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The origin of the dopaminergic innervation of the central extended amygdala (EAc; i.e., the lateral bed nucleus of the stria terminalis [BSTl]-central amygdaloid nucleus [Ce] continuum) and accumbens shell (AcSh) was studied in the rat by combining retrograde transport of Fluoro-Gold (FG) with tyrosine hydroxylase (TH) immunofluorescence. Perikaryal profiles (PP) immunoreactive to FG and to both FG and TH were counted in A8-A14 dopaminergic districts. Our results suggest that dopaminergic inputs to the EAc and AcSh arise from the ventral tegmental area-A10, substantia nigra, pars compacta-A9, and retrorubral nucleus-A8 groups as well as from the dorsal raphe nucleus and periaqueductal gray substance, housing the dorsocaudal part of A10 group (A10dc). Quantitative estimates reveal that the A10dc group contains approximately half of the total number of FG/TH double-labeled PP projecting to Ce and BSTl. By using an anti-dopamine serum, DR/PAG projections to Ce were confirmed to be in part dopaminergic. In contrast, modest numbers of FG/TH double-labeled PP were seen in the A10dc group after injections in the sublenticular extended amygdala, interstitial nucleus of the posterior limb of the anterior commissure or AcSh. Ventral mesencephalic projections to the EAc display a crude mediolateral topographic organization, whereas those to the AcSh are topographically organized along a mediolateral and an inverted dorsoventral dimension. The diencephalic dopaminergic groups do not innervate the EAc or AcSh, except for the periventricular gray-A11 which sends light dopaminergic projections to Ce and BSTl. Overall, the present results provide additional details on the organization of the mesolimbic dopaminergic system that critically controls behavioral responsiveness to salient environmental stimuli.

BackgroundFoot musculoskeletal deficits are seldom addressed by preventive medicine despite their high prevalence in patients with diabetic polyneuropathy.AIM: To investigate the effects of strengthening, stretching, and functional training on foot rollover process during gait.MethodsA two-arm parallel-group randomized controlled trial with a blinded assessor was designed. Fifty-five patients diagnosed with diabetic polyneuropathy, 45 to 65 years-old were recruited. Exercises for foot-ankle and gait training were administered twice a week, for 12 weeks, to 26 patients assigned to the intervention group, while 29 patients assigned to control group received recommended standard medical care: pharmacological treatment for diabetes and foot care instructions. Both groups were assessed after 12 weeks, and the intervention group at follow-up (24 weeks). Primary outcomes involved foot rollover changes during gait, including peak pressure (PP). Secondary outcomes involved time-to-peak pressure (TPP) and pressure–time integral (PTI) in six foot-areas, mean center of pressure (COP) velocity, ankle kinematics and kinetics in the sagittal plane, intrinsic and extrinsic muscle function, and functional tests of foot and ankle.ResultsEven though the intervention group primary outcome (PP) showed a not statistically significant change under the six foot areas, intention-to-treat comparisons yielded softening of heel strike (delayed heel TPP, p=.03), better eccentric control of forefoot contact (decrease in ankle extensor moment, p<.01; increase in function of ankle dorsiflexion, p<.05), earlier lateral forefoot contact with respect to medial forefoot (TPP anticipation, p<.01), and increased participation of hallux (increased PP and PTI, p=.03) and toes (increase in PTI, medium effect size). A slower COP mean velocity (p=.05), and an increase in overall foot and ankle function (p<.05) were also observed. In most cases, the values returned to baseline after the follow-up (p<.05).ConclusionsIntervention discreetly changed foot rollover towards a more physiological process, supported by improved plantar pressure distribution and better functional condition of the foot ankle complex. Continuous monitoring of the foot status and patient education are necessary, and can contribute to preserving the integrity of foot muscles and joints impaired by polyneuropathy.Trial registrationClinicalTrials.gov Identifier: NCT01207284, registered in 20th September 2010.

Key PointsQuestionIs there an association between general movement assessment results and neurodevelopment in infants with vertical Zika virus exposure?FindingsIn this cohort study of 444 children, including 111 prenatally exposed to acute maternal illness with rash during the Zika epidemic, general movement assessment was associated with neurodevelopment at age 12 months (94% negative predictive value, 78% positive predictive value, 70% sensitivity, 96% specificity, and 91% accuracy). The Motor Optimality Score was 23 in children with normal development, 12 in children with adverse outcomes, and 5 in children with microcephaly, a significant difference.MeaningGeneral movement assessment is a helpful tool in the evaluation of neurodevelopment in Zika virus–exposed children.

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Background: Recent evidence suggests that chronic low back pain is associated with plastic changes in the brain that can be modified by neuromodulation strategies. This study investigated the efficacy of transcranial direct current stimulation (tDCS) combined simultaneously with peripheral electrical stimulation (PES) for pain relief, disability and global perception in patients with chronic low back pain (CLBP). Methods: Ninety-two patients with CLBP were randomized to receive 12 sessions on nonconsecutive days of anodal tDCS (primary motor cortex, M1), 100 Hz sensory PES (lumbar spine), tDCS + PES or sham tDCS + PES. Pain intensity (11-point numerical rating scale), disability and global perception were applied before treatment and four weeks, three months and six months post randomization. Results: A two points reduction was achieved only by the tDCS + PES (mean reduction [MR] = À2.6, CI95% = À4.4 to À0.9) and PES alone (MR = À2.2, CI95% = À3.9 to À0.4) compared with the sham group, but not of tDCS alone (MR = À1.7, CI95% = À3.4 to À0.0). In addition to maintaining the analgesic effect for up to three months, tDCS + PES had a higher proportion of respondents in different cutoff points. Global perception was improved at four weeks and maintained three months after treatment only with tDCS + PES. None of the treatments improved disability and the affective aspect of pain consistently with pain reduction. Conclusion:The results suggest that tDCS + PES and PES alone are effective in relieving CLBP in the short term. However, only tDCS + PES induced a long-lasting analgesic effect. tDCS alone showed no clinical meaningful pain relief. Significance: Transcranial direct current stimulation combined simultaneously with PES leads to a significant and clinical pain relief that can last up to three months in chronic low back pain patients.

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