Theta and alpha oscillations may underlie improved attention and working memory in musically trained children.

INTRODUCTION: Attention and working memory are key cognitive functions that allow us to select and maintain information in our mind for a short time, being essential for our daily life and, in particular, for learning and academic performance. It has been shown that musical training can improve working memory performance, but it is still unclear if and how the neural mechanisms of working memory and particularly attention are implicated in this process. In this work, we aimed to identify the oscillatory signature of bimodal attention and working memory that contributes to improved working memory in musically trained children. MATERIALS AND METHODS: We recruited children with and without musical training and asked them to complete a bimodal (auditory/visual) attention and working memory task, whereas their brain activity was measured using electroencephalography. Behavioral, time-frequency, and source reconstruction analyses were made. RESULTS: Results showed that, overall, musically trained children performed better on the task than children without musical training. When comparing musically trained children with children without musical training, we found modulations in the alpha band pre-stimuli onset and the beginning of stimuli onset in the frontal and parietal regions. These correlated with correct responses to the attended modality. Moreover, during the end phase of stimuli presentation, we found modulations correlating with correct responses independent of attention condition in the theta and alpha bands, in the left frontal and right parietal regions. CONCLUSIONS: These results suggest that musically trained children have improved neuronal mechanisms for both attention allocation and memory encoding. Our results can be important for developing interventions for people with attention and working memory difficulties.

Pupil Size Tracks Attentional Performance In Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) diagnosis is based on reported symptoms, which carries the potential risk of over- or under-diagnosis. A biological marker that helps to objectively define the disorder, providing information about its pathophysiology, is needed. A promising marker of cognitive states in humans is pupil size, which reflects the activity of an 'arousal' network, related to the norepinephrine system. We monitored pupil size from ADHD and control subjects, during a visuo-spatial working memory task. A sub group of ADHD children performed the task twice, with and without methylphenidate, a norepinephrine-dopamine reuptake inhibitor. Off-medication patients showed a decreased pupil diameter during the task. This difference was no longer present when patients were on-medication. Pupil size correlated with the subjects' performance and reaction time variability, two vastly studied indicators of attention. Furthermore, this effect was modulated by medication. Through pupil size, we provide evidence of an involvement of the noradrenergic system during an attentional task. Our results suggest that pupil size could serve as a biomarker in ADHD.

Chronic fluoxetine treatment induces structural plasticity and selective changes in glutamate receptor subunits in the rat cerebral cortex.

It has been postulated that chronic administration of antidepressant drugs induces delayed structural and molecular adaptations at glutamatergic forebrain synapses that might underlie mood improvement. To gain further insight into these changes in the cerebral cortex, rats were treated with fluoxetine (flx) for 4 weeks. These animals showed decreased anxiety and learned helplessness. N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit levels (NR1, NR2A, NR2B, GluR1 and GluR2) were analysed in the forebrain by both western blot of homogenates and immunohistochemistry. Both methods demonstrated an upregulation of NR2A, GluR1 and GluR2 that was especially significant in the retrosplenial granular b cortex (RSGb). However, when analysing subunit content in postsynaptic densities and synaptic membranes, we found increases of NR2A and GluR2 but not GluR1. Instead, GluR1 was augmented in a microsomal fraction containing intracellular membranes. NR1 and GluR2 were co-immunoprecipitated from postsynaptic densities and synaptic membranes. In the immunoprecipitates, NR2A was increased while GluR1 was decreased supporting a change in receptor stoichiometry. The changes of subunit levels were associated with an upregulation of dendritic spine density and of large, mushroom-type spines. These molecular and structural adaptations might be involved in neuronal network stabilization following long-term flx treatment.

Densidad neuronal en la corteza visual primaria (área 17), en dos especies de octodon / Neuronal density in primary visual cortex (17 visual area), in two species of octodon

Estudios experimentales demuestran que modificaciones medioambientales pueden producir alteraciones en el desarrollo normal de la corteza cerebral visual y sus conexiones. Por otra parte, es posible que en condiciones naturales, las especies animales hayan desarrollado adaptaciones genéticas a las distintas condiciones de luminosidad en que realizan su actividad. Recientemente, se han observado variaciones significativas en la densidad neuronal cortical del área 17 (área visual primaria), en roedores silvestres con diferentes períodos diarios de actividad y relación filogenética distante (Abrothrix olivaceus y Phyllotis darwini), pero aún no se ha determinado la naturaleza genética o plástica de dichas diferencias. En este trabajo se compararon especies con una mayor cercanía filogenética, para disminuir al máximo la variable taxonómica. Se estudió la corteza visual primaria (área 17), de roedores silvestres nativos, de las especies Octodon degus (n=5) y Octodon bridgesi (n=3), pertenecientes a la Familia Octodontidae, con el propósito de evidenciar cambios a través de la medición de la densidad neuronal, mediante la técnica del disector óptico, en cortes de 40 µm, incluidos en celoidina y teñidos con Nissl. Complementariamente, se realizó una cuantificación de la densidad neuronal de la corteza motora de las especies en estudio. O. degus, que presenta un período de actividad diurna, evidenció una densidad neuronal menor en la corteza visual (34,32 +/- 2,51 x 104 neuronas/mm3), que la observada en O. bridgesi (39,55 +/- 0,64 x 104 neuronas/mm3), especie de período de actividad nocturna; lo cual fue estadísticamente significativo (t=3,44; p<0,05). Las diferencias encontradas se podrían relacionar con el tipo de condiciones de luminosidad en que se desenvuelven dichas especies, aunque no se puede descartar la influencia de otros factores.

Studies show that environmental modifications can produce profound alterations in the normal development of the visual cortex and its connectivity. For the other hand it is possible that in natural conditions, animal species have developed genetic adaptations to the different conditions of luminance in which they normally behave. Recently have observed significant changes in cortical neuronal density of area 17 (primary visual area), in two sympatric Chilean rodents with different daily activity (Phyllotis darwini and Abrothrix olivaceus), but have not yet determined the genetic nature or plastic such differences. In this paper we compared species with a closer phylogenetic relation so as to minimize the taxonomic variable. We studied the primary visual cortex (area 17) of wild rodents native of the species Octodon degus (n=5) and Octodon bridgesi (n=3), belonging to the Octodontidae family, in order to show changes in the neuronal density, using celloidin-embedded, 40µm-thickness Nissl sections, with the aid of an optical dissector. In addition, we performed a quantification of the neuronal density of the motor cortex of the species under study. O. degus, bearing a crepuscular-diurnal activity pattern, showed a lower neuronal density in the visual cortex (34.32 +/- 2.51 x10(4) neuron/mm³) than that observed in O. bridgesi (39.55 +/- 0.64 x10(4) neuron/mm³), a species that exhibits a nocturnal phase preference, which was statistically significant (t=3.44; p<0.05). These differences might be related to differences in daily activity in two species, but we cannot discount the influence of other factors.

Modelos neurocognitivos para el trastorno por déficit de atención/hiperactividad y sus implicaciones en el reconocimiento de endofenotipos / Neurocognitive models for attention deficit hyperactivity disorder and their consequences on the searching of endophenotypes

(TDAH) ha sido difícil hasta el momento. Algunos autores sugieren que el poder estadístico de los estudios de asociación geneticomolecular podría aumentarse si se abandona el diagnóstico clínico de enfermedad como definición de caso y se adoptan en su reemplazo marcadores biológicos de riesgo, conceptualmente más cercanos a las vías fisiopatológicas de susceptibilidad génica. Dichos marcadores, llamados genéricamente ‘endofenotipos’, han atraído considerable interés en la comunidad científica. La identificación de endofenotipos debe estar fundada en los modelos etiológicos más aceptados para el TDAH. Objetivo. Revisar las características de los modelos neurocognitivos propuestos para el TDAH y sus implicaciones en la búsqueda de endofenotipos. Desarrollo. Se discute la evolución de los modelos neurocognitivos para el TDAH, desde modelos simples basados en vías etiopatogénicas únicas hasta los actuales modelos complejos que plantean dos o más vías paralelas. Asimismo, se describe el sistema estriadotalamocortical, sustrato anatómico común para los modelos actuales de TDAH. Conclusiones. El sistema estriadotalamocortical se reconoce como el sustrato anatómico y funcional de los modelos neurocognitivos postulados para el TDAH. En este contexto, cualquier marcador electrofisiológico, conductual, bioquímico o anatómico asociado a las funciones comandadas por dicho sistema (principalmente funciones ejecutivas y/o sistema de evaluación de la recompensa) podría constituir un eventual endofenotipo. Es de especial interés explorar aquellas características potencialmente capaces de ‘disecar’ vías etiopatogénicas redundantes o paralelas, como es el caso de los marcadores electrofisiológicos o las neuroimágenes. Las características psicométricas del marcador deben permitir su cuantificación sensible, específica y reproducible (AU)

Introduction. The influence of genetics in attention deficit hyperactivity disorder (ADHD) is well confirmed. However, identification of the specific genes involved in the pathogenesis of the disorder has proved to be difficult. Some authors suggest that the statistical power of molecular genetic studies could improve by replacing the diagnosis of the disease on the basis of clinical phenotype by quantitative risk markers closer to underlying genetic pathophysiology and gene action. Such markers, generically called ‘endophenotypes’, have attracted considerable scientific interest. When searching for new endophenotypes, priority must be given to markers that are based or anchored in the actual neuro-cognitive etiological models for ADHD. Aim. To describe the principal concepts involved in current models of ADHD and to briefly discuss their implication for identification of endophenotypes in ADHD. Development. Herein we discuss the evolution of causal models for ADHD, from simple core deficit models to complex multiple-pathways models. Additionally, we describe the thalamo-cortico-striatal circuits, which is the common anatomic substrate for all causal models for ADHD. Conclusion. Thalamo-cortico-striatal circuits are recognized as the anatomic and functional substrate for all causal neurocognitive odels for ADHD. In this context, any electrophysiological, behavioral, neuro-humoral or anatomic marker related with functions commanded by such system (mainly executive functions and reward functions) could be a promising endophenotype for ADHD. Special interest must be taken in markers that potentially allow us to ‘dissect’ parallels etiological pathways, like electrophysiological parameters or functional neuroimages. Finally, the psychometric properties of potential endophenotypes must be adequate for a reliable, sensitive and specific quantification (AU)

Efecto de la Desnutrición Oculta Prenatal Sobre la Histología del Esplenio Callosal / Effect of Mild Protein Prenatal Malnutrition in the Callosal Splenium Histology

Ratas malnutridas prenatalmente con una dieta isocalórica y baja en proteínas, presentaron un menor diámetro axonal promedio en el esplenio callosal que los animales control, tanto de las fibras mielínicas como amielínicas. También se observó una mayor densidad axonal promedio, con respecto a los controles. Estas observaciones sugieren que: 1) las conexiones cortico-corticales (interhemisféricas) son vulnerables a la malnutrición proteica; y 2) lo anterior tendría incidencia en la velocidad de conducción interhemisférica, en particular con lo que dice relación con las conexiones visuales.

Adult rats malnourished prenatally with a low-protein, isocaloric diet showed smaller median fiber diameter of myelinated and unmyelinated fibers and a higher axonal density in the callosal splenium than controls. These findings suggest (i) that cortico-cortical (interhemispheric) connections are vulnerable to protein malnutrition; and (ii) this may affect interhemispheric conduction velocity, particularly in visual connections.

Attention-deficit hyperactivity disorder involves differential cortical processing in a visual spatial attention paradigm.

OBJECTIVE: Inattention is undoubtedly one of the main characteristics of Attention-deficit hyperactivity disorder (ADHD). Nevertheless, a growing corpus of evidence shows that not all attentional processes are affected in this condition. This study aimed to explore the distribution of attentional resources in children with ADHD via a spatially shifted double-oddball visual task. METHODS: We recorded event-related potentials (ERPs) for all visual stimuli. Subjects were instructed to allocate attention in a specific area of visual space while ignoring all stimuli presented outside. Ten male children (age: 9-14; mean = 11.6 +/- 2.1) who met DSM-IV criteria for the ADHD combined subtype participated in the study, along with ten age- and sex-matched healthy controls (9-14; mean = 11.2 +/- 2.3). RESULTS: ADHD subjects showed late differential cortical responses to initially suppressed irrelevant stimuli. The amplitude of early N1-P1 components were mainly modulated by stimulus location and showed no significant differences between groups, but a late P300-like positivity was clearly evoked in the ADHD group by peripheral stimuli. CONCLUSIONS: These results suggest that ADHD may not compromise the early attentional spatial filter but rather entails a different distribution of attentional resources at later stages of cortical processing. Perhaps these differences may be attributable to individual differences in attentional mechanisms. SIGNIFICANCE: ADHD may not affect initial focusing of visual attention but rather the allocation of processing resources in later stages.

Chronic stress impairs acoustic conditioning more than visual conditioning in rats: morphological and behavioural evidence.

Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.

Densidad neuronal en la corteza visual primaria (area 17(, de dos especies de roedores silvestres / Neuronal density in primary visual cortex (17 visual area), in two wild rodent species

Diversos estudios experimentales demuestran que modificaciones medioambientales (por ejemplo: nutricionales y lumínicas), pueden producir alteraciones en el desarrollo normal de la corteza visual y sus conexiones. Por otro lado, es posible que en condiciones naturales, las especies animales hayan desarrollado adaptaciones a las distintas condiciones de luminosidad en que realizan su actividad. Por ende, la finalidad de este trabajo, fue estudiar la corteza visual primaria (área 17), de dos especies de roedores silvestres, relacionados filogenéticamente, pero con diferentes períodos de actividad; Abrothrix olivaceus (n=7) y Phyllotis darwini (n=7), con el propósito de evidenciar cambios detectados a través de la medición de la densidad neuronal, mediante la técnica del disector óptico, en cortes de 40µm de grosor, incluidos en celoidina y teñidos con cresyl violeta (Nissl). A. olivaceus, el cual presenta un periodo de actividad continuo en la zona central de Chile, evidenció una densidad neuronal menor (34.75 x 104 ± 1.35 x 104 neuronas/mm3) que la observada en P. darwini (37.23 x 104 ± 2.20 x 104 neuronas/mm3), especie de actividad nocturna en la misma región del país; siendo lo anterior estadísticamente significativo (t=2.54; p<0.05). Las diferencias encontradas se relacionarían con el tipo de conducta que presentan ambas especies, dado principalmente por las características de luminosidad en que se desenvuelven, así como también, de otros factores que se relacionarían con este parámetro, como son la relación predador-presa y la alimentación, entre otros.

Presencia de los alelos DRD4/7R y DAT1/10R en miembros de familias chilenas con síndrome de déficit atencional con hiperactividad / Presence of DRD4/7R and DAT1/10R allele in Chilean family members with attention deficit hyperactivity disorder

BACKGROUND: Genes for dopamine receptor DRD4 and dopamine transporter DAT1 have been implicated in attention deficit with hyperactivity disorder (ADHD). However, the findings are not conclusive. More studies in populations with different genetic backgrounds may contribute to solve the discrepancies observed. AIM: To test the hypothesis that affected members of Chilean families exhibit higher frequencies of the DRD4/7R and DAT1/10R alleles then their healthy sibs. MATERIAL AND METHODS: The parents of 51 children belonging to families of the Metropolitan Region of Chile, were approached to obtain clinical histories and blood samples, after the signature of a written informed consent. ADHD was diagnosed according to DSM-IV criteria, ancd intellectual coefficient was tested using the WISC-R test. Genomic DNA was extracted from lymphocytes and amplified by PCR. RESULTS: The 7R allele was identified in 13 out of 26 subjects diagnosed as ADHD and in 6 of 25 healthy sibs (p < 0.05). Parents with a history of ADHD, were conmpared with their healthy counterparts, exhibiting an identical tendency, that did not reach statistical significance. No significant differences in the frequencies of DAT1/10R alleles, were observed between cases and controls or their parents. CONCLUSIONS: Our results showed that ADHD in Chilean families is associated with the presence of DRD4/7R allele.

The alien hand syndrome: classification of forms reported and discussion of a new condition.

The term "alien hand" refers to a variety of clinical conditions whose common characteristic is the uncontrolled behavior or the feeling of strangeness of one extremity, most commonly the left hand. A common classification distinguishes between the posterior or sensory form of the alien hand, and the anterior or motor form of this condition. However, there are inconsistencies, such as the phenomenon of diagonistic dyspraxia, which is largely a motor syndrome despite being more frequently associated with posterior callosal lesions. We discuss critically the existing nomenclature and we also describe a case recently reported by us which does not fit any previously reported condition, termed agonistic dyspraxia. We propose that the cases of alien hand described in the literature can be classified into at least five broad categories: (i) diagonistic dyspraxia and related syndromes, (ii) alien hand, (iii) way-ward hand and related syndromes, (iv) supernumerary hands and (v) agonistic dyspraxia.

One hundred million years of interhemispheric communication: the history of the corpus callosum.

Analysis of regional corpus callosum fiber composition reveals that callosal regions connecting primary and secondary sensory areas tend to have higher proportions of coarse-diameter, highly myelinated fibers than callosal regions connecting so-called higher-order areas. This suggests that in primary/secondary sensory areas there are strong timing constraints for interhemispheric communication, which may be related to the process of midline fusion of the two sensory hemifields across the hemispheres. We postulate that the evolutionary origin of the corpus callosum in placental mammals is related to the mechanism of midline fusion in the sensory cortices, which only in mammals receive a topographically organized representation of the sensory surfaces. The early corpus callosum may have also served as a substrate for growth of fibers connecting higher-order areas, which possibly participated in the propagation of neuronal ensembles of synchronized activity between the hemispheres. However, as brains became much larger, the increasingly longer interhemispheric distance may have worked as a constraint for efficient callosal transmission. Callosal fiber composition tends to be quite uniform across species with different brain sizes, suggesting that the delay in callosal transmission is longer in bigger brains. There is only a small subset of large-diameter callosal fibers whose size increases with increasing interhemispheric distance. These limitations in interhemispheric connectivity may have favored the development of brain lateralization in some species like humans.

One hundred million years of interhemispheric communication: the history of the corpus callosum

Analysis of regional corpus callosum fiber composition reveals that callosal regions connecting primary and secondary sensory areas tend to have higher proportions of coarse-diameter, highly myelinated fibers than callosal regions connecting so-called higher-order areas. This suggests that in primary/secondary sensory areas there are strong timing constraints for interhemispheric communication, which may be related to the process of midline fusion of the two sensory hemifields across the hemispheres. We postulate that the evolutionary origin of the corpus callosum in placental mammals is related to the mechanism of midline fusion in the sensory cortices, which only in mammals receive a topographically organized representation of the sensory surfaces. The early corpus callosum may have also served as a substrate for growth of fibers connecting higher-order areas, which possibly participated in the propagation of neuronal ensembles of synchronized activity between the hemispheres. However, as brains became much larger, the increasingly longer interhemispheric distance may have worked as a constraint for efficient callosal transmission. Callosal fiber composition tends to be quite uniform across species with different brain sizes, suggesting that the delay in callosal transmission is longer in bigger brains. There is only a small subset of large-diameter callosal fibers whose size increases with increasing interhemispheric distance. These limitations in interhemispheric connectivity may have favored the development of brain lateralization in some species like humans. "...if the currently received statements are correct, the appearance of the corpus callosum in the placental mammals is the greatest and most sudden modification exhibited by the brain in the whole series of vertebrated animals..." T.H. Huxley (1)

Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization

Analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. In order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. Nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.

Critical steps in the early evolution of the isocortex. Insights from developmental biology

This article proposes a comprehensive view of the origin of the mammalian brain. We discuss i) from which region in the brain of a reptilian-like ancestor did the isocortex originate, and ii) the origin of the multilayered structure of the isocortex from a simple-layered structure like that observed in the cortex of present-day reptiles. Regarding question i there have been two alternative hypotheses, one suggesting that most or all the isocortex originated from the dorsal pallium, and the other suggesting that part of the isocortex originated from a ventral pallial component. The latter implies that a massive tangential migration of cells from the ventral pallium to the dorsal pallium takes place in isocortical development, something that has not been shown. Question ii refers to the origin of the six-layered isocortex from a primitive three-layered cortex. It is argued that the superficial isocortical layers can be considered to be an evolutionary acquisition of the mammalian brain, since no equivalent structures can be found in the reptilian brain. Furthermore, a characteristic of the isocortex is that it develops according to an inside-out neurogenetic gradient, in which late-produced cells migrate past layers of early-produced cells. It is proposed that the inside-out neurogenetic gradient was partly achieved by the activation of a signaling pathway associated with the Cdk5 kinase and its activator p35, while an extracellular protein called reelin (secreted in the marginal zone during development) may have prevented migrating cells from penetrating into the developing marginal zone (future layer I)

Critical steps in the early evolution of the isocortex: insights from developmental biology.

This article proposes a comprehensive view of the origin of the mammalian brain. We discuss i) from which region in the brain of a reptilian-like ancestor did the isocortex originate, and ii) the origin of the multilayered structure of the isocortex from a simple-layered structure like that observed in the cortex of present-day reptiles. Regarding question i there have been two alternative hypotheses, one suggesting that most or all the isocortex originated from the dorsal pallium, and the other suggesting that part of the isocortex originated from a ventral pallial component. The latter implies that a massive tangential migration of cells from the ventral pallium to the dorsal pallium takes place in isocortical development, something that has not been shown. Question ii refers to the origin of the six-layered isocortex from a primitive three-layered cortex. It is argued that the superficial isocortical layers can be considered to be an evolutionary acquisition of the mammalian brain, since no equivalent structures can be found in the reptilian brain. Furthermore, a characteristic of the isocortex is that it develops according to an inside-out neurogenetic gradient, in which late-produced cells migrate past layers of early-produced cells. It is proposed that the inside-out neurogenetic gradient was partly achieved by the activation of a signaling pathway associated with the Cdk5 kinase and its activator p35, while an extracellular protein called reelin (secreted in the marginal zone during development) may have prevented migrating cells from penetrating into the developing marginal zone (future layer I).

Behavioral effects of aminochrome and dopachrome injected in the rat substantia nigra.

The exact mechanism of cell death in neurodegenerative diseases remains obscure, although there is evidence that their pathogenesis may involve the formation of free radicals originating from the oxidative metabolism of catecholamines. The purpose of this study was to evaluate the degree of neurodegenerative changes and behavioral impairments induced by unilateral injection into the rat substantia nigra of cyclized o-quinones, aminochrome and dopachrome, derived from oxidizing dopamine and L-DOPA, respectively, with Mn(3+)-pyrophosphate complex. The behavioral changes were compared with those induced after selective lesions of dopaminergic neurons with 6-hydroxydopamine (6-OHDA). Intranigral injection of aminochrome and dopachrome produced impairment in motor and cognitive behaviors. The behavioral impairment was also revealed by apomorphine-induced rotational asymmetry. Apomorphine (0.5 mg/kg sc) significantly increased rotational behavior in rats injected with aminochrome and dopachrome. These rats presented a clear motor bias showing a significant contralateral rotation activity, similar but less vigorous that in rats injected with 6-OHDA. The avoidance conditioning was seriously impaired in rats injected with aminochrome and dopachrome although only dopachrome-injected rats showed a similar hypomotility to 6-OHDA-injected rats. The behavioral effects were correlated to the extent of striatal tyrosine hydroxylase (TH)-positive fiber loss. Rats receiving unilateral intranigral aminochrome and dopachrome injections exhibited a 47.9+/-5.1% and a 39.7+/-4.4% reduction in nigrostriatal TH-positive fiber density. In conclusion, this study provided evidence that oxidizing DA and L-DOPA to cytotoxic quinones, aminochrome and dopachrome appears to be an important mediator of oxidative damage in vivo.