, 2009) rather than being predominantly involved in sensorimotor coordination as traditionally thought. Human fMRI studies have revealed functional cerebellar networks that are systematically related to cerebral networks at a relatively coarse level (Buckner et al., 2011). However, until methods improve to the point that accurate surface-based mapping can be done in individual subjects, it seems likely that important Vemurafenib research buy organizational principles for the cerebellum will be hidden from view. Regarding subcortical structures, conventional in vivo neuroimaging enables

visualization and analysis of the larger nuclei; accurate automated segmentation of these nuclei (e.g., using FreeSurfer) is facilitated by their low degree

of individual variability. However, there are many small subnuclei (e.g., of the hypothalamus) that cannot be discerned using conventional structural scans (e.g., T1w and T2w scans). On the other hand, conventional histological atlases can be complemented by specialized MR-based imaging that reveals considerably greater neuroanatomical detail using ultra-high field strength (7T or higher), specialized pulse sequences such as susceptibility-weighted imaging (Abosch et al., 2010), and/or postmortem scans (e.g., Augustinack Alpelisib concentration et al., 2013). Our understanding of the amazing complexity of long-range neural connections in the mammalian brain has evolved dramatically in recent decades. Key recurring themes that have emerged are (1) an unexpectedly large number of identified pathways, implying a dense rather than sparse connectivity matrix at the level of area-to-area connections; (2) a range of interareal connection strengths that is remarkably broad but conforms to

a stereotyped statistical distribution; and (3) organization into highly distributed and interconnected networks and subnetworks. As in the cartography section, the focus here is on cerebral cortex, starting with the macaque and mouse. These are of great interest in their own right, but they also provide a vital form of “ground truth” when considering human brain circuits that can only be explored using indirect methods. Quantitative “parcellated connectomes” have recently tuclazepam been reported for all three species, representing major progress even though the connectomes remain incomplete for the mouse and macaque and are indirect for the human brain. Early studies using classical axonal degeneration-based methods suggested that each cortical area was directly connected to only a handful of other cortical areas (Van Essen, 1979). The advent of modern anterograde and retrograde tracers starting in the 1970s gradually revealed that connectivity patterns are far more complex. The finding that most pathways are bidirectional but asymmetric in their laminar pattern led Rockland and Pandya (1979) to propose that laminar pattern could be used to distinguish between feedforward and feedback directions of information flow.