Using functional neuroimaging techniques, regional brain activities can be characterized in vivo
and can be made available as a basis for the self-regulation/modulation of brain function. We have demonstrated that rtfMRI helped individuals better guide their cortical activity in somatomotor areas compared to the matched control group during the performance of a motor imagery task, confirming the results from the previous work by de Charms et al. [2004
]. These individuals were able to consolidate the learned degree of activation after a time-lapse of two weeks through self-practice, as paced by the use of a PDA-device. The control group did not receive any benefit from either the rtfMRI trials or the self-practice. The differential effect of the rtfMRI was also observed based on subjective evaluation as the majority of control subjects had difficulty in adopting a strategy to attain the desired level of functional modulation in their target modulatory ROIs.
Based on the correlation between subjective ratings and BOLD activity from the M1 (), the participants in the experimental group were able to associate and correctly evaluate their own brain activity based on the feedback information from the rtfMRI. Since the given motor imagery task is not an impossible task to perform, we found that four individuals in the control group managed to reach the target regulatory level in a sufficient duration of time. However, their self-evaluation, based on the randomized pseudo-feedback, was disassociated from their actual performance. This indicates that control subjects, in the absence of feedback, were indeed deceived and blinded to the task outcome while the rtfMRI-guided feedback provided the basis for learning the difficult motor imagery task.
From the analysis of the effects of the two-week practice period after the initial rtfMRI trials, we confirmed that the learned level of increased BOLD signal was maintained after the self-practice sessions. It indicates that the effects of rtfMRI were consolidated in the target ROI (i.e.
M1 contralateral to the task). Meanwhile, both the ROI analysis () and the subjective evaluation score () showed the two-week practice period did not result in any further increase in either the level of BOLD signal or the perception of task performance. The seemingly plateaued level of activation that we have seen in this study is in accordance with other behavioral/neuroimaging studies whereby newly acquired motor skill, once rapidly consolidated (‘fast learning’), tapers off in terms of both performance and functional representation in the long term [Karni et al., 1998
; Muellbacher et al., 2002
; Krakauer and Shadmehr 2006
]. However the current study does not provide enough data to examine this ‘learning curve’ effect and calls for the examination of the longitudinal studies extending to longer terms beyond the tested two-week practice period. In addition, the detailed utility of the PDA-driven self-practice after the rtfMRI, which was embedded in our study protocol, was not able to be isolated, and warrants further investigation.
Off-line data analysis revealed that effects of rtfMRI-mediated neural activation, as compared to the control participants, were shown in the left precentral gyrus (PrCG; BA4) as well as the bilateral postcentral gyrus (PoCG; BA3), suggesting the successful regulatory effects on the primary target-of-interest. We could not completely rule out the possibility of the presence of active sensory stimulation via isometric muscle movement since the EMG activity was not measured in this study. However, the absence of apparent finger movement (there were no physical restraints to the hand) suggests that the observed involvement of PoCG may indeed have been implicated in motor learning [Krakauer and Shadmehr, 2006
One of the intriguing findings from the retrospective group fMRI processing was the elevated level of activation identified from the right parahippocampal gyrus among the experimental group. The parahippocampus has been known to be mediated in the process of conditional motor learning, which requires the formation of an association between stimuli and motor responses [Brasted et al., 2005
], or in general learning and memory procedures [Aguirre et al., 1998
]. In this regards, we conjecture that the experimental group started to engage the hippocampal gyrus to learn the motor imagery task after the rtfMRI trials, whereas the control group did not receive any useful information to learn from. The relative increased level of activation in the parahippocampal gyrus was still observed after the self-practice period, which is suggestive of an incomplete or even on-going consolidation of a newly learned process (and thus the remaining role of the hippocampal gyrus).
We found that there were much wider areas of cortical activation that showed an enhanced level of activation compared to the control group upon the completion of the self-practice. These areas include the anterior cingulate gyrus (BA24), the frontal gyri (inferior frontal: BA47), and the dorsolateral frontal gyrus (BA46/8). The bilateral thalamus (medial pulvinar) and the putamen/caudate complex also showed increased activation with the involvement of the insular cortex. The medial pulvinar is known to have widespread connections with the cingulate, posterior parietal, and prefrontal cortical areas [Jueptner et al., 1997a
], whereas the putamen and caudate are implicated in motor learning [Jueptner et al., 1997b
]. Therefore, the involvement of these additional neural substrates detected during the post-practice session may support the engagement of the limbo-thalamo-cortical pathway associated with the consolidation of motor learning [Kew et al., 1993
Apart from the neural substrates that showed the increased signal contrast from the experimental group, the right medial frontal gyrus (BA6; a part of SMA) along with the parietal lobule (BA40) and the occipital lobe (Precuneus) showed greater BOLD activation in the control comparison group (). The parietal lobule, especially, remained with greater BOLD signal from the control group after the two-week practice period (). Although we could not isolate the definite cause of this relative increase in BOLD signal among the control subjects, we conjecture that a visual imagery of hand movement, often reported by the individual from the control group, might have contributed to the findings. Medial frontal gyrus and parietal areas including the Precuneus have been commonly involved in visual imagery and the subsequent association with perception of objects [Grezes et al., 2002
The ability to learn and consolidate specific task strategies and associated cortical function, as mediated by rtfMRI, may provide crucial early evidence that rtfMRI-based training can be used for planning rehabilitation strategies and monitoring the functional recovery/reorganization after CNS damage. The ultimate goal of neuro-rehabilitation is to induce functional reorganization at the affected cortical areas through the induction neural plasticity. However, conventional rehabilitation efforts have been directed toward the modification of motor activity and physical training, demanding a new adjunctive paradigm accounting for other than physical rehabilitation was sought after. Recently, You and colleagues 
have shown such a possibility whereby virtual-reality assisted feedback of body-movement helped to improve the locomotor ability of patients who did not respond to conventional physical therapy. Although the detailed mechanisms associated with training-dependent functional recovery are not clearly understood, rtfMRI mediated engagement of region-specific cortical areas may induce effective synaptic potentiation or even facilitate the re-establishment of functional connectivity through region-specific regulation of cortical activity.
Future applications of rtfMRI-training may include self-initiated monitoring/improvement of mental states to external cues and stimulation (such as emotional responses in patients with depression or craving-inducing stimulation for the individuals with substance abuse). Since rtfMRI has been employed to reinforce the induction of mood states by feedback of amygdala activation [Posse et al., 2003
], it is reasonable to believe that neuro-psychiatric conditions associated with (but not limited to) the pathology of the amygdala-hippocampus circuitry could be treated using an rtfMRI approach.