Biology subjects

Ford, T. C.

Publications and source records attributed to Ford, T. C..

7 recordsLinked to original sources

bioRxiv2025

Examining excitation-inhibition modulation during social processing using functional Magnetic Resonance Spectroscopy

An imbalance of brain excitation-inhibition has been implicated in social communication function across neurodevelopmental and psychiatric conditions. Recent advances in functional magnetic resonance spectroscopy (fMRS) allow non-invasive measurement of dynamic changes in excitation-inhibition neurometabolites (glutamate and GABA), revealing potential links with cognitive processes. This study used functional MRS (fMRS) to investigate whether socially-laden stimuli modulate excitatory or inhibitory neurometabolites, and whether modulation relates to social function. Forty neurotypical adults (18-40 years; 20 male) underwent 3T MRI, with fMRS data acquired using a J-difference edited MRS sequence. GABA+macromolecules (GABA+) and glutamate+glutamine (Glx) were quantified in a right social brain region (superior temporal/temporoparietal junction [STG/TPJ]) and a control region (occipital cortex). Participants viewed a fixation cross (traditional resting state MRS; 5 min), silent video clips of social interaction, and a flashing checkerboard as control stimulus (5 min each; counterbalanced). The Social Responsiveness Scale (SRS-2) assessed social function. Block analysis showed no significant differences between resting and functional (social or checkerboard) GABA+ or Glx levels (ps<.05), although Bayesian analyses showed evidence for decreased STG/TPJ GABA+ and increased occipital cortex Glx for checkerboard compared to rest. Higher SRS-2 scores were associated with higher resting STG/TPJ Glx but not GABA+, and functional metabolite levels were not associated with SRS-2 scores (ps>.1). Sliding time- window analyses showed significantly reduced Glx in social brain during social stimulation. Despite sound data collection and analysis techniques, shifts in Glx and GABA+ following social stimuli were minimal. Future research could utilise more challenging social stimuli and examine alternate social brain regions.

neuroscience↗

bioRxiv2024

EEG During Dynamic Facial Emotion Processing Reveals Neural Activity Patterns Associated with Autistic Traits in Children

Altered brain connectivity and atypical neural oscillations have been observed in autism, yet their relationship with autistic traits in non-clinical populations remains underexplored. Here, we employ electroencephalography (EEG) to examine functional connectivity, oscillatory power, and broadband aperiodic activity during a dynamic facial emotion processing (FEP) task in 101 typically developing children aged 4-12 years. We investigate associations between these electrophysiological measures of brain dynamics and autistic traits as assessed by the Social Responsiveness Scale, 2nd Edition (SRS-2). Our results revealed that increased FEP-related connectivity across theta (4-7 Hz) and beta (13-30 Hz) frequencies correlated positively with higher SRS-2 scores, predominantly in right-lateralized (theta) and bilateral (beta) cortical networks. Additionally, a steeper 1/f-like aperiodic slope (spectral exponent) across fronto-central electrodes was associated with higher SRS-2 scores. Greater aperiodic-adjusted theta and alpha oscillatory power further correlated with both higher SRS-2 scores and steeper aperiodic slopes. These findings underscore important links between FEP-related brain dynamics and autistic traits in typically developing children. Future work could extend these findings to assess these EEG-derived markers as potential mechanisms underlying behavioural difficulties in autism.

neuroscience↗

bioRxiv2023

Resting state aperiodic slope predicts Research Domain Criteria Social Processes in young typically developing adults

The aperiodic exponent of the electrophysiological signal has been utilised to demonstrate differences in brain excitation-inhibition in ageing, cognition, and neuro- and psycho-pathology. Furthermore, excitation-inhibition imbalance has been associated with social communication difficulties in clinical and non-clinical cohorts. No work to date, however, has explored the association between aperiodic activity and social communication difficulties. A total of 40 neurotypical young adults aged 18-24 (24 female; age mean = 21.6, SD = 1.9) each underwent 5 minutes of eyes open and eyes closed resting state electroencephalography using a 64-channel HydroCel Geodesic Sensor Net. Participants also completed Research Domain Criteria social processes measures: Social Responsiveness Scale, Reading the Mind in the Eyes task, and Penn Emotional Recognition Task. Sex differences in aperiodic exponent and offset were observed, with larger exponent and greater offset observed in males, suggestive of greater inhibitory tone. Whole-brain, as well as left and right social brain, aperiodic exponent were moderately correlated with Social Responsiveness Scale Social Communication Index, but not Reading the Mind in the Eyes or Penn Emotional Recognition tasks. However, the correlations between aperiodic exponent and Social Responsiveness Scale Social Communication Index did not survive multiple comparisons correction, and regression models demonstrated that neither aperiodic exponent or offset were significantly predictive of social processes outcomes. These preliminary data provide some evidence that increased aperiodic activity may be associated with social communication difficulties, however, larger samples are needed to validate these initial findings.

neuroscience↗

bioRxiv2023

GABA and Glutamate response to social processing; a functional MRS study

Several studies have suggested that atypical social processing in multiple psychiatric conditions (e.g., autism) is associated with differences in excitation and inhibition, through changes in the levels of glutamate and GABA levels. While associations between baseline metabolite levels and behaviours can be insightful, assessing the neurometabolic response of GABA and Glutamate during social processing may inform altered neurochemical function in more depth. Thus far, there have been no attempts to determine whether changes in metabolite levels are detectable using functional magnetic resonance spectroscopy (fMRS) during social processing in a control population. We performed MEGA-PRESS edited fMRS to measure the dynamic response of GABA and glutamate in the superior temporal sulcus (STS) and visual cortex (V1) while viewing social stimuli, using a design that allows for analysis in both block and event-related approaches. Sliding window analyses were used to investigate GABA and glutamate dynamics at higher temporal resolution. A small decrease in GABA levels was observed during social stimulus presentation in V1, but no change was observed in STS. Conversely, non-social stimulus elicited changes in both GABA and glutamate levels in both regions. We discuss the feasibility of using fMRS analysis approaches to assess changes in metabolite response during social processing.

neuroscience↗

bioRxiv2022

Functional MRS studies of GABA and Glutamate/Glx: a systematic review and meta-analysis

Functional magnetic resonance spectroscopy (fMRS) can be used to investigate neurometabolic responses to external stimuli in-vivo, but findings are inconsistent. We performed a systematic review and meta-analysis on fMRS studies of the primary neurotransmitters Glutamate (Glu), Glx (Glutamate + Glutamine), and GABA. Data were extracted, grouped by metabolite, stimulus domain, and brain region, and analysed by determining standardized effect sizes. The quality of individual studies was rated. When results were analysed by metabolite type small to moderate effect sizes of 0.29-0.47 (p < 0.05) were observed for changes in Glu and Glx regardless of stimulus domain and brain region, but no significant effects were observed for GABA. Further analysis suggests that Glu, Glx and GABA responses differ by stimulus domain or task and vary depending on the time course of stimulation and data acquisition. Here, we establish effect sizes and directionality of GABA, Glu and Glx response in fMRS. This work highlights the importance of standardised reporting and minimal best practice for fMRS research.

neuroscience↗

bioRxiv2021

The relationship between affective visual mismatch negativity to interpersonal difficulties across autism and schizotypal traits

ObjectiveSensory deficits are a feature of autism and schizophrenia, as well as the upper end of their non-clinical spectra. The mismatch negativity (MMN), an index of pre-attentive auditory processing, is particularly sensitive in detecting such deficits; however, little is known about the relationship between the visual MMN (vMMN) to emotional faces and autism and schizophrenia spectrum symptom domains. MethodsWe probed the vMMN to happy, sad, and neutral faces in 77 young adults (18-40 years, 41 female), and evaluated their degree of autism and schizophrenia spectrum traits using the Autism Spectrum Quotient (AQ) and Schizotypal Personality Questionnaire (SPQ). Results: The vMMN to happy faces was significantly larger than the vMMNs to sad and neutral faces (p > 0.05). The vMMN to happy faces was associated with interpersonal difficulties as indexed by AQ Communication and Attention to Detail subscales, and SPQ Interpersonal Features (p < 0.05, uncorrected), such that a larger vMMN was associated with more interpersonal difficulties. ConclusionsPre-attentive processing of positive affect might be more specific to the interpersonal features associated with autism and schizophrenia. SignificanceThese findings add valuable insights into the growing body of literature investigating symptom-specific neurobiological markers of autism and schizophrenia spectrum conditions. Highlights- The visual Mismatch Negativity (vMMN) is larger in response to happy compared to sad or neutral facial expressions - The vMMN to happy facial expressions is specifically associated with more social communication difficulties - vMMN to positive affect may be a neural mechanism associated with social communication difficulties in autism and schizophrenia

neuroscience↗

bioRxiv2019

Cortical excitation-inhibition ratio mediates the effect of pre-attentive auditory processing deficits on interpersonal difficulties

Several lines of evidence identify aberrant excitatory-inhibitory neural processes across autism and schizophrenia spectrum disorders, particularly within the psychosocial domain. Such neural processes include increased excitatory glutamate and reduced inhibitory GABA concentrations, which may affect auditory pre-attentive processing as indexed by the mismatch negativity (MMN); thus, an excitation-inhibition imbalance might lead to aberrant MMN, which might in turn drive the relationship between the MMN and psychosocial difficulties. This research has the potential to enhance the neurochemical understanding of the relationship between electrophysiology (MMN) and behavioural/clinical measures (psychosocial difficulties).\n\nThirty-eight adults (18 male, 18-40 years) completed the Schizotypal Personality Questionnaire (SPQ) and Autism-Spectrum Quotient (AQ). Glutamate and GABA concentrations in bilateral superior temporal cortex (STC) were quantified using proton magnetic resonance spectroscopy (1H-MRS) while auditory MMN to a duration deviant was measured with magnetoencephalography. Spearman correlations probed the relationships between STC glutamate/GABA ratios, MMN amplitude and latency, and AQ and SPQ dimensions. Mediation effects of glutamate/GABA ratios on the relationship between MMN and AQ-SPQ dimensions were probed using causal mediation analysis.\n\nOnly SPQ-interpersonal and AQ-communication were significantly correlated with right hemisphere glutamate/GABA ratios and MMN latency (ps<.05), which were themselves correlated (p=.038). Two mediation models were investigated, with right MMN latency as predictor and SPQ-interpersonal and AQ-communication as outcome variables. Right STC glutamate/GABA ratios significantly mediated the relationship between MMN latency and SPQ-interpersonal scores ({beta}=86.6, p=.033), but only partially mediated the relationship between MMN latency and AQ-communication scores ({beta}=21.0, p=.093).\n\nThese findings support the growing body of literature pointing toward an excitation-inhibition imbalance that is central to psychosocial functioning across multi-dimensional spectrum disorders, such as autism and schizophrenia, and provides neurochemical indicators of the processes that underlie psychosocial dysfunction.

neuroscience↗