Altered effective connectivity in sensorimotor cortices is a signature of severity and clinical course in depression.

Functional neuroimaging research on depression has traditionally targeted neural networks associated with the psychological aspects of depression. In this study, instead, we focus on alterations of sensorimotor function in depression. We used resting-state functional MRI data and dynamic causal modeling (DCM) to assess the hypothesis that depression is associated with aberrant effective connectivity within and between key regions in the sensorimotor hierarchy. Using hierarchical modeling of between-subject effects in DCM with parametric empirical Bayes we first established the architecture of effective connectivity in sensorimotor cortices. We found that in (interoceptive and exteroceptive) sensory cortices across participants, the backward connections are predominantly inhibitory, whereas the forward connections are mainly excitatory in nature. In motor cortices these parities were reversed. With increasing depression severity, these patterns are depreciated in exteroceptive and motor cortices and augmented in the interoceptive cortex, an observation that speaks to depressive symptomatology. We established the robustness of these results in a leave-one-out cross-validation analysis and by reproducing the main results in a follow-up dataset. Interestingly, with (nonpharmacological) treatment, depression-associated changes in backward and forward effective connectivity partially reverted to group mean levels. Overall, altered effective connectivity in sensorimotor cortices emerges as a promising and quantifiable candidate marker of depression severity and treatment response.

Real-time fMRI neurofeedback compared to cognitive behavioral therapy in a pilot study for the treatment of mild and moderate depression.

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback was found to reduce depressive symptoms. However, no direct comparison of drug-free patients with an active psychotherapy control group is available. The present study compared rt-fMRI neurofeedback with cognitive behavioral therapy, as the standard treatment in patients declining anti-depressants. Twenty adult, drug-free patients with mild or moderate depression were non-randomly assigned either to a course of eight half-hour sessions of neurofeedback targeting the left medial prefrontal cortex (N = 12) or to a 16-session course of cognitive behavioral therapy (N = 8). Montgomery-Asberg Depression Rating Scale was introduced at baseline, mid-treatment, and end-treatment points. In each group, 8 patients each remained in the study to a mid-treatment evaluation and 6 patients each to the study end-point. ANOVA revealed a depression reduction with a significant effect of Time (F(3,6) = 19.0, p < 0.001, η2 = 0.76). A trend to greater improvement in the cognitive behavioral therapy group compared to neurofeedback emerged (Group × Time; p = 0.078). Percent signal change in the region of interest between up- and down-regulation conditions was significantly correlated with session number (Pearson's r = 0.85, p < 0.001) indicating a learning effect. As limitations, small sample size could lead to insufficient power and non-random allocation to selection bias. Both neurofeedback and cognitive behavioral therapy improved mild and moderate depression. Neurofeedback was not superior to cognitive behavioral therapy. Noteworthy, the neurofeedback training course was associated with continuous improvement in the self-regulation skill, without plateau. This study delivers data to plan clinical trials comparing neurofeedback with cognitive behavioral interventions.

Neuroimaging Study of Alpha and Beta EEG Biofeedback Effects on Neural Networks.

Neural networks interaction was studied in healthy men (20-35 years old) who underwent 20 sessions of EEG biofeedback training outside the MRI scanner, with concurrent fMRI-EEG scans at the beginning, middle, and end of the course. The study recruited 35 subjects for EEG biofeedback, but only 18 of them were considered as "successful" in self-regulation of target EEG bands during the whole course of training. Results of fMRI analysis during EEG biofeedback are reported only for these "successful" trainees. The experimental group (N = 23 total, N = 13 "successful") upregulated the power of alpha rhythm, while the control group (N = 12 total, N = 5 "successful") beta rhythm, with the protocol instructions being as for alpha training in both. The acquisition of the stable skills of alpha self-regulation was followed by the weakening of the irrelevant links between the cerebellum and visuospatial network (VSN), as well as between the VSN, the right executive control network (RECN), and the cuneus. It was also found formation of a stable complex based on the interaction of the precuneus, the cuneus, the VSN, and the high level visuospatial network (HVN), along with the strengthening of the interaction of the anterior salience network (ASN) with the precuneus. In the control group, beta enhancement training was accompanied by weakening of interaction between the precuneus and the default mode network, and a decrease in connectivity between the cuneus and the primary visual network (PVN). The differences between the alpha training group and the control group increased successively during training. Alpha training was characterized by a less pronounced interaction of the network formed by the PVN and the HVN, as well as by an increased interaction of the cerebellum with the precuneus and the RECN. The study demonstrated the differences in the structure and interaction of neural networks involved into alpha and beta generating systems forming and functioning, which should be taken into account during planning neurofeedback interventions. Possibility of using fMRI-guided biofeedback organized according to the described neural networks interaction may advance more accurate targeting specific symptoms during neurotherapy.

Assignment of metal-ligand modes in Pt(II) diimine complexes relevant to solar energy conversion.

This work describes a comprehensive assignment of the vibrational spectra of the platinum(II) diimine bisthiolate and chloride complexes as a prototype structure for a diversity of Pt(II) diimine chromophores. The dynamics and energy dissipation pathways in excited states of light harvesting molecules relies largely on the coupling between the high frequency and the low frequency modes. As such, the assignment of the vibrational spectrum of the chromophore is of utmost importance, especially in the low-frequency region, below 500 cm(-1), where the key metal-ligand framework modes occur. This region is experimentally difficult to access with infrared spectroscopy and hence frequently remains elusive. However, this region is easily accessible with Raman and inelastic neutron scattering (INS) spectroscopies. Accordingly, a combination of inelastic neutron scattering and Raman spectroscopy with the aid of computational results from periodic-DFT and the mode visualizations, as well as isotopic substitution, allowed for an identification of the modes that contain significant contributions from Pt-Cl, Pt-S, and Pt-N stretch modes. The results also demonstrate that it is not possible to assign transition energies to "pure", localized modes in the low frequency region, as a consequence of the anticipated severe coupling that occurs among the skeletal modes. The use of INS has proved invaluable in identifying and assigning the modes in the lowest frequency region, and overall the results will be of assistance in analyzing the structure of the electronic excited state in the families of chromophores containing a Pt(diimine) core.

Sterically hindered Re- and Mn-CO2 reduction catalysts for solar energy conversion.

Novel molecular Re and Mn tricarbonyl complexes bearing a bipyridyl ligand functionalised with sterically hindering substituents in the 6,6'-position, [M(HPEAB)(CO)3(X)] (M/X = Re/Cl, Mn/Br; HPEAB = 6,6'-{N-(4-hexylphenyl)-N(ethyl)-amido}-2,2'-bipyridine) have been synthesised, fully characterised including by single crystal X-ray crystallography, and their propensity to act as catalysts for the electrochemical and photochemical reduction of CO2 has been established. Controlled potential electrolysis showed that the catalysts are effective for electrochemical CO2-reduction, yielding CO as the product (in MeCN for the Re-complex, in 95 : 5 (v/v) MeCN : H2O mixture for the Mn-complex). The recyclability of the catalysts was demonstrated through replenishment of CO2 within solution. The novel catalysts had similar reduction potentials to previously reported complexes of similar structure, and results of the foot-of-the-wave analysis showed comparable maximum turnover rates, too. The tentative mechanisms for activation of the pre-catalysts were proposed on the basis of IR-spectroelectrochemical data aided by DFT calculations. It is shown that the typical dimerisation of the Mn-catalyst was prevented by incorporation of sterically hindering groups, whilst the Re-catalyst undergoes the usual mechanism following chloride ion loss. No photochemical CO2 reduction was observed for the rhenium complex in the presence of a sacrificial donor (triethylamine), which was attributed to the short triplet excited state lifetime (3.6 ns), insufficient for diffusion-controlled electron transfer. Importantly, [Mn(HPEAB)(CO)3Br] can act as a CO2 reduction catalyst when photosensitised by a zinc porphyrin under red light irradiation (λ > 600 nm) in MeCN : H2O (95 : 5); there has been only one reported example of photoactivating Mn-catalysts with porphyrins in this manner. Thus, this work demonstrates the wide utility of sterically protected Re- and Mn-diimine carbonyl catalysts, where the rate and yield of CO-production can be adjusted based on the metal centre and catalytic conditions, with the advantage of suppressing unwanted side-reactions through steric protection of the vacant coordination site.

Pt(II) mono-carbonyl complexes of a cyclometallating 2-(2'-thienyl)-(pyridinato-C,3N') ligand: nature and dynamics of the lowest excited state of the chloro- and thiolato-complexes.

The synthesis of a cyclometallated Pt(II) thiolate carbonyl complex Pt(thpy)(CO)(mts), (thpy = 2-(2'-thienyl)-pyridinate, mts = methylthiosalicylate) is reported. A combination of emission and time-resolved infrared (TRIR) techniques revealed for both Pt(thpy)(CO)(mts) and its chloride analogue Pt(thpy)(CO)Cl the predominant intra 2-(2'-thienyl)-pyridinate 3pi pi* character of the lowest electronic excited state. The unusually short lifetime (780 ps) of the intraligand 3pi pi* lowest excited state of Pt(thpy)(CO)(mts) indicates that this electronic state is influenced by another close-lying excited state, probably charge-transfer in origin.

PtII diimine chromophores with perfluorinated thiolate ligands: nature and dynamics of the charge-transfer-to-diimine lowest excited state.

The synthesis of new Pt(II) diimine complexes bearing perfluorinated thiolate ligands, Pt(II)(NN)(4-X-C(6)F(4)-S)(2), where NN = 2,2'-bipyridine or 1,10-phenanthroline and X = F or CN, is reported, together with an investigation of the nature and dynamics of their lowest excited states. A combined UV-vis, (spectro)electrochemical, resonance Raman, and time-resolved infrared (TRIR) study has suggested that the HOMO is mainly composed of thiolate(pi)/S(p)/Pt(d) orbitals and that the LUMO is largely localized on the pi*(diimine) orbital, thus revealing the [charge-transfer-to-diimine] nature of the lowest excited state. An enhancement of the thiolate ring vibrations, C-F vibrations, and the vibration of the CN-substituent on the thiolate moiety was observed in the resonance Raman spectra, whereas no such enhancement was seen for the nonfluorinated analogues. Thus, the introduction of fluorine substituents on the thiolate moiety probably leads to a more pronounced contribution of the intrathiolate modes to the HOMO compared to the analogous complexes with nonfluorinated thiolates. Furthermore, the introduction of the p-CN group into the thiolate moiety has allowed the dynamics of the lowest excited state of Pt(bpy)(4-CN-C(6)F(4)-S)(2) to be monitored by picosecond TRIR spectroscopy. The dynamics of the lowest [charge-transfer-to-diimine] excited state are governed by ca. 2-ps vibrational cooling and 35-ps back electron transfer.