Generalization performance in monkey and model.

<p>Reaches performed by monkey (black) and model (white) were analyzed when generalizing from cardinal to oblique spatial cue directions. Bars show proportion of reaches in a direction relative to the rewarded goal (this means, 0° reaches are directed towards the correct goal, all others are failed reaches). Direct reaches to cardinal (A) and oblique (C) goals are almost always performed correctly. Inferred reaches to trained (cardinal) goals (B) are also almost always performed correctly, as was to be expected. If inferred reaches were required to oblique positions (D), both monkey and model show a similar pattern of failed reaches, illustrated in the inset of panel (D): Most reaches were made either in a previously trained cardinal direction adjacent to the goal direction (red, deviation of 45°) or in the direction of the spatial cue, meaning that a direct reach was performed (green, deviation of 180° from the goal direction).</p

Model architecture and interactions in neural fields.

<p>(A) The model consists of four interconnected DNFs and a set of dynamic nodes. The spatial input field, motor preparation field, and motor field are one-dimensional fields that span the space of possible spatial cue/reach directions. The two-dimensional association field is defined over this directional space as well as a second dimension along which selectivity for the contextual cue develops. Its activation is shown color coded (red highest, blue lowest activation). The activation of the two context nodes is shown as a bar plot. Fixed projections between the fields are shown as white arrows; variable projections (that are subject to learning) are shown through dark red arrows with a weight matrix W. (B) Lateral interactions in DNFs, shown exemplarily for the motor preparation field. Exogenous input from other fields (indicated by grey arrows at the bottom) locally increases activation (red). Regions of high activation produce an output signal (the soft threshold of the sigmoid output function is indicated by the dashed line), which acts on other parts of the field and is also projected to other fields of the architecture. The lateral interactions consist of local excitatory connections and surrounding inhibitory connections, which together implement a soft competition between distant field regions. This creates a selection property in the field, promoting the formation of a single peak even for multi-modal input.</p

Influence of input statistics on model behavior and activation pattern during the memory period.

<p>(A) The behavioral bias for inferred reaches in the free-choice trials depends on the percentage of inferred trials during IR training and rises continuously in a sigmoidal fashion (logistic fit function; black curve). (B) The difference of the mean activation of the motor preparation field at the preferred and opposite-to-preferred position during the memory period shows a softer, but also approximately sigmoid increase when the number of inferred trials is increased.</p

Choice behavior of monkeys and model in PMG-NC trials.

<p>If no context instruction is given in a trial, both model and monkeys show an inherent bias to perform the inferred reach after training (A). A balanced choice behavior (B) can be achieved by application of an appropriate reward schedule (BRMS).</p

Origin of generalization errors in the model.

<p>Two snapshots of the activation patterns in the model during the memory period are shown, taken from different trials that developed different movement plans due to random noise in the model. In both cases, the spatial cue was located at 225° (an oblique direction not used during training), the blue context input indicates that an inferred reach should be performed. The model is depicted in the same form as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002774#pcbi-1002774-g001" target="_blank">Figure 1</a>. Arrows show the dominant active projections between fields that arise from the current activation patterns. Regions with pronounced preference for one context are outlined in the association field (green for direct context, white for inferred). (A) When the spatial cue was presented at the beginning of the trial (white arrow), it created an activation peak in the association field at the untrained oblique direction. This active region in the association field projects topologically to the motor preparation field, therefore preparing a reach to the spatial cue direction. This corresponds to a deviation of 180° from the goal direction, since the context cue indicates that an inferred reach should be performed. (B) If the activation peak in the association overlaps partly with a region that is selective for the inferred context, the activation peak may shift over to that region (the figure shows an intermediate step of this shift). This is driven by the input from the context node. The region of the association field that is now active has adapted its projection to the motor preparation field during training, and induces a new activation peak in the motor preparation field around 360°. This yields a deviation of 45° from the goal location, since the model now prepares one of the trained reaches in a cardinal direction.</p

Comparison of population activation in model and electrophysiological data.

<p>Plots show the averaged and normalized field output from the motor preparation field in the model (A, C) and from electrophysiological recordings in PRR (B, D) during the PMG task. Prior to averaging and normalizing, the real and model neurons' selectivity profiles were aligned according to their preferred directions in DMG trials (PD: preferred direction, OD: opposite-to-preferred direction). The averaged and normalized activity of real neurons during the PMG task in the biased (B) and balanced (D) datasets is shown for three epochs, aligned to cue onset, ‘go’-signal, and movement onset, since the length of the epochs was variable. The model neurons were aligned accordingly even though the epochs had fixed lengths. It can be seen that during the memory period in the model and in the real data plots, only one activation ridge is stable throughout the memory period, before a bias minimizing reward schedule (BMRS; see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002774#s2" target="_blank">Methods</a>) was introduced (A, B). After application of the BMRS, two stable ridges with a lower activation remain during the memory period (C, D).</p

Structure of the context-dependent reach task that model and monkeys had to perform.

<p>In the beginning either a single spatial cue (PMG task, B) or a spatial and a contextual cue (DMG task, A) were presented, indicated by a white circle (spatial cue) and a colored rectangle (contextual cue). During the memory period no cue was shown. The ‘go’-signal indicated the subject to make a reach movement towards the goal, which was either at the same location as the spatial cue (direct trial; green) or at the diametrically opposite location (inferred trial; blue). In one part of the PMG trials the contextual cue was presented at the end of the memory period (PMG-CI), and in another part no contextual cue was shown at all (PMG-NC) and a free choice had to be made (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002774#s2" target="_blank">Methods</a>). In the inferred reach training task (C), a second spatial cue (target cue) is shown at the end of the memory period to indicate the rewarded goal position. This cue is gradually faded out over many trials during the training.</p

Emergence of bias for inferred reaches in the DNF model.

<p>The figure shows two snapshots of the activation patterns in the model during a single PMG trial. (A) During the memory period, after the presentation of a spatial cue, an activation peak has formed in the association field. Its position along the spatial axis reflects the direction of the spatial cue, while its location along the second dimension is unspecific and spans both context-sensitive regions (shown as outlines in the association field, green for direct, white for inferred context). The region that shows preference for the inferred context is substantially larger than the direct-context region, due to the high proportion of inferred trials during training. This region projects to the location in the motor preparation field which codes for a reach in the direction opposite to the spatial cue. The competitive interactions in the motor preparation field further amplify this stronger input that supports the inferred reach. (B) When a context signal for a direct trial is given at the end of the memory period, the context input induces a shift of the peak in the association field: It is pulled almost completely onto the region specific for the direct context with which it partly overlapped. The input to the motor preparation field changes accordingly, leading to a switch in that field's activation pattern and a stronger activation of the ‘direct’ reach direction.</p

Table_7_Engineering Artificial Somatosensation Through Cortical Stimulation in Humans.DOCX

<p>Sensory feedback is a critical aspect of motor control rehabilitation following paralysis or amputation. Current human studies have demonstrated the ability to deliver some of this sensory information via brain-machine interfaces, although further testing is needed to understand the stimulation parameters effect on sensation. Here, we report a systematic evaluation of somatosensory restoration in humans, using cortical stimulation with subdural mini-electrocorticography (mini-ECoG) grids. Nine epilepsy patients undergoing implantation of cortical electrodes for seizure localization were also implanted with a subdural 64-channel mini-ECoG grid over the hand area of the primary somatosensory cortex (S1). We mapped the somatotopic location and size of receptive fields evoked by stimulation of individual channels of the mini-ECoG grid. We determined the effects on perception by varying stimulus parameters of pulse width, current amplitude, and frequency. Finally, a target localization task was used to demonstrate the use of artificial sensation in a behavioral task. We found a replicable somatotopic representation of the hand on the mini-ECoG grid across most subjects during electrical stimulation. The stimulus-evoked sensations were usually of artificial quality, but in some cases were more natural and of a cutaneous or proprioceptive nature. Increases in pulse width, current strength and frequency generally produced similar quality sensations at the same somatotopic location, but with a perception of increased intensity. The subjects produced near perfect performance when using the evoked sensory information in target acquisition tasks. These findings indicate that electrical stimulation of somatosensory cortex through mini-ECoG grids has considerable potential for restoring useful sensation to patients with paralysis and amputation.</p

Table_6_Engineering Artificial Somatosensation Through Cortical Stimulation in Humans.DOCX

<p>Sensory feedback is a critical aspect of motor control rehabilitation following paralysis or amputation. Current human studies have demonstrated the ability to deliver some of this sensory information via brain-machine interfaces, although further testing is needed to understand the stimulation parameters effect on sensation. Here, we report a systematic evaluation of somatosensory restoration in humans, using cortical stimulation with subdural mini-electrocorticography (mini-ECoG) grids. Nine epilepsy patients undergoing implantation of cortical electrodes for seizure localization were also implanted with a subdural 64-channel mini-ECoG grid over the hand area of the primary somatosensory cortex (S1). We mapped the somatotopic location and size of receptive fields evoked by stimulation of individual channels of the mini-ECoG grid. We determined the effects on perception by varying stimulus parameters of pulse width, current amplitude, and frequency. Finally, a target localization task was used to demonstrate the use of artificial sensation in a behavioral task. We found a replicable somatotopic representation of the hand on the mini-ECoG grid across most subjects during electrical stimulation. The stimulus-evoked sensations were usually of artificial quality, but in some cases were more natural and of a cutaneous or proprioceptive nature. Increases in pulse width, current strength and frequency generally produced similar quality sensations at the same somatotopic location, but with a perception of increased intensity. The subjects produced near perfect performance when using the evoked sensory information in target acquisition tasks. These findings indicate that electrical stimulation of somatosensory cortex through mini-ECoG grids has considerable potential for restoring useful sensation to patients with paralysis and amputation.</p