Increasing numbers of healthcare professionals are using smartphones and their associated applications (apps) in daily clinical care. While these medical apps hold great potential for improving clinical practice, little is known about the possible dangers associated with their use. Breaches of patient confidentiality, conflicts of interests and malfunctioning clinical decision-making apps could all negatively impact on patient care. We propose several strategies to enhance the development of evidence-based medical apps while retaining their open nature. The increasing use of medical apps calls for broader discussion across medicine's organising and accrediting bodies. The field of medical apps is currently one of the most dynamic in medicine, with real potential to change the way evidence-based healthcare is delivered in the future. Establishing appropriate regulatory procedures will enable this potential to be fulfilled, while at all times ensuring the safety of the patient.

Although involvement of the cerebello-thalamo-cortical network has often been suggested in essential tremor, the source of oscillatory activity remains largely unknown. To elucidate mechanisms of tremor generation, it is of crucial importance to study the dynamics within the cerebello-thalamo-cortical network. Using a combination of electromyography and functional magnetic resonance imaging, it is possible to record the peripheral manifestation of tremor simultaneously with brain activity related to tremor generation. Our first aim was to study the intrinsic activity of regions within the cerebello-thalamo-cortical network using dynamic causal modelling to estimate effective connectivity driven by the concurrently recorded tremor signal. Our second aim was to objectify how the functional integrity of the cerebello-thalamo-cortical network is affected in essential tremor. We investigated the functional connectivity between cerebellar and cortical motor regions showing activations during a motor task. Twenty-two essential tremor patients and 22 healthy controls were analysed. For the effective connectivity analysis, a network of tremor-signal related regions was constructed, consisting of the left primary motor cortex, premotor cortex, supplementary motor area, left thalamus, and right cerebellar motor regions lobule V and lobule VIII. A measure of variation in tremor severity over time, derived from the electromyogram, was included as modulatory input on intrinsic connections and on the extrinsic cerebello-thalamic connections, giving a total of 128 models. Bayesian model selection and random effects Bayesian model averaging were used. Separate seed-based functional connectivity analyses for the left primary motor cortex, left supplementary motor area and right cerebellar lobules IV, V, VI and VIII were performed. We report two novel findings that support an important role for the cerebellar system in the pathophysiology of essential tremor. First, in the effective connectivity analysis, tremor variation during the motor task has an excitatory effect on both the extrinsic connection from cerebellar lobule V to the thalamus, and the intrinsic activity of cerebellar lobule V and thalamus. Second, the functional integrity of the motor network is affected in essential tremor, with a decrease in functional connectivity between cortical and cerebellar motor regions. This decrease in functional connectivity, related to the motor task, correlates with an increase in clinical tremor severity. Interestingly, increased functional connectivity between right cerebellar lobules I-IV and the left thalamus correlates with an increase in clinical tremor severity. In conclusion, our findings suggest that cerebello-dentato-thalamic activity and cerebello-cortical connectivity is disturbed in essential tremor, supporting previous evidence of functional cerebellar changes in essential tremor.

BackgroundEssential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities.ObjectiveIn this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging (EMG-fMRI) to study a group of ET patients selected according to strict criteria to achieve maximal homogeneity. With this approach we expected to improve upon the localization of the bilateral cerebellar abnormalities found in earlier fMRI studies.MethodsWe included 21 propranolol sensitive patients, who were not using other tremor medication, with a definite diagnosis of ET defined by the Tremor Investigation Group. Simultaneous EMG-fMRI recordings were performed while patients were off tremor medication. Patients performed unilateral right hand and arm extension, inducing tremor, alternated with relaxation (rest). Twenty-one healthy, age- and sex-matched participants mimicked tremor during right arm extension. EMG power variability at the individual tremor frequency as a measure of tremor intensity variability was used as a regressor, mathematically independent of the block regressor, in the general linear model used for fMRI analysis, to find specific tremor-related activations.ResultsBlock-related activations were found in the classical upper-limb motor network, both for ET patients and healthy participants in motor, premotor and supplementary motor areas. In ET patients, we found tremor-related activations bilaterally in the cerebellum: in left lobules V, VI, VIIb and IX and in right lobules V, VI, VIIIa and b, and in the brainstem. In healthy controls we found simulated tremor-related activations in right cerebellar lobule V.ConclusionsOur results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.