The current finding provides the first neuroimaging evidence of a dose-dependent change induced by an established therapeutic agent in brain regions known to be critical for the mediation of anxiety. This investigation may help to support the use of BOLD-fMRI with pharmacological probes to investigate the neural circuits underlying anxiety and the use of fMRI as a tool in the development of new anxiolytic agents.

BackgroundParkinson's disease (PD) disrupts temporal processing, but the neuronal sources of deficits and their response to dopamine (DA) therapy are not understood. Though the striatum and DA transmission are thought to be essential for timekeeping, potential working memory (WM) and executive problems could also disrupt timing.Methodology/FindingsThe present study addressed these issues by testing controls and PD volunteers ‘on’ and ‘off’ DA therapy as they underwent fMRI while performing a time-perception task. To distinguish systems associated with abnormalities in temporal and non-temporal processes, we separated brain activity during encoding and decision-making phases of a trial. Whereas both phases involved timekeeping, the encoding and decision phases emphasized WM and executive processes, respectively. The methods enabled exploration of both the amplitude and temporal dynamics of neural activity. First, we found that time-perception deficits were associated with striatal, cortical, and cerebellar dysfunction. Unlike studies of timed movement, our results could not be attributed to traditional roles of the striatum and cerebellum in movement. Second, for the first time we identified temporal and non-temporal sources of impaired time perception. Striatal dysfunction was found during both phases consistent with its role in timekeeping. Activation was also abnormal in a WM network (middle-frontal and parietal cortex, lateral cerebellum) during encoding and a network that modulates executive and memory functions (parahippocampus, posterior cingulate) during decision making. Third, hypoactivation typified neuronal dysfunction in PD, but was sometimes characterized by abnormal temporal dynamics (e.g., lagged, prolonged) that were not due to longer response times. Finally, DA therapy did not alleviate timing deficits.Conclusions/SignificanceOur findings indicate that impaired timing in PD arises from nigrostriatal and mesocortical dysfunction in systems that mediate temporal and non-temporal control-processes. However, time perception impairments were not improved by DA treatment, likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity.

Huntington disease is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this paper, which is based on a dataset extracted from the PREDICT-HD study, we use statistical shape analysis with deformation markers obtained through Large Deformation Diffeomorphic Metric Mapping of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. Based on the relation to cortico-basal-ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention.

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Auditory signals (A) are perceived as lasting longer than visual signals (V) of the same physical duration when they are compared together. Despite considerable debate about how this illusion arises psychologically, the neural underpinnings have not been studied. We used functional magnetic resonance imaging (fMRI) to investigate the neural bases of audiovisual temporal distortions and more generally, intersensory timing. Adults underwent fMRI while judging the relative duration of successively presented standard interval–comparison interval (CI) pairs, which were unimodal (A–A, V–V) or crossmodal (V–A, A–V). Mechanisms of time dilation and compression were identified by comparing the two crossmodal pairs. Mechanisms of intersensory timing were identified by comparing the unimodal and crossmodal conditions. The behavioral results showed that auditory CIs were perceived as lasting longer than visual CIs. There were three novel fMRI results. First, time dilation and compression were distinguished by differential activation of higher-sensory areas (superior temporal, posterior insula, middle occipital), which typically showed stronger effective connectivity when time was dilated (V–A). Second, when time was compressed (A–V) activation was greater in frontal cognitive-control centers, which guide decision making. These areas did not exhibit effective connectivity. Third, intrasensory timing was distinguished from intersensory timing partly by decreased striatal and increased superior parietal activation. These regions showed stronger connectivity with visual, memory, and cognitive-control centers during intersensory timing. Altogether, the results indicate that time dilation and compression arise from the connectivity strength of higher-sensory systems with other areas. Conversely, more extensive network interactions are needed with core timing (striatum) and attention (superior parietal) centers to integrate time codes for intersensory signals.