Robert S. Ross

Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting.

Both norepinephrine and acetylcholine have been shown to be critically involved in mediating attention but there remains debate about whether they serve similar or unique functions. Much of what is known about the role of these neurochemicals in cognition is based on manipulations done at the level of the cell body but these findings are difficult to reconcile with data regarding the unique contribution of cortical subregions, e.g. the dorsolateral prefrontal cortex, to attention. In the current study, we directly compared the effects of noradrenergic and cholinergic deafferentation of the rat medial prefrontal cortex, the homologue of primate dorsolateral prefrontal cortex, using an intradimensional/extradimensional attentional set shifting task, a task previously shown to be able to dissociate the function of the primate dorsolateral prefrontal cortex from orbitofrontal cortex. We found that noradrenergic, but not cholinergic, deafferentation produces specific impairments in the ability to shift attentional set. We also clarified the nature of the attentional deficits by assessing the ability of rats to disregard irrelevant stimuli. Noradrenergic lesions did not alter the ability of rats to ignore irrelevant stimuli, suggesting that the attentional deficit results from an overly focused attentional state that retards learning that a new stimulus dimension predicts reward.

Dynamics of Hippocampal and Cortical Activation during Consolidation of a Nonspatial Memory

Observations of temporally graded retrograde amnesia after hippocampal damage suggest that the hippocampal region plays a critical, time-limited role in memory consolidation. However, these observations do not indicate where permanent memory is stored, nor do they clarify whether the hippocampus normally remains involved in a nonessential way. Evidence from multiple neural imaging studies indicate the time-limited role of the hippocampus and suggest that the anterior cingulate cortex is a critical storage site of different types of long-term memory. However, each of the previous studies examined spatial memory, leaving open the question of whether different cortical areas support long-term memory for other types of material. We characterized the course of involvement of cortical and hippocampal areas in animals trained in an explicitly nonspatial task. First, we confirmed previous findings that hippocampal damage produces temporally graded retrograde amnesia for the social transmission of a food preference (STFP) within our experimental protocol. Damage to the hippocampal region 1 d, but not 21 d, after training impaired subsequent recall of STFP. Then, we characterized the anatomical patterns of activation of the immediate early gene c-fos during retrieval of STFP immediately and 1, 2, and 21 d after training. The ventral subiculum was activated during retrieval shortly after learning, but the level of activation declined at successive times. In contrast, olfactory recipient regions including piriform, entorhinal, and orbitofrontal cortex showed the opposite pattern, increasingly greater activation in successively later retrieval tests. These findings support the view that different cortical networks support long-term memory for different types of information.

Memory retrieval of smoking-related images induce greater insula activation as revealed by an fMRI-based delayed matching to sample task.

Nicotine dependence is a chronic and difficult to treat disorder. While environmental stimuli associated with smoking precipitate craving and relapse, it is unknown whether smoking cues are cognitively processed differently than neutral stimuli. To evaluate working memory differences between smoking‐related and neutral stimuli, we conducted a delay‐match‐to‐sample (DMS) task concurrently with functional magnetic resonance imaging (fMRI) in nicotine‐dependent participants. The DMS task evaluates brain activation during the encoding, maintenance and retrieval phases of working memory. Smoking images induced significantly more subjective craving, and greater midline cortical activation during encoding in comparison to neutral stimuli that were similar in content yet lacked a smoking component. The insula, which is involved in maintaining nicotine dependence, was active during the successful retrieval of previously viewed smoking versus neutral images. In contrast, neutral images required more prefrontal cortex‐mediated active maintenance during the maintenance period. These findings indicate that distinct brain regions are involved in the different phases of working memory for smoking‐related versus neutral images. Importantly, the results implicate the insula in the retrieval of smoking‐related stimuli, which is relevant given the insulas emerging role in addiction.

Functional connections between optic flow areas and navigationally responsive brain regions during goal-directed navigation

Recent computational models suggest that visual input from optic flow provides information about egocentric (navigator-centered) motion and influences firing patterns in spatially tuned cells during navigation. Computationally, self-motion cues can be extracted from optic flow during navigation. Despite the importance of optic flow to navigation, a functional link between brain regions sensitive to optic flow and brain regions important for navigation has not been established in either humans or animals. Here, we used a beta-series correlation methodology coupled with two fMRI tasks to establish this functional link during goal-directed navigation in humans. Functionally defined optic flow sensitive cortical areas V3A, V6, and hMT+ were used as seed regions. fMRI data was collected during a navigation task in which participants updated position and orientation based on self-motion cues to successfully navigate to an encoded goal location. The results demonstrate that goal-directed navigation requiring updating of position and orientation in the first person perspective involves a cooperative interaction between optic flow sensitive regions V3A, V6, and hMT+ and the hippocampus, retrosplenial cortex, posterior parietal cortex, and medial prefrontal cortex. These functional connections suggest a dynamic interaction between these systems to support goal-directed navigation.

Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson’s Disease

OBJECTIVESnCognitive impairment is common in Parkinsons disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants.nnnMETHODSnWe investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains.nnnRESULTSnPD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinsons disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling.nnnCONCLUSIONSnSuccessful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinsons disease.

Genetic variation in the serotonin transporter gene influences ERP old/new effects during recognition memory

Recognition memory is defined as the ability to recognize a previously encountered stimulus and has been associated with spatially and temporally distinct event-related potentials (ERPs). Allelic variations of the serotonin transporter gene (SLC6A4) have recently been shown to impact memory performance. Common variants of the serotonin transporter-linked polymorphic region (5HTTLPR) of the SLC6A4 gene result in long (l) and short (s) allelic variants with carriers of the s allele having lowered transcriptional efficiency. Thus, the current study examines the effects polymorphisms of the SLC6A4 gene have on performance and ERP amplitudes commonly associated with recognition memory. Electroencephalogram (EEG), genetic, and behavioral data were collected from sixty participants as they performed an item and source memory recognition task. In both tasks, participants studied and encoded 200 words, which were then mixed with 200 new words during retrieval. Participants were monitored with EEG during the retrieval portion of each memory task. EEG electrodes were grouped into four ROIs, left anterior superior, right anterior superior, left posterior superior, and right posterior superior. ERP mean amplitudes during hits in the item and source memory task were compared to correctly recognizing new items (correct rejections). Results show that s-carriers have decreased mean hit amplitudes in both the right anterior superior ROI 1000-1500ms post stimulus during the source memory task and the left anterior superior ROI 300-500ms post stimulus during the item memory task. These results suggest that individual differences due to genetic variation of the serotonin transporter gene influences recognition memory.

Individual differences in EEG correlates of recognition memory due to DAT polymorphisms

Although previous research suggests that genetic variation in dopaminergic genes may affect recognition memory, the role dopamine transporter expression may have on the behavioral and EEG correlates of recognition memory has not been well established.

Predictability matters: role of the hippocampus and prefrontal cortex in disambiguation of overlapping sequences

Previous research has demonstrated that areas in the medial temporal lobe and prefrontal cortex (PFC) show increased activation during retrieval of overlapping sequences. In this study, we designed a task in which degree of overlap varied between conditions in order to parse out the contributions of hippocampal and prefrontal subregions as overlap between associations increased. In the task, participants learned sequential associations consisting of a picture frame, a face within the picture frame, and an outdoor scene. The control condition consisted of a single frame-face-scene sequence. In the low overlap condition, each frame was paired with two faces and two scenes. In the high overlap condition, each frame was paired with four faces and four scenes. In all conditions the correct scene was chosen among four possible scenes and was dependent on the frame and face that preceded the choice point. One day after training, participants were tested on the retrieval of learned sequences during fMRI scanning. Results showed that the middle and posterior hippocampus (HC) was active at times when participants acquired information that increased predictability of the correct response in the overlapping sequences. Activation of dorsolateral PFC occurred at time points when the participant was able to ascertain which set of sequences the correct response belonged to. The ventrolateral PFC was active when inhibition was required, either of irrelevant stimuli or incorrect responses. These results indicate that areas of lateral PFC work in concert with the HC to disambiguate between overlapping sequences and that sequence predictability is key to when specific brain regions become active.

MAO-A Phenotype Effects Response Sensitivity and the Parietal Old/New Effect during Recognition Memory

A critical problem for developing personalized treatment plans for cognitive disruptions is the lack of understanding how individual differences influence cognition. Recognition memory is one cognitive ability that varies from person to person and that variation may be related to different genetic phenotypes. One gene that may impact recognition memory is the monoamine oxidase A gene (MAO-A), which influences the transcription rate of MAO-A. Examination of how MAO-A phenotypes impact behavioral and event-related potentials (ERPs) correlates of recognition memory may help explain individual differences in recognition memory performance. Therefore, the current study uses electroencephalography (EEG) in combination with genetic phenotyping of the MAO-A gene to determine how well-characterized ERP components of recognition memory, the early frontal old/new effect, left parietal old/new effect, late frontal old/new effect, and the late posterior negativity (LPN) are impacted by MAO-A phenotype during item and source memory. Our results show that individuals with the MAO-A phenotype leading to increased transcription have lower response sensitivity during both item and source memory. Additionally, during item memory the left parietal old/new effect is not present due to increased ERP amplitude for correct rejections. The results suggest that MAO-A phenotype changes EEG correlates of recognition memory and influences how well individuals differentiate between old and new items.