Asymmetrical Brain Plasticity: Physiology and Pathology.

The brain is inherently asymmetrical. How that attribute, manifest both structurally (volumetric, cytological, molecular) as well as functionally, relates to cognitive function, is not fully understood. Since the early descriptions of Paul Broca and Marc Dax it has been known that the processing of language in the brain is fundamentally asymmetrical. Contemporary imaging studies have corroborated early observations, and have also revealed significant functional links to multiple other systems, such as those sub serving memory or emotion. Recent studies have demonstrated that laterality is both plastic and adaptive. Learning and training have shown to affect regional changes in asymmetry, such as that observed in the volume of the planum temporale associated with musical practice. Increasing task complexity has been demonstrated to induce recruitment of contralateral regions, suggesting that laterality is a manifestation of functional reserve. Indeed, in terms of cognitive function, successful aging is often associated with a reduction of asymmetrical activity. The goal of this review is to survey and critically appraise the current literature addressing brain laterality, both morphological and functional, with particular emphasis on the asymmetrical plasticity associated with environmental factors and training. The plastic recruitment of contralateral areas associated with aging and unilateral lesions will be discussed in the context of the loss of asymmetry as a compensatory mechanism, and specific instances of maladaptive plasticity will be explored.

Unilateral accumbal dopamine depletion affects decision-making in a side-specific manner.

Mechanisms underlying affective and cognitive deficits in Parkinson's disease (PD) remain less studied than motor symptoms. Nucleus accumbens (NAc) is affected in PD and due to its well-known involvement in motivation is an interesting target in this context. Furthermore, PD is frequently asymmetrical, with side-specific deficits aligning with evidences of accumbal laterality. We therefore used a 6-hydroxydopamine (6-OHDA) model to study the role of left and right NAc dopamine depletion in a battery of behavioral tasks. 2 months old male rats were used in all experiments. Habitual-based and goal-directed decision-making, impulsivity, anxiety- and depressive-like behavior and motor performance were tested 3 weeks after left (6-OHDA L) or right (6-OHDA R) NAc lesion was induced. Upon contingency degradation, 6-OHDA R decrease their lever press rate less than Sham and 6-OHDA L, indicating an impairment in the shift from habit-based to goal-directed strategies. On the other hand, 6-OHDA L lesions lead to increased rates of premature responding when delays where increased in the variable delay-to-signal test. Importantly, in both paradigms task acquisition was similar between groups. In the same line we found no differences in the amount of sugared pellets eaten when freely available as well as in both general and fine motor behaviors. In conclusion, left and right NAc play distinct roles in the contingency degradation and impulsivity. More studies are needed to understand the mechanisms behind this functional lateralization and its implications for PD patients.

The nucleus reuniens: a key node in the neurocircuitry of stress and depression.

The hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC-hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression. Additionally, RE lesioning before CMS abrogates the well-known neuromorphological and endocrine correlates of CMS. In summary, this work highlights the importance of the reciprocal connectivity between the hippocampus and PFC in the establishment of stress-induced brain pathology and suggests a role for the RE in promoting resilience to depressive illness.

Structural laterality is associated with cognitive and mood outcomes: An assessment of 105 healthy aged volunteers.

The human brain presents multiple asymmetries that dynamically change throughout life. These phenomena have been associated with cognitive impairments and psychiatric disorders although possible associations with specific patterns of cognitive aging are yet to be determined. We have therefore mapped and quantified morphological asymmetries in a heterogeneous and aged population (65.2±8.0 years old, 52 male and 53 female) to explore potential associations between the asymmetries in specific brain regions and cognitive performance. The sample was characterized in a battery of neuropsychological tests and in terms of brain structural asymmetries using a ROI-based approach. A substantial number of brain areas presented some degree of asymmetry. Such biases survived a stringent statistical correction and were largely confirmed in a voxel-based analysis. In specific brain areas, like the thalamus and insula, asymmetry was correlated with cognition and mood descriptors as the Stroop words/colors test or depressive mood scale, respectively. Curiously in the latter, the association was independent of its left/right direction. Altogether, results reveal that asymmetry is widespread in the aged brain and that area-specific biases (degree and direction) associate with the functional profile of the individual.

Brain projections from the medullary dorsal reticular nucleus: an anterograde and retrograde tracing study in the rat.

In the last 15 years a role has been ascribed for the medullary dorsal reticular nucleus as a supraspinal pain modulating area. The medullary dorsal reticular nucleus is reciprocally connected with the spinal dorsal horn, is populated mainly by nociceptive neurons and regulates spinal nociceptive processing. Here we analyze the distribution of brain projections from the medullary dorsal reticular nucleus using the iontophoretic administration of the anterograde tracer biotinylated-dextran amine and the retrograde tracer cholera toxin subunit B. Fibers and terminal boutons labeled from the medullary dorsal reticular nucleus were located predominately in the brainstem, although extending also to the forebrain. In the medulla oblongata, anterograde labeling was observed in the orofacial motor nuclei, inferior olive, caudal ventrolateral medulla, rostral ventromedial medulla, nucleus tractus solitarius and most of the reticular formation. Labeling at the pons-cerebellum level was present in the locus coeruleus, A5 and A7 noradrenergic cell groups, parabrachial and deep cerebellar nuclei, whereas in the mesencephalon it was located in the periaqueductal gray matter, deep mesencephalic, oculomotor and anterior pretectal nuclei, and substantia nigra. In the diencephalon, fibers and terminal boutons were found mainly in the parafascicular, ventromedial, and posterior thalamic nuclei and in the arcuate, lateral, posterior, peri- and paraventricular hypothalamic areas. Telencephalic labeling was consistent but less intense and concentrated in the septal nuclei, globus pallidus and amygdala. The well-known role of the medullary dorsal reticular nucleus in nociception and its pattern of brain projections in rats suggests that the nucleus is possibly implicated in the modulation of: (i) the ascending nociceptive transmission involved in the motivational-affective dimension of pain; (ii) the endogenous supraspinal pain control system centered in the periaqueductal gray matter-rostral ventromedial medulla-spinal cord circuitry; (iii) the motor reactions associated with pain.

Differential expression of collagens type I and type IV in lymphangiogenesis during the angiogenic process associated with bleomycin-induced pulmonary fibrosis in rat.

In order to assess the role of collagens I and IV during the angiogenic process associated with bleomycin-induced pulmonary fibrosis in rat, in situ hybridization and immunocytochemical studies were carried out. An increased expression of collagen IV was observed before an enhanced expression of collagen I after intratracheal instillation of bleomycin. Deposits of both collagen types were detected on the 21st day after treatment with bleomycin, surrounding the new blood vessels formed during the fibrotic process. At this time, the presence of new lymphatic vessels was associated uniquely with deposition of collagen I. These observations lead us to conclude that, at least during pulmonary fibrosis, lymphangiogenesis takes place after blood angiogenesis.