Spatiotemporal dynamics of cortical somatosensory network in typically developing children.

Sense of touch is essential for our interactions with external objects and fine control of hand actions. Despite extensive research on human somatosensory processing, it is still elusive how involved brain regions interact as a dynamic network in processing tactile information. Few studies probed temporal dynamics of somatosensory information flow and reported inconsistent results. Here, we examined cortical somatosensory processing through magnetic source imaging and cortico-cortical coupling dynamics. We recorded magnetoencephalography signals from typically developing children during unilateral pneumatic stimulation. Neural activities underlying somatosensory evoked fields were mapped with dynamic statistical parametric mapping, assessed with spatiotemporal activation analysis, and modeled by Granger causality. Unilateral pneumatic stimulation evoked prominent and consistent activations in the contralateral primary and secondary somatosensory areas but weaker and less consistent activations in the ipsilateral primary and secondary somatosensory areas. Activations in the contralateral primary motor cortex and supramarginal gyrus were also consistently observed. Spatiotemporal activation and Granger causality analysis revealed initial serial information flow from contralateral primary to supramarginal gyrus, contralateral primary motor cortex, and contralateral secondary and later dynamic and parallel information flows between the consistently activated contralateral cortical areas. Our study reveals the spatiotemporal dynamics of cortical somatosensory processing in the normal developing brain.

Case Report: Laser Ablation Guided by State of the Art Source Imaging Ends an Adolescent's 16-Year Quest for Seizure Freedom.

Epilepsy surgery is the most effective therapeutic approach for children with drug resistant epilepsy (DRE). Recent advances in neurosurgery, such as the Laser Interstitial Thermal Therapy (LITT), improved the safety and non-invasiveness of this method. Electric and magnetic source imaging (ESI/MSI) plays critical role in the delineation of the epileptogenic focus during the presurgical evaluation of children with DRE. Yet, they are currently underutilized even in tertiary epilepsy centers. Here, we present a case of an adolescent who suffered from DRE for 16 years and underwent surgery at Cook Children's Medical Center (CCMC). The patient was previously evaluated in a level 4 epilepsy center and treated with multiple antiseizure medications for several years. Presurgical evaluation at CCMC included long-term video electroencephalography (EEG), magnetoencephalography (MEG) with simultaneous conventional EEG (19 channels) and high-density EEG (256 channels) in two consecutive sessions, MRI, and fluorodeoxyglucose - positron emission tomography (FDG-PET). Video long-term EEG captured nine focal-onset clinical seizures with a maximal evolution over the right frontal/frontal midline areas. MRI was initially interpreted as non-lesional. FDG-PET revealed a small region of hypometabolism at the anterior right superior temporal gyrus. ESI and MSI performed with dipole clustering showed a tight cluster of dipoles in the right anterior insula. The patient underwent intracranial EEG which indicated the right anterior insular as seizure onset zone. Eventually LITT rendered the patient seizure free (Engel 1; 12 months after surgery). Retrospective analysis of ESI and MSI clustered dipoles found a mean distance of dipoles from the ablated volume ranging from 10 to 25 mm. Our findings highlight the importance of recent technological advances in the presurgical evaluation and surgical treatment of children with DRE, and the underutilization of epilepsy surgery in children with DRE.

Frustrative nonreward and cannabinoid receptors: Chronic (but not acute) WIN 55,212-2 treatment increased resistance to change in two reward downshift tasks.

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects. In Experiment 1, chronic WIN (7 daily injections, 10 mg/kg, ip) accelerated the recovery of consummatory behavior after a 32-to-4% sucrose downshift relative to vehicle controls. In addition, chronic WIN eliminated the preference for an unshifted lever when the other lever was subject to a 12-to-2 pellet downshift in free-choice trials, but only in animals with previous experience with a sucrose downshift. In Experiment 2, acute WIN (1 mg/kg, ip) reduced consummatory behavior, but did not affect recovery from a 32-to-4% sucrose downshift. The antagonist SR 141716A (3 mg/kg, ip) also failed to interfere with recovery after the sucrose downshift. In Experiment 3, acute WIN administration (1 mg/kg, ip) did not affect free-choice behavior after a pellet downshift, although it reduced lever pressing and increased magazine entries relative to vehicle controls. The effects of chronic WIN on frustrative nonreward were not reducible to acute effects of the drug. Chronic WIN treatment in rats, like chronic marijuana use in humans, seems to increase resistance to the effects of frustrative nonreward.

Reinforcing properties of alcohol in rats: Progressive ratio licking performance reinforced with 66% alcohol.

Rodents are generally reluctant to consume high concentrations of alcohol. However, few experiments have reported the behavior of rats when they are given access to high alcohol concentrations. Four experiments with food-deprived Wistar rats were designed to determine whether 66% alcohol could be used as a positive reinforcer for operant responses. In Experiment 1, animals learned to lick an empty sipper to gain access to 66% alcohol in a second tube; licking extinguished after it if provided a only access to water (operant licking task, OL). Experiment 2 used the OL task combined with a progressive ratio (PR) schedule in a within-subject design with the order of alcohol concentrations counterbalanced across subjects. The breakpoint (the last completed ratio in the PR schedule) was higher for 10% and 66% alcohol concentrations than for water. In Experiment 3, animals trained in the same PR task gained access to water, 10%, or 66% alcohol in a between-subject design. Breakpoints were higher for 66% alcohol than for water, but not for 10% alcohol relative to water. Experiment 4 tested the effects of the orexin-1 receptor antagonist SB-334,867 on licking reinforced with access to 66% alcohol in the PR task. The antagonist reduced the breakpoint at 1- and 5-mg/kg doses, but not at 10 mg/kg. These results suggest that 66% alcohol can be used to reinforce operant behavior. Although the effects were modest, they were reliable. The estimated amount of alcohol consumed in the OL task suggests that these reinforcing effects were not dependent on the pharmacological effects of 66% alcohol, but could perhaps reflect a sensation-seeking effect.

Frustrative nonreward: Chemogenetic inactivation of the central amygdala abolishes the effect of reward downshift without affecting alcohol intake.

The role of the central amygdala (CeA) in the adjustment to a 32-to-2% sucrose downshift in the consummatory successive negative contrast (cSNC) task and in a free-choice 10% alcohol-water preference task (PT) was studied using chemogenetic inactivation. cSNC is a model of frustrative nonreward that enhances alcohol consumption. In Experiment 1, sessions 1-10 involved 5-min access to 32% sucrose and sessions 11-12 involved access to 2% sucrose. Vehicle or clozapine N-oxide (CNO; 1 or 3 mg/kg, ip), used later to activate the inhibitory designer receptor, was administered 30 min before sessions 11-12. There was no evidence that CNO affected consummatory behavior after the sucrose downshift. In Experiment 2, all animals received an infusion of the inhibitory designer receptor hM4D(Gi) into the CeA. After recovery, animals received access to either 32% or 2% sucrose on sessions 1-10, followed by 2% sucrose on sessions 11-12. Immediately after each 5-min sucrose session, animals received a 2-bottle, 1-h PT with 10% alcohol and water. CNO (3 mg/kg, ip) or vehicle was administered 30 min before sessions 11-12. CeA inactivation prior to sucrose downshift eliminated the cSNC effect, which was observed in vehicle controls. However, there was no evidence that CeA inactivation affected preference for 10% alcohol over water. These results support the hypothesis that CeA activity is critical for cSNC effect, an outcome consistent with the view that the amygdala plays a central role in frustrative nonreward.

Reward shifts in forced-choice and free-choice autoshaping with rats.

Successive negative contrast (SNC) involves a disruption of behavior when the paired reward is unexpectedly reduced from a large to a small amount, relative to a control always receiving the small amount. Five experiments with rats explored SNC in the Pavlovian autoshaping procedure in which a retractable lever is paired with the delivery of food pellets. In Experiment 1, a 12-to-2 pellet downshift either early in training (after 3 sessions) or late in training (after 20 sessions) yielded no significant evidence of SNC either in terms of lever pressing or goal entries. Experiment 2 showed that presession feeding (another form of reward devaluation) suppressed lever pressing in nonreinforced tests early in training. However, no statistical evidence of lever pressing suppression was found late in training. Presession feeding also suppressed lever pressing late in training if the test session included reinforcements. Experiment 3, using reward downshift, showed that adding a nontarget lever produced no statistical evidence of response suppression to the target lever during the downshift. Lever pressing to the target lever increased and goal entries tended to decrease after a 12-to-2 pellet downshift. Using a within-subject design and two target levers with distinct reward values (Experiment 4), reward downshift produced evidence of lever pressing enhancement in single-lever trials, but lever pressing suppression and a switch in preference to the unshifted lever in nonreinforced free-choice trials. Experiment 5 replicated these within-subject SNC effects, but found only modest evidence for a successive positive contrast effect in free-choice behavior. These results suggest that autoshaping in rats may induce response invigoration in forced-choice situations, but response suppression in free-choice situations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Augmented voluntary consumption of ethanol induced by reward downshift increases locomotor activity of male Wistar rats in the elevated plus maze.

Rats exposed to unexpected reward loss increase voluntary oral consumption of ethanol. Such consumption has been assumed to attenuate loss-induced negative affect (called emotional self-medication). To test this assumption, food-deprived male Wistar rats were exposed to 10 sessions of access to 32% sucrose followed by 5 sessions of access to 4% sucrose (reward downshift). A two-bottle preference test was initiated immediately after each consummatory session to assess ethanol intake. The experimental group received access to 2% ethanol and water, whereas the control group received access to two water bottles. On sessions 11, 12, and 15, immediately after the preference test, animals were tested in the elevated plus maze (EPM) for signs of anxiety. Sucrose consumption was reduced after the 32-to-4% sucrose downshift on sessions 11 and 12, but behavior recovered by session 15. Consummatory suppression was followed by increased ethanol intake in the preference test after sessions 11 and 12, but intake was reduced to preshift levels by session 15; no changes were observed in water controls. Finally, general activity (closed-arm entries and total arm entries) in the EPM increased in the ethanol group on session 12, but not on session 15, relative to water controls. The increase in ethanol consumption induced by reward downshift had measurable effects on activity as assessed in the EPM. These results show that voluntary oral 2% ethanol consumption after reward downshift can affect subsequent behavior, but fall short of providing unambiguous evidence that such ethanol consumption reduces negative affect.

Dorsomedial striatum lesions affect adjustment to reward uncertainty, but not to reward devaluation or omission.

The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons.

Complex effects of reward upshift on consummatory behavior.

Exposing rats to an upshift from a small reward to a larger reward sometimes yields evidence of consummatory successive positive contrast (cSPC), an effect that could be a suitable animal model of positive emotion. However, cSPC is an unreliable effect. Ten experiments explored the effects of an upshift in sucrose or saccharin concentration on consummatory behavior under several conditions. There was occasional evidence of cSPC, but mostly a combination of increased consummatory behavior relative to preshift reward concentrations and a reduced behavioral level relative to unshifted controls. Such a pattern is consistent with processes causing opposite changes on behavior. Reward upshift may induce processes that suppress behavior, such as taste neophobia (induced by an intense sucrose taste) and generalization decrement (induced by novelty in reward conditions after the upshift). An experiment tested the role of such novelty-related effects by preexposing animals to either the upshift concentration (12% sucrose) or water during three days before the start of the experiment. Sucrose-preexposed animals drank significantly more than water-preexposed animals during the upshift, but just as much as unshifted controls (i.e., no evidence of cSPC). These results suggest that cSPC may be difficult to obtain reliably because reward upshift induces opposing processes. However, they also seriously question the ontological status of cSPC.