Biorobotics/Biomechanics

Spinal cord

Modelling

Neuron

Brain

Analytics

Intracellular

Cerebellum

For three decades our founders challenged the common consensus of one of the biggest scientific questions of our time: How does the brain work?

IntuiCell | Research

Born in the intersection
of AI and Neuroscience.

IntuiCell is a Lund University spin-off with presence in Lund and Stockholm. 

For three decades our founders challenged the common consensus 
of one of the biggest scientific questions of our time:

Today, we apply those groundbreaking neurophysiological insights 
to redesign artificial intelligence. Creating AI that is 

Explore our contrarian research on the mechanisms by which the 
brain predicts the world.

Research

CO Norrsken House
Birger Jarlsgatan 57C
SE-113 56 Stockholm

About

AI isn't actually intelligent. IntuiCell already is.

IntuiCell

Complexity is important for flexibility of natural behavior and for the remarkably efficient learning of the brain. Here we assessed the signal complexity among neuron populations in somatosensory cortex (S1). To maximize our chances of capturing population-level signal complexity, we used highly repeatable resolvable visual, tactile, and visuo-tactile inputs and neuronal unit activity recorded at high temporal resolution. We found the state space of the spontaneous activity to be extremely high-dimensional in S1 populations. Their processing of tactile inputs was profoundly modulated by visual inputs and even fine nuances of visual input patterns were separated. Moreover, the dynamic activity states of the S1 neuron population signaled the preceding specific input long after the stimulation had terminated, i.e., resident information that could be a substrate for a working memory. Hence, the recorded high-dimensional representations carried rich multimodal and internal working memory-like signals supporting high complexity in cortical circuitry operation.

Complexity is important for flexibility of natural behavior and for the remarkably efficient learning of the brain.

High-dimensional cortical signals reveal rich bimodal and working memory-like representations among S1 neuron populations

Cortical sensory processing is greatly impacted by internally generated activity. But controlling for that activity is difficult since the thalamocortical network is a high-dimensional system with rapid state changes. Therefore, to unwind the cortical computational architecture there is a need for physiological ‘landmarks’ that can be used as frames of reference for computational state. Here we use a waveshape transform method to identify conspicuous local field potential sharp waves (LFP-SPWs) in the somatosensory cortex (S1). LFP-SPW events triggered short-lasting but massive neuronal activation in all recorded neurons with a subset of neurons initiating their activation up to 20 ms before the LFP-SPW onset. In contrast, LFP-SPWs differentially impacted the neuronal spike responses to ensuing tactile inputs, depressing the tactile responses in some neurons and enhancing them in others. When LFP-SPWs coactivated with more distant cortical surface (ECoG)-SPWs, suggesting an involvement of these SPWs in global cortical signaling, the impact of the LFP-SPW on the neuronal tactile response could change substantially, including inverting its impact to the opposite. These cortical SPWs shared many signal fingerprint characteristics as reported for hippocampal SPWs and may be a biomarker for a particular type of state change that is possibly shared byboth hippocampus and neocortex.

Cortical sensory processing is greatly impacted by internally generated activity.

Local field potential sharp waves with diversified impact on cortical neuronal encoding of haptic input

Whereas studies of the V1 cortex have focused mainly on neural line orientation preference, color inputs are also known to have a strong presence among these neurons. Individual neurons typically respond to multiple colors and nearby neurons have different combinations of preferred color inputs. However, the computations performed by V1 neurons on such color inputs have not been extensively studied. Here we aimed to address this issue by studying how different V1 neurons encode different combinations of inputs composed of four basic colors. We quantified the decoding accuracy of individual neurons from multi-electrode array recordings, comparing multiple individual neurons located within 2 mm along the vertical axis of the V1 cortex of the anesthetized rat. We found essentially all V1 neurons to be good at decoding spatiotemporal patterns of color inputs and they did so by encoding them in different ways. Quantitative analysis showed that even adjacent neurons encoded the specific input patterns differently, suggesting a local cortical circuitry organization which tends to diversify rather than unify the neuronal responses to each given input. Using different pairs of monocolor inputs, we also found that V1 neocortical neurons had a diversified and rich color opponency across the four colors, which was somewhat surprising given the fact that rodent retina express only two different types of opsins. We propose that the processing of color inputs in V1 cortex is extensively composed of multiple independent circuitry components that reflect abstract functionalities resident in the internal cortical processing rather than the raw sensory information 

Whereas studies of the V1 cortex have focused mainly on neural line orientation preference, color inputs are also known to have a strong presence among these neurons.

Differential encoding of temporally evolving color patterns across nearby V1 neurons

Due to continuous state variations in neocortical circuits, individual somatosensory cortex (SI) neurons in vivo display a variety of intracellular responses to the exact same spatiotemporal tactile input pattern. To manipulate the internal cortical state, we here used brief electrical stimulation of the output region of the hippocampus, which preceded the delivery of specific tactile afferent input patterns to digit 2 of the anesthetized rat. We find that hippocampal output had a diversified, remarkably strong impact on the intracellular response types displayed by each neuron in the primary SI to each given tactile input pattern. Qualitatively, this impact was comparable to that previously described for cortical output, which was surprising given the widely assumed specific roles of the hippocampus, such as in cortical memory formation. The findings show that hippocampal output can profoundly impact the state-dependent interpretation of tactile inputs and hence influence perception, potentially with affective and semantic components.

Due to continuous state variations in neocortical circuits, individual somatosensory cortex (SI) neurons in vivo display a variety of intracellular responses to the exact same spatiotemporal tactile input pattern.

Hippocampal output profoundly impacts the interpretation of tactile input patterns in SI cortical neurons

The spinal cord is engaged in all forms of motor performance but its functions are far from understood. Because network connectivity defines function, we explored the connectivity of muscular, tendon, and tactile sensory inputs among a wide population of spinal interneurons in the lower cervical segments. Using low noise intracellular whole cell recordings in the decerebrated, non-anesthetized cat in vivo, we could define mono-, di-, and trisynaptic inputs as well as the weights of each input. Whereas each neuron had a highly specific input, and each indirect input could moreover be explained by inputs in other recorded neurons, we unexpectedly also found the input connectivity of the spinal interneuron population to form a continuum. Our data hence contrasts with the currently widespread notion of distinct classes of interneurons. We argue that this suggested diversified physiological connectivity, which likely requires a major component of circuitry learning, implies a more flexible functionality.

The spinal cord is engaged in all forms of motor performance but its functions are far from understood. Because network connectivity defines function, we explored the connectivity of muscular, tendon, and tactile sensory inputs among a wide population of spinal interneurons in the lower cervical segments.

Diversified physiological sensory input connectivity questions the existence of distinct classes of spinal interneurons

The neocortex has a globally encompassing network structure, which for each given input constrains the possible combinations of neuronal activations across it. Hence, its network contains solutions. But in addition, the cortex has an ever-changing multidimensional internal state, causing each given input to result in a wide range of specific neuronal activations. Here we use intracellular recordings in somatosensory cortex (SI) neurons of anesthetized rats to show that remote, subthreshold intracortical electrical perturbation can impact such constraints on the responses to a set of spatiotemporal tactile input patterns. Whereas each given input pattern normally induces a wide set of preferred response states, when combined with cortical perturbation response states that did not otherwise occur were induced and consequently made other response states less likely. The findings indicate that the physiological network structure can dynamically change as the state of any given cortical region changes, thereby enabling a rich, multifactorial, perceptual capability.

The neocortex has a globally encompassing network structure, which for each given input constrains the possible combinations of neuronal activations across it.

Remote cortical perturbation dynamically changes the network solutions to given tactile inputs in neocortical neurons

Hodgkin and Huxley's seminal neuron model describes the propagation of voltage spikes in 

 features crucial for understanding the neural code. We consider channel current fluctuations in a trisection of the Hodgkin-Huxley model, allowing an analytic-mechanistic explanation of these features and yielding consistently excellent matches with 

 recordings of cerebellar Purkinje neurons, which we use as model systems. This shows that the neuronal encoding is described conclusively by a soft-thresholding function having just three parameters.

Hodgkin and Huxley's seminal neuron model describes the propagation of voltage spikes in axons, but it cannot explain certain full-neuron features crucial for understanding the neural code. 

Channel current fluctuations conclusively explain neuronal encoding of internal potential into spike trains

The brain has a never-ending internal activity, whose spatiotemporal evolution interacts with external inputs to constrain their impact on brain activity and thereby how we perceive them. We used reproducible touch-related spatiotemporal sensory inputs and recorded intracellularly from rat (Sprague-Dawley, male) neocortical neurons to characterize this interaction. The synaptic responses, or the summed input of the networks connected to the neuron, varied greatly to repeated presentations of the same tactile input pattern delivered to the tip of digit 2. Surprisingly, however, these responses tended to sort into a set of specific time-evolving response types, unique for each neuron. Further, using a set of eight such tactile input patterns, we found each neuron to exhibit a set of specific response types for each input provided. Response types were not determined by the global cortical state, but instead likely depended on the time-varying state of the specific subnetworks connected to each neuron. The fact that some types of responses recurred indicates that the cortical network had a non-continuous landscape of solutions for these tactile inputs. Therefore, our data suggest that sensory inputs combine with the internal dynamics of the brain networks, thereby causing them to fall into one of the multiple possible perceptual attractor states. The neuron-specific instantiations of response types we observed suggest that the subnetworks connected to each neuron represent different components of those attractor states. Our results indicate that the impact of cortical internal states on external inputs is substantially more richly resolvable than previously shown.

The brain has a never-ending internal activity, whose spatiotemporal evolution interacts with external inputs to constrain their impact on brain activity and thereby how we perceive them.

Multi-structure Cortical States Deduced From Intracellular Representations of Fixed Tactile Input Patterns

How the brain represents the external world is an unresolved issue for neuroscience, which could provide fundamental insights into brain circuitry operation and solutions for artificial intelligence and robotics. The neurons of the cuneate nucleus form the first interface for the sense of touch in the brain. They were previously shown to have a highly skewed synaptic weight distribution for tactile primary afferent inputs, suggesting that their connectivity is strongly shaped by learning. Here we first characterized the intracellular dynamics and inhibitory synaptic inputs of cuneate neurons in vivo and modeled their integration of tactile sensory inputs. We then replaced the tactile inputs with input from a sensorized bionic fingertip and modeled the learning-induced representations that emerged from varied sensory experiences. The model reproduced both the intrinsic membrane dynamics and the synaptic weight distributions observed in cuneate neurons in vivo. In terms of higher level model properties, individual cuneate neurons learnt to identify specific sets of correlated sensors, which at the population level resulted in a decomposition of the sensor space into its recurring high-dimensional components. Such vector components could be applied to identify both past and novel sensory experiences and likely correspond to the fundamental haptic input features these neurons encode in vivo. In addition, we show that the cuneate learning architecture is robust to a wide range of intrinsic parameter settings due to the neuronal intrinsic dynamics. Therefore, the architecture is a potentially generic solution for forming versatile representations of the external world in different sensor systems.

How the brain represents the external world is an unresolved issue for neuroscience, which could provide fundamental insights into brain circuitry operation and solutions for artificial intelligence and robotics. 

Intracellular Dynamics in Cuneate Nucleus Neurons Support Self-Stabilizing Learning of Generalizable Tactile Representations

Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation. To obtain reproducible spatiotemporal patterns of activation of sensory afferents, we used an artificial fingertip equipped with an array of neuromorphic sensors. The artificial fingertip was used to transduce real-world haptic stimuli into spatiotemporal patterns of spikes. These spike patterns were delivered to the skin afferents of the second digit of rats via an array of stimulation electrodes. Combined with low-noise intra- and extracellular recordings from neocortical neurons 

, this approach provided a previously inaccessible high resolution analysis of the representation of tactile information in the neocortical neuronal circuitry. The results indicate high information content in individual neurons and reveal multiple novel neuronal tactile coding features such as heterogeneous and complementary spatiotemporal input selectivity also between neighboring neurons. Such neuronal heterogeneity and complementariness can potentially support a very high decoding capacity in a limited population of neurons. Our results also indicate a potential neuroprosthetic approach to communicate with the brain at a very high resolution and provide a potential novel solution for evaluating the degree or state of neurological disease in animal models.

Investigations of the mechanisms of touch perception and decoding has been hampered by difficulties in achieving invariant patterns of skin sensor activation.

Born in the intersection
of AI and Neuroscience.

IntuiCell is a Lund University spin-off with presence in Lund and Stockholm.

For three decades our founders challenged the common consensus
of one of the biggest scientific questions of our time:

How does the brain work?

Today, we apply those groundbreaking neurophysiological insights
to redesign artificial intelligence. Creating AI that is actually intelligent.

Explore our contrarian research on the mechanisms by which the
brain predicts the world.

All Publications.

Born in the intersectionof AI and Neuroscience.

IntuiCell is a Lund University spin-off with presence in Lund and Stockholm.

For three decades our founders challenged the common consensus of one of the biggest scientific questions of our time:

How does the brain work?

Today, we apply those groundbreaking neurophysiological insights to redesign artificial intelligence. Creating AI that is actually intelligent.

Explore our contrarian research on the mechanisms by which the brain predicts the world.

All Publications.

Born in the intersection
of AI and Neuroscience.

For three decades our founders challenged the common consensus
of one of the biggest scientific questions of our time:

Today, we apply those groundbreaking neurophysiological insights
to redesign artificial intelligence. Creating AI that is actually intelligent.

Explore our contrarian research on the mechanisms by which the
brain predicts the world.