Neurofeedback protocol.

<p>During the neurofeedback runs (3 in each of the 4 sessions), participants alternated between 20 s periods of rest and 20 s periods where they had to upregulate activity in the target area. The level of activation was fed back in real time (updated for each TR of 2 s) through the thermometer display.</p

Network activation and deactivation during neurofeedback.

<p>a) Activation of the insular cortex (INS) bilaterally and the right ventral striatum (VS) supported the neurofeedback task, whereas the temporoparietal junctions (TPJ) of both hemispheres were deactivated. The TPJ is recognised as part of the brain’s “default mode network” that is deactivated during effortful tasks. For a full documentation of the activated and deactivated networks see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038115#pone-0038115-t003" target="_blank">Table 3</a>. View from the front and above. The right side of the brain is on the observer’s left (Talairach coordinates of virtual cuts: y = 25, z = −2). b) Successive training sessions produced further increases of activation during upregulation periods in the VS bilaterally (coronal view at y = 7, the right side of the brain is on the observer’s left).</p

Neurofeedback-related activation and deactivation (group whole-brain analysis).

<p>Abbreviations: See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038115#pone-0038115-t002" target="_blank">Table 2</a>; additionally: DMPFC  =  dorsomedial prefrontal cortex; HC  =  hippocampal complex; IFG  =  inferior frontal gyrus; PHG  =  parahippocampal gyrus; PVC  =  primary visual cortex; TPJ  =  temporo-parietal junction; VS  =  ventral striatum; EVC  =  extrastriate visual cortex.</p

Areas activated for contrast “positive” vs. “neutral” images in the group map of the localizer procedure.

<p>Abbreviations: R  =  right, L  =  left, Bil  =  bilateral, ACC  =  anterior cingulate gyrus; D/VLPFC  =  dorso/ventrolateral prefrontal cortex; D/VPMC  =  dorsal/ventral premotor cortex, EVC  =  extrastriate visual cortex; IPL  =  inferior parietal lobule, POJ  =  parieto-occipital junction; IT  =  inferior temporal cortex.</p

Neurofeedback produced clinical improvement that was not seen in the control group.

<p>Patients in the neurofeedback (NF) treatment group, but not those in the imagery (IM) control group, improved significantly on the 17-item Hamilton Depression Rating scale, a standard clinical measure of depression severity and treatment effects. Lower values denote clinical improvement (error bars: standard errors).</p

The localiser procedure identified networks of positive mood.

<p>Higher activation of right insula (INS), ventral striatum (VS), anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (VMPFC) during presentation of positive compared to neutral images in the localiser runs (for full list of areas see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038115#pone-0038115-t002" target="_blank">Table 2</a>). The localiser runs were effective in identifying brain areas responsive to positive images, which were used as target regions of interests (ROIs) for the subsequent neurofeedback procedure. The figure shows the contrast map thresholded at p&lt;.05 (cluster level corrected) on a sample brain seen from the right and front (Talairach coordinates of virtual cuts: x = 0, y = 0, z = −2).</p

Patient demographic characteristics.

<p>Patient demographic characteristics.</p

Neurofeedback success.

<p>Although self-regulation performance was varied during the first run (indicated by the low <i>t</i> values, scaled on the y-axis), participants achieved reliable upregulation during runs 2 and 3, with more stability in the later sessions. Data points represent group means and error bars represent the SD.</p