Network Localization of Executive Function Deficits in Patients with Focal Thalamic Lesions.

The human thalamus has been suggested to be involved in executive function, based on animal studies and correlational evidence from functional neuroimaging in humans. Human lesion studies, examining behavioral deficits associated with focal brain injuries, can directly test the necessity of the human thalamus for executive function. The goal of our study was to determine the specific lesion location within the thalamus as well as the potential disruption of specific thalamocortical functional networks, related to executive dysfunction. We assessed executive function in 15 patients with focal thalamic lesions and 34 comparison patients with lesions that spared the thalamus. We found that patients with mediodorsal thalamic lesions exhibited more severe impairment in executive function when compared to both patients with thalamic lesions that spared the mediodorsal nucleus and to comparison patients with lesions outside the thalamus. Furthermore, we employed a lesion network mapping approach to map cortical regions that show strong functional connectivity with the lesioned thalamic subregions in the normative functional connectome. We found that thalamic lesion sites associated with more severe deficits in executive function showed stronger functional connectivity with ACC, dorsomedial PFC, and frontoparietal network, compared to thalamic lesions not associated with executive dysfunction. These are brain regions and functional networks whose dysfunction could contribute to impaired executive functioning. In aggregate, our findings provide new evidence that delineates a thalamocortical network for executive function.

A new device to improve target localization for transcranial magnetic stimulation therapy.

BACKGROUND: Accurate identification of cranial midline structures is essential for many targeting techniques that use repetitive transcranial magnetic stimulation (rTMS), including the Beam F3 method used for depression treatment. OBJECTIVE: Evaluate whether a novel, laser-sighted device will assist with more accurate identification of the cranial midline relative to standard scalp-based measurement procedures. METHODS: Three trained TMS technicians performed repeated scalp-based measurements to identify the inion and vertex on five subjects (n = 54 measurements). Measurements were compared to points identified with the midline localizer device and the true midline as defined by MRI midline structures. RESULTS: Use of the midline localizer was more accurate for midline identification than technician measurement (p = 0.00025) and the ratio of localizing the midline within 5 mm was higher (78% versus 54%, p = 0.008). CONCLUSION: Use of a laser-sighted midline localizer device can improve the accuracy of scalp measurements associated with target localization for rTMS treatment protocols.

Thalamic strokes that severely impair arousal extend into the brainstem.

In this study, we evaluate the role of the thalamus in the neural circuitry of arousal. Level of consciousness within the first 12 hours of a thalamic stroke is assessed with lesion symptom mapping. Impaired arousal correlates with lesions in the paramedian posterior thalamus near the centromedian and parafascicular nuclei, posterior hypothalamus, and midbrain tegmentum. All patients with severely impaired arousal (coma, stupor) had lesion extension into the midbrain and/or pontine tegmentum, whereas purely thalamic lesions did not severely impair arousal. These results are consistent with growing evidence that pathways most critical for human arousal lie outside the thalamus. Ann Neurol 2018;84:926-930.

Connectivity of sleep- and wake-promoting regions of the human hypothalamus observed during resting wakefulness.

The hypothalamus is a central hub for regulating sleep-wake patterns, the circuitry of which has been investigated extensively in experimental animals. This work has identified a wake-promoting region in the posterior hypothalamus, with connections to other wake-promoting regions, and a sleep-promoting region in the anterior hypothalamus, with inhibitory projections to the posterior hypothalamus. It is unclear whether a similar organization exists in humans. Here, we use anatomical landmarks to identify homologous sleep- and wake-promoting regions of the human hypothalamus and investigate their functional relationships using resting-state functional connectivity magnetic resonance imaging in healthy awake participants. First, we identify a negative correlation (anticorrelation) between the anterior and posterior hypothalamus, two regions with opposing roles in sleep-wake regulation. Next, we show that hypothalamic connectivity predicts a pattern of regional sleep-wake changes previously observed in humans. Specifically, regions that are more positively correlated with the posterior hypothalamus and more negatively correlated with the anterior hypothalamus correspond to regions with the greatest change in cerebral blood flow between sleep-wake states. Taken together, these findings provide preliminary evidence relating a hypothalamic circuit investigated in animals to sleep-wake neuroimaging results in humans, with implications for our understanding of human sleep-wake regulation and the functional significance of anticorrelations.