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Objective Obesity is associated with decreased activity in the prefrontal cortex. Transcranial direct current stimulation (tDCS) modifies cortical excitability and may facilitate improved control of eating. The energy intake (EI) and body weight in subjects who received cathodal versus sham (study 1) and subsequent anodal versus sham (study 2) tDCS aimed at the left dorsolateral prefrontal cortex (LDLPFC) were measured. Methods Nine (3m, 6f) healthy volunteers with obesity (94 ± 15 kg [M ± SD]; 42 ± 8 y) were admitted as inpatients for 9 days to participate in a double-blind, randomized, placebo-controlled crossover experiment. Study 1: following 5 days of a weight-maintaining diet, participants received cathodal or sham tDCS (2 mA, 40 min) on three consecutive mornings and then ate ad libitum from a computerized vending machine, which recorded EI. Weight was measured daily. Study 2: participants repeated the study, maintaining original assignment to active (this time anodal) and sham. Results Participants tended to consume fewer kilocalories per day (P = 0.07), significantly fewer kilocalories from soda (P = 0.02) and fat (P = 0.03), and had a greater % weight loss (P = 0.009) during anodal versus cathodal tDCS. Conclusions The results indicated a role for the LDLPFC in obesity and food intake. This proof of concept study suggested, for the first time, the potential application of anodal tDCS to facilitate weight loss.

r Abstract: Apathy, common in neurological disorders, is defined as disinterest and loss of motivation, with a reduction in self-initiated activity. Research in diseased populations has shown that apathy is associated with variations in the volume of brain regions such as the anterior cingulate and the frontal lobes. The goal of this study was to determine the neural signatures of apathy in people with penetrat- ing traumatic brain injuries (pTBIs), as to our knowledge, these have not been studied in this sample. We studied 176 male Vietnam War veterans with pTBIs using voxel-based lesion-symptom mapping (VLSM) and apathy scores from the UCLA Neuropsychiatric Inventory (NPI), a structured inventory of symptoms completed by a caregiver. Our results revealed that increased apathy symptoms were associated with brain damage in limbic and cortical areas of the left hemisphere including the anterior cingulate, inferior, middle, and superior frontal regions, insula, and supplementary motor area. Our results are consistent with the literature, and extend them to people with focal pTBI. Apathy is a sig- nificant symptom since it can reduce participation of the patient in family and other social interactions, and diminish affective decision-making. Hum Brain Mapp 00:000-000, 2013. V C 2013 Wiley-Periodicals, Inc.

Background We have explored the potential prefrontal hemodynamic biomarkers to characterize subjects with Traumatic Brain Injury (TBI) by employing the multivariate machine learning approach and introducing a novel task‐related hemodynamic response detection followed by a heuristic search for optimum set of hemodynamic features. To achieve this goal, the hemodynamic response from a group of 31 healthy controls and 30 chronic TBI subjects were recorded as they performed a complexity task. Methods To determine the optimum hemodynamic features, we considered 11 features and their combinations in characterizing TBI subjects. We investigated the significance of the features by utilizing a machine learning classification algorithm to score all the possible combinations of features according to their predictive power. Results and Conclusions The identified optimum feature elements resulted in classification accuracy, sensitivity, and specificity of 85%, 85%, and 84%, respectively. Classification improvement was achieved for TBI subject classification through feature combination. It signified the major advantage of the multivariate analysis over the commonly used univariate analysis suggesting that the features that are individually irrelevant in characterizing the data may become relevant when used in combination. We also conducted a spatio‐temporal classification to identify regions within the prefrontal cortex (PFC) that contribute in distinguishing between TBI and healthy subjects. As expected, Brodmann areas (BA) 10 within the PFC were isolated as the region that healthy subjects (unlike subjects with TBI), showed major hemodynamic activity in response to the High Complexity task. Overall, our results indicate that identified temporal and spatio‐temporal features from PFC's hemodynamic activity are promising biomarkers in classifying subjects with TBI.

The objective of this study is to assess the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for gait and bradykinesia in patients with Parkinson's disease (PD). In a double-blind placebo-controlled study, we evaluated the effects of 25 Hz rTMS in 18 PD patients. Eight rTMS sessions were performed over a 4-week period. Four cortical targets (left and right motor and dorsolateral prefrontal cortex) were stimulated in each session, with 300 pulses each, 100% of motor threshold intensity. Left motor cortex (MC) excitability was assessed using motor evoked potentials (MEPs) from the abductor pollicis brevis. During the 4 weeks, times for executing walking and complex hand movements tests gradually decreased. The therapeutic rTMS effect lasted for at least 1 month after treatment ended. Right-hand bradykinesia improvement correlated with increased MEP amplitude evoked by left MC rTMS after individual sessions, but improvement overall did not correlate with MC excitability. rTMS sessions appear to have a cumulative benefit for improving gait, as well as reducing upper limb bradykinesia in PD patients. Although short-term benefit may be due to MC excitability enhancement, the mechanism of cumulative benefit must have another explanation.

A pediatric kidney transplant recipient receiving tacrolimus for immunosuppression experienced symptoms consistent with idiopathic intracranial hypertension. The diagnosis of idiopathic intracranial hypertension and possible secondary causes of intracranial hypertension are reviewed in association with the patient's clinical course. Treatment options for the reversal of intracranial hypertension are summarized. Because of the complexity of associated conditions in kidney transplant recipients, symptoms of persistent headaches, visual changes and nausea and vomiting should be promptly investigated by fundoscopic examination in the setting of immunosuppression therapy to prevent vision loss.

Objective.—To characterize the temporal course of transcranial magnetic stimulation-induced phosphene thresholds in subjects with migraine and in controls. Methods.—Eleven subjects with migraine with aura, 10 subjects with migraine without aura, 9 subjects with menstrual migraine, and 15 controls (no history of migraine and without migraine during the study) were studied. Subjects were not on preventive medication. Transcranial magnetic stimulation was performed, and a phosphene threshold was measured 3 times a week over 3 weeks in a manner timed to incorporate the menstrual period in females. A headache calendar was kept during the study. Results.—Mean transcranial magnetic stimulation thresholds were lower for each migraine group compared with controls (P < .001) for each comparison. There was a trend for lower thresholds among subjects with migraine with aura compared with subjects with migraine without aura (P < .10), but not subjects with menstrual migraine. There was consistent lowering of thresholds from the first to the last stimulation in all migraine groups and in the controls. Maximum and minimum thresholds did not predict headache occurrence, nor did the occurrence of headache predict an ensuing maximum or minimum phosphene threshold. Conclusions.—Transcranial magnetic stimulation thresholds are lower in subjects with migraine compared with controls. The reported phosphene threshold is lowered with repeated measurement. Neither high nor low phosphene thresholds predict a subsequent headache, nor do migraines predict a subsequent high or low threshold.

Ovarian steroids appear to alter neuronal function in women, but direct physiological evidence is lacking. In animals, estradiol enhances excitatory neurotransmission. Progesterone-derived neurosteroids increase GABAergic inhibition. The effect of weak transcranial magnetic stimulation of the motor cortex on the motor evoked potential (MEP) from transcranial magnetic stimulation given milliseconds later is changed by GABAergic and glutamatergic agents. Using this technique previously, we showed more inhibition in the luteal phase relative to the midfollicular menstrual phase, which is consistent with a progesterone effect. To detect the effects of estradiol, we have now divided the follicular phase. We tested 14 healthy women during the early follicular (low estradiol, low progesterone), late follicular (high estradiol, low progesterone), and luteal (high estradiol, high progesterone) phases, with interstimulus intervals from 2 to 10msec (10 trials at each interval and 40 unconditioned trials). We calculated the ratio of the conditioned MEP at each interval to the mean unconditioned MEP: the higher the ratio, the less inhibition and the more facilitation caused by the first stimulus. The combined ratios increased significantly from the early follicular phase to the late follicular phase and then decreased again in the luteal phase. These findings demonstrate an excitatory neuronal effect associated with estradiol and confirm our earlier finding of inhibition associated with progesterone.

Five healthy volunteers were studied using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) and an averaged single trial (AST) protocol. Blood oxygenation level-dependent (BOLD)-fMRI response to single TMS pulses over the motor cortex was detectable in both the ipsilateral motor cortex under the TMS coil and the contralateral motor cortex, as well as bilaterally in the auditory cortex. The associated BOLD signal increase showed the typical fMRI hemodynamic response time course. The brain's response to a single TMS pulse over the motor cortex at 120% of the level required to induce thumb movement (1.0%-1.5% signal increase) was comparable in both level and duration to the auditory cortex response to the sound accompanying the TMS pulse (1.5% -2.0% signal increase).

1. Transcranial magnetic stimulation (TMS) of the human motor cortex results in multiple discharges (D and I waves) in the corticospinal tract. We tested whether these volleys can be explored non-invasively with paired TMS. The intensity of the first stimulus (S1) was set to produce a motor-evoked potential (MEP) of 1 mV in the resting contralateral abductor digiti minimi (ADM) muscle; the second stimulus (S2) was set to 90 % of the resting motor threshold. At interstimulus intervals of 1.1-1.5, 2.3-2.9 and 4.1-4.4 ms the MEP elicited by S1 plus S2 was larger than that produced by S1 alone. 2. Varying the S1 intensity between 70 and 130 % resting motor threshold with S2 held constant at 90 % resting motor threshold showed that the threshold for the first MEP peak was

We attempted to map the representations of movements in 2 normal subjects by delivering five transcranial magnetic stimuli (TMS) with a focal coil to each of a grid of positions over the primary motor area (M1). Isometric forces were recorded from the contralateral index finger. Maps were made with the hand in a semiflexed “neutral” position, and with the thumb and index finger opposed in a “pincer” grip. The electromyogram (EMG) was monitored to ensure relaxation. The wrist was immobilized. In the neutral position, TMS at almost all positions produced abduction. Flexion was produced in the pincer position. Thus, while sensitive to changes in posture, TMS mapping may not be sensitive to the topographical organization of the M1 by movements as detected with direct cortical stimulation. Hum. Brain Mapping 6:390–393, 1998. © 1998 Wiley‐Liss, Inc.

We compare the use of two-dimensional Laplacian smoothing splines and median polish kriging for an exploratory analysis of spatial data sets. Splines were developed originally for modelling a process with determinstic mean structure, while median polish kriging was developed for predicting a spatial random process. We review the fundamentals of both methods, including smoothing parameter selection for splines and variogram estimation and solving the kriging equations for median polish kriging. We demonstrate application of the methods on maps of muscle representations on the human motor cortex (cortical maps). After applying both methods to 20 cortical maps (left and right hemispheres on each of 10 subjects), we compare the fitted surfaces on the basis of predictive ability, aesthetic appeal, and ease of computation.

We studied the effects of transcranial motor cortex stimulation on the electromyographic characteristics of tremor in 9 patients with familial essential tremor and in 12 patients with postural tremor associated with Parkinson's disease. Transcranial magnetic stimulation reset both types of tremor equally. The resetting depended on the stimulus intensity, but was most closely correlated with the duration of the electromyographic silent period that followed the stimulus-induced motor evoked potential. Tremor resetting was present bilaterally even after focal, unilateral stimulation. Transcranial electrical stimulation failed to reset the tremor in either patient group. These results emphasize the role of central, intracortical structures in the generation of essential tremor and postural tremor in Parkinson's disease. © 1994 John Wiley & Sons, Inc.