Differential projection from the motor and limbic cortical regions to the mediodorsal thalamic nucleus in the dog

The cortical afferents to the mediodorsal thalamic nucleus in the dog were studied by using horseradish peroxidase. Small injections allowed to establish two specific projection zones connected separately with the lateral and medial segments of the nucleus. The lateral segment received the major projection from the dorsal half of the hemisphere. It included premotor and part of the motor cortices in the anterior sigmoid gyrus and precruciate areas as well as the presylvian cortex. The medial segment of the nucleus was innervated by the limbic areas of the ventral half of the hemisphere. These areas included the medioventrally located genual, subcallosal and piriform cortices, as well as the cortex of the ventral bank of the anterior rhinal sulcus and the caudal part of the orbital gyrus. The cortical fields situated between these two main cortical zones, both on the lateral and medial surfaces (rhinal and sylvian sulci and anterior cingular gyrus, respectively) sent projections to both medial and lateral segments of the nucleus. These results indicate that in the mediodorsal thalamic nucleus may take place the integration of information from two functionally defined systems, the motor and limbic ones.     

Callosal connections of the parabelt auditory cortex in macaque monkeys

Auditory cortex of macaque monkeys is located on the lower bank of the lateral sulcus and the adjoining superior temporal gyrus. This region of cortex contains a core of primary-like areas surrounded by a narrow belt of associated fields. Adjacent to the lateral belt on the superior temporal gyrus is a parabelt region which contains at least two subdivisions (rostral and caudal). In previous studies we defined the parabelt region as cortex with topographic cortical connections with the belt areas surrounding the core, and connections with the dorsal and magnocellular divisions of the medial geniculate complex, but minimal connections with the core region and ventral division of the medial geniculate complex. The callosal connections of the parabelt auditory cortex were determined by placing injections, of up to six distinguishable tracers, into different locations of the parabelt region in each of four macaque monkeys. The results indicated that the strongest callosal projections arise from homotopic areas in parabelt cortex, and they roughly matched the rostrocaudal levels of the medial and lateral belt cortex. Weaker callosal inputs to the parabelt originate from the corresponding levels of the superior temporal gyrus and superior temporal sulcus. The core region does not contribute significant callosal projections to the parabelt region. The results provide further support for the conclusion that the parabelt region represents a third level of auditory cortical processing beyond direct activation by primary subcortical and cortical auditory structures.     

Pallidal and cerebellar afferents to pre-supplementary motor area thalamocortical neurons in the owl monkey: a multiple labeling study

In the present study, we determined where thalamic neurons projecting to the pre-supplementary motor area (pre-SMA) are located relative to pallidothalamic and cerebellothalamic inputs and nuclear boundaries. We employed a triple-labeling technique in the same owl monkey (Aotus trivirgatus). The cerebellothalamic projections were labeled with injections of wheat germ agglutinin conjugated to horseradish peroxidase, and the pallidothalamic projections were labeled with biotinylated dextran amine. The pre-SMA was identified by location and movement patterns evoked by intracortical microstimulation and injected with the retrograde tracer cholera toxin subunit B. Brain sections were processed sequentially using different chromogens to visualize all three tracers in the same section. Alternate sections were processed for Nissl cytoarchitecture or acetylcholinesterase chemoarchitecture for nuclear boundaries. The cerebellar nuclei primarily projected to posterior (VLp), medial (VLx), and dorsal (VLd) divisions of the ventral lateral nucleus; the pallidum largely projected to the anterior division (VLa) of the ventral lateral nucleus and the parvocellular part of the ventral anterior nucleus (VApc). However, we also found zones of overlapping projections, as well as interdigitating foci of pallidal and cerebellar label, particularly in border regions of the VLa and VApc. Thalamic neurons labeled by pre-SMA injections occupied a wide band and were especially concentrated in the VLx and VApc, cerebellar and pallidal territories, respectively. Labeled thalamocortical neurons overlapped cerebellar inputs in the VLd and VApc and overlapped pallidal inputs in the VLa and the ventral medial nucleus. The results demonstrate that inputs from both the cerebellum and globus pallidus are relayed to the pre-SMA.     

Attentional and Interpretational Biases Toward Pain-Related Stimuli in Children and Adolescents: ASystematic Review of the Evidence

This review investigated whether youth exhibit attention or interpretation biases toward pain-related information and whether such biases are more pronounced in youth with chronic pain. Three databases were searched to identify studies that assessed attention or interpretation biases using an accepted experimental paradigm. Ten studies were identified, 8 examining attentional biases and 2 examining interpretation biases. As in the adult literature, there was no evidence of attentional biases toward pain in youth without chronic pain. Three studies investigating youth without chronic pain found evidence for relationships between catastrophizing or anxiety and indicators of vigilance or avoidance (in 2 cases, for youth with low self-reported attentional control). For attentional biases, 5 studies compared youth with and without chronic pain. Two of these studies measured cortical correlates and found evidence of neurologic activity indicating a bias in orienting to pain-related stimuli. Three studies examined biases toward pain-related words or pictures. Of those, 2 found evidence of biases at subliminal presentation times, indicating vigilance (although 1 only after a stressful task). For supraliminal presentations, 1 study found evidence of avoidance, one of difficulty disengaging, and one of general slowing of responses. Only 1 study compared youth with and without pain for interpretation bias in adolescents, and interpretation biases were greater for youth with chronic pain. As with attention, no evidence for interpretation biases were found in youth without chronic pain. Overall, there is weak evidence to support vigilance in youth with chronic pain compared with those without. However, whether pain affects the subsequent deployment of attention is unclear. There is no evidence for biases toward pain in youth without chronic pain, but evidence suggests that anxiety or catastrophizing and attentional control may moderate pain-related attentional biases. There is also weak evidence of interpretation bias in youth with chronic pain compared with those without.

PSD-95 in CA1 Area Regulates Spatial Choice Depending on Age

Cognitive processes that require spatial information rely on synaptic plasticity in the dorsal CA1 area (dCA1) of the hippocampus. Since the function of the hippocampus is impaired in aged individuals, it remains unknown how aged animals make spatial choices. Here, we used IntelliCage to study behavioral processes that support spatial choices of aged female mice living in a group. As a proxy of training-induced synaptic plasticity, we analyzed the morphology of dendritic spines and the expression of a synaptic scaffold protein, PSD-95. We observed that spatial choice training in young adult mice induced correlated shrinkage of dendritic spines and downregulation of PSD-95 in dCA1. Moreover, long-term depletion of PSD-95 by shRNA in dCA1 limited correct choices to a reward corner, while reward preference was intact. In contrast, old mice used behavioral strategies characterized by an increased tendency for perseverative visits and social interactions. This strategy resulted in a robust preference for the reward corner during the spatial choice task. Moreover, training decreased the correlation between PSD-95 expression and the size of dendritic spines. Furthermore, PSD-95 depletion did not impair place choice or reward preference in old mice. Thus, our data indicate that while young mice require PSD-95-dependent synaptic plasticity in dCA1 to make correct spatial choices, old animals observe cage mates and stick to a preferred corner to seek the reward. This strategy is resistant to the depletion of PSD-95 in the CA1 area. Overall, our study demonstrates that aged mice combine alternative behavioral and molecular strategies to approach and consume rewards in a complex environment.SIGNIFICANCE STATEMENT It remains poorly understood how aging affects behavioral and molecular processes that support cognitive functions. It is, however, essential to understand these processes to develop therapeutic interventions that support successful cognitive aging. Our data indicate that while young mice require PSD-95-dependent synaptic plasticity in dCA1 to make correct spatial choices (i.e., choices that require spatial information), old animals observe cage mates and stick to a preferred corner to seek the reward. This strategy is resistant to the depletion of PSD-95 in the CA1 area. Overall, our study demonstrates that aged mice combine alternative behavioral and molecular strategies to approach and consume rewards in a complex environment. Second, the contribution of PSD-95-dependent synaptic functions in spatial choice changes with age.     

Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain. METHODS: We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first-line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9-month morbidity and mortality were compared between adults infected with susceptible and those infected with drug-resistant organisms. RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and was independently associated with human immunodeficiency virus infection. CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first-line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death.     

Topographic patterns of V2 cortical connections in macaque monkeys

Patterns of connections of dorsal and ventral portions of the second visual area (V2) were used to evaluate and extend current theories of cortical organization and processing streams in macaque monkeys. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and up to four different fluorochromes in V2 labeled neurons and terminations in V2 and in 1) caudal (DLc) and rostral (DLr) subdivisions of dorsolateral cortex between V2 and the middle temporal area (MT); 2) regions we define as dorsomedial (DM) and dorsointermediate (DI) areas; 3) MT, medial superior temporal area (MST), and fundal superior temporal area (FST); 4) the dorsal part of inferior temporal (TEO) cortex; and 5) two locations in posterior parietal cortex. The largest extrastriate connection zone was DLc, which occupied the caudal one-third to one-half of the fourth visual area (V4) region of other proposals. Based on the connection pattern, foveal vision in DLc is represented adjacent to foveal vision in V2, with the lower quadrant represented dorsally and the upper quadrant ventrally, as in V2, but within a much less extensive region of cortex. The sparser connections of DLr formed a more compressed but parallel visuotopic pattern. A third visuotopic pattern of connections was located in a moderately myelinated region of cortex just rostral to dorsomedial V2. Whereas the region would include parts of dorsal visual area 3 (V3), V3a, and possibly other areas of other proposals, we interpret the connection pattern as reflecting a dorsomedial visual area, DM, with foveal vision represented caudolaterally and other parts of the lower and upper quadrants represented more medially and rostrally. A fourth pattern of label in dorsointermediate cortex suggested the location and organization of another visual area (DI). Most of a fifth connection pattern with MT was congruent with the known visuotopic organization of MT area, but visuotopically mismatched foci of connections were observed as well. Sparser foci of label in MST suggested a rostrodorsal representation of foveal vision, with paracentral vision represented more caudally. Separate dorsal and ventral foci of label in FST were consistent with previous evidence for dorsal (FSTd) and ventral (FSTv) visual areas. Finally, connections with TEO and posterior parietal cortex were sparse. Our results suggest that much of visual cortex organization is similar in New and Old World monkeys. © 1996 Wiley-Liss, Inc.     

Alterations in pain processing circuitries in episodic migraine

BackgroundThe precise underlying mechanisms of migraine remain unknown. Although we have previously shown acute orofacial pain evoked changes within the brainstem of individuals with migraine, we do not know if these brainstem alterations are driven by changes in higher cortical regions. The aim of this investigation is to extend our previous investigation to determine if higher brain centers display altered activation patterns and connectivity in migraineurs during acute orofacial noxious stimuli.MethodsFunctional magnetic resonance imaging was performed in 29 healthy controls and 25 migraineurs during the interictal and immediately (within 24-h) prior to migraine phases. We assessed activation of higher cortical areas during noxious orofacial heat stimulation using a thermode device and assessed whole scan and pain-related changes in connectivity.ResultsDespite similar overall pain intensity ratings between all three groups, migraineurs in the group immediately prior to migraine displayed greater activation of the ipsilateral nucleus accumbens, the contralateral ventrolateral prefrontal cortex and two clusters in the dorsolateral prefrontal cortex (dlPFC). Reduced whole scan dlPFC [Z + 44] connectivity with cortical/subcortical and brainstem regions involved in pain modulation such as the putamen and primary motor cortex was demonstrated in migraineurs. Pain-related changes in connectivity of the dlPFC and the hypothalamus immediately prior to migraine was also found to be reduced with brainstem pain modulatory areas such as the rostral ventromedial medulla and dorsolateral pons.ConclusionsThese data reveal that the modulation of brainstem pain modulatory areas by higher cortical regions may be aberrant during pain and these alterations in this descending pain modulatory pathway manifests exclusively prior to the development of a migraine attack.     

Can increased spatial resolution solve the crossing fiber problem for diffusion MRI?

It is now widely recognized that voxels with crossing fibers or complex geometrical configurations present a challenge for diffusion MRI (dMRI) reconstruction and fiber tracking, as well as microstructural modeling of brain tissues. This “crossing fiber” problem has been estimated to affect anywhere from 30% to as many as 90% of white matter voxels, and it is often assumed that increasing spatial resolution will decrease the prevalence of voxels containing multiple fiber populations. The aim of this study is to estimate the extent of the crossing fiber problem as we progressively increase the spatial resolution, with the goal of determining whether it is possible to mitigate this problem with higher resolution spatial sampling. This is accomplished using ex vivo MRI data of the macaque brain, followed by histological analysis of the same specimen to validate these measurements, as well as to extend this analysis to resolutions not yet achievable in practice with MRI. In both dMRI and histology, we find unexpected results: the prevalence of crossing fibers increases as we increase spatial resolution. The problem of crossing fibers appears to be a fundamental limitation of dMRI associated with the complexity of brain tissue, rather than a technical problem that can be overcome with advances such as higher fields and stronger gradients.