Deep brain stimulation of subthalamic nuclei affects arm response inhibition in Parkinson's patients.

The precise localizations of the neural substrates of voluntary inhibition are still debated. It has been hypothesized that, in humans, this executive function relies upon a right-lateralized pathway comprising the inferior frontal gyrus and the presupplementary motor area, which would control the neural processes for movement inhibition acting through the right subthalamic nucleus (STN). We assessed the role of the right STN, via a countermanding reaching task, in 10 Parkinson's patients receiving high-frequency electrical stimulation of the STN of both hemispheres (deep brain stimulation, DBS) and in 13 healthy subjects. We compared the performance of Parkinson's patients in 4 experimental conditions: DBS-ON, DBS-OFF, DBS-OFF right, and DBS-OFF left. We found that 1) inhibitory control is improved only when both DBS are active, that is, the reaction time to the stop signal is significantly shorter in the DBS-ON condition than in all the others, 2) bilateral stimulation of STN restores the inhibitory control to a near-normal level, and 3) DBS does not cause a general improvement in task-related motor function as it does not affect the length of the reaction times of arm movements, that is, in our experimental context, STN seems to play a selective role in response inhibition.

Neural correlates of cognitive control of reaching movements in the dorsal premotor cortex of rhesus monkeys.

Canceling a pending movement is a hallmark of voluntary behavioral control because it allows us to quickly adapt to unattended changes either in the external environment or in our thoughts. The countermanding paradigm allows the study of inhibitory processes of motor acts by requiring the subject to withhold planned movements in response to an infrequent stop-signal. At present the neural processes underlying the inhibitory control of arm movements are mostly unknown. We recorded the activity of single units in the rostral and caudal portion of the dorsal premotor cortex (PMd) of monkeys trained in a countermanding reaching task. We found that among neurons with a movement-preparatory activity, about one-third exhibit a modulation before the behavioral estimate of the time it takes to cancel a planned movement. Hence these neurons exhibit a pattern of activity suggesting that PMd plays a critical role in the brain networks involved in the control of arm movement initiation and suppression.

Inhibitory control is not lateralized in Parkinson's patients.

Parkinson's disease (PD) is often characterized by asymmetrical symptoms, which are more prominent on the side of the body contralateral to the most extensively affected brain hemisphere. Therefore, lateralized PD presents an opportunity to examine the effects of asymmetric subcortical dopamine deficiencies on cognitive functioning. As it has been hypothesized that inhibitory control relies upon a right-lateralized pathway, we tested whether left-dominant PD (LPD) patients suffered from a more severe deficit in this key executive function than right-dominant PD patients (RPD). To this end, via a countermanding task, we assessed both proactive and reactive inhibition in 20 LPD and 20 RPD patients, and in 20 age-matched healthy subjects. As expected, we found that PD patients were significantly more impaired in both forms of inhibitory control than healthy subjects. However, there were no differences either in reactive or proactive inhibition between LPD and RPD patients. All in all, these data support the idea that brain regions affected by PD play a fundamental role in subserving inhibitory function, but do not sustain the hypothesis according to which this executive function is predominantly or solely computed by the brain regions of the right hemisphere.

The effect of abnormal intrauterine thyroid hormone economies on infant cognitive abilities.

OBJECTIVE: To evaluate how intrauterine and neonatal thyroid hormone deficiencies affect infant cognitive abilities. METHOD: 26 infants with intrauterine or neonatal thyroid hormone deficiency and 20 full-term infants with normal thyroid economies were studied at 6 months of age or corrected age. Reasons for thyroid hormone deficiency were maternal hypothyroidism, maternal hyperthyroidism treated with antithyroid medication, congenital hypothyroidism, and low-risk prematurity. A computer-generated task during which infants' eye-movements were videotaped was used to assess attention, memory, and learning abilities RESULTS: Data from transcribed videotapes showed the study group was significantly less attentive and had longer reaction times than controls but did not differ on indices of sustaining attention or learning. Within thyroid-deficient groups, offspring of treated hyperthyroid mothers showed an atypical profile suggestive of hypervigilance. CONCLUSION: A decreased fetal or maternal thyroid hormone supply in pregnancy is associated with infants' poorer attention and altered rates of information processing.

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements.

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal-basal ganglia-thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmann's area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal-basal ganglia-thalamic network.

[Alpha1 adrenoceptors in human urinary tract:expression, distribution and clinical implications].

Adrenergic receptors (ARs) are a class of proteins belonging to the G proteincoupled receptor family. Pharmacological and molecular studies allowed dividing ARs into three different categories: α1, α2 and ß. In this review, we focused on α1 ARs and α1 AR antagonists, since α1 ARs play an important role in the pathophysiology of a number of urinary tract (UT) dysfunctions. α1 ARs are widely expressed in human UT; in particular, the three ureter areas (distal, medial and proximal) show different patterns of receptor expression (i.e. distal > medial = proximal), giving the molecular basis for the use of α1 ARs antagonist in the expulsive therapy of distal ureter calculi. Bladder areas are characterized by important differences among trigone, detrusor and neck, the first showing a different pattern of expression compared to the other parts. Further, there are evidences of both density and subtype gender-dependent expressions. α1 ARs expression in prostate and detrusor is a widely investigated area of research, mainly due to the clinical impact of benign prostatic hyperplasia (BPH). Urethra has not been well studied in human, although it plays a role in the control of continence. Studies carried out on α1 AR subtype expression in the UT indicate that, although the presence of each subtype is observed, α1A firstly and then α1D ARs seem to be more expressed than α1B ARs. Thus, drugs that demonstrate high α1A/D AR selectivity have drawn the researchers' attention. As it relates specifically to the α1 AR antagonists used in the treatment of lower UT symptoms, the concept of uroselectivity has been operationally defined; indeed, in a number of recent publications uroselectivity has been defined as the degree to which a given compound inhibits norepinephrine-induced increase in urinary muscle contractions and/or its propensity to generate unwanted cardiovascular effects, such as decreases in blood pressure.

Which way is upright and normal? Haptic perception of letters above head level.

In three experiments, the perception of the apparent orientation of block letters shown in various orientations above the subject's head in the horizontal plane was examined. A block letter F with its front facing down toward the observer has two crossbars on its right side; the top is the part with the long crossbar, and the base has no bar. The experiments involved changing the locations of these parts with respect to the observer. In Experiment 1, the subjects using touch most often identified a letter as having its left and right sides in a normal orientation if the front of the block letter faced upwards away from the observer, with the bar on the right and the top of the letter farther from the subject than the letter's base. In Experiment 2, the subjects judging visual uprightness favored positions in which the bars were on the right, the top of the block letter was near them, and the letter's front faced downwards toward the observer. In Experiment 3, the subjects using touch most often assessed letters as being upright if the top of the letter was the farthest part and the bar was on the right. The results suggest that, when assessing orientation, subjects using touch favored positions that would be reached by a letter moving vertically upwards from table height, but subjects relying on vision favored positions reached by a letter moving in an are centered on the subject's head (on the eyes, in particular).

Integration of multiple-whisker inputs in rat somatosensory cortex.

Rats explore their surroundings through rhythmic movement of their mystacial vibrissae. At any given moment, multiple whiskers are simultaneously moved and may contact the surface of an object. The aim of this work is to understand how simultaneous multiple-whisker deflections are processed in the somatosensory cortex. Arrays of 25 electrodes were inserted into the vibrissal representation of barrel cortex of adult rats. Multi-unit responses were recorded during (i) stimulation of single whiskers, and (ii) simultaneous stimulation of two, three or four whiskers of a whisker arc or whisker row. The whole-array response elicited by the simultaneous stimulation of multiple-whiskers (observed response) was compared to a multiple-whisker response predictor, defined as the sum of the whole-array responses to the separate stimulation of the corresponding single whiskers. The observed response to stimulation of four whiskers was nearly always less than the predicted response, indicating a sublinear summation of multiple coincident inputs. Examining the poststimulus time course of sublinearity, we found that the earliest cortical response to whisker deflection - reflecting the thalamocortical volley - was linear, whereas the successive cortical response was highly sublinear. This suggests a cortical origin of the phenomenon.

Experience-dependent plasticity of rat barrel cortex: redistribution of activity across barrel-columns.

The redistribution of neuronal activity across rat barrel cortex following an alteration in whisker usage has been investigated. In adult rats, two mystacial vibrissae - D(2) and one neighbor, D(1) or D(3) - were left intact while all other vibrissae on that side of the snout were clipped. Neurons in contralateral barrel cortex were sampled with a microelectrode array 3.5 days later. Stimulation of clipped vibrissae produced a narrow spatial distribution of cortical activity, whereas stimulation of intact vibrissae produced a widened spatial distribution. Simultaneous recordings from multiple cortical barrel-columns suggest that changes in the effective connectivity between barrel-columns may partially account for this redistribution of sensory responses. Evidence is also presented for a second mechanism, a release from inhibition in sensory-deprived cortical areas. A model is therefore proposed where these two mechanisms operate together to regulate the cortical distribution of evoked activity.