Paul J. Fitzgerald

Receptive Field Properties of the Macaque Second Somatosensory Cortex: Evidence for Multiple Functional Representations

The detailed functional organization of the macaque second somatosensory cortex (SII) is not well understood. Here we report the results of a study of the functional organization of the SII hand region that combines microelectrode mapping using hand-held stimuli with single-unit recordings using a motorized, computer-controlled tactile oriented bar. The data indicate that the SII hand region extends ∼10 mm in the anteroposterior (AP) dimension, primarily within the upper bank of the lateral sulcus. Furthermore, we find evidence that this region consists of multiple functional fields, with a central field containing neurons that are driven well by cutaneous stimuli, flanked by an anterior field and a posterior field that each contain neurons that are driven well by proprioceptive stimuli and less well by cutaneous stimuli. The anterior field extends ∼4-5 mm AP, the central field extends ∼3-4 mm, and the posterior field extends ∼3 mm. Data from the motorized stimulator indicate that neurons in the central field are more responsive to oriented bars, more frequently exhibit orientation tuning, and have larger receptive fields than neurons in the anterior and posterior fields. We speculate that the three putative fields play different functional roles in tactile perception; the anterior and posterior fields process information that involves both proprioceptive and cutaneous input such as sensorimotor integration or stereognosis, whereas the central field processes primarily cutaneous information.

Receptive Field Properties of the Macaque Second Somatosensory Cortex: Representation of Orientation on Different Finger Pads

Orientation tuning has been studied extensively in the visual system, but little is known about it in the somatosensory system. Here we investigate tuning in the second somatosensory (SII) region using a motorized stimulator that presented a small oriented bar to the 12 finger pads of digits 2–5 (D2–D5) of the macaque monkey. A subset (23%; n = 218) of the 928 SII region neurons [the same 928 neurons studied by Fitzgerald et al. (2004, 2006)] exhibited tuning, and most of these were tuned on one or two finger pads. All eight 22.5° separated orientations were represented as the preferred orientation of multiple neurons, although not necessarily in equal numbers. A measure of bandwidth indicated that tuning in the SII region is sharp and is similar to the tuning observed in visual cortical areas. In addition, two-dimensional Gaussians that were fit to the tuning curves had very high r2 values, indicating that most tuning curves are both unimodal and symmetrical with respect to their preferred orientation. Most tuned neurons had additional untuned pads, although the responsiveness of these pads tended to be less than the responsiveness of tuned pads. Neurons with multiple tuned pads tended to have similar preferred orientations on their tuned pads, which can be interpreted as evidence for integration of information across fingers or as a form of positional invariance. Finally, comparison of the tuning properties showed that there are small but significant differences between the posterior, central, and anterior fields of the SII region.

Receptive Field (RF) Properties of the Macaque Second Somatosensory Cortex: RF Size, Shape, and Somatotopic Organization

The detailed structure of multidigit receptive fields (RFs) in somatosensory cortical areas such as the SII region has not been investigated previously using systematically controlled stimuli. Recently (Fitzgerald et al., 2004), we showed that the SII region comprises three adjoining fields: posterior, central, and anterior. Here we characterize the RF structures of the 928 neurons that were reported in that study using a motorized oriented bar that was indented into the 12 finger pads of digits 2–5. Most (81%) of the neurons were responsive to the oriented bar stimuli, and 81% of those neurons had RFs that spanned multiple digits. Furthermore, the RFs varied greatly in size, shape, and complexity. Some RFs contained only excitatory finger pads, some contained only inhibitory pads, and some contained both types of pads. A subset of the neurons (23%) showed orientation tuning within one or more pads. The RFs spread across different digits more than within individual digits, and the responsive finger pads for a given neuron tended to cluster together within the hand. Distal and lateral finger pads were better represented than proximal and medial finger pads. Furthermore, neurons in the posterior, central, and anterior SII region fields contained different proportions of RF types. These results collectively indicate that most SII region neurons are selective for different stimulus forms either within single finger pads or across multiple pads. We hypothesize that these RFs represent the kernels underlying the representation of tactile shape.

Representation of orientation in the somatosensory system

In this paper we discuss how orientation is represented and transformed in the somatosensory system. Information about stimulus orientation plays an important role in sensory processing. In touch it provides critical information about how stimuli are positioned on the hand, which is important for grasping and lifting objects. It also provides important information about tactile shape. Psychophysical studies show that humans have a high capacity to discriminate the orientation of shapes and gratings indented into the finger pad. Further, these studies demonstrate that orientation discrimination is a reliable and stable method for assessing tactile spatial acuity. Neurophysiological studies suggest that orientation information is processed by the slowly adapting type 1 (SA1) afferent system. While orientation is poorly represented in the responses of individual afferent fibers, it is well represented in the population response properties of peripheral SA1 afferents and in the responses of central neurons in the primary (S1) and secondary (S2) somatosensory cortex. In S2, neurons with orientation selective and orientation non-selective responses tend to have large receptive fields that span multiple pads on multiple digits. Neurons in S2 that are orientation selective have similar tuning functions on different finger pads. These neurons may provide position-invariant responses or may be responsible for integrating features across hands, which is important for haptic object recognition of large shapes from the hand. Neurophysiological studies in trained animals show that the responses of about 85% of the neurons in S2 are affected by the animals focus of attention and that attention to the orientation of a bar modifies both the mean firing rate (i.e. gain) of neurons encoding orientation information and the degree of synchronous firing between pairs of neurons.

Is norepinephrine an etiological factor in some types of cancer

I examine evidence that the signaling molecule norepinephrine (NE) is an etiological factor in some types of cancer. In support of this hypothesis, I cite the following 7 lines of evidence: (i) rodent studies of tumorigenesis in the context of NE manipulation; (ii) human studies of tricyclic antidepressant use and cancer rate; (iii) existence of pheochromocytoma, a cancer of the adrenal glands; (iv) cancer rate in families with individuals who have bipolar disorder; (v) hypertension and cancer risk; (vi) excessive body weight and cancer risk; and (vii) psychological stressors and cancer risk. Three aspects of the bodys NE system are consistent with it playing an etiological role in various types of cancer: (i) NE circulates in the blood and can thereby access organ systems throughout the body, in addition to direct peripheral release by the sympathetic nervous system and being released within the brain; (ii) many of the bodys organs possess NE receptors on the outer surface of at least some of their cells; (iii) by binding to its extracellular receptors, NE affects intracellular second messenger systems that could influence carcinogenesis. Most importantly, use of existing pharmaceutical drugs that either lower the level of NE (such as clonidine) or block NE receptors may lower the probability of an individual developing cancer, and this hypothesis could be tested immediately by an epidemiologist through examination of existing medical records.

Analogous intermediate shape coding in vision and touch.

We recognize, understand, and interact with objects through both vision and touch. Conceivably, these two sensory systems encode object shape in similar ways, which could facilitate cross-modal communication. To test this idea, we studied single neurons in macaque monkey intermediate visual (area V4) and somatosensory (area SII) cortex, using matched shape stimuli. We found similar patterns of shape sensitivity characterized by tuning for curvature direction. These parallel tuning patterns imply analogous shape coding mechanisms in intermediate visual and somatosensory cortex.

A neurochemical yin and yang: does serotonin activate and norepinephrine deactivate the prefrontal cortex?

IntroductionThe prefrontal cortex (PFC) receives serotonergic input from the dorsal raphe nucleus of the brainstem, as well as noradrenergic input from another brainstem nucleus, the locus coeruleus. A large number of studies have shown that these two neurotransmitter systems, and drugs that affect them, modulate the functional properties of the PFC in both humans and animal models.ResultsHere I examine the hypothesis that serotonin (5-HT) plays a general role in activating the PFC, whereas norepinephrine (NE) plays a general role in deactivating this brain region. In this manner, the two neurotransmitter systems may have opposing effects on PFC-influenced behavior. To assess this hypothesis, three primary lines of evidence are examined comprising the effects of 5-HT and NE on impulsivity, cognitive flexibility, and working memory.DiscussionWhile all of the existing data do not unequivocally support the activation/deactivation hypothesis, there is a large body of support for it.

Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

There is growing evidence that the neurotransmitter norepinephrine (NE) and its sister molecule epinephrine (EPI) (adrenaline) affect some types of cancer. Several recent epidemiological studies have shown that chronic use of beta blocking drugs (which antagonize NE/EPI receptors) results in lower recurrence, progression, or mortality of breast cancer and malignant melanoma. Preclinical studies have shown that manipulation of the levels or receptors of NE and EPI with drugs affects experimentally induced cancers. Psychological stress may play an etiological role in some cases of cancer (which has been shown epidemiologically), and this could be partly mediated by NE and EPI released by the sympathetic nervous system as part of the body’s “fight or flight” response. A less well-appreciated phenomenon is that the genetic tone of NE/EPI may play a role in cancer. NE and EPI may affect cancer by interacting with molecular pathways already implicated in abnormal cellular replication, such as the P38/MAPK pathway, or via oxidative stress. NE/EPI-based drugs other than beta blockers also may prevent or treat various types of cancer, as may cholinesterase inhibitors that inhibit the sympathetic nervous system, which could be tested epidemiologically.

Receptive Field Properties of the Macaque Second Somatosensory Cortex: Nonlinear Mechanisms Underlying the Representation of Orientation Within a Finger Pad

We investigate the position invariant receptive field properties of neurons in the macaque second somatosensory (SII) cortical region. Previously we reported that many SII region neurons show orientation tuning in the center of multiple finger pads of the hand and further that the tuning is similar on different pads, which can be interpreted as position invariance. Here we study the receptive field properties of a single finger pad for a subset (n = 61) of those 928 neurons, using a motorized oriented bar that we positioned at multiple locations across the pad. We calculate both vector fields and linear receptive fields of the finger pad to characterize the receptive field properties that give rise to the tuning, and we perform an additional regression analysis to quantify linearity, invariance, or both in individual neurons. We show that orientation tuning of SII region neurons is based on a variety of mechanisms. For some neurons, the tuning is explained by simple excitatory regions, simple inhibitory regions, or some combination of these structures. However, a large fraction of the neurons (n = 20 of 61, 33%) show position invariance that is not explained well by their linear receptive fields. Finding invariance within a finger pad, coupled with the previous result of similar tuning on different pads, indicates that some SII region neurons may exhibit similar tuning throughout large regions of the hand. We hypothesize that invariant neurons play an important role in tactile form recognition.

Is elevated norepinephrine an etiological factor in some cases of epilepsy

It is well established that the neurotransmitter norepinephrine (NE) has anticonvulsant properties. However, NE may also have proconvulsant properties under some conditions, both in animal epilepsy models and in humans. This paper examines the hypothesis that this neurotransmitter has proconvulsant properties, where much of the pharmaceutical evidence comes from rodent models. In assessing the elevated NE epilepsy hypothesis, the following seven lines of evidence are examined that include studies of: (1) antidepressants that raise the level of NE; (2) clonidine and other alpha 2 adrenergic agonist drugs that lower the level of NE; (3) prazosin and other drugs that affect alpha adrenoceptors; (4) propranolol and other drugs that affect beta adrenoceptors; (5) pheochromocytoma, which is a rare cancer of the adrenal glands that can boost NE levels; (6) comorbidity of epilepsy with bipolar disorder, hypertension, and obesity, where all four conditions may involve elevated NE; and (7) psychological stress, which is associated with increased release of NE. The body of evidence supporting the NE proconvulsant hypothesis is consistent with the notion that elevated, endogenous noradrenergic transmission is an etiological factor in some cases of epilepsy.