying the recognition of time and demonstrate, for the first time, that the representation of an abstract feature such as time can be instantiated by a topographical arrangement of duration-sensitive neural populations.

The role of cortical beta oscillations in time estimation.

Estimation of time is central to perception, action, and cognition. Human functional magnetic resonance imaging (fMRI) and positron emission topography (PET) have revealed a positive correlation between the estimation of multi-second temporal durations and neuronal activity in a circuit of sensory and motor areas, prefrontal and temporal cortices, basal ganglia, and cerebellum. The systems-level mechanisms coordinating the collective neuronal activity in these areas have remained poorly understood. Synchronized oscillations regulate communication in neuronal networks and could hence serve such coordination, but their role in the estimation and maintenance of multi-second time intervals has remained largely unknown. We used source-reconstructed magnetoencephalography (MEG) to address the functional significance of local neuronal synchronization, as indexed by the amplitudes of cortical oscillations, in time-estimation. MEG was acquired during a working memory (WM) task where the subjects first estimated and then memorized the durations, or in the contrast condition, the colors of dynamic visual stimuli. Time estimation was associated with stronger beta (ß, 14 - 30 Hz) band oscillations than color estimation in sensory regions and attentional cortical structures that earlier have been associated with time processing. In addition, the encoding of duration information was associated with strengthened gamma- (γ, 30 - 120 Hz), and the retrieval and maintenance with alpha- (α, 8 - 14 Hz) band oscillations. These data suggest that ß oscillations may provide a mechanism for estimating short temporal durations, while γ and α oscillations support their encoding, retrieval, and maintenance in memory. Hum Brain Mapp 37:3262-3281, 2016. © 2016 Wiley Periodicals, Inc.

Localization of cortical phase and amplitude dynamics during visual working memory encoding and retention.

Several studies show that the amplitudes of human brain oscillations are modulated during the performance of visual working memory (VWM) tasks in a load-dependent manner. Less is known about the dynamics and identities of the cortical regions in which these modulations take place, and hence their functional significance has remained unclear. We used magnetoencephalography and electroencephalography together with minimum norm estimate-based source modeling to study the dynamics of ongoing brain activity during a parametric VWM task. Early stimulus processing and memory encoding were associated with a memory load-dependent spread of neuronal activity from occipital to temporal, parietal, and frontal cortical regions. During the VWM retention period, the amplitudes of oscillations in theta/alpha- (5-9 Hz), high-alpha- (10-14 Hz), beta- (15-30 Hz), gamma- (30-50 Hz), and high-gamma- (50-150 Hz) frequency bands were suppressed below baseline levels, and yet, in frontoparietal regions, load dependently strengthened. However, in occipital and occipitotemporal structures, only beta, gamma, and high-gamma amplitudes were robustly strengthened by memory load. Individual behavioral VWM capacity was predicted by both the magnitude of the N1 evoked response component in early visual regions and by the amplitudes of frontoparietal high-alpha and high-gamma band oscillations. Thus, both early stimulus processing and late retention period activities may influence the behavioral outcome in VWM tasks. These data support the notion that beta- and gamma-band oscillations support the maintenance of object representations in VWM whereas alpha-, beta-, and gamma-band oscillations together contribute to attentional and executive processing.

Impaired conflict monitoring in Parkinson's disease patients during an oculomotor redirect task.

Fallibility is inherent in human cognition and so a system that will monitor performance is indispensable. While behavioral evidence for such a system derives from the finding that subjects slow down after trials that are likely to produce errors, the neural and behavioral characterization that enables such control is incomplete. Here, we report a specific role for dopamine/basal ganglia in response conflict by accessing deficits in performance monitoring in patients with Parkinson's disease. To characterize such a deficit, we used a modification of the oculomotor countermanding task to show that slowing down of responses that generate robust response conflict, and not post-error per se, is deficient in Parkinson's disease patients. Poor performance adjustment could be either due to impaired ability to slow RT subsequent to conflicts or due to impaired response conflict recognition. If the latter hypothesis was true, then PD subjects should show evidence of impaired error detection/correction, which was found to be the case. These results make a strong case for impaired performance monitoring in Parkinson's patients.

Neuronal synchrony reveals working memory networks and predicts individual memory capacity.

Visual working memory (VWM) is used to maintain sensory information for cognitive operations, and its deficits are associated with several neuropsychological disorders. VWM is based on sustained neuronal activity in a complex cortical network of frontal, parietal, occipital, and temporal areas. The neuronal mechanisms that coordinate this distributed processing to sustain coherent mental images and the mechanisms that set the behavioral capacity limit have remained unknown. We mapped the anatomical and dynamic structures of network synchrony supporting VWM by using a neuro informatics approach and combined magnetoencephalography and electroencephalography. Interareal phase synchrony was sustained and stable during the VWM retention period among frontoparietal and visual areas in alpha- (10-13 Hz), beta- (18-24 Hz), and gamma- (30-40 Hz) frequency bands. Furthermore, synchrony was strengthened with increasing memory load among the frontoparietal regions known to underlie executive and attentional functions during memory maintenance. On the other hand, the subjects' individual behavioral VWM capacity was predicted by synchrony in a network in which the intraparietal sulcus was the most central hub. These data suggest that interareal phase synchrony in the alpha-, beta-, and gamma-frequency bands among frontoparietal and visual regions could be a systems level mechanism for coordinating and regulating the maintenance of neuronal object representations in VWM.

Impaired inhibitory oculomotor control in patients with Parkinson's disease.

A hallmark of voluntary control is the capacity to inhibit or change partially prepared responses, an ability thought to be compromised in patients with Parkinson's disease (PD). To test this hypothesis in relation to oculomotor control, PD patients and age-matched controls performed a redirect task in which they were instructed to cancel a partially prepared saccade on some random fraction of trials. Using a race model framework, the time it takes to cancel a saccade, the target switch reaction time (TSRT), was estimated for PD and control subjects. While saccadic reaction times of control and PD subjects were similar, the average TSRT in PD subjects was 139 ms, and was significantly greater than the TSRT in controls, which was 113 ms. These results support the hypothesis that poor voluntary control exhibited by PD patients in a variety of complex behaviors may be caused by impaired inhibitory control as a result of basal ganglia dysfunction.