Executive function deficits and glutamatergic protein alterations in a progressive 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse model of Parkinson's disease

Changes in executive function are at the root of most cognitive problems associated with Parkinson's disease. Because dopaminergic treatment does not necessarily alleviate deficits in executive function, it has been hypothesized that dysfunction of neurotransmitters/systems other than dopamine (DA) may be associated with this decrease in cognitive function. We have reported decreases in motor function and dopaminergic/glutamatergic biomarkers in a progressive 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) Parkinson's mouse model. Assessment of executive function and dopaminergic/glutamatergic biomarkers within the limbic circuit has not previously been explored in our model. Our results show progressive behavioral decline in a cued response task (a rodent model for frontal cortex cognitive function) with increasing weekly doses of MPTP. Although within the dorsolateral (DL) striatum mice that had been given MPTP showed a 63% and 83% loss of tyrosine hydroxylase and dopamine transporter expression, respectively, there were no changes in the nucleus accumbens or medial prefrontal cortex (mPFC). Furthermore, dopamine‐1 receptor and vesicular glutamate transporter (VGLUT)?1 expression increased in the mPFC following DA loss. There were significant MPTP‐induced decreases and increases in VGLUT‐1 and VGLUT‐2 expression, respectively, within the DL striatum. We propose that the behavioral decline following MPTP treatment may be associated with a change not only in cortical–cortical (VGLUT‐1) glutamate function but also in striatal DA and glutamate (VGLUT‐1/VGLUT‐2) input. © 2015 Wiley Periodicals, Inc.     

Human perceptual decision making: Disentangling task onset and stimulus onset

The left dorsolateral prefrontal cortex (ldlPFC) has been highlighted as a key actor in human perceptual decision‐making (PDM): It is theorized to support decision‐formation independently of stimulus type or motor response. PDM studies however generally confound stimulus onset and task onset: when the to‐be‐recognized stimulus is presented, subjects know that a stimulus is shown and can set up processing resources—even when they do not know which stimulus is shown. We hypothesized that the ldlPFC might be involved in task preparation rather than decision‐formation. To test this, we asked participants to report whether sequences of noisy images contained a face or a house within an experimental design that decorrelates stimulus and task onset. Decision‐related processes should yield a sustained response during the task, whereas preparation‐related areas should yield transient responses at its beginning. The results show that the brain activation pattern at task onset is strikingly similar to that observed in previous PDM studies. In particular, they contradict the idea that ldlPFC forms an abstract decision and suggest instead that its activation reflects preparation for the upcoming task. We further investigated the role of the fusiform face areas and parahippocampal place areas which are thought to be face and house detectors, respectively, that feed their signals to higher level decision areas. The response patterns within these areas suggest that this interpretation is unlikely and that the decisions about the presence of a face or a house in a noisy image might instead already be computed within these areas without requiring higher‐order areas. Hum Brain Mapp 35:3170–3187, 2014. © 2013 Wiley Periodicals, Inc.     

Probabilistic classification learning with corrective feedback is associated with in vivo striatal dopamine release in the ventral striatum,while learning without feedback is not

The basal ganglia (BG) mediate certain types of procedural learning, such as probabilistic classification learning on the ‘weather prediction task’ (WPT). Patients with Parkinson's disease (PD), who have BG dysfunction, are impaired at WPT‐learning, but it remains unclear what component of the WPT is important for learning to occur. We tested the hypothesis that learning through processing of corrective feedback is the essential component and is associated with release of striatal dopamine. We employed two WPT paradigms, either involving learning via processing of corrective feedback (FB) or in a paired associate manner (PA). To test the prediction that learning on the FB but not PA paradigm would be associated with dopamine release in the striatum, we used serial ¹¹C‐raclopride (RAC) positron emission tomography (PET), to investigate striatal dopamine release during FB and PA WPT‐learning in healthy individuals. Two groups, FB, (n = 7) and PA (n = 8), underwent RAC PET twice, once while performing the WPT and once during a control task. Based on a region‐of‐interest approach, striatal RAC‐binding potentials reduced by 13–17% in the right ventral striatum when performing the FB compared to control task, indicating release of synaptic dopamine. In contrast, right ventral striatal RAC binding non‐significantly increased by 9% during the PA task. While differences between the FB and PA versions of the WPT in effort and decision‐making is also relevant, we conclude striatal dopamine is released during FB‐based WPT‐learning, implicating the striatum and its dopamine connections in mediating learning with FB. Hum Brain Mapp 35:5106–5115, 2014. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Depressive mood modulates the anterior lateral CA1 and DG/CA3 during a pattern separation task in cognitively intact individuals: A functional MRI study

Although patients with major depressive disorder typically have a reduced hippocampal volume, particularly in the cornu ammonis 1 (CA1), animal studies suggest that depressive mood is related to the dentate gyrus (DG). In this study, our objective was to clarify which hippocampal subregions are functionally associated with depressive mood in humans. We conducted a functional MRI (fMRI) study on 27 cognitively intact volunteers. Subjects performed a modified version of a delayed matching‐to‐sample task in an MRI scanner to investigate pattern separation‐related activity during each phase of encoding, delay, and retrieval. In each trial, subjects learned a pair of sample cues. Functional MR images were acquired at a high spatial resolution, focusing on the hippocampus. Subjects also completed the Beck Depression Inventory (BDI), a questionnaire about depressive mood. Depending on the similarity between sample cues, activity in the DG/CA3 and medial CA1 in the anterior hippocampus changed only during encoding. Furthermore, the DG/CA3 region was more active during successful encoding trials compared to false trials. Activity in the DG/CA3 and lateral CA1 was negatively correlated with BDI scores. These results suggest that the DG/CA3 is the core region for pattern separation during the encoding phase and interacts with the medial CA1, depending on the similarity of the stimuli, to achieve effective encoding. Impaired activity in the DG/CA3, as well as in the lateral CA1, was found to be associated with depressive symptoms, even at a subclinical level. © 2013 Wiley Periodicals, Inc.     

Functional connectivity‐based parcellation of the human sensorimotor cortex

Task‐based functional magnetic resonance imaging (fMRI) has been successfully employed to obtain somatotopic maps of the human sensorimotor cortex. Here, we showed through direct comparison that a similar functional map can be obtained, independently of a task, by performing a connectivity‐based parcellation of the sensorimotor cortex based on resting‐state fMRI. Cortex corresponding to two adjacent Brodmann areas (BA 3 and BA 4) was selected as the sensorimotor area. Parcellation was obtained along a medial–lateral axis, which was confirmed to be somatotopic (corresponding roughly to an upper, middle and lower limb, respectively) by comparing it with maps obtained using motoric task‐based fMRI in the same participants. Interestingly, the resting‐state parcellation map demonstrated higher correspondence to the task‐based divisions after individuals performed the motor task. Using the resting‐state fMRI data, we also observed higher functional correlations between the centrally located hand region and the other two regions, than between the foot and tongue. The functional relevance of these somatosensory parcellation results indicates the feasibility of a wide range of potential applications to brain mapping.     

Evoked phase synchronization between adjacent high-density electrodes in human scalp EEG: duration and time course related to behavior.

OBJECTIVE: Data from a previous event-related potential (ERP) study in visual-perceptual grouping [Nikolaev AR, van Leeuwen C. Flexibility in spatial and non-spatial feature grouping: an event-related potentials study. Brain Res Cogn Brain Res 2004;22:13-25] were re-analyzed to identify event-related dynamics of phase-synchronization. METHODS: In 20 Hz activity, uniform spreading of phase synchronization in closely spaced (approximately 2 cm) scalp electrodes appears and disappears spontaneously. The lengths of synchronized activity intervals and how they vary as a function of stimulus presentation were compared between task and control conditions. RESULTS: Synchronization reached a maximum in the task condition about 180 ms post-stimulus onset, coinciding with the peak N180 ERP marking the deployment of task-specific attention. Synchronized intervals were longer in the task than in the control condition. Long (above 80 ms) intervals occurred at a stable rate before and just after stimulus onset, but steeply decreased 200-400 ms afterwards. CONCLUSIONS: Perceptual tasks lead to longer synchronized intervals in early visual areas. Attention deployment resets the ongoing synchronization. Event-related activity, besides low-frequency ERP, consists of high-frequency short and long synchronized intervals corresponding to evoked bursts and ongoing oscillations, respectively. SIGNIFICANCE: High-density scalp recorded EEG revealed synchronization dynamics in a local, early visual area of cortex that can be interpreted as modulation of spontaneous ongoing task-related processes by attention.     

A specific attentional bias in panic disorder?

According to cognitive theories, panic patients are assumed to have an attentional bias toward bodily sensations. To date, there is only some indirect evidence of such a bias measured by an emotional Stroop task. Moreover, the content and disorder specificity of this bias is rather unclear. The aim of this study was to investigate the specificity of attentional bias in patients with panic disorder (PD). Patients with PD (n=32), patients with mixed anxiety disorders (n=25), and a healthy control group (n=26) performed an emotional Stroop task with three word types: panic threat, general threat, and neutral. There were no differences on reaction times between the different groups, or on the different word types. Despite the generally accepted existence of attentional biases in anxiety disorders, we found no evidence of a specific attentional bias in patients with PD.     

The effect of non-visual working memory load on top-down modulation of visual processing

While a core function of the working memory (WM) system is the active maintenance of behaviorally relevant sensory representations, it is also critical that distracting stimuli are appropriately ignored. We used functional magnetic resonance imaging to examine the role of domain-general WM resources in the top-down attentional modulation of task-relevant and irrelevant visual representations. In our dual-task paradigm, each trial began with the auditory presentation of six random (high load) or sequentially ordered (low load) digits. Next, two relevant visual stimuli (e.g., faces), presented amongst two temporally interspersed visual distractors (e.g., scenes), were to be encoded and maintained across a 7-s delay interval, after which memory for the relevant images and digits was probed. When taxed by high load digit maintenance, participants exhibited impaired performance on the visual WM task and a selective failure to attenuate the neural processing of task-irrelevant scene stimuli. The over-processing of distractor scenes under high load was indexed by elevated encoding activity in a scene-selective region-of-interest relative to low load and passive viewing control conditions, as well as by improved long-term recognition memory for these items. In contrast, the load manipulation did not affect participants’ ability to upregulate activity in this region when scenes were task-relevant. These results highlight the critical role of domain-general WM resources in the goal-directed regulation of distractor processing. Moreover, the consequences of increased WM load in young adults closely resemble the effects of cognitive aging on distractor filtering [Gazzaley, A., Cooney, J. W., Rissman, J., & D’Esposito, M. (2005). Top-down suppression deficit underlies working memory impairment in normal aging. Nature Neuroscience 8, 1298-1300], suggesting the possibility of a common underlying mechanism.     

Neural correlates of lower limbs proprioception: An fMRI study of foot position matching

Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right‐handed and right‐footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching.     

Oxyhemoglobin changes in the prefrontal cortex in response to cognitive tasks: a systematic review

Purpose of the study: the aim of this study was to synthesize PFC fNIRS outcomes on the effects of cognitive tasks compared to resting/baseline tasks in healthy adults from studies utilizing a pre/post design.

Material and methods: original research studies were searched from seven databases (MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, PEDro and PubMed). Subsequently, two independent reviewers screened the titles and abstracts followed by full-text reviews to assess the studies' eligibility.

Results: eleven studies met the inclusion criteria and had data abstracted and quality assessed. Methodology varied considerably and yet cognitive tasks resulted in the ΔO₂Hb increasing in 8 of the 11 and ΔHHb decreasing in 8 of 8 studies that reported this outcome. The cognitive tasks from 10 of the 11 studies were classified as “Working Memory” and “Verbal Fluency Tasks”.

Conclusions: although, the data comparison was challenging provided the heterogeneity in methodology, the results across studies were similar.