Accelerated iTBS treatment applied to the left DLPFC in depressed patients results in a rapid volume increase in the left hippocampal dentate gyrus,not driven by brain perfusion

BackgroundAccelerated intermittent Theta Burst Stimulation (aiTBS) has been shown to be an effective antidepressant treatment. Although neurobiological changes shortly after this intervention have been reported, whether aiTBS results in structural brain changes must still be determined. Furthermore, it possible that rapid volumetric changes are driven by factors other than neurotrophic processes.ObjectivesWe examined whether possible grey matter volumetric (GMV) increases after aiTBS treatment could be driven by increased brain perfusion, measured by Arterial Spin Labeling (ASL).Methods46 treatment-resistant depressed patients were randomized to receive 20 sessions of active or sham iTBS applied to the left dorsolateral prefrontal cortex. All sessions were delivered over 4 days at 5 sessions per day (trial registration: http://clinicaltrials.gov/show/NCT01832805). Patients were scanned the day before starting stimulation and three days after aiTBS.ResultsThere was a significant cluster of increased left hippocampal GMV in the dentate gyrus related to HRSD changes after active aiTBS, but not after sham stimulation. These GMV increases became more pronounced when accounting for changes in cerebral perfusion.ConclusionsActive, but not sham, aiTBS, resulted in acute volumetric changes in parts of the left dentate gyrus, suggesting a connection with adult neurogenesis. Furthermore, taking cerebral perfusion measurements into account impacts on detection of the GMV changes. Whether these hippocampal volumetric changes produced by active aiTBS are necessary for long-term clinical improvement remains to be determined.     

Treating the brain at the speed of sound

One of the most important public issues in our rapidly ageing society are brain disorders and neurodegenerative diseases. Effective therapies are limited and therefore costs for public health systems rapidly increase in this sector. However, recently the first clinical evidence for a new class of therapies has emerged - ultrasound for the brain. With the first clinical data on ultrasound brain activation just now published, three fascinating options are available to revolutionize non-invasive brain therapy. All three ultrasound therapies currently receive widespread attention from patients and doctors.     

Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration.If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results.Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS.     

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.     

Task-dependent effects of intracranial hippocampal stimulation on human memory and hippocampal theta power

BackgroundDespite its potential to revolutionize the treatment of memory dysfunction, the efficacy of direct electrical hippocampal stimulation for memory performance has not yet been well characterized. One of the main challenges to cross-study comparison in this area of research is the diversity of the cognitive tasks used to measure memory performance.ObjectiveWe hypothesized that the tasks that differentially engage the hippocampus may be differentially influenced by hippocampal stimulation and the behavioral effects would be related to the underlying hippocampal activity.MethodsTo investigate this issue, we recorded intracranial EEG from and directly applied stimulation to the hippocampus of 10 epilepsy patients while they performed two different verbal memory tasks – a word pair associative memory task and a single item memory task.ResultsHippocampal stimulation modulated memory performance in a task-dependent manner, improving associative memory performance, while impairing item memory performance. In addition, subjects with poorer baseline cognitive function improved much more with stimulation. iEEG recordings from the hippocampus during non-stimulation encoding blocks revealed that the associative memory task elicited stronger theta oscillations than did item memory and that stronger theta power was related to memory performance.ConclusionsWe show here for the first time that stimulation-induced associative memory enhancement was linked to increased theta power during retrieval. These results suggest that hippocampal stimulation enhances associative memory but not item memory because it engages more hippocampal theta activity and that, in general, increasing hippocampal theta may provide a neural mechanism for successful memory enhancement.