Activation Of Pre-supplementary Motor Area Research Articles

Low-frequency transcranial stimulation of pre-supplementary motor area alleviates levodopa-induced dyskinesia in Parkinson's disease: a randomized cross-over trial.

Levodopa-induced dyskinesia gradually emerges during long-term dopamine therapy, causing major disability in patients with Parkinson disease. Using pharmacodynamic functional MRI, we have previously shown that the intake of levodopa triggers an excessive activation of the pre-supplementary motor area in Parkinson disease patients with peak-of-dose dyskinesia. In this pre-registered, interventional study, we tested whether the abnormal responsiveness of the pre-supplementary motor area to levodopa may constitute a ‘stimulation target’ for treating dyskinesia. A gender-balanced group of 17 Parkinson disease patients with peak-of-dose dyskinesia received 30 min of robot-assisted repetitive transcranial magnetic stimulation, after they had paused their anti-Parkinson medication. Real-repetitive transcranial magnetic stimulation at 100% or sham-repetitive transcranial magnetic stimulation at 30% of individual resting corticomotor threshold of left first dorsal interosseous muscle was applied on separate days in counterbalanced order. Following repetitive transcranial magnetic stimulation, patients took 200 mg of oral levodopa and underwent functional MRI to map brain activity, while they performed the same go/no-go task as in our previous study. Blinded video assessment revealed that real-repetitive transcranial magnetic stimulation delayed the onset of dyskinesia and reduced its severity relative to sham-repetitive transcranial magnetic stimulation. Individual improvement in dyskinesia severity scaled linearly with the modulatory effect of real-repetitive transcranial magnetic stimulation on task-related activation in the pre-supplementary motor area. Stimulation-induced delay in dyskinesia onset correlated positively with the induced electrical field strength in the pre-supplementary motor area. Our results provide converging evidence that the levodopa-triggered increase in pre-supplementary motor area activity plays a causal role in the pathophysiology of peak-of-dose dyskinesia and constitutes a promising cortical target for brain stimulation therapy.

P26-T Coil orientation matters: TMS-EEG to optimise the activation of pre-Supplementary motor area

Background Studies using Transcranial Magnetic Stimulation (TMS) have demonstrated the possibility to target different neuronal populations within the primary motor cortex (M1) by changing coil orientation and stimulation intensity. The absence of a direct electrophysiological response such as motor evoked potentials has limited this investigation in areas outside M1. This problem can be solved with the use of combined TMS and electroencephalography, which allows direct recording of cortical responses to TMS pulses. Materials and methods In this work on healthy human subjects we compared early (10–70 ms) and late (70–250 ms) transcranial evoked potentials (TEP) and TMS-related spectral perturbation (TRSP) obtained by delivering magnetic pulses over the pre-SMA with variable coil orientation (0°; 90°; 180° and 270°) and stimulation intensity (100%, 120% and 140% of resting motor threshold). Results both early and late TEP were generally larger when the coil handle was pointing backwards (0[o). This result was true also for early TRSP but, surprisingly, late TRSP was greater when the coil was pointing at 180°. Additionally, stimulating the pre-SMA with a 90° orientation activated the right M1, thus limiting the spatial specificity of the stimulation. Conclusions these results suggest that parameters such as coil orientation and stimulation intensity are critical when stimulating the pre-SMA and they should be taken into account in physiological and clinical studies.

Neural network retuning and neural predictors of learning success associated with cello training

The auditory and motor neural systems are closely intertwined, enabling people to carry out tasks such as playing a musical instrument whose mapping between action and sound is extremely sophisticated. While the dorsal auditory stream has been shown to mediate these audio-motor transformations, little is known about how such mapping emerges with training. Here, we use longitudinal training on a cello as a model for brain plasticity during the acquisition of specific complex skills, including continuous and many-to-one audio-motor mapping, and we investigate individual differences in learning. We trained participants with no musical background to play on a specially designed MRI-compatible cello and scanned them before and after 1 and 4 wk of training. Activation of the auditory-to-motor dorsal cortical stream emerged rapidly during the training and was similarly activated during passive listening and cello performance of trained melodies. This network activation was independent of performance accuracy and therefore appears to be a prerequisite of music playing. In contrast, greater recruitment of regions involved in auditory encoding and motor control over the training was related to better musical proficiency. Additionally, pre-supplementary motor area activity and its connectivity with the auditory cortex during passive listening before training was predictive of final training success, revealing the integrative function of this network in auditory-motor information processing. Together, these results clarify the critical role of the dorsal stream and its interaction with auditory areas in complex audio-motor learning.

Proactive Control Strategies for Overt and Covert Go/NoGo Tasks: An Electrical Neuroimaging Study.

Proactive and reactive inhibition are generally intended as mechanisms allowing the withholding or suppression of overt movements. Nonetheless, inhibition could also play a pivotal role during covert actions (i.e., potential motor acts not overtly performed, despite the activation of the motor system), such as Motor Imagery (MI). In a previous EEG study, we analyzed cerebral activities reactively triggered during two cued Go/NoGo tasks, requiring execution or withholding of overt or covert imagined actions, respectively. This study revealed activation of pre-supplementary motor area (pre-SMA) and right inferior frontal gyrus (rIFG), key nodes of the network underpinning reactive inhibition of overt responses in NoGo trials, also during MI enactment, enabling the covert nature of the imagined motor response. Taking into account possible proactive engagement of inhibitory mechanisms by cue signals, for an exhaustive interpretation of these previous findings in the present study we analyzed EEG activities elicited during the preparatory phase of our cued overt and covert Go/NoGo tasks. Our results demonstrate a substantial overlap of cerebral areas activated during proactive recruitment and subsequent reactive implementation of motor inhibition in both overt and covert actions; also, different involvement of pre-SMA and rIFG emerged, in accord with the intended type (covert or overt) of incoming motor responses. During preparation of the overt Go/NoGo task, the cue is encoded in a pragmatic mode, as it primes the possible overt motor response programs in motor and premotor cortex and, through preactivation of a pre-SMA-related decisional mechanism, it triggers a parallel preparation for successful response selection and/or inhibition during the response phase. Conversely, the preparatory strategy for the covert Go/NoGo task is centered on priming of an inhibitory mechanism in rIFG, tuned to the instructed covert modality of motor performance and instantiated during subsequent MI, which allows the imagined response to remain a potential motor act.

Neural correlates of negative emotion processing in bipolar disorder.

Bipolar disorder type I (BD-I) is characterized by a severe impairment in emotional processing during both acute and euthymic phases of the illness. The aim of the present study was to investigate negative emotion processing in both euthymic patients and non-affected first-degree relatives, looking for state and trait markers of BD-I. 22 healthy relatives of BD-I patients (mean age 31.5±7.3 years; 15 females), 23 euthymic BD-I patients (mean age 35.2±7.9 years; 14 females), and 24 matched controls (mean age 32.5±6.2 years; 16 females) performed an IAPS-based emotional task during 1.5T fMRI. They were required to identify vegetable items (targets) inside neutral or negative pictures. Euthymic BD-I patients showed a significant reduced accuracy in target detection during both neutral and negative images presentation, whereas first-degree relatives performed similarly to normal comparisons. We found a reduced activation of Left precuneus during negative images condition in the patients only. By contrast, both patients and relatives hyperactivated the Left insula and hypoactivated the Right supramarginal gyrus with respect to controls. Moreover, relatives showed an increased activation of Right lingual gyrus and lower activation of pre-supplementary motor area and Right superior frontal gyrus. During a negative emotion task, euthymic BD-I patients and non-affected first-degree relatives shared an abnormal activation of a limbic area (Left insula) coupled with a reduced activation of a parietal region (Right supramarginal gyrus), thus suggesting a trait-like anomalous processing of affective contents. On the other hand, functional abnormalities found only in unaffected relatives and not in patients and controls may correspond to resilience factors.

Presupplementary Motor Area Hyperactivity During Response Inhibition: A Candidate Endophenotype of Obsessive-Compulsive Disorder

Endophenotype studies of obsessive-compulsive disorder (OCD) may uncover heritable traits that are related to genetic susceptibility to OCD. Deficient response inhibition is a promising endophenotype of OCD, although its functional neural correlates have not been extensively studied. The authors sought to determine the functional neural correlates of response inhibition in a large sample of medication-free OCD patients and their unaffected siblings. Forty-one OCD patients, 17 of their siblings, and 37 matched healthy comparison subjects performed a stop-signal task during 3-T functional MRI. The stop-signal reaction time provided a behavioral measure of response inhibition. The neural correlates of response inhibition were assessed in a region-of-interest analysis that included the presupplementary motor area, inferior frontal gyrus, subthalamic nucleus, and inferior parietal cortex. Patients with OCD had greater stop-signal reaction times relative to healthy comparison subjects. The numerical stop-signal reaction time difference between siblings and comparison subjects failed to reach significance. Both patients with OCD and their siblings showed greater activity in the left presupplementary motor area during successful inhibition relative to comparison subjects. Relative to both the comparison subjects and the siblings, patients with OCD showed decreased activity in the right inferior parietal cortex and inferior frontal gyrus. In patients and siblings, presupplementary motor area activity correlated negatively with stop-signal reaction time. These findings suggest that presupplementary motor area hyperactivity is a neurocognitive endophenotype of OCD that is possibly related to inefficient neural processing within the presupplementary motor area itself. Patients with OCD further showed a state-dependent deficit in recruiting right inferior parietal cortex and inferior frontal gyrus, which may contribute to their inhibition deficit.

Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research

Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth-)amphetamine, ecstasy and nicotine dependence, and excessive caffeine use, comparing stimulant abusers (SAs) to nondrug using healthy controls (HCs). Despite some inconsistencies, most studies indicated altered brain activation in prefrontal cortex (PFC) and insula in response to reward and punishment, and higher limbic and anterior cingulate cortex (ACC)/PFC activation during craving and attentional bias paradigms in SAs compared with HCs. Impulsivity in SAs was associated with lower ACC and presupplementary motor area activity compared with HCs, and related to both ventral (amygdala, ventrolateral PFC, insula) and dorsal (dorsolateral PFC, dorsal ACC, posterior parietal cortex) systems. Decision making in SAs was associated with low dorsolateral PFC activity and high orbitofrontal activity. Finally, executive function in SAs was associated with lower activation in frontotemporal regions and higher activation in premotor cortex compared with HCs. It is concluded that the lower activations compared with HCs are likely to reflect the neural substrate of impaired neurocognitive functions, whereas higher activations in SAs compared with HCs are likely to reflect compensatory cognitive control mechanisms to keep behavioral task performance to a similar level as in HCs. However, before final conclusions can be drawn, additional research is needed using neuroimaging in SAs and HCs using larger and more homogeneous samples as well as more comparable task paradigms, study designs, and statistical analyses.

Activation of pre-supplementary motor area (SMA) and SMA proper during unimanual and bimanual complex sequences: an analysis using functional magnetic resonance imaging.

Several functional imaging studies have shown that the extent of activation and percentage change in cerebral blood flow in the supplementary motor area (SMA) during a bimanual mirror performance of a simple repetitive movement are almost identical to those during a unimanual movement. The aim of this study was to investigate whether this finding was also applicable to a more complex movement. Eight right-handed, healthy volunteers performed unimanually (with their right and left hands) and bimanually (in a mirror fashion) thumb-finger opposition in a nonconsecutive order (index-middle-index-ring-index-little-index-middle ... fingers). The SMA proper was more activated during the bimanual movement than the unimanual movement with either hand. This is in accordance with the hypothesis that bimanual movement, even in a mirror fashion, is more difficult than unimanual movement when the task is complex but not when the task is simple. Pre-SMA was inconsistently activated. The results suggest that the SMA proper plays an active role in executive processing during bimanual mirror performance of complex movements.

Different activation of presupplementary motor area, supplementary motor area proper, and primary sensorimotor area, depending on the movement repetition rate in humans.

In order to clarify the functional role of the supplementary motor area (SMA) and its rostral part (pre-SMA) in relation to the rate of repetitive finger movements, we recorded movement-related cortical potentials (MRCPs) directly from the surface of the mesial frontal lobe by using subdural electrode grids implanted in four patients with intractable partial epilepsy. Two subregions in the SMA were identified based on the anatomical location and the different response to cortical stimulation. In three of the four subjects, we also recorded MRCPs from the surface of the lateral convexity covering the primary sensorimotor areas (SI-MI), which were defined by cortical stimulation and SEP recording. The subjects extended the middle finger or opposed the thumb against other fingers of the same hand at a self-paced rate of 0.2 Hz (slow) and 2 Hz (rapid), each in separate sessions. As a result, pre-and postmovement potentials were clearly seen at the SI-MI in both slow- and rapid-rate movements. By contrast, in the SMA, especially in the pre-SMA, premovement potentials were not seen and postmovement potentials were seldom seen in the rapid rate movement. In the slow-rate condition, pre- and postmovement potentials were clearly seen in both the pre-SMA and the SMA proper. In conclusion, the SMA, especially the pre-SMA, is less activated electrophysiologically in the rapid-rate movements, while the SI-MI remains active regardless of the movement rate.