Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (± 1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

The left inferior frontal gyrus (LIFG) has consistently been associated with both phonologic and semantic operations in functional neuroimaging studies. Two main theories have proposed a different functional organization in the LIFG for these processes. One theory suggests an anatomic parcellation of phonologic and semantic operations within the LIFG. An alternative theory proposes that both processes are encompassed within a supramodal executive function in a single region in the LIFG. To test these theories, we carried out a systematic review of functional magnetic resonance imaging studies employing phonologic and semantic verbal fluency tasks. Seventeen articles meeting our pre-established criteria were found, consisting of 22 relevant experiments with 197 healthy subjects and a total of 41 peak activations in the LIFG. We determined 95% confidence intervals of the mean location (x, y, and z coordinates) of peaks of blood oxygenation level-dependent (BOLD) responses from published phonologic and semantic verbal fluency studies using the nonparametric technique of bootstrap analysis. Significant differences were revealed in dorsal-ventral (z-coordinate) localizations of the peak BOLD response: phonologic verbal fluency peak BOLD response was significantly more dorsal to the peak associated with semantic verbal fluency (confidence interval of difference: 1.9-17.4 mm). No significant differences were evident in antero-posterior (x-coordinate) or medial-lateral (y-coordinate) positions. The results support distinct dorsal-ventral locations for phonologic and semantic processes within the LIFG. Current limitations to meta-analytic integration of published functional neuroimaging studies are discussed.

Movement-related brain activation patterns after subcortical stroke are characterized by relative overactivations in cortical motor areas compared with controls. In patients able to perform a motor task, overactivations are greater in those with more motor impairment. We hypothesized that recruitment of motor regions would shift from primary to secondary motor networks in response to impaired functional integrity of the corticospinal system (CSS). We measured the magnitude of brain activation using functional MRI during a motor task in eight chronic subcortical stroke patients. CSS functional integrity was assessed using transcranial magnetic stimulation to obtain stimulus/response curves for the affected first dorsal interosseus muscle, with a shallower gradient representing increasing disruption of CSS functional integrity. A negative correlation between the gradient of stimulus/response curve and magnitude of task-related brain activation was found in several motor-related regions, including ipsilesional posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional superior cingulate sulcus. There were no significant positive correlations in any brain region. These results suggest that impaired functional integrity of the CSS is associated with recruitment of secondary motor networks in both hemispheres in an attempt to generate motor output to spinal cord motoneurons. Secondary motor regions are less efficient at generating motor output so this reorganization can only be considered partially successful in reducing motor impairment after stroke.

Repetitive transcranial magnetic stimulation (rTMS) of human primary motor cortex (M1) changes cortical excitability at the site of stimulation and at distant sites without affecting simple motor performance. The aim of this study was to explore how rTMS changes regional excitability and how the motor system compensates for these changes. Using functional brain imaging, activation was mapped at rest and during freely selected finger movements after 30 min of 1 Hz rTMS. rTMS increased synaptic activity in the stimulated left M1 and induced widespread changes in activity throughout areas engaged by the task. In particular, movement-related activity in the premotor cortex of the nonstimulated hemisphere increased after 1 Hz rTMS. Analyses of effective connectivity confirmed that the stimulated part of M1 became less responsive to input from premotor and mesial motor areas. Conversely, after rTMS our results were consistent with increased coupling between an inferomedial portion of left M1 and anterior motor areas. These results are important for three reasons. First, they show changes in motor excitability to central inputs from other cortical areas (as opposed to peripheral or exogenous inputs used in previous studies). Second, they suggest that maintenance of task performance may involve activation of premotor areas contralateral to the site of rTMS, similar to that seen in stroke patients. Third, changes in motor activations at the site of rTMS suggest an rTMS-induced remodeling of motor representations during movement. This remapping may provide a neural substrate for acute compensatory plasticity of the motor system in response to focal lesions such as stroke.