Suppressing versus Releasing a Habit: Frequency-dependent Effects of Prefrontal Transcranial Magnetic Stimulation

When subjects are required to generate a random sequence of numbers they typically produce too many forward and backward ‘counts' (e.g. 5-6, 4-3). This counting bias is interpreted as the consequence of an interference by overlearned tendencies to arrange numbers according to their natural order. Inhibition of such well-learned routines is known to rely on frontal lobe functioning. We examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen healthy men performed an RNG task. Those subjects stimulated over the left DLPFC showed a frequency-dependent rTMS effect: counting bias was significantly reduced after the 1 Hz stimulation compared with baseline, but significantly exaggerated after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the sequences of the subjects stimulated over the right DLPFC showed the well-known excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These findings confirm the functional importance of specifically the left DLPFC in sequential response production and show, for the first time, that rTMS affects cognitive processing in a frequency-dependent manne

Differential impact of posterior lesions in the left and right hemisphere on visual category learning and generalization to contrast reversal

Hemispheric differences in the learning and generalization of pattern categories were explored in two experiments involving sixteen patients with unilateral posterior, cerebral lesions in the left (LH) or right (RH) hemisphere. In each experiment participants were first trained to criterion in a supervised learning paradigm to categorize a set of patterns that either consisted of simple geometric forms (Experiment 1) or unfamiliar grey-level images (Experiment 2). They were then tested for their ability to generalize acquired categorical knowledge to contrast-reversed versions of the learning patterns. The results showed that RH lesions impeded category learning of unfamiliar grey-level images more severely than LH lesions, whereas this relationship appeared reversed for categories defined by simple geometric forms. With regard to generalization to contrast reversal, categorization performance of LH and RH patients was unaffected in the case of simple geometric forms. However, generalization to of contrast-reversed grey-level images distinctly deteriorated for patients with LH lesions relative to those with RH lesions, with the latter (but not the former) being consistently unable to identify the pattern manipulation. These findings suggest a differential use of contrast information in the representation of pattern categories in the two hemispheres. Such specialization appears in line with previous distinctions between a predominantly lefthemispheric, abstract-analytical and a righthemispheric, specific-holistic representation of object categories, and their prediction of a mandatory representation of contrast polarity in the RH. Some implications for the well-established dissociation of visual disorders for the recognition of faces and letters are discussed

What is the role of the corpus callosum in intermanual transfer of motor skills? A study of three cases with callosal pathology

Intermanual transfer for a skilled motor task was studied in two patients with total callosal agenesis, and one with an acquired partial callosal lesion and clinical evidence for disturbed transfer of motor signals. Patients had to draw meaningless figures with one upper extremity (original learning, OL) and to reproduce their mirror-reversals thereafter with the other side (transfer learning, TL). Both directions of intermanual transfer were tested in two conditions, that is, between either proximal or distal muscle groups. Transfer was evaluated by comparing OL and TL performance at the same effector. The main variable of interest was movement time during the first eight trials of OL and TL. All three patients displayed a significant benefit for transfer from the dominant to the non-dominant hand but not vice versa during proximal motor activity. When compared with the performance of healthy subjects tested in almost identical conditions in a previously reported study, the proximal transfer behavior was found to be similar for all patients and the normal group. Although patients exhibited no significant benefit for distal transfer, their non-dominant-to-dominant distal transfer was above the normal range. The similar transfer pattern of the patients and healthy subjects when using proximal musculature suggests that proximal transfer may be subserved by identical extracallosal pathways, most probably by the ipsilaterally descending motor systems. Since non-dominant-to-dominant distal transfer was found to be disadvantageous in healthy subjects, the patients' relative superiority in this condition may reflect missing callosal influences of an inhibitory natur

Uplift of the Bolivian orocline coastal areas based on geomorphologic evolution of marine terraces and abrasion surfaces: preliminary results

The southern Pacific coast morphology and especially the presence of marine surfaces gives information on the dynamics of Andean forearc evolution from the Neogene. Along most of the Southern Peru and Northern Chilean coasts, discontinuous uplifts are recorded by marine terraces and marine abrasion surfaces; they have thus, preserved a record of eustatic sea level changes and the uplift history of the coastal area in the Andean forearc. One approach to study the tectonic history of the Andean forearc is to identify its effects in marine sedimentation or erosion patterns along the coastal area. To investigate these processes, the Neogene marine formations are studied in various coastal sections either in southern Peru, at Chala (15°50'S) and Ilo (17°32'S-17°48'S), situated above a steep subduction segment and at San Juan de Marcona (15°20'S), situated above the southern part of the Nazca ridge; or in Chile, from Tongoy (30°15'S) to Los Vilos (31°55'S), situated above a flat subduction segment (Fig.1). We chose various sites from each branch of the Arica bend in order to sample possibly different time spans during the Neogene and different response of the continental plate to the subduction process. Various studies were already undertaken on such problems either in Peru or Chile but mainly leaded to the datation of the 5th isotopic stage. So, differential GPS and cosmogenic datations are pursued in order to propose robust ages on these sites and subtract the effects of eustatic sea-level changes from local curves, identifying tectonic uplifts

Compressive active fault systems along the Central Andean piedmont

It’s now established that Andean forearc is not concentrating as much tectonic shortening as the foreland since Middle Miocene. GPS measurements are neither available to inform on the long-term deformation across the Andes in Peru and anyway rather describe the elastic response of the Andean forearc to the Nasca-South American Plate convergence. Few neotectonic studies focuses on the Western side of the Andes and little is known about the active deformation in the Central Andes Pacific lowlands (Sébrier et al., 1988). Recent publications mainly improved the description of geomorphic surfaces (Thouret et al. 2007) and cosmogenic dating of the latter show much younger ones than expected (Hall et al., 2008). The topographic gradient on the western side of the Peruvian Andes is quite high as the trench (-7000m) lies only 200km away from the highest point (6000m). Moreover, authors still question the fact that the Andes build through a giant focused monocline or normal fault and demonstrate doing so the need of further mapping of the fault systems on the western side of the Central Andes (Schildgen et al., 2007)

HIF-Independent Regulation of Thioredoxin Reductase 1 Contributes to the High Levels of Reactive Oxygen Species Induced by Hypoxia

Cellular adaptation to hypoxic conditions mainly involves transcriptional changes in which hypoxia inducible factors (HIFs) play a critical role. Under hypoxic conditions, HIF protein is stabilized due to inhibition of the activity of prolyl hydroxylases (EGLNs). Because the reaction carried out by these enzymes uses oxygen as a co-substrate it is generally accepted that the hypoxic inhibition of EGLNs is due to the reduction in oxygen levels. However, several studies have reported that hypoxic generation of mitochondrial reactive oxygen species (ROS) is required for HIF stabilization. Here, we show that hypoxia downregulates thioredoxin reductase 1 (TR1) mRNA and protein levels. This hypoxic TR1 regulation is HIF independent, as HIF stabilization by EGLNs inhibitors does not affect TR1 expression and HIF deficiency does not block TR1 hypoxic-regulation, and it has an effect on TR1 function, as hypoxic conditions also reduce TR1 activity. We found that, when cultured under hypoxic conditions, TR1 deficient cells showed a larger accumulation of ROS compared to control cells, whereas TR1 over-expression was able to block the hypoxic generation of ROS. Furthermore, the changes in ROS levels observed in TR1 deficient or TR1 over-expressing cells did not affect HIF stabilization or function. These results indicate that hypoxic TR1 down-regulation is important in maintaining high levels of ROS under hypoxic conditions and that HIF stabilization and activity do not require hypoxic generation of ROS

Der „unmoralische Patient“. Eine Analyse der Nutzung hirnverletzter Menschen in der Moralforschung

Die empirische Erforschung des moralischen Entscheidens und Handelns stützt sich zunehmend auf Patienten, die selten auftretende Hirnläsionen in bestimmten Regionen des Frontallappens aufweisen. Dies stellt sowohl die neuroethische Frage zur Bedeutung solcher Erkenntnisse für unser Verständnis von Moral als auch die medizinethische Frage nach dem Umgang mit solchen Patienten im Kontext von Forschung und Klinik. Basierend auf einer Auswertung der Literatur über den Zusammenhang von Hirnläsionen und Sozialverhalten sowie gut 40 Jahren eigene Erfahrung in der neuropsychologischen Abklärung zeigen wir zwei Wahrnehmungslücken: Zum einen propagieren diese Studien einen Neurodeterminismus des menschlichen Moralverhaltens, der aber wissenschaftlich nicht ausreichend untermauert ist. Zum anderen zeigt sich eine Verschiebung des Forschungsinteresses weg von einem klinischen Fokus hin zur neuropsychologischen Grundlagenforschung über das menschliche Moralvermögen. Letzterer Punkt ist insofern bedeutsam, als dass der klinische und alltägliche Umgang mit solchen Patienten schwierig ist und diese Menschen die Grenzen der Anwendung klassischer medizinethischer Prinzipien wie Autonomie und Fürsorge aufzeigen

Suppressing versus releasing a habit: frequency-dependent effects of prefrontal transcranial magnetic stimulation.

When subjects are required to generate a random sequence of numbers they typically produce too many forward and backward 'counts' (e.g. 5-6, 4-3). This counting bias is interpreted as the consequence of an interference by overlearned tendencies to arrange numbers according to their natural order. Inhibition of such well-learned routines is known to rely on frontal lobe functioning. We examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen healthy men performed an RNG task. Those subjects stimulated over the left DLPFC showed a frequency-dependent rTMS effect: counting bias was significantly reduced after the 1 Hz stimulation compared with baseline, but significantly exaggerated after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the sequences of the subjects stimulated over the right DLPFC showed the well-known excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These findings confirm the functional importance of specifically the left DLPFC in sequential response production and show, for the first time, that rTMS affects cognitive processing in a frequency-dependent manner