Cortical and Subcortical Contributions to Short-Term Memory for Orienting Movements.
ABSTRACT: Neural activity in frontal cortical areas has been causally linked to short-term memory (STM), but whether this activity is necessary for forming, maintaining, or reading out STM remains unclear. In rats performing a memory-guided orienting task, the frontal orienting fields in cortex (FOF) are considered critical for STM maintenance, and during each trial display a monotonically increasing neural encoding for STM. Here, we transiently inactivated either the FOF or the superior colliculus and found that the resulting impairments in memory-guided orienting performance followed a monotonically decreasing time course, surprisingly opposite to the neural encoding. A dynamical attractor model in which STM relies equally on cortical and subcortical regions reconciled the encoding and inactivation data. We confirmed key predictions of the model, including a time-dependent relationship between trial difficulty and perturbability, and substantial, supralinear, impairment following simultaneous inactivation of the FOF and superior colliculus during memory maintenance.
Project description:Anatomical, stimulation, and lesion data have suggested a homology between the rat frontal orienting fields (FOF) (centered at +2 AP, ±1.3 ML mm from Bregma) and primate frontal cortices such as the frontal or supplementary eye fields. We investigated the functional role of the FOF using rats trained to perform a memory-guided orienting task, in which there was a delay period between the end of a sensory stimulus instructing orienting direction and the time of the allowed motor response. Unilateral inactivation of the FOF resulted in impaired contralateral responses. Extracellular recordings of single units revealed that 37% of FOF neurons had delay period firing rates that predicted the direction of the rats' later orienting motion. Our data provide the first electrophysiological and pharmacological evidence supporting the existence in the rat, as in the primate, of a frontal cortical area involved in the preparation and/or planning of orienting responses.
Project description:Numerous brain regions have been shown to have neural correlates of gradually accumulating evidence for decision-making, but the causal roles of these regions in decisions driven by accumulation of evidence have yet to be determined. Here, in rats performing an auditory evidence accumulation task, we inactivated the frontal orienting fields (FOF) and posterior parietal cortex (PPC), two rat cortical regions that have neural correlates of accumulating evidence and that have been proposed as central to decision-making. We used a detailed model of the decision process to analyze the effect of inactivations. Inactivation of the FOF induced substantial performance impairments that were quantitatively best described as an impairment in the output pathway of an evidence accumulator with a long integration time constant (>240 ms). In contrast, we found a minimal role for PPC in decisions guided by accumulating auditory evidence, even while finding a strong role for PPC in internally-guided decisions.
Project description:Gradual accumulation of evidence is thought to be fundamental for decision-making, and its neural correlates have been found in several brain regions. Here we develop a generalizable method to measure tuning curves that specify the relationship between neural responses and mentally accumulated evidence, and apply it to distinguish the encoding of decision variables in posterior parietal cortex and prefrontal cortex (frontal orienting fields, FOF). We recorded the firing rates of neurons in posterior parietal cortex and FOF from rats performing a perceptual decision-making task. Classical analyses uncovered correlates of accumulating evidence, similar to previous observations in primates and also similar across the two regions. However, tuning curve assays revealed that while the posterior parietal cortex encodes a graded value of the accumulating evidence, the FOF has a more categorical encoding that indicates, throughout the trial, the decision provisionally favoured by the evidence accumulated so far. Contrary to current views, this suggests that premotor activity in the frontal cortex does not have a role in the accumulation process, but instead has a more categorical function, such as transforming accumulated evidence into a discrete choice. To probe causally the role of FOF activity, we optogenetically silenced it during different time points of the trial. Consistent with a role in committing to a categorical choice at the end of the evidence accumulation process, but not consistent with a role during the accumulation itself, a behavioural effect was observed only when FOF silencing occurred at the end of the perceptual stimulus. Our results place important constraints on the circuit logic of brain regions involved in decision-making.
Project description:Deciding in which direction to move is a ubiquitous feature of animal behavior, but the neural substrates of locomotor choices are not well understood. The superior colliculus (SC) is a midbrain structure known to be important for controlling the direction of gaze, particularly when guided by visual or auditory cues, but which may play a more general role in behavior involving spatial orienting. To test this idea, we recorded and manipulated activity in the SC of freely moving rats performing an odor-guided spatial choice task. In this context, not only did a substantial majority of SC neurons encode choice direction during goal-directed locomotion, but many also predicted the upcoming choice and maintained selectivity for it after movement completion. Unilateral inactivation of SC activity profoundly altered spatial choices. These results indicate that the SC processes information necessary for spatial locomotion, suggesting a broad role for this structure in sensory-guided orienting and navigation.
Project description:The superior colliculus (SC) plays a highly conserved role in visual processing and mediates visual orienting behaviors across species, including both overt motor orienting [1, 2] and orienting of attention [3, 4]. To determine the specific circuits within the superficial superior colliculus (sSC) that drive orienting and approach behavior toward appetitive stimuli, we explored the role of three genetically defined cell types in mediating prey capture in mice. Chemogenetic inactivation of two classically defined cell types, the wide-field (WF) and narrow-field (NF) vertical neurons, revealed that they are involved in distinct aspects of prey capture. WF neurons were required for rapid prey detection and distant approach initiation, whereas NF neurons were required for accurate orienting during pursuit as well as approach initiation and continuity. In contrast, prey capture did not require parvalbumin-expressing (PV) neurons that have previously been implicated in fear responses. The visual coding and projection targets of WF and NF cells were consistent with their roles in prey detection versus pursuit, respectively. Thus, our studies link specific neural circuit connectivity and function with stimulus detection and orienting behavior, providing insight into visuomotor and attentional mechanisms mediated by superior colliculus.
Project description:Background: A better understanding of the neural mechanisms that underlie the development of fear of falling (FoF) in seniors may help to detect potential treatable factors and reduce future falls. We therefore investigate the neural correlates of FoF in older adults using 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Methods: This cohort study included 117 community-dwelling older adults. At baseline, participants were assessed for FoF, psychiatric symptoms, walking speed, global cognition and cerebral glucose metabolism with FDG-PET. The incidence of FoF in the participants who did not report FoF (N-FoF) at baseline was again ascertained 2 years later. FDG uptake was compared between the FoF and non-FoF groups. Logistic regression analyses to examine the predictors of newly developed FoF (D-FoF) using normalized regional FDG uptake were then performed. Results: At baseline, 50.4% (n = 59) of participants had FoF. The FoF group had significantly decreased glucose metabolism in the left superior frontal gyrus (supplementary motor area, SMA; BA6) compared to the non-FoF group. After 2 years, 19 out of the 58 participants in the non-FoF group developed FoF. Logistic regression analysis revealed that decreased cerebral glucose metabolism in the left SMA at the baseline was a significant predictor of the future development of FoF, independently of psychiatric symptoms and walking speed. Conclusion: In healthy older adults, hypometabolism in the left SMA, which is involved in motor planning and motor coordination, contributes to the development of FoF. Our result might help elucidate underlying mechanism of the association between deficits in motor control and FoF.
Project description:Individuals diagnosed with major depressive disorder (MDD) often ruminate about their depression and their life situations, impairing their concentration and performance on daily tasks. We examined whether rumination might be due to a deficit in the ability to expel negative information from short-term memory (STM), and fMRI was used to examine the neural structures involved in this ability. MDD and healthy control (HC) participants were tested using a directed-forgetting procedure in a short-term item recognition task. As predicted, MDD participants had more difficulty than did HCs in expelling negative, but not positive, words from STM. Overall, the neural networks involved in directed forgetting were similar for both groups, but the MDDs exhibited more spatial variability in activation in the left inferior frontal gyrus (a region critical for inhibiting irrelevant information), which may contribute to their relative inability to inhibit negative information.
Project description:Despite strong evidence to the contrary in the literature, microsaccades are overwhelmingly described as involuntary eye movements. Here we show in both human subjects and monkeys that individual microsaccades of any direction can easily be triggered: (1) on demand, based on an arbitrary instruction, (2) without any special training, (3) without visual guidance by a stimulus, and (4) in a spatially and temporally accurate manner. Subjects voluntarily generated instructed "memory-guided" microsaccades readily, and similarly to how they made normal visually-guided ones. In two monkeys, we also observed midbrain superior colliculus neurons that exhibit movement-related activity bursts exclusively for memory-guided microsaccades, but not for similarly-sized visually-guided movements. Our results demonstrate behavioral and neural evidence for voluntary control over individual microsaccades, supporting recently discovered functional contributions of individual microsaccade generation to visual performance alterations and covert visual selection, as well as observations that microsaccades optimize eye position during high acuity visually-guided behavior.
Project description:Background: The ability to strategically retrieve task-relevant information from episodic memory is thought to rely on goal-directed executive processes, and there is evidence that neural correlates of strategic retrieval are sensitive to reserves of cognitive control. The present study extended this work, exploring the role of cognitive control in the flexible orienting of strategic retrieval processes across alternating retrieval goals. Method: Pre-stimulus cues directed participants to endorse memory targets from one of two encoding contexts, with the target encoding context alternating every two trials. Items from the nontarget encoding context were rejected alongside new items. One group of participants completed a Stroop task prior to the memory test in order to deplete their reserves of cognitive control, while a second group performed a control task. Event-related potentials (ERPs) were recorded throughout the memory task, and time-locked to both pre-stimulus cues and memory probes. Results: Control participants' pre-stimulus ERPs showed sustained divergences at frontal electrode sites according to retrieval goal. This effect was evident on the first trial of each memory task, and linked with the initiation of goal-specific retrieval orientations. Control participants also showed enhanced ERP correlates of recollection (the 'left parietal effect') for correctly classified targets relative to nontargets on the second trial of each memory task, indexing strategic retrieval of task-relevant information. Both the pre-stimulus index of retrieval orientation and the target/nontarget left parietal effect were significantly attenuated in participants that completed the Stroop task. Conclusions: The reduction of pre-stimulus and stimulus-locked ERP effects following the Stroop task indicates that available reserves of cognitive control play an important role in both proactive and recollection-related aspects of strategic retrieval.
Project description:Subjective memory (SM), a self-evaluation of memory, in contrast to objective memory (OM) measured by neuropsychological testing, is less well studied in patients with epilepsy. We assessed SM before and after temporal lobectomy. The Frequency of Forgetting 10 scale (FOF-10), developed to evaluate SM in dementia, was given before and one year after temporal lobectomy. Reliability and validity for use in epilepsy were first assessed. Measures of depression (CES-D) and neuroticism (PANAS) were done before and after surgery as well as complete neuropsychological assessment of OM. Correlation analysis between FOF-10 results and all the other variables was implemented. In 48 patients the FOF-10 was reliable and valid showing high internal consistency in all items (Cronbach's alpha >0.82) and high reproducibility (p<0.01). The FOF-10 also correlated with the memory assessment clinics self rating scale (MAC-S) (p<0.01). FOF-10 scores improved or were unchanged postoperatively in 28 patients (58%) and worsened in 20 (42%). The FOF-10 did not significantly correlate with memory scores from neuropsychological testing but did correlate with perceived word finding difficulty (p<0.001) and postoperative depression (p<0.05). A reduction in number of antiepileptic drugs (AEDs) after surgery distinguished those with improved postoperative SM. No correlation was found between SM and neuroticism, side of surgery or number of seizures. The FOF-10 is a brief and reliable measure of subjective memory in patients with epilepsy. Perceived memory impairment reflects more emotional state, language problems and quantity of AEDs than actual defects in memory function. These results would potentially be useful in presurgical counselling and management of memory issues after temporal lobe surgery.