"Hit the missing stimulus". A simultaneous EEG-fMRI study to localize the generators of endogenous ERPs in an omitted target paradigm.

Event-Related Potentials (ERPs) occurring independently from any stimulus are purely endogenous (emitted potentials) and their neural generators can be unequivocally linked with cognitive processes. In the present study, the subjects performed two similar visual counting tasks: a standard two-stimulus oddball, and an omitted-target oddball task, characterized by the physical absence of the target stimulus. Our investigation aimed at localizing the neural sources of the scalp-recorded endogenous/emitted ERPs. To optimize the source localization, the high temporal resolution of electrophysiology was combined with the fine spatial information provided by the simultaneous recording of functional magnetic resonance (fMRI). Both tasks identified two endogenous ERP components in the 300 to 520 ms interval. An earlier component, pP2, showed a bilateral generator in the anterior Insula. A later P3 component (P3b) was generated bilaterally in the temporal-parietal junction, the premotor and motor area and the anterior intraparietal sulcus (this latter one only in the standard oddball). Anticipatory slow waves (beginning 900 to 500 ms pre-stimulus), also of endogenous nature, were produced by the inferior and middle frontal gyrus and the supplementary and cingulate motor areas. Our protocol disentangled pre- from post-stimulus fMRI activations and provided original clues to the psychophysiological interpretation of emitted/endogenous ERPs.

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition.

OBJECTIVE: Transcutaneous spinal direct current stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We assessed changes in intracortical excitability following tsDCS by evaluating changes in cortical silent period (cSP), paired-pulse short intracortical inhibition (SICI), and intracortical facilitation (ICF). MATERIALS AND METHODS: Healthy subjects were studied before (T0) and at different intervals (T1 and T2) after anodal, cathodal, and sham tsDCS (20', 2.0 mA) applied over the thoracic spinal cord (T10-T12). We assessed changes in cSP, SICI (interstimulus interval, ISI = 3 ms) and ICF (ISI = 10 ms). Motor-evoked potentials (MEPs) were recorded from first digital interosseus (FDI) and tibialis anterior (TA) muscles. RESULTS: Cathodal tsDCS increased MEP amplitudes at interstimulus interval of 3 ms, while anodal one elicited opposite effects (FDI: p = 0.0023; TA: p = 0.0004); conversely, tsDCS left MEP amplitudes unchanged at ISI of 10 ms (FDI: p = 0.39; TA: p = 0.45). No significant change in cSP duration was found from upper limb (p = 0.81) and lower limb (p = 0.33). CONCLUSION: tsDCS modulates inhibitory GABA(A)ergic drive, as assessed by SICI, without interfering with cSP and ICF. The possibility to interfere with cortical processing makes tsDCS a useful approach to modulate spinal drive through nonspinal mechanisms. tsDCS could also represent an early rehabilitation strategy in patients with acute brain lesions, when other noninvasive brain stimulation (NIBS) tools are not indicated due to safety concerns, as well as in the treatment of spinal diseases or pain syndromes.

Phantom limb pain: low frequency repetitive transcranial magnetic stimulation in unaffected hemisphere.

Phantom limb pain is very common after limb amputation and is often difficult to treat. The motor cortex stimulation is a valid treatment for deafferentation pain that does not respond to conventional pain treatment, with relief for 50% to 70% of patients. This treatment is invasive as it uses implanted epidural electrodes. Cortical stimulation can be performed noninvasively by repetitive transcranial magnetic stimulation (rTMS). The stimulation of the hemisphere that isn't involved in phantom limb (unaffected hemisphere), remains unexplored. We report a case of phantom limb pain treated with 1 Hz rTMS stimulation over motor cortex in unaffected hemisphere. This stimulation produces a relevant clinical improvement of phantom limb pain; however, further studies are necessary to determine the efficacy of the method and the stimulation parameters.

Donepezil versus vitamin E in Alzheimer's disease: Part 2: mild versus moderate-severe Alzheimer's disease.

SUMMARY: Early studies showed that the latency of P300 (P3) event related potential increases or diminishes when anticholinergic or cholinergic drugs are administered. We tested the hypothesis that new cholinesterase inhibitors like Donepezil (DPZ) may have an effect on the often abnormal P300 of patients with Alzheimer's Disease (AD), and therefore, that P300 recordings might simplify the evaluation of responses to cholinesterase inhibitor in patients with mild and moderate-severe AD. We evaluated 60 patients with AD: 30 patients with "mild" (Mini Mental State Examination 26-19) and 30 patients with "moderate-severe" (Mini Mental State Examination 18-10), according to the National Institute of Neurological and Communicative Disorders and Alzheimer's Disease and Related Disorders Association criteria in comparison with 40 age-matched controls. All subjects underwent P300 recordings and neuropsychologic examinations (Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale) during the 6-month follow-up. Patients were divided into four groups of 15 patients each: Group I DPZ (10 mg/day) and Group I Vitamin E (2000 IU/day) with "mild" AD; Group II DPZ and Group II Vitamin E with "moderate-severe" AD and same drug dosages. In patients treated with Vitamin E, we observed P3 latency increments (delta) by 11.8 +/- 1.8 ms in Group I and by 12.8 +/- 2.8 ms in Group II at 6 months; neuropsychologic test scores significantly worsened at 6 months (p < 0.001) in Group II patients. Donepezil induced significant P3 latency reductions (11.2 +/- 2.4 ms) in nine patients of Group I and all patients of Group II (16.1 +/- 4.0 ms), reaching a maximum at 3 months (23.2 +/- 2.7 ms). Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale scores improved during the same period, and the difference between Vitamin E and DPZ treated patients was highly significant for P3 (analysis of variance) and for P3-Alzheimer's Diseases Assessment Scale-Cognition (analysis of covariance) with p < 0.001 for pooled groups of patients with AD and Group II (DPZ) versus Group II (Vitamin E). Combined P3 event related potentials measurements, neuropsychologic test comparison evidences significant effects of DPZ in mild and in moderate-severe AD.