Cortical Inhibition and Plasticity in Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is a severe psychiatric disorder that is associated with various cognitive impairments, including learning and memory deficits. As synaptic plasticity is considered an important mechanism underlying learning and memory, deficits in cortical plasticity might play a role in the pathophysiology of patients with MDD. We used Transcranial Magnetic Stimulation (TMS) to assess inhibitory neurotransmission and cortical plasticity in the motor cortex of MDD patients and controls. METHODS: We measured the cortical silent period (CSP) and short interval cortical inhibition (SICI), as well as intermittent theta-burst stimulation (iTBS), in 9 drug-free MDD inpatients and 18 controls. RESULTS: The overall response to the CSP, SICI, and iTBS paradigms was not significantly different between the patient and control groups. iTBS induction resulted in significant potentiation after 20 mins in the control group (t (17) = -2.8, p = 0.01), whereas no potentiation was observed in patients. CONCLUSIONS: Potentiation of MEP amplitudes was not observed within the MDD group. No evidence was found for medium-to-large effect size differences in CSP and SICI measures in severely depressed drug-free patients, suggesting that reduced cortical inhibition is unlikely to be a robust correlate of the pathophysiological mechanism in MDD. However, these findings should be interpreted with caution due to the high inter-subject variability and the small sample size. SIGNIFICANCE: These findings advance our understanding of neurophysiological functioning in drug-free severely depressed inpatients.

Attention and Motor Learning in Adult Patients with Neurofibromatosis Type 1.

OBJECTIVE: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that is associated with cognitive disabilities, including attention and motor learning problems. These disabilities have been extensively studied in children with NF1 but limited studies have been performed in adults. METHOD: Attention, motor learning and intellectual performance were studied with neuropsychological tasks in 32 adults with NF1 and 32 controls. RESULTS: The NF1 and control group performed similarly on attention and motor learning tasks, although controls had shorter reaction times than adults with NF1 during the motor learning task (t[60] = -2.20, p = .03). Measures of attention or motor learning were not significantly associated with reduced intellectual performance in NF1. CONCLUSION: In contrast to many studies in children with NF1, our findings did not provide evidence for presence of attention or motor learning problems in adults with NF1 in neuropsychological tasks. Our observations may be of clinical importance to determine treatment focus in adults with NF1.

Motor cortical excitability and plasticity in patients with neurofibromatosis type 1.

OBJECTIVE: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that is associated with cognitive disabilities. Based on studies involving animals, the hypothesized cause of these disabilities results from increased activity of inhibitory interneurons that decreases synaptic plasticity. We obtained transcranial magnetic stimulation (TMS)-based measures of cortical inhibition, excitability and plasticity in individuals with NF1. METHODS: We included 32 NF1 adults and 32 neurotypical controls. Cortical inhibition was measured with short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Excitability and plasticity were studied with intermittent theta burst stimulation (iTBS). RESULTS: The SICI and CSP response did not differ between NF1 adults and controls. The response upon iTBS induction was significantly increased in controls (70%) and in NF1 adults (83%). This potentiation lasted longer in controls than in individuals with NF1. Overall, the TMS response was significantly lower in NF1 patients (F(1, 41) = 7.552, p = 0.009). CONCLUSIONS: Individuals with NF1 may have reduced excitability and plasticity, as indicated by their lower TMS response and attenuation of the initial potentiated response upon iTBS induction. However, our findings did not provide evidence for increased inhibition in NF1 patients. SIGNIFICANCE: These findings have potential utility as neurophysiological outcome measures for intervention studies to treat cognitive deficits associated with NF1.

Lateralized modulation of posterior alpha oscillations in children.

The evidence for a functionally inhibitory role of alpha oscillations is growing stronger, mostly derived from studies in healthy adults investigating spatial attention. It remains unexplored if the modulation of alpha band oscillations plays a similar functional role in typically developing children. The aim of this study was to characterize alpha modulations in children in relation to attentional performance. To this end, the posterior alpha activity (8-12Hz) in children between 7 and 10years old was measured using EEG while they performed a visuospatial covert attention task. We found that the alpha activity decreased in the hemisphere contralateral to the attended hemifield, whereas it relatively increased in the other hemisphere. In addition, we found that the degree of lateralized alpha modulation predicted performance on the attention task by negatively predicting the response time on invalid trials. Of note, children who were behaviorally less influenced by spatial cueing also were children with a clear lateralized alpha modulation pattern, with a significantly stronger alpha lateralization in the left hemisphere than children who were influenced more by spatial cueing. In addition, a bias to the right visual field such as that commonly observed in children, was significantly smaller or absent in the children influenced least by spatial cueing. Among all children, the magnitude of this visual field bias was positively related to the ability to modulate alpha activity. In conclusion, we have shown that the pattern of alpha oscillations modulated by attention is already present in 7-10year old typically developing children. Although a similar pattern is observed in adults, the consequences for behavior are different. The fact that alpha modulation is already present at this age opens up the possibility of using hemispheric alpha lateralization as a tool to study the physiological basis of attention deficits in clinical disorders such as ADHD.