Non-primary motor areas in the human frontal lobe are connected directly to hand muscles S. Teitti, a, ⁎ S. Määttä, a L. Säisänen, a M. Könönen, a,b R. Vanninen, b H. Hannula, c E. Mervaala, a and J. Karhu a,c a Clinical Neurophysiology, NBS Laboratory, Kuopio University Hospital, Finland b Department of Clinical Radiology, Kuopio University Hospital, Finland c Nexstim Ltd., Helsinki, Finland Received 15 October 2007; revised 21 December 2007; accepted 31 December 2007 Available online 17 January 2008 Structural studies in primates have shown that, in addition to the pri- mary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional con- nections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits. © 2008 Elsevier Inc. All rights reserved. Keywords: Corticospinal tract; Non-primary motor areas; Human motor cortex; Transcranial magnetic stimulation; Neuronavigation Introduction The human primary motor cortex (M1) is located in the pre- central gyrus and is the area where upper motoneurons reside with the primary function to execute motor commands. It is characterized by a somatotopic organization of body representations (Penfield, 1954). Non-primary motor areas (NPMAs) in the frontal lobe anterior to the M1 are thought to represent “higher” motor functions such as creating a model of movement and control of the movements (Fulton, 1935). NPMAs are divided both anatomically and physio- logically into separate units: premotor areas (PMA) and supple- mentary motor areas (SMA), which can be further divided into ventral and dorsal premotor areas (PMv, PMd), and pre-SMA and SMA-proper. PMA play an important role in the selection of move- ments for execution (Crammond and Kalaska, 1996; Picard and Strick, 2001; Rizzolatti and Luppino, 2001; Toni et al., 2001; Dum and Strick, 2002; Thoenissen et al., 2002), while SMA are active during motor tasks that demand the retrieval of motor memories. SMA are also crucial to the temporal organization of multiple movements, especially in sequential performance (Wiesendanger, 1986; Rizzolatti et al., 1990; Tanji, 1994). M1 efferent activity leads to movements in contralateral body parts mainly via the corticospinal tract. NPMAs connect predomi- nantly to the M1 but also contain nerve cells with direct corticospinal projections (Kandel et al., 2000). The function of these direct corticospinal projections in humans is unclear. In other primates, it has been established that the frontal lobe contains corticospinal neurons with direct motor functions besides the motor control of movements (Dum and Strick, 1991; Dum and Strick, 2002). Human NPMAs may thus also contain corticospinal tracts with some motor functions (Laplane et al., 1977; Uematsu et al., 1992; Fink et al., 1997; Krainik et al., 2001; Johansen-Berg et al., 2004). Most previous human studies are based on indirect imaging methods. Movement-related potentials recorded from subdural elec- trodes show equal temporal evolution from the contralateral primary motor area and both SMAs, suggesting a role for SMA in voluntary movements (Ikeda et al., 1992). PET studies in humans show that frontal areas that are active during the execution of simple movements correspond to premotor areas projecting corticospinal tracts in macaques (Fink et al., 1997). Combined functional and diffusion- weighted MRI techniques have revealed that parts of the supplemen- tary motor area activated during motor tasks contain cell populations with direct projections to the corticospinal tract (Johansen-Berg et al., www.elsevier.com/locate/ynimg NeuroImage 40 (2008) 1243 – 1250 ⁎ Corresponding author. NBS Laboratory, Department of Clinical Neurophysiology, Kuopio University Hospital, Box 1777, 70211 Kuopio, Finland. Fax: +358 17173244. E-mail address: steitti@hytti.uku.fi (S. Teitti). Available online on ScienceDirect (www.sciencedirect.com). 1053-8119/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2007.12.065