Attention and Working Memory Deficits in OCD Checking Behaviour

The evidence for memory impairments in obsessive-compulsive disorder (OCD) is mixed (Hermans et al., 2008). For example, findings are inconsistent, whether OCD have poorer memory capacity compared to neuro-typical controls, or whether verbal memory is less affected than visuospatial memory (Muller and Roberts, 2005b). Some evidence (Greisberg and McKay, 2003) pointed to a more subtle interaction with executive dysfunction leading to impaired memory performance. In a review of 58 experiments Harkin and Kessler (2011) argued that rather than classifying memory deficits in OCD by modality, for example verbal vs visuospatial, it is more instructive to classify the experiments by their task demand in terms of Executive function (E), Binding complexity (B) and memory Load (L). Using the EBL classification system in combination with the Baddeley model of working memory (Baddeley 2000) with an episodic buffer, performance in working memory tasks could be better explained in terms of task demands of executive function. For example, working memory (WM) performance of subclinical OCD checkers can be impaired if presented with irrelevant but misleading information during the retention period. The aim of this thesis was firstly, using magnetoencephalography (MEG) and a paradigm designed to provoke executive dysfunction in OCD participants, to measure the neural correlates of deficient working memory processing. Secondly, to use MEG to investigate the neural correlates of attentional bias and executive dysfunction in OCD checking behaviour when engaged in an endogenous attention (Stroop) task. Lastly, using transcranial magnetic stimulation (TMS) to target task relevant brain areas in attempt to affect beneficially the task performance of OCD checker participants engaged in an exogenous attention (Inhibition of Return) task, an endogenous attention (Stroop) task and in the working memory task. Using ecologically valid stimuli that resonate with the checkers’ OCD related concerns, the neuroimaging data revealed different patterns of activity, comparing subclinical OCD checkers with neuro-typical controls. These patterns are consistent with the stimuli provoking deficient executive function in the subclinical checkers. The brain activity recorded was consistent with repeated memory checking and poor suppression of irrelevant stimuli. Efforts to remediate executive dysfunction with TMS were only partially successful. In accord with the EBL classification system, the ecologically valid threat stimuli in combination with the WM and Stroop tasks were successful in exploiting executive dysfunction in subclinical checkers in domains of working memory and endogenous attention. Neural correlates of the impaired processing were measured successfully using MEG

Rhythm makes the world go round:an MEG-TMS study on the role of right TPJ theta oscillations in embodied perspective taking

While some aspects of social processing are shared between humans and other species, some aspects are not. The former seems to apply to merely tracking another's visual perspective in the world (i.e., what a conspecific can or cannot perceive), while the latter applies to perspective taking in form of mentally “embodying” another's viewpoint. Our previous behavioural research had indicated that only perspective taking, but not tracking, relies on simulating a body schema rotation into another's viewpoint. In the current study we employed Magnetoencephalography (MEG) and revealed that this mechanism of mental body schema rotation is primarily linked to theta oscillations in a wider brain network of body-schema, somatosensory and motor-related areas, with the right posterior temporo-parietal junction (pTPJ) at its core. The latter was reflected by a convergence of theta oscillatory power in right pTPJ obtained by overlapping the separately localised effects of rotation demands (angular disparity effect), cognitive embodiment (posture congruence effect), and basic body schema involvement (posture relevance effect) during perspective taking in contrast to perspective tracking. In a subsequent experiment we interfered with right pTPJ processing using dual pulse Transcranial Magnetic Stimulation (dpTMS) and observed a significant reduction of embodied processing. We conclude that right TPJ is the crucial network hub for transforming the embodied self into another's viewpoint, body and/or mind, thus, substantiating how conflicting representations between self and other may be resolved and potentially highlighting the embodied origins of high-level social cognition in general

Dysregulated oscillatory connectivity in the visual system in autism spectrum disorder

Autism spectrum disorder is increasingly associated with atypical perceptual and sensory symptoms. Here we explore the hypothesis that aberrant sensory processing in autism spectrum disorder could be linked to atypical intra- (local) and interregional (global) brain connectivity. To elucidate oscillatory dynamics and connectivity in the visual domain we used magnetoencephalography and a simple visual grating paradigm with a group of 18 adolescent autistic participants and 18 typically developing control subjects. Both groups showed similar increases in gamma (40-80 Hz) and decreases in alpha (8-13 Hz) frequency power in occipital cortex. However, systematic group differences emerged when analysing intra- and interregional connectivity in detail. First, directed connectivity was estimated using non-parametric Granger causality between visual areas V1 and V4. Feedforward V1-to-V4 connectivity, mediated by gamma oscillations, was equivalent between autism spectrum disorder and control groups, but importantly, feedback V4-to-V1 connectivity, mediated by alpha (8-13 Hz) oscillations, was significantly reduced in the autism spectrum disorder group. This reduction was positively correlated with autistic quotient scores, consistent with an atypical visual hierarchy in autism, characterized by reduced top-down modulation of visual input via alpha-band oscillations. Second, at the local level in V1, coupling of alpha-phase to gamma amplitude (alpha-gamma phase amplitude coupling) was reduced in the autism spectrum disorder group. This implies dysregulated local visual processing, with gamma oscillations decoupled from patterns of wider alpha-band phase synchrony (i.e. reduced phase amplitude coupling), possibly due to an excitation-inhibition imbalance. More generally, these results are in agreement with predictive coding accounts of neurotypical perception and indicate that visual processes in autism are less modulated by contextual feedback information

THETA-rhythm makes the world go round:dissociative effects of TMS theta versus alpha entrainment of right pTPJ on embodied perspective transformations

Being able to imagine another person's experience and perspective of the world is a crucial human ability and recent reports suggest that humans "embody" another's viewpoint by mentally rotating their own body representation into the other's orientation. Our recent Magnetoencephalography (MEG) data further confirmed this notion of embodied perspective transformations and pinpointed the right posterior temporo-parietal junction (pTPJ) as the crucial hub in a distributed network oscillating at theta frequency (3-7 Hz). In a subsequent transcranial magnetic stimulation (TMS) experiment we interfered with right pTPJ processing and observed a modulation of the embodied aspects of perspective transformations. While these results corroborated the role of right pTPJ, the notion of theta oscillations being the crucial neural code remained a correlational observation based on our MEG data. In the current study we therefore set out to confirm the importance of theta oscillations directly by means of TMS entrainment. We compared entrainment of right pTPJ at 6 Hz vs. 10 Hz and confirmed that only 6 Hz entrainment facilitated embodied perspective transformations (at 160° angular disparity) while 10 Hz slowed it down. The reverse was true at low angular disparity (60° between egocentric and target perspective) where a perspective transformation was not strictly necessary. Our results further corroborate right pTPJ involvement in embodied perspective transformations and highlight theta oscillations as a crucial neural code

Mild traumatic brain injury impairs the coordination of intrinsic and motor-related neural dynamics

Mild traumatic brain injury (mTBI) poses a considerable burden on healthcare systems. Whilst most patients recover quickly, a significant number suffer from sequelae that are not accompanied by measurable structural damage. Understanding the neural underpinnings of these debilitating effects and developing a means to detect injury, would address an important unmet clinical need. It could inform interventions and help predict prognosis. Magnetoencephalography (MEG) affords excellent sensitivity in probing neural function and presents significant promise for assessing mTBI, with abnormal neural oscillations being a potential specific biomarker. However, growing evidence suggests that neural dynamics are (at least in part) driven by transient, pan-spectral bursting and in this paper, we employ this model to investigate mTBI. We applied a Hidden Markov Model to MEG data recorded during resting state and a motor task and show that previous findings of diminished intrinsic beta amplitude in individuals with mTBI are largely due to the reduced beta band spectral content of bursts, and that diminished beta connectivity results from a loss in the temporal coincidence of burst states. In a motor task, mTBI results in diminished burst amplitude, altered modulation of burst probability during movement, and a loss in connectivity in motor networks. These results suggest that, mechanistically, mTBI disrupts the structural framework underlying neural synchrony, which impairs network function. Whilst the damage may be too subtle for structural imaging to see, the functional consequences are detectable and persist after injury. Our work shows that mTBI impairs the dynamic coordination of neural network activity and proposes a potent new method for understanding mTBI

Spike firing and IPSPs in layer V pyramidal neurons during beta oscillations in rat primary motor cortex (M1) in vitro

Beta frequency oscillations (10-35 Hz) in motor regions of cerebral cortex play an important role in stabilising and suppressing unwanted movements, and become intensified during the pathological akinesia of Parkinson's Disease. We have used a cortical slice preparation of rat brain, combined with concurrent intracellular and field recordings from the primary motor cortex (M1), to explore the cellular basis of the persistent beta frequency (27-30 Hz) oscillations manifest in local field potentials (LFP) in layers II and V of M1 produced by continuous perfusion of kainic acid (100 nM) and carbachol (5 µM). Spontaneous depolarizing GABA-ergic IPSPs in layer V cells, intracellularly dialyzed with KCl and IEM1460 (to block glutamatergic EPSCs), were recorded at -80 mV. IPSPs showed a highly significant (P< 0.01) beta frequency component, which was highly significantly coherent with both the Layer II and V LFP oscillation (which were in antiphase to each other). Both IPSPs and the LFP beta oscillations were abolished by the GABAA antagonist bicuculline. Layer V cells at rest fired spontaneous action potentials at sub-beta frequencies (mean of 7.1+1.2 Hz; n = 27) which were phase-locked to the layer V LFP beta oscillation, preceding the peak of the LFP beta oscillation by some 20 ms. We propose that M1 beta oscillations, in common with other oscillations in other brain regions, can arise from synchronous hyperpolarization of pyramidal cells driven by synaptic inputs from a GABA-ergic interneuronal network (or networks) entrained by recurrent excitation derived from pyramidal cells. This mechanism plays an important role in both the physiology and pathophysiology of control of voluntary movement generation

Layer V pyramidal cells action potentials are coherent with and phase-locked to LFPs.

<p>(A) membrane potential (Vm) recording (without DC current injection), with spontaneous action potentials (spikes), together with concurrent (unfiltered) records of LFPs. (B), left panels: Power spectral densities in LFPs are significant (99% above red lines) in beta range, but for Vm are close to spontaneous spike firing rate. Right panels: coherence between Vm and layers V and II LFP is seen in beta range, and harmonics thereof (same recordings as A). (C), upper panel: spike-triggered averages of LFPs from layer V (red) and II (blue), time-locked to each of 84 spikes occurring over a 10 s period (at t = 0 on x-axis). Spikes precede by 2–3 ms the trough, and peak, of the layer V and II oscillations respectively, both of which display a period of around 40 ms. Taken from same cell as in A and B. Lower panel: pooled, normalised, layer V LFP spike-triggered average data (mean ± SEM) from all the 10 recordings that showed significant coherence in the 15–40 Hz range between layer V LFP and Vm (during spontaneous firing). The layer V LFP peak follows the spike by approximately 20 ms. (D), upper panels: Records of (Vm) recorded at rest, during spontaneous spike firing, and of layer V and II LFPs, in absence (left) and presence (right) of bicuculline (10 µM). While spikes persist in bicuculline, LFP oscillations are abolished. Lower panels: significant beta range coherence between Vm and both layer V and II LFP (left) is abolished in bicuculline (right). Different preparation from panels A–C. (E), data pooled from all recordings showing the distribution of frequencies at which significant coherence between LFPs in layer II and layer V, and spikes, was detected, grouped into 3 frequency bands (mean ± SEM in red, n in parentheses).</p

Basic intracellular properties of recorded cells used in this study.

<p>¹ 4 cells were quiescent; ² at ½ maximal amplitude; ³ in range −55 to −75 mV.</p

Properties of a layer V pyramidal cell, demonstrated with sharp microelectrode intracellular recording.

<p>(A), recording of resting membrane potential, showing spontaneous action potential firing at 18.1 Hz. Right panel: a single action potential on an expanded time scale, with dashed cursor lines indicating method of measuring amplitude (between top and bottom horizontal cursors: 65.3 mV) and duration at ½ maximal amplitude (between vertical cursors: 1.10 ms). (B), superimposed records of membrane potential showing response to successive 200 ms hyperpolarizing pulses of current (not shown) injected in multiples of 0.2 nA from baseline of zero (ie. resting potential). (C), voltage-current plot derived from a series of current pulses injected in multiples of 0.1 nA into the same cell [including those in (B)] in which steady-state voltage attained near end of current pulse [dashed vertical line in (B)] is plotted. Slope of line (best fit in range −55 to −75 mV) yields input resistance value of 45 MΩ. All records from the same cell.</p

IPSPs in layer V cells are strongly coherent with LFPs in the beta range.

<p>(A) Concurrent LFPs from layers V and II, and intracellularly recorded membrane potential (Vm) from a cell in layer V. Oscillations and IPSPs (at −80 mV, optimised for IPSPs) are blocked following application of GABA_A receptor antagonist bicuculline (right panel). (B) Power spectral densities (PSD) of LFPs from layers V and II, and of Vm (with IPSPs), showing 99% significance levels (above red lines) at beta frequencies, and harmonics thereof, which (right panels) are blocked by bicuculline. Vertical dashed lines indicate 27 Hz for reference. Same recordings as (A). (C), upper panel: cross-correlograms of LFPs from layers II (blue) and V (red) with Vm from same recordings as in (A) and (B). Lower panel: normalised, cross-correlated data (means+SEM) between Vm (displaying IPSPs) and LFPs in layer V (red) and layer II (blue) pooled from all 20 recordings showing significant IPSP-LFP coherence in 15–40 Hz range. The IPSP leads layer V peak (red dashed line) by 7.2 ms and layer II peak (blue dashed line) by 20.5 ms. (D) Left column: coherence between each of layer II and layer V LFP (top row), layer II LFP and IPSPs (middle row), and layer V LFP and IPSPs (bottom row) in each case demonstrates single significant (>99%) peaks at beta frequencies, and harmonics thereof, which is abolished by bicuculline (right panels). Same recordings as A, B and C. (E) and (F), data pooled from all recordings within 3 frequency ranges (demarked by vertical dashed lines, with mean ± SEM in red, n in parentheses) showing (E) the distribution of the single largest significant (>99%) power spectrum peaks for Vm (optimised for IPSPs), and (F) peak frequencies of coherence between LII, LV, and Vm (IPSPs).</p