P 124. Behavioral and fMRI changes associated with combined tDCS and cognitive rehabilitation in a case series of patients with mild cognitive impairment

A growing body of evidence supports the use of transcranial direct current stimulation (tDCS) for motor rehabilitation; however, the use of tDCS for cognitive rehabilitation has rarely been examined. Patients with mild cognitive impairment (MCI) demonstrate significant learning and memory deficits and are likely to develop Alzheimer’s disease. Functional magnetic resonance imaging (fMRI) typically demonstrates hypoactivation in MCI patients relative to healthy individuals, suggesting reduced neuronal functioning. tDCS provides a non-invasive method through which it may be possible to facilitate neuronal functioning. However, such facilitation may only reinforce the suboptimal networks that have emerged as a result of the disease process. We previously demonstrated that cognitive rehabilitation enhances learning and memory, alters the pattern of task-based activation, and increases connectivity in those with MCI. The primary question is whether the combined use of tDCS and cognitive rehabilitation can engage and reinforce adaptive brain networks more than either approach in isolation. Methods We present a case series of MCI patients who were administered 5 consecutive days of tDCS (2 mA for 20 min; 35 cm2 anode over FP1, cathode on right deltoid). Patients underwent fMRI during rest-state and task-based (memory encoding of object location associations) conditions before and after tDCS. One patient received only tDCS, while the other two received tDCS and cognitive rehabilitation (combined treatment). Behavioral change was measured using an object-location task in which the distance (in cm) between the recalled vs. actual object location was the dependent variable. Change in task-based activation used the contrast: (novel stimuli (post > pre) > repeated (post > pre)). Regions of interest were selected based on these changes and theoretical rationale and used as seed regions for rest-state cross-correlation based functional connectivity. Results Behaviorally, patients receiving combined treatment became more accurate (3–4 cm improvement) whereas the tDCS only patient showed minimal change (∼0.6 cm improvement). fMRI showed increased activation within task-relevant regions including the prefrontal, parietal, and inferior temporal cortices, bilaterally. Conversely, the tDCS only patient showed a pattern of increased activation that was restricted to the right superior temporal gyrus and reduced activation in the temporal poles bilaterally. Across all patients, increased activation seemed to be more common in sulcal depths, possibly reflecting the pooling of electrical current in these regions. Reduced activation was observed in the frontopolar cortex (i.e., the area immediately under the anode). Rest-state analyses consistently demonstrated more focused patterns of connectivity post-compared to pre-training in the combined treatment patients. These changes seemed to restore the “normal” differences between the attention and default mode networks in at least some areas (dorsolateral prefrontal cortex). The tDCS only patient showed substantial increases in connectivity that appeared non-specific and involved a number of both lateral and medial prefrontal and parietal cortices. Conclusions Although caution is warranted in interpreting our findings, these cases provide behavioral and physiologic evidence suggesting the combination of tDCS and cognitive rehabilitation may facilitate learning and memory in patients with MCI.