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PURPOSE: To develop a high temporal resolution functional MRI (fMRI) method for tracking repeating events in the brain. METHODS: We developed a novel fMRI method using Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT), termed EVEnt-Recurring SWIFT (EVER-SWIFT). The method is able to image similar repeating events with sub-second temporal resolution. Here, we demonstrate the use of EVER-SWIFT for detecting fMRI responses during deep brain stimulation (DBS) of the medial septal nucleus (MSN) and during spontaneous isoflurane-induced burst suppression in the rat brain at 9.4 T with 200-ms temporal resolution. RESULTS: EVER-SWIFT showed that the shapes and time-to-peak values of the response curves to DBS stimulation significantly differed between downstream brain regions connected to the MSN, resembling findings obtained with traditional 2-s temporal resolution. In contrast, EVER-SWIFT allowed for detailed temporal measurement of a spontaneous isoflurane-induced bursting activity pattern, which was not achieved with traditional temporal resolution. CONCLUSION: EVER-SWIFT enables sub-second 3-dimensional imaging of both stimulated and spontaneously recurring brain activities, and thus holds great potential for studying the mechanisms of neuromodulation and spontaneous brain activity.

There has been a growing interest toward mitochondrial fatty acid synthesis (mtFAS) since the recent discovery of a neurodegenerative human disorder termed MEPAN (mitochondrial enoyl reductase protein associated neurodegeneration), which is caused by mutations in the mitochondrial enoyl-CoA/ACP (acyl carrier protein) reductase (MECR) carrying out the last step of mtFAS. We show here that MECR protein is highly expressed in mouse Purkinje cells (PCs). To elucidate mtFAS function in neural tissue, here, we generated a mouse line with a PC-specific knock-out (KO) of Mecr, leading to inactivation of mtFAS confined to this cell type. Both sexes were studied. The mitochondria in KO PCs displayed abnormal morphology, loss of protein lipoylation, and reduced respiratory chain enzymatic activities by the time these mice were 6 months of age, followed by nearly complete loss of PCs by 9 months of age. These animals exhibited balancing difficulties ∼7 months of age and ataxic symptoms were evident from 8–9 months of age on. Our data show that impairment of mtFAS results in functional and ultrastructural changes in mitochondria followed by death of PCs, mimicking aspects of the clinical phenotype. This KO mouse represents a new model for impaired mitochondrial lipid metabolism and cerebellar ataxia with a distinct and well trackable cellular phenotype. This mouse model will allow the future investigation of the feasibility of metabolite supplementation approaches toward the prevention of neurodegeneration due to dysfunctional mtFAS.