Title : Modular processing in the hand representation of primate primary somatosensory cortex

34 Neurons in the hand representation of primary somatosensory cortex (area 3b) are known 35 to have discretely localized receptive fields; and these neurons form modules that can be 36 visualized histologically as distinct digit and palm representations. Despite these indicators of the 37 importance of local processing in area 3b, widespread interactions between stimuli presented to 38 locations across the hand have been reported. We investigated the relationship of neuron firing 39 rate with distance from the site of maximum activation in cortex by recording from a 10040 electrode array with electrodes spaced 400 μm apart, implanted into the area 3b hand 41 representation in anesthetized owl monkeys. For each stimulated location on the hand, the 42 electrode site where neurons had the highest peak firing rate was defined as the Peak Activation 43 site. The lesser firing rates of neurons at all other electrode sites in the grid were compared to the 44 firing rates of neurons at the Peak Activation site. On average, peak firing rates of neurons 45 decreased rapidly with distance away from the Peak Activation site. The effect of distance on the 46 variance of firing rates was highly significant (p < 0.0001). However, individual neurons retained 47 high firing rates for distances over 3 mm. The clear decline in firing rate with distance from the 48 most activated location indicates that local processing is emphasized in area 3b, while the 49 distance of neurons with reduced but maintained firing rates up to 3-4 mm from the site of best 50 activation demonstrated widespread activation in primary somatosensory cortex. 51 52 Introduction 53 The emphasis on modular processing in the somatosensory system has been recently 54 supplemented by concepts of more widespread interactions, including surround modulation and 55 stimulus integration. In the primary somatosensory cortex, area 3b in primates, there is good 56 evidence that local or modular processing occurs within individual representations of the parts of 57 the hand, via neurons with small, discrete receptive fields (e.g., Sur 1980; Iwamura et al. 1983; 58 Sur et al. 1985; Pons et al. 1987; DiCarlo et al. 1998). As reported by Jain et al. (1998) and Qi et 59 al. (2004), the representations of individual digits and pads of the palm can be visualized in area 60 3b of monkeys as myelin-dense regions surrounded by myelin-light septa. These histologically 61 visible representations of the digits and palm pads are relatively consistent across individual 62 monkeys and do not change in adults that have experienced a sensory loss that alters the 63 somatotopy of the hand representation (Jain et al. 1998). The presence of such delimiting septa is 64 consistent with the evidence that neurons in the hand representation in area 3b normally have 65 small excitatory receptive fields confined to single digits, at least during development. 66 In contrast, other observations point to widespread interactions between neurons 67 distributed across the hand representation in area 3b. We reported that cross-correlations between 68 pairs of neurons demonstrate the existence of functional connections between neurons separated 69 by 3 mm or more in cortex (Reed et al. 2008) and firing rates of area 3b neurons are modulated 70 by stimuli outside their receptive fields (e.g., Reed et al. 2010). Further evidence that even a 71 discrete tactile stimulus produces widespread activation in primary somatosensory cortex has 72 been long known. For example, 2-deoxyglucose metabolic labeling combined with 73 neurophysiological mapping studies in macaque monkeys suggested that widespread increases in 74 metabolic activity following repetitive, precisely controlled tactile stimulation can occur even 75 when conventional receptive field mapping techniques fail to detect activation (Juliano and 76 Whitsel 1987). In addition, the spatial and temporal activation patterns across large regions of 77 primary somatosensory cortex have been explored using optical imaging techniques in New 78 World squirrel monkeys (e.g., Tommerdahl et al. 2002; Simons et al. 2007). Notably, responses 79 to single-site flutter stimulation results in widespread cortical activity that shrinks in size after a 80 few seconds of continued stimulation (Tommerdahl et al. 2002). We tested responses to 81 indentation rather than flutter stimulation; however, flutter stimulation presented for the same 82 duration as our indentation stimuli (0.5 s) resulted in spatially widespread cortical activation over 83 the 3-mm imaged radius in primary somatosensory cortex (Simons et al. 2007). While our 84 stimulus and methods differ from these previous studies, their results and our previous studies 85 (Reed et al. 2008; Reed et al. 2010) provide reason to expect widespread activation in response 86 to single-site stimulation. 87 This phenomenon of widespread activation beyond that expected based on receptive field 88 mapping is not unique to the primary somatosensory cortex. Research continues to show that 89 somatosensory cortex has similarities to other sensory cortices, like visual cortex. While a review 90 of the extensive literature on primary visual cortex is beyond our scope, we highlight a 91 particularly relevant study. Using optical imaging in macaque monkeys, Grinvald et al. (1994) 92 reported as a primary finding that 350 ms after onset of a 1 x 1 degree stimulus, a cortical region 93 larger than 6 x 6 mm was activated. Thus, activity in primary visual cortex quickly spread 94 beyond the distance expected based on receptive field mapping. 95 These results are compatible with other physiological studies specific to the cortical 96 forelimb representation which have determined spatial characteristics for stimulus interactions 97 when one stimulus is presented inside the receptive field and a second stimulus is presented 98 nearby (e.g., Mountcastle and Powell 1959; Laskin and Spencer 1979; Gardner and Costanzo 99 1980a,b; Burton et al. 1998; DiCarlo et al. 1998, 2000, 2002; Greek et al. 2003; Sripati et al. 10