Sensory stimuli arrive in a continuous stream. By learning statistical regularities in the sequence of stimuli, the brain can predict future stimuli (Xu et al. 2012;Gavornik and Bear 2014; Maniscalco et al. 2018; J. Fiser and Aslin 2002). Such learning requires associating immediate sensory information with the memory of recently encountered stimuli (Ostojic and Fusi 2013;Kiyonaga et al. 2017). However, new sensory information can also interfere with short-term memories (Parthasarathy et al. 2017). How the brain prevents such interference is unknown. Here, we show that sensory representations rotate in neural space over time, to form an independent memory representation, thus reducing interference with future sensory inputs. We used an implicit learning paradigm in mice to study how statistical regularities in a sequence of stimuli are learned and represented in primary auditory cortex. Mice experienced both common sequences of stimuli (e.g. ABCD) and uncommon sequences (e.g. XYCD). Over four days of learning, the neural population representation of commonly associated stimuli (e.g. A and C) converged. This facilitated the prediction of upcoming stimuli, but also led unexpected sensory inputs to overwrite the sensory representation of previous stimuli (postdiction). Surprisingly, we found the memory of previous stimuli persisted in a second, orthogonal dimension. Unsupervised clustering of functional cell types revealed that the emergence of this second memory dimension is supported by two separate types of neurons; a 'stable' population that maintained its selectivity throughout the sequence and a 'switching' population that dynamically inverted its selectivity. This combination of sustained and dynamic representations produces a rotation of the encoding dimension in the neural population. This rotational dynamic may be a general principle, by which the cortex protects memories of prior events from interference by incoming stimuli.

à These authors contributed equally to this work.Carpal tunnel syndrome is the most common entrapment neuropathy, affecting the median nerve at the wrist. Acupuncture is a minimally-invasive and conservative therapeutic option, and while rooted in a complex practice ritual, acupuncture overlaps significantly with many conventional peripherally-focused neuromodulatory therapies. However, the neurophysiological mechanisms by which acupuncture impacts accepted subjective/psychological and objective/physiological outcomes are not well understood. Eligible patients (n = 80, 65 female, age: 49.3 AE 8.6 years) were enrolled and randomized into three intervention arms: (i) verum electro-acupuncture 'local' to the more affected hand; (ii) verum electro-acupuncture at 'distal' body sites, near the ankle contralesional to the more affected hand; and (iii) local sham electro-acupuncture using non-penetrating placebo needles. Acupuncture therapy was provided for 16 sessions over 8 weeks. Boston Carpal Tunnel Syndrome Questionnaire assessed pain and paraesthesia symptoms at baseline, following therapy and at 3-month follow-up. Nerve conduction studies assessing median nerve sensory latency and brain imaging data were acquired at baseline and following therapy. Functional magnetic resonance imaging assessed somatotopy in the primary somatosensory cortex using vibrotactile stimulation over three digits (2, 3 and 5). While all three acupuncture interventions reduced symptom severity, verum (local and distal) acupuncture was superior to sham in producing improvements in neurophysiological outcomes, both local to the wrist (i.e. median sensory nerve conduction latency) and in the brain (i.e. digit 2/3 cortical separation distance). Moreover, greater improvement in second/third interdigit cortical separation distance following verum acupuncture predicted sustained improvements in symptom severity at 3-month follow-up. We further explored potential differential mechanisms of local versus distal acupuncture using diffusion tensor imaging of white matter microstructure adjacent to the primary somatosensory cortex. Compared to healthy adults (n = 34, 28 female, 49.7 AE 9.9 years old), patients with carpal tunnel syndrome demonstrated increased fractional anisotropy in several regions and, for these regions we found that improvement in median nerve latency was associated with reduction of fractional anisotropy near (i) contralesional hand area following verum, but not sham, acupuncture; (ii) ipsilesional hand area following local, but not distal or sham, acupuncture; and (iii) ipsilesional leg area following distal, but not local or sham, acupuncture. As these primary somatosensory cortex subregions are distinctly targeted by local versus distal acupuncture electrostimulation, acupuncture at local versus distal sites may improve median nerve function at the wrist by somatotopically distinct neuroplasticity in the primary somatosensory cortex following therapy. Our study further suggests that improvements in primary somatosensory cortex ...

The linkage between brain response to acupuncture and subsequent analgesia remains poorly understood. Our aim was to evaluate this linkage in chronic pain patients with carpal tunnel syndrome (CTS). Brain response to electroacupuncture (EA) was evaluated with functional MRI. Subjects were randomized to 3 groups: (1) EA applied at local acupoints on the affected wrist (PC-7 to TW-5), (2) EA at distal acupoints (contralateral ankle, SP-6 to LV-4), and (3) sham EA at nonacupoint locations on the affected wrist. Symptom ratings were evaluated prior to and following the scan. Subjects in the local and distal groups reported reduced pain. Verum EA produced greater reduction of paresthesia compared to sham. Compared to sham EA, local EA produced greater activation in insula and S2 and greater deactivation in ipsilateral S1, while distal EA produced greater activation in S2 and deactivation in posterior cingulate cortex. Brain response to distal EA in prefrontal cortex (PFC) and brain response to verum EA in S1, SMA, and PFC were correlated with pain reduction following stimulation. Thus, while greater activation to verum acupuncture in these regions may predict subsequent analgesia, PFC activation may specifically mediate reduced pain when stimulating distal acupoints.