Bilateral sequential theta burst stimulation for multiple-therapy-resistant depression: A naturalistic observation study.

Depression is a significant health issue with treatment resistance reported in about one third of patients. Treatment resistance results in significant disability, impaired quality of life, and increased healthcare costs. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option for treatment resistant depression (TRD) with response and remission rates in open-label studies being as high as 58% and 37% respectively. Theta-burst is a faster and novel rTMS paradigm that has shown promise as a treatment for TRD in some preliminary studies. In a naturalistic design, we evaluated the response, remission and tolerability of bilateral sequential (right then left) prefrontal theta-burst rTMS (bsTBS) in 50 patients with TRD (600 pulses/session, 20 sessions, 100% of resting motor threshold (80% if intolerant to 100%, n = 2), F4/F3 of 10-20-20 EEG localization). Data was collected over 36 months from a specialized academic TMS clinic. Patients had multiple-treatment resistance with at least two failed trials of different antidepressants with 20% also having failed electroconvulsive therapy and 66% having received professional therapy. We found a 28% remission rate (HAMD-17 score of ≤7) and a 52% response rate (≥50% reduction in HAMD-17) with a 42% reduction in average HAMD-17 score. The treatment was well tolerated, with muscle contractions, mild pain or discomfort, headache, scalp irritation, and changes to vitals being captured as occasional adverse events with two instances of syncope (0.22% of treatments). This naturalistic study shows that bsTBS is a promising paradigm for a multiple-TRD patient population with approximately one-third of treatments achieving remission and over half achieving significant response.

Theta and beta synchrony coordinate frontal eye fields and anterior cingulate cortex during sensorimotor mapping.

The frontal eye fields (FEFs) and the anterior cingulate cortex (ACC) are commonly coactivated for cognitive saccade tasks, but whether this joined activation indexes coordinated activity underlying successful guidance of sensorimotor mapping is unknown. Here we test whether ACC and FEF circuits coordinate through phase synchronization of local field potential and neural spiking activity in macaque monkeys performing memory-guided and pro- and anti-saccades. We find that FEF and ACC showed prominent synchronization at a 3-9 Hz theta and a 12-30 Hz beta frequency band during the delay and preparation periods with a strong Granger-causal influence from ACC to FEF. The strength of theta- and beta-band coherence between ACC and FEF but not variations in power predict correct task performance. Taken together, the results support a role of ACC in cognitive control of frontoparietal networks and suggest that narrow-band theta and to some extent beta rhythmic activity indexes the coordination of relevant information during periods of enhanced control demands.

Functional connectivity patterns of medial and lateral macaque frontal eye fields reveal distinct visuomotor networks.

It has been previously shown that small- and large-amplitude saccades have different functions during vision in natural environments. Large saccades are associated with reaching movements toward objects, whereas small saccades facilitate the identification of more detailed object features necessary for successful grasping and manual manipulation. To determine whether these represent dichotomous processing streams, we used resting-state functional MRI to examine the functional connectivity patterns of the medial and lateral frontal eye field (FEF) regions that encode large- and small-amplitude saccades, respectively. We found that the spontaneous blood oxygen level-dependent signals of the medial FEF were functionally correlated with areas known to be involved in reaching movements and executive control processes, whereas lateral FEF was functionally correlated with cortical areas involved in object processing and in grasping, fixation, and manipulation of objects. The results provide strong evidence for two distinct visuomotor network systems in the primate brain that likely reflect the alternating phases of vision for action in natural environments.

Involvement of opioidergic system of the ventral hippocampus, the nucleus accumbens or the central amygdala in anxiety-related behavior.

In the present study, the influence of opioidergic system of the ventral hippocampus, the nucleus accumbens or the central amygdala on anxiety-related behaviour was investigated in rats. As a model of anxiety, the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents was used. Bilateral microinjection of different doses of morphine (2.5, 5 and 7.5 microg/rat) into the ventral hippocampus or the nucleus accumbens increased the percentage of open arm time (%OAT) and open arm entries (%OAE) but not locomotor activity, indicating an anxiolytic response. However, intra-central amygdala administration of the opioid did not show any response. On the other hand, microinjection of a dose of naloxone into the ventral hippocampus (2 microg/rat) or the nucleus accumbens (1 microg/rat) increased open arm time (%OAT), but not open arm entry (%OAE) which may indicate an anxiolytic effect. Pre-treatment administration of naloxone (0.5, 1 and 2 microg/rat) reversed the anxiolytic effect of morphine (7.5 microg/rat) injected into the ventral hippocampus in a dose-dependent manner. A dose of the antagonist (1 microg/rat) also reduced the morphine response (2.5 microg/rat) when injected in the nucleus accumbens. In conclusion, it seems that the opioidergic system in the ventral hippocampus and the nucleus accumbens are involved in anxiety-related behaviors and the ventral hippocampus may be the main site of action of the anxiolytic properties of morphine.